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A Study to Assess the Safety of Single Doses of GSK189075 in Subjects With Type 1 Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT00575159
Recruitment Status : Completed
First Posted : December 18, 2007
Results First Posted : October 9, 2017
Last Update Posted : October 9, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 1
Interventions Drug: GSK189075
Drug: placebo
Enrollment 10
Recruitment Details A total of 10 participants with type 1 diabetes mellitus (T1DM) were randomized in this study. Study was conducted between 31 Mach 2008 to 19 January 2009 at a single center in the United States (US).
Pre-assignment Details Participants were screened within 28 days of the first dose and a total of 10 participants were randomized to receive the study drug. The participants were admitted on Day -2 and were analyzed of all Baseline safety and glucose control on Day -1.
Arm/Group Title Overall Study Arm
Hide Arm/Group Description Participants received 5 treatments P0, P1, A, B, C in each of the treatment period in a randomized manner separated by a 5 to 35-day washout period between treatments, where Treatment P0 consisted of Basal insulin [continuous subcutaneous insulin injection (CSII)], mealtime placebo injection, and placebo tablet. Treatment P1 consisted of CSII, mealtime bolus insulin injection, and Placebo tablet. Treatment A consisted of CSII, mealtime placebo injection, GSK189075 50 milligram (mg) tablet. Treatment B consisted of CSII, mealtime placebo injection, GSK189075 150 mg tablet. Treatment C consisted of CSII, mealtime placebo injection, GSK189075 500 mg tablet. The two placebo sessions (P0 and P1) were designed to provide information about the relative efficacy of GSK189075 versus each individual participant’s usual mealtime insulin bolus. The number of tablets administered will be same for each treatment arm.
Period Title: Overall Study
Started 10
Completed 10
Not Completed 0
Arm/Group Title Overall Study Arm
Hide Arm/Group Description Participants received 5 treatments P0, P1, A, B, C in each of the treatment period in a randomized manner separated by a 5 to 35-day washout period between treatments, where Treatment P0 consisted of Basal insulin [continuous subcutaneous insulin injection (CSII)], mealtime placebo injection, and placebo tablet. Treatment P1 consisted of CSII, mealtime bolus insulin injection, and Placebo tablet. Treatment A consisted of CSII, mealtime placebo injection, GSK189075 50 mg tablet. Treatment B consisted of CSII, mealtime placebo injection, GSK189075 150 mg tablet. Treatment C consisted of CSII, mealtime placebo injection, GSK189075 500 mg tablet. The two placebo sessions (P0 and P1) were designed to provide information about the relative efficacy of GSK189075 versus each individual participant’s usual mealtime insulin bolus. The number of tablets administered will be same for each treatment arm.
Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants
42.9  (8.08)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
3
  30.0%
Male
7
  70.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
10
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE)
Hide Description Data for number of participants who presented one or more adverse events (serious or non serious) was reported. An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Time Frame Up to 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population comprised of all enrolled participants who have received at least one dose of study drug were included in the safety population.
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250 milliliter (mL) of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
3
  30.0%
4
  40.0%
5
  50.0%
6
  60.0%
4
  40.0%
Any SAE
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Number of Participants With Hypoglycemia Episodes/Events
Hide Description A hypoglycemic event was defined as symptoms of hypoglycemia confirmed by a blood glucose value below normal limits [less than 3.89 millimoles per liter (mmol/L)] or 70 milligrams per deciliter (mg/dL). Symptoms of hypoglycemia without confirmed blood glucose values were reported as AEs instead of hypoglycemic events. Number of participants with hypoglycemic events were reported.
Time Frame Day 1 of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
5
  50.0%
5
  50.0%
3
  30.0%
5
  50.0%
6
  60.0%
3.Primary Outcome
Title Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP)
Hide Description SBP and DBP were obtained during each treatment period at the indicated time points. Measurements were made with the participant lying semi-recumbent having rested in this position for at least 10 minute before the initial reading.
Time Frame Day 1 of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury (mmHg)
SBP,Day1,0.5 H 1.6  (10.63) -5.1  (5.32) -0.7  (18.03) -3.4  (12.97) -1.9  (8.82)
SBP,Day1,1 H 1.8  (14.70) -1.7  (9.17) -4.7  (12.78) -7.8  (8.77) 5.6  (14.75)
SBP,Day1,2 H -1.8  (14.01) -6.5  (6.29) -5.1  (14.30) -3.5  (13.19) -2.2  (9.38)
SBP,Day1,4 H -2.9  (11.86) -0.9  (7.56) -8.4  (8.37) -2.5  (18.52) -4.3  (7.49)
SBP,Day1,6 H -2.1  (9.88) -5.5  (13.10) -8.2  (7.18) -8.4  (15.43) -6.9  (13.58)
SBP,Day1,8 H -1.4  (13.12) -2.1  (10.80) -3.2  (10.21) -7.3  (18.50) -2.4  (12.56)
SBP,Day1,24 H 2.6  (7.27) -1.4  (11.77) -0.4  (9.54) -0.2  (12.20) -4.6  (12.85)
DBP,Day1,0.5 H -1.1  (10.36) -5.3  (9.38) -9.8  (11.73) -7.4  (13.13) -5.2  (13.36)
DBP,Day1,1 H -5.4  (11.61) -7.7  (12.31) -11.5  (8.32) -15.1  (11.06) -5.7  (9.59)
DBP,Day1,2 H -8.8  (7.50) -8.7  (11.29) -11.7  (10.04) -11.0  (12.72) -7.2  (10.55)
DBP,Day1,4 H -6.4  (7.52) -6.4  (13.08) -11.7  (7.45) -8.5  (13.04) -7.7  (9.84)
DBP,Day1,6 H -8.4  (8.88) -7.0  (10.70) -13.2  (8.31) -12.3  (15.36) -8.0  (12.91)
DBP,Day1,8 H -2.2  (7.79) -5.8  (9.24) -10.1  (5.76) -10.7  (15.40) -4.7  (15.05)
DBP,Day1,24 H 0.5  (9.97) 1.6  (11.55) -4.2  (6.71) -3.6  (11.51) -2.0  (9.51)
4.Primary Outcome
Title Change From Baseline Vital Signs: Heart Rate
Hide Description Heart rate was obtained during each treatment period at indicated time points. Measurements were made with the participants lying semi-recumbent having rested in this position for at least 10 minutes before the initial reading.
Time Frame Day 1 of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: beats/minute
Day 1,0.5 H -1.4  (9.69) -5.4  (8.57) -4.5  (7.21) -4.7  (7.58) -5.2  (12.67)
Day 1,1 H 1.7  (11.46) -2.8  (8.65) -1.4  (8.23) -4.3  (11.20) -5.1  (12.96)
Day 1,2 H 1.0  (13.79) -4.0  (7.90) -4.4  (8.22) -3.3  (7.42) -5.1  (14.05)
Day 1,4 H -1.4  (11.37) -4.6  (10.46) -6.5  (7.94) -2.6  (9.79) -6.8  (10.90)
Day 1,6 H 2.5  (11.20) -2.0  (8.46) -1.3  (10.36) 3.5  (11.54) -1.4  (12.17)
Day 1,8 H 0.7  (12.48) -6.6  (10.60) -4.6  (6.95) 1.6  (10.16) -3.4  (12.04)
Day 1,24 H 5.4  (13.92) 6.6  (11.67) 4.2  (10.99) 10.0  (11.50) 0.4  (12.39)
5.Primary Outcome
Title Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Hide Description Standard semi-recumbent 12-lead ECG was obtained after the participant rested for a minimum of 10 minutes (If questionable abnormality was noted on the ECG, 2 more measurements were allowed to provide an average of 3 measurements). Number of participants with abnormal ECG were reported.
Time Frame Day 1 of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
DAY -2
0
   0.0%
1
  10.0%
1
  10.0%
3
  30.0%
0
   0.0%
DAY -2 (2)
0
   0.0%
0
   0.0%
1
  10.0%
2
  20.0%
0
   0.0%
DAY -2 (3)
0
   0.0%
1
  10.0%
1
  10.0%
2
  20.0%
0
   0.0%
DAY -1
1
  10.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
DAY -1 (2)
1
  10.0%
0
   0.0%
1
  10.0%
0
   0.0%
0
   0.0%
DAY -1 (3)
1
  10.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
DAY 1 PRE-DOSE
1
  10.0%
3
  30.0%
3
  30.0%
2
  20.0%
3
  30.0%
DAY 1 PRE-DOSE (2)
1
  10.0%
3
  30.0%
3
  30.0%
3
  30.0%
3
  30.0%
DAY 1 PRE-DOSE (3)
1
  10.0%
3
  30.0%
3
  30.0%
3
  30.0%
3
  30.0%
DAY 1 4 H
2
  20.0%
1
  10.0%
2
  20.0%
3
  30.0%
3
  30.0%
DAY 1 24 H
2
  20.0%
0
   0.0%
1
  10.0%
2
  20.0%
1
  10.0%
6.Primary Outcome
Title Number of Participants With Abnormal Clinical Chemistry Data
Hide Description Clinical Chemistry data for parameters: Alanine Amino Transferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Bicarbonate, Calcium, Chloride, Creatine Kinase, Creatinine, Gamma Glutamyl Transferase (GGT), Glucose, Lactate Dehydrogenase, Magnesium, Phosphorus, Potassium, Total Bilirubin, Sodium, Total protein, triglycerides and urea/BUN was reported. Data for number of participants with abnormal clinical Chemistry data was presented.
Time Frame Day 1 of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specific time points were analyzed.
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
ALT,DAY 1, PRE-DOSE,Normal Number Analyzed 5 participants 6 participants 7 participants 6 participants 6 participants
4
  80.0%
5
  83.3%
6
  85.7%
6
 100.0%
5
  83.3%
ALT,DAY 1 ,PRE-DOSE,Low Number Analyzed 2 participants 6 participants 7 participants 6 participants 6 participants
1
  50.0%
1
  16.7%
1
  14.3%
0
   0.0%
1
  16.7%
ALT,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 10 participants 8 participants 10 participants
8
  80.0%
8
  80.0%
7
  70.0%
6
  75.0%
7
  70.0%
ALT,DAY 1, 24 H,Low Number Analyzed 10 participants 10 participants 10 participants 8 participants 10 participants
2
  20.0%
1
  10.0%
2
  20.0%
1
  12.5%
2
  20.0%
ALT,DAY 1, 24 H,Missing Number Analyzed 10 participants 10 participants 10 participants 8 participants 10 participants
0
   0.0%
1
  10.0%
1
  10.0%
1
  12.5%
1
  10.0%
Albumin,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
6
 100.0%
Albumin,DAY 1, 24 H,High Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
1
  10.0%
0
   0.0%
1
  10.0%
0
   0.0%
0
   0.0%
Albumin,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
9
  90.0%
10
 100.0%
9
  90.0%
10
 100.0%
10
 100.0%
ALP,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
6
 100.0%
ALP,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
AST,DAY 1, PRE-DOSE,Normal Number Analyzed 5 participants 6 participants 7 participants 6 participants 6 participants
5
 100.0%
6
 100.0%
6
  85.7%
5
  83.3%
6
 100.0%
AST,DAY 1 ,PRE-DOSE,Low Number Analyzed 5 participants 6 participants 7 participants 6 participants 6 participants
0
   0.0%
0
   0.0%
1
  14.3%
1
  16.7%
0
   0.0%
AST,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 10 participants 8 participants 10 participants
9
  90.0%
9
  90.0%
6
  60.0%
6
  75.0%
8
  80.0%
AST,DAY 1, 24 H,Low Number Analyzed 10 participants 10 participants 10 participants 8 participants 10 participants
1
  10.0%
1
  10.0%
3
  30.0%
2
  25.0%
2
  20.0%
AST,DAY 1, 24 H,Missing Number Analyzed 10 participants 10 participants 10 participants 8 participants 10 participants
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
0
   0.0%
Bicarbonate,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
6
  85.7%
6
 100.0%
6
 100.0%
Bicarbonate,DAY 1 ,PRE-DOSE,Low Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
Calcium,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
6
 100.0%
Chloride,DAY 1, PRE-DOSE,High Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Chloride,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
5
  83.3%
6
 100.0%
7
 100.0%
6
 100.0%
6
 100.0%
Chloride,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
Creatine Kinase,DAY 1, PRE-DOSE,High Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
2
  33.3%
2
  33.3%
2
  28.6%
1
  16.7%
1
  16.7%
Creatine Kinase,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
4
  66.7%
4
  66.7%
5
  71.4%
5
  83.3%
5
  83.3%
Creatinine,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
6
 100.0%
Creatinine,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
GGT,DAY 1, PRE-DOSE,Normal Number Analyzed 5 participants 5 participants 6 participants 6 participants 6 participants
5
 100.0%
5
 100.0%
5
  83.3%
6
 100.0%
6
 100.0%
GGT,DAY 1, PRE-DOSE,Missing Number Analyzed 5 participants 5 participants 6 participants 6 participants 6 participants
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
GGT,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 9 participants 10 participants 10 participants
10
 100.0%
10
 100.0%
9
 100.0%
10
 100.0%
10
 100.0%
Glucose,DAY 1, PRE-DOSE,High Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
3
  50.0%
5
  83.3%
4
  57.1%
3
  50.0%
0
   0.0%
Glucose,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
2
  33.3%
1
  16.7%
3
  42.9%
3
  50.0%
6
 100.0%
Glucose,DAY 1 ,PRE-DOSE,Low Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Glucose,DAY 1, 24 H,High Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
7
  70.0%
8
  80.0%
6
  60.0%
7
  70.0%
7
  70.0%
Glucose,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
3
  30.0%
2
  20.0%
3
  30.0%
3
  30.0%
3
  30.0%
Glucose,DAY 1, 24 H,Low Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
0
   0.0%
Lactate Dehydrogenase,DAY 1, PRE-DOSE,Normal Number Analyzed 5 participants 5 participants 6 participants 4 participants 5 participants
5
 100.0%
5
 100.0%
6
 100.0%
4
 100.0%
5
 100.0%
Magnesium,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
Phosphorus, inorganic,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
6
 100.0%
Potassium,DAY 1, PRE-DOSE,High Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
Potassium,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
6
  85.7%
6
 100.0%
6
 100.0%
Potassium,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 10 participants 8 participants 10 participants
10
 100.0%
10
 100.0%
10
 100.0%
8
 100.0%
10
 100.0%
Sodium,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
6
 100.0%
Sodium,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
Total Bilirubin,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
6
  85.7%
5
  83.3%
6
 100.0%
Total Bilirubin,DAY 1, PRE-DOSE,Low Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
0
   0.0%
0
   0.0%
1
  14.3%
1
  16.7%
0
   0.0%
Total Bilirubin,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
Total Protein,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
4
  66.7%
5
  83.3%
5
  71.4%
4
  66.7%
5
  83.3%
Total Protein,DAY 1 ,PRE-DOSE,Low Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
2
  33.3%
1
  16.7%
2
  28.6%
2
  33.3%
1
  16.7%
Total Protein,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
9
  90.0%
9
  90.0%
10
 100.0%
9
  90.0%
10
 100.0%
Total Protein,DAY 1, 24 H,Low Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
1
  10.0%
1
  10.0%
0
   0.0%
1
  10.0%
0
   0.0%
Triglycerides,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
6
 100.0%
Urea/BUN,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
6
 100.0%
Urea/BUN,DAY 1, 24 H,Normal Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
10
 100.0%
8
  80.0%
10
 100.0%
10
 100.0%
10
 100.0%
Urea/BUN,DAY 1, 24 H,Low Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
0
   0.0%
2
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
7.Primary Outcome
Title Number of Participants With Abnormal Hematology Data
Hide Description Data for abnormal Hematology parameters: Basophils, Eosinophils, Hematocrit, Hemoglobin, Lymphocytes, Mean Corpuscle Hemoglobin (MCH), Mean Corpuscle Volume (MCV), Monocytes, Platelet count, Red Blood Cell (RBC), Reticulocytes, Total Neutrophils, White Blood Cell (WBC) were reported. Data for number of participants with abnormal Hematology were reported.
Time Frame Day 1 of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specific time points were analyzed.
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
Basophils,DAY 1, PRE-DOSE,High Number Analyzed 6 participants 5 participants 7 participants 6 participants 6 participants
1
  16.7%
0
   0.0%
2
  28.6%
1
  16.7%
0
   0.0%
Basophils,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 5 participants 7 participants 6 participants 6 participants
5
  83.3%
5
 100.0%
5
  71.4%
5
  83.3%
6
 100.0%
Basophils,DAY 1, 24 H,High Number Analyzed 9 participants 9 participants 9 participants 9 participants 10 participants
2
  22.2%
1
  11.1%
0
   0.0%
0
   0.0%
2
  20.0%
Basophils,DAY 1, 24 H,Normal Number Analyzed 9 participants 9 participants 9 participants 9 participants 10 participants
7
  77.8%
8
  88.9%
9
 100.0%
9
 100.0%
8
  80.0%
Eosinophils,DAY 1, PRE-DOSE,High Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
5
  83.3%
5
  83.3%
5
  71.4%
5
  83.3%
6
 100.0%
Eosinophils,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
1
  16.7%
1
  16.7%
2
  28.6%
1
  16.7%
0
   0.0%
Eosinophils,DAY 1, 24 H,High Number Analyzed 9 participants 9 participants 9 participants 9 participants 10 participants
5
  55.6%
4
  44.4%
4
  44.4%
4
  44.4%
7
  70.0%
Eosinophils,DAY 1, 24 H,Normal Number Analyzed 9 participants 9 participants 9 participants 9 participants 10 participants
4
  44.4%
5
  55.6%
5
  55.6%
5
  55.6%
3
  30.0%
Hematocrit,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
2
  33.3%
1
  16.7%
4
  57.1%
2
  33.3%
2
  33.3%
Hematocrit,DAY 1 ,PRE-DOSE,Low Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
4
  66.7%
5
  83.3%
3
  42.9%
4
  66.7%
4
  66.7%
Hematocrit,DAY 1, 24 H,Normal Number Analyzed 9 participants 10 participants 9 participants 9 participants 10 participants
4
  44.4%
6
  60.0%
7
  77.8%
8
  88.9%
6
  60.0%
Hematocrit,DAY 1, 24 H,Low Number Analyzed 9 participants 10 participants 9 participants 9 participants 10 participants
5
  55.6%
4
  40.0%
2
  22.2%
1
  11.1%
4
  40.0%
Hemoglobin,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
4
  66.7%
4
  66.7%
6
  85.7%
5
  83.3%
5
  83.3%
Hemoglobin,DAY 1 ,PRE-DOSE,Low Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
2
  33.3%
2
  33.3%
1
  14.3%
1
  16.7%
1
  16.7%
Hemoglobin,DAY 1, 24 H,Normal Number Analyzed 9 participants 10 participants 9 participants 9 participants 10 participants
7
  77.8%
8
  80.0%
7
  77.8%
8
  88.9%
8
  80.0%
Hemoglobin,DAY 1, 24 H,Low Number Analyzed 9 participants 10 participants 9 participants 9 participants 10 participants
2
  22.2%
2
  20.0%
2
  22.2%
1
  11.1%
2
  20.0%
Lymphocytes,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
6
  85.7%
6
 100.0%
6
 100.0%
Lymphocytes,DAY 1 ,PRE-DOSE,Low Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
Lymphocytes,DAY 1, 24 H,High Number Analyzed 9 participants 9 participants 9 participants 9 participants 10 participants
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
Lymphocytes,DAY 1, 24 H,Normal Number Analyzed 9 participants 9 participants 9 participants 9 participants 10 participants
9
 100.0%
8
  88.9%
8
  88.9%
7
  77.8%
9
  90.0%
Lymphocytes,DAY 1, 24 H,Low Number Analyzed 9 participants 9 participants 9 participants 9 participants 10 participants
0
   0.0%
1
  11.1%
0
   0.0%
2
  22.2%
1
  10.0%
MCH,DAY 1, PRE-DOSE,High Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
4
  66.7%
3
  50.0%
4
  57.1%
2
  33.3%
2
  33.3%
MCH,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
2
  33.3%
3
  50.0%
3
  42.9%
4
  66.7%
4
  66.7%
MCHC,DAY 1, PRE-DOSE,High Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
4
  66.7%
4
  66.7%
5
  71.4%
5
  83.3%
3
  50.0%
MCHC,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
2
  33.3%
2
  33.3%
2
  28.6%
1
  16.7%
3
  50.0%
MCV,DAY 1, PRE-DOSE,High Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
1
  16.7%
1
  16.7%
2
  28.6%
1
  16.7%
1
  16.7%
MCV,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
5
  83.3%
5
  83.3%
5
  71.4%
5
  83.3%
5
  83.3%
Monocytes,DAY 1, PRE-DOSE,High Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
2
  33.3%
2
  33.3%
2
  28.6%
3
  50.0%
2
  33.3%
Monocytes,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
4
  66.7%
4
  66.7%
5
  71.4%
3
  50.0%
4
  66.7%
Monocytes,DAY 1, 24 H,High Number Analyzed 9 participants 9 participants 9 participants 9 participants 10 participants
0
   0.0%
1
  11.1%
1
  11.1%
1
  11.1%
1
  10.0%
Monocytes,DAY 1, 24 H,Normal Number Analyzed 9 participants 9 participants 9 participants 9 participants 10 participants
9
 100.0%
8
  88.9%
8
  88.9%
8
  88.9%
9
  90.0%
Platelet count,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
6
 100.0%
Platelet count,DAY 1, 24 H,Normal Number Analyzed 9 participants 10 participants 9 participants 9 participants 10 participants
9
 100.0%
10
 100.0%
9
 100.0%
8
  88.9%
10
 100.0%
Platelet count,DAY 1, 24 H,Low Number Analyzed 9 participants 10 participants 9 participants 9 participants 10 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
RBC,DAY 1 ,PRE-DOSE,Low Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
6
 100.0%
RBC,DAY 1, 24 H,Normal Number Analyzed 9 participants 10 participants 9 participants 9 participants 10 participants
2
  22.2%
2
  20.0%
3
  33.3%
4
  44.4%
1
  10.0%
RBC,DAY 1, 24 H,Low Number Analyzed 9 participants 10 participants 9 participants 9 participants 10 participants
7
  77.8%
8
  80.0%
6
  66.7%
5
  55.6%
9
  90.0%
Reticulocytes,DAY 1, PRE-DOSE,High Number Analyzed 6 participants 5 participants 6 participants 6 participants 6 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Reticulocytes,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 5 participants 6 participants 6 participants 6 participants
6
 100.0%
5
 100.0%
5
  83.3%
5
  83.3%
6
 100.0%
Reticulocytes,DAY 1, PRE-DOSE,Missing Number Analyzed 6 participants 5 participants 6 participants 6 participants 6 participants
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
Total Neutrophils,DAY 1, PRE-DOSE,High Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
0
   0.0%
1
  16.7%
1
  14.3%
1
  16.7%
0
   0.0%
Total Neutrophils,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
5
  83.3%
5
  83.3%
6
  85.7%
4
  66.7%
6
 100.0%
Total Neutrophils,DAY 1 ,PRE-DOSE,Low Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
1
  16.7%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Total Neutrophils,DAY 1, 24 H,High Number Analyzed 9 participants 9 participants 9 participants 9 participants 10 participants
2
  22.2%
2
  22.2%
1
  11.1%
1
  11.1%
3
  30.0%
Total Neutrophils,DAY 1, 24 H,Normal Number Analyzed 9 participants 9 participants 9 participants 9 participants 10 participants
7
  77.8%
7
  77.8%
8
  88.9%
8
  88.9%
7
  70.0%
WBC,DAY 1, PRE-DOSE,Normal Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
3
  50.0%
3
  50.0%
4
  57.1%
3
  50.0%
3
  50.0%
WBC,DAY 1 ,PRE-DOSE,Low Number Analyzed 6 participants 6 participants 7 participants 6 participants 6 participants
3
  50.0%
3
  50.0%
3
  42.9%
3
  50.0%
3
  50.0%
WBC,DAY 1, 24 H,Normal Number Analyzed 9 participants 10 participants 9 participants 9 participants 10 participants
8
  88.9%
7
  70.0%
8
  88.9%
9
 100.0%
7
  70.0%
WBC,DAY 1, 24 H,Low Number Analyzed 9 participants 10 participants 9 participants 9 participants 10 participants
1
  11.1%
3
  30.0%
1
  11.1%
0
   0.0%
3
  30.0%
8.Primary Outcome
Title Summary of Urine Osmolality
Hide Description Urine sample was collected at screening, Day –2 (18:00h) and Day 1 (7:45h) for determination of urine osmolality which was measured in Millimole per kilogram (mmol/kg).
Time Frame Day 1 (pre dose) of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: mmol/kg
DAY -2 Number Analyzed 9 participants 10 participants 8 participants 8 participants 10 participants
631.8  (226.85) 651.6  (229.44) 647.1  (314.81) 618.3  (314.15) 702.2  (167.39)
DAY 1,PRE-DOSE Number Analyzed 6 participants 5 participants 6 participants 4 participants 6 participants
330.5  (88.89) 364.4  (100.89) 425.0  (257.05) 304.3  (73.13) 441.8  (87.61)
9.Primary Outcome
Title Mean Creatinine Clearance
Hide Description Creatinine clearance was calculated and reported in Milliliters per minute (mL/min) on Day 1 of each period for each collection interval 0-4, 4-8, 8-12, 12-16 and 16-24 hour, as well as the combined intervals of 0-12 and 0-24 hour. For urine measurements, participants were instructed to void within 30 minutes before administration of study medication.
Time Frame Up to 24 hours post dose of each treatment period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: mL/min
0-4 H Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
116.9  (43.28) 134.5  (38.76) 130.2  (44.13) 142.2  (66.83) 134.3  (61.43)
4-8 H Number Analyzed 10 participants 10 participants 10 participants 10 participants 9 participants
111.5  (42.94) 129.6  (54.27) 122.7  (52.45) 102.3  (31.01) 134.0  (34.48)
8-12 H Number Analyzed 10 participants 10 participants 10 participants 10 participants 9 participants
131.3  (63.82) 123.3  (52.40) 105.6  (37.92) 140.6  (54.35) 120.4  (43.29)
12-16 H Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
120.8  (49.47) 117.9  (66.22) 125.3  (78.45) 89.5  (50.43) 117.8  (61.66)
16-24 H Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants
100.5  (40.47) 119.5  (62.30) 120.8  (33.73) 126.4  (64.91) 120.0  (33.91)
0-12 H Number Analyzed 10 participants 10 participants 10 participants 10 participants 9 participants
119.9  (34.08) 129.1  (28.34) 119.5  (28.74) 128.4  (37.85) 132.7  (24.28)
0-24 H Number Analyzed 10 participants 10 participants 10 participants 10 participants 9 participants
113.6  (30.30) 124.0  (35.48) 120.9  (30.05) 121.3  (38.01) 128.2  (26.45)
10.Primary Outcome
Title Summary of Fluid Balance
Hide Description On Day 1, fluid intake, urine volume and number of micturations were recorded over the intervals for each of the following dosing periods: 0-4h, 4-8h, 8-12h, 12-16h and 16-24h. From these measures, fluid balance was calculated over the 24-hour period. Fluid Balance=total fluid intake minus total urine volume. The 0-24h amounts of total Fluid Intake, total urine output, and fluid balance were calculated by adding the amounts collected during these time intervals.
Time Frame Up to 24 hours post dose of each treatment period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population.
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: Milliliters (mL)
Total Fluid Intake,0-4h 1240.0  (372.32) 1274.4  (407.31) 1221.0  (278.07) 1009.5  (155.64) 1201.0  (355.73)
Total Fluid Intake,0-24h 4196.3  (1399.83) 4210.0  (1034.02) 3934.7  (762.13) 4164.4  (853.18) 3998.2  (1110.77)
Total urine output,0-4h 1031.0  (277.04) 1107.0  (294.54) 1670.5  (451.39) 1546.5  (593.86) 1212.0  (424.94)
Total urine output,0-24h 4669.0  (757.00) 4421.0  (741.14) 5168.0  (1212.52) 5004.0  (884.00) 4941.0  (962.68)
Fluid Balance,0-4h 209.0  (352.43) 167.4  (468.47) -449.5  (533.77) -537.0  (607.98) -11.0  (541.71)
Fluid Balance,0-24h -472.7  (1076.26) -211.0  (984.94) -1233.3  (841.19) -839.6  (772.69) -942.8  (513.29)
11.Primary Outcome
Title Mean of Derived Plasma Glucose Parameters
Time Frame Up to 24 hours post dose of each treatment period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population.
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: mmol/L
Pre-Dose 5.75639  (1.285496) 6.65953  (1.165222) 6.18659  (1.696588) 5.72419  (0.850452) 5.86796  (0.881584)
2 h 18.26279  (2.222558) 13.70542  (4.831705) 16.11455  (3.711572) 14.76566  (2.542980) 15.00435  (3.158931)
4 h 15.31521  (3.646185) 9.47778  (4.288005) 11.52943  (3.154919) 10.68068  (3.161241) 11.04094  (3.184558)
6 h 19.53952  (4.101401) 9.91464  (3.978186) 16.02019  (4.685123) 14.97660  (5.647356) 15.50949  (4.792842)
8 h 18.01300  (5.158167) 8.87790  (2.958162) 14.21611  (5.359803) 13.69432  (6.375146) 14.47146  (5.477677)
12 h 14.67129  (6.061024) 11.34791  (3.897886) 12.95048  (4.566692) 11.31849  (3.376891) 11.87914  (4.053962)
12.Secondary Outcome
Title Incremental Adjusted Weighted Means of Plasma Glucose AUC(0-4) and AUC(0-10) on Day 1
Hide Description AUC(0-10) was the plasma glucose weighted mean AUC for 0 to 10 h post-dosing and AUC(0-4) was the plasma glucose weighted mean AUC for 0 to 4 h post-dosing. Incremental Adjusted Weighted Means were presented.
Time Frame Up to 24 hours post dose of each treatment period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: mmol/L
AUC(0-4) 8.739  (2.4304) 4.480  (2.9942) 6.632  (2.0126) 6.044  (1.9444) 6.099  (2.3135)
AUC(0-10) 10.535  (3.8388) 3.127  (2.2467) 7.112  (3.3103) 6.653  (3.2809) 7.054  (3.5440)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 50mg
Comments Difference from placebo to GSK189075 50mg AUC(0-4) Incremental Adjusted Weighted Mean
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -2.728
Confidence Interval (2-Sided) 95%
-4.219 to -1.236
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 150mg
Comments Difference from placebo toGSK189075 150mg AUC(0-4) Incremental Adjusted Weighted Mean
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.325
Confidence Interval (2-Sided) 95%
-3.735 to -0.916
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500mg
Comments Difference from placebo to GSK189075 500mg AUC(0-4) Incremental Adjusted Weighted Mean
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.402
Confidence Interval (2-Sided) 95%
-3.862 to -0.942
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo+ Prandial Insulin, GSK189075 50mg
Comments Difference from Placebo+ Prandial insulin to GSK189075 50mg AUC(0-4) Incremental Adjusted Weighted Mean
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0382
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.556
Confidence Interval (2-Sided) 95%
0.090 to 3.021
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo+ Prandial Insulin, GSK189075 150mg
Comments Difference from Placebo+ Prandial insulin to GSK189075 150mg AUC(0-4) Incremental Adjusted Weighted Mean
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0132
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.958
Confidence Interval (2-Sided) 95%
0.439 to 3.477
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo+ Prandial Insulin, GSK189075 500mg
Comments Difference from Placebo+ Prandial insulin to GSK189075 500mg AUC(0-4) Incremental Adjusted Weighted Mean
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0161
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.881
Confidence Interval (2-Sided) 95%
0.373 to 3.389
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 50mg
Comments Difference from placebo to GSK189075 50mg AUC(0-10) Incremental Adjusted Weighted Mean
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.592
Confidence Interval (2-Sided) 95%
-5.162 to -2.022
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 150mg
Comments Difference from placebo to GSK189075 150mg AUC(0-10) Incremental Adjusted Weighted Mean
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0000
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.820
Confidence Interval (2-Sided) 95%
-5.304 to -2.337
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK189075 500mg
Comments Difference from placebo to GSK189075 500mg AUC(0-10) Incremental Adjusted Weighted Mean
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.887
Confidence Interval (2-Sided) 95%
-4.424 to -1.350
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo+ Prandial Insulin, GSK189075 50mg
Comments Difference from Placebo+ Prandial insulin to GSK189075 50mg AUC(0-10) Incremental Adjusted Weighted Mean
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.953
Confidence Interval (2-Sided) 95%
1.411 to 4.496
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo+ Prandial Insulin, GSK189075 150mg
Comments Difference from Placebo+ Prandial insulin to GSK189075 150mg AUC(0-10) Incremental Adjusted Weighted Mean
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.725
Confidence Interval (2-Sided) 95%
1.126 to 4.324
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo+ Prandial Insulin, GSK189075 500mg
Comments Difference from Placebo+ Prandial insulin to GSK189075 500mg AUC(0-10) Incremental Adjusted Weighted Mean
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.659
Confidence Interval (2-Sided) 95%
2.071 to 5.246
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Urinary Glucose Excretion (UGE) for Timed Subintervals up to 24 Hours Post Dose (0-24 H)
Hide Description UGE was assessed for timed subintervals up to 24h post-dose. Urine samples were collected at intervals: 0-4h, 4-8h, 8-12h, 12-16h and 16-24h on study days. The 0-24h amounts excreted in urine were calculated by adding the amounts collected during these time intervals.
Time Frame Up to 24 hours post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: mmol
324.849  (252.6604) 135.119  (191.6857) 579.060  (227.9230) 601.879  (206.4860) 770.249  (245.1817)
14.Secondary Outcome
Title Percent of Filtered Glucose in the Urine.
Hide Description Filtered glucose in the urine was assessed at indicated time points and was presented as Percentage. The 0-12h and 0-24h amounts Percent of filtered glucose in the urine were calculated by adding the amounts collected during these time intervals.
Time Frame Up to 24 hours post dose of each treatment period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: Percentage
0-4 H 10.8661  (6.21239) 6.5576  (5.24295) 40.4788  (7.00049) 41.5290  (14.95891) 41.3449  (12.49532)
0-12 H 16.7543  (9.04186) 7.0663  (8.62344) 42.3900  (5.75325) 47.5648  (10.41524) 47.8442  (12.01952)
0-24 H 11.1012  (5.76206) 5.6518  (5.12934) 25.4355  (4.74207) 29.9386  (5.99518) 34.5245  (10.00663)
15.Secondary Outcome
Title Mean Total Urine Volume 0-24 H
Hide Description Urine volume was recorded over intervals : 0-4h, 4-8h, 8-12h, 12-16h and 16- 24h on Day 1 for each dosing period. Mean total Urine volume over 24 hours was presented.
Time Frame Day 1 of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: mL
4628.5  (746.74) 4623.0  (828.93) 5267.5  (1077.76) 4962.0  (885.86) 5274.4  (899.07)
16.Secondary Outcome
Title Mean Creatinine Clearance 0-24 H
Hide Description Urine samples for calculating creatinine clearance were obtained over the intervals: 0-4h, 4-8h, 8-12h, 12-16h and 16-24h. Mean creatinine clearance over 0-24 H was presented.
Time Frame Day 1 of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10 10 10
Mean (Standard Deviation)
Unit of Measure: mL/min
113.6  (30.30) 124.0  (35.48) 120.9  (30.05) 121.3  (38.01) 128.2  (26.45)
17.Secondary Outcome
Title Area Under the Plasma Concentration vs. Time Curve (AUC) From Time Zero (Time of Dosing) to the Last Time Point With Measurable Analyte Concentration, AUC(0-last), AUC From Time Zero to Infinite Time, AUC(0-inf) of GSK189075 Over Period
Hide Description AUC(0-last) was defined as area under the plasma concentration vs. time curve from time zero (time of dosing) to the last time point with measurable analyte concentration and AUC(0-inf) was defined as area under the plasma concentration vs. time curve from time zero to infinite time. Blood samples were collected on time points: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period.
Time Frame Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour*nanograms per milliliter (hr*ng/mL)
AUC(0-inf)
8.101
(24%)
25.922
(38%)
58.362
(60%)
AUC(0-last)
3.966
(95%)
16.552
(57%)
47.390
(67%)
18.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of GSK189075 Over Period
Hide Description Plasma samples for pharmacokinetic analysis were drawn at indicated time points of each treatment period. Cmax was defined as maximal measured plasma concentration over the time span specified. Values were reported as Geometric Means with respective Geometric Coefficient of Variation (% CV).
Time Frame Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
5.266
(90%)
11.903
(92%)
39.029
(128%)
19.Secondary Outcome
Title Time to Maximum Observed Plasma Concentration (Tmax) and Terminal Half Life, (T1/2) of GSK189075 Over Period
Hide Description Tmax was defined as the time to the maximum or “peak” concentration of a drug observed after multiple administration. T1/2 was defined as the time to when half of the total amount of a particular substance is eliminated from the body. Blood samples obtained during indicated time points. T1/2 was calculated as t1/2 = ln2/λz, with λz (the terminal elimination rate-constant) estimated from log-linear regression analysis of the terminal phase of the plasma concentration-time profile.Tmax and t1/2 values for GSK189075 were presented.
Time Frame Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at specified time points were analyzed.
Arm/Group Title GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour
Tmax Number Analyzed 10 participants 10 participants 10 participants
0.446
(68%)
0.521
(81%)
1.054
(145%)
t1/2 Number Analyzed 5 participants 5 participants 5 participants
0.915
(20%)
1.019
(41%)
0.678
(29%)
20.Secondary Outcome
Title AUC From Time Zero to 4 Hours Post Dose, AUC(0-4) for GSK189074 Over Period
Hide Description AUC(0-4) was defined as AUC from time zero to 4 hours post dose. Blood samples were collected on time points: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period.
Time Frame Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
243.281
(34%)
700.970
(38%)
2038.298
(34%)
21.Secondary Outcome
Title Oral Clearance (CL/F) Over Period
Hide Description Oral clearance is a measure of the rate at which the drug is cleared from the body via metabolism. Blood samples were collected on time points: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
Time Frame Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL/min
2849.947
(36%)
2732.322
(41%)
2903.590
(37%)
22.Secondary Outcome
Title The Metabolite to Parent AUC Ratio, AUCmetabolite/AUCparent Ratio for GSK189074 Over Period
Hide Description Blood samples were collected on time points: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period to obtain the metabolite to parent AUC ratio for GSK189074
Time Frame Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
90.436
(70%)
67.801
(36%)
74.281
(52%)
23.Secondary Outcome
Title The Metabolite to Parent AUC Ratio, AUCmetabolite/AUCparent Ratio for GSK279782 Over Period
Hide Description Blood samples were collected on time points: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period to obtain the metabolite to parent AUC ratio for GSK279782
Time Frame Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Parameter Population comprised of all participants for whom pharmacokinetic parameter estimates were derived during any treatment period
Arm/Group Title GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description:
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
Overall Number of Participants Analyzed 10 10 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio
0.427
(58%)
0.442
(60%)
0.433
(55%)
Time Frame Approximately up to 6 months
Adverse Event Reporting Description Safety population was used.
 
Arm/Group Title Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Hide Arm/Group Description Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water. Participants received a single dose of Basal insulin (CSII), mealtime bolus insulin injection and matching GSK189075 placebo tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water. Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 50 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water. Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 150 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water. Participants received a single dose of Basal insulin (CSII), mealtime placebo injection and GSK189075 500 mg tablet. On Day 1, all study doses and mealtime insulin boluses were administered 15 minutes before the Participant begins to eat the scheduled meal (on dosing day, breakfast was the oral glucose load; lunch was the standard meal). On Day -1 (day prior to dosing day), basal insulin and insulin boluses before each meal were administered by the continuous insulin infusion pump. Study medication was administered orally in a fasted state before breakfast with 250mL of water.
All-Cause Mortality
Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%)   0/10 (0.00%)   0/10 (0.00%)   0/10 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%)   0/10 (0.00%)   0/10 (0.00%)   0/10 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Placebo+ Prandial Insulin GSK189075 50mg GSK189075 150mg GSK189075 500mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/10 (30.00%)   4/10 (40.00%)   5/10 (50.00%)   6/10 (60.00%)   4/10 (40.00%) 
Gastrointestinal disorders           
Abdominal pain lower  1  0/10 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/10 (10.00%) 
Dyspepsia  1  0/10 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/10 (0.00%) 
Nausea  1  0/10 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/10 (0.00%) 
General disorders           
Catheter site related reaction  1  0/10 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/10 (0.00%)  0/10 (0.00%) 
Discomfort  1  0/10 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/10 (0.00%) 
Infections and infestations           
Bronchitis  1  0/10 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/10 (0.00%) 
Injury, poisoning and procedural complications           
Muscle strain  1  1/10 (10.00%)  0/10 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/10 (0.00%) 
Thermal burn  1  0/10 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/10 (0.00%) 
Nervous system disorders           
Headache  1  2/10 (20.00%)  2/10 (20.00%)  3/10 (30.00%)  2/10 (20.00%)  2/10 (20.00%) 
Psychiatric disorders           
Insomnia  1  0/10 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  1/10 (10.00%)  1/10 (10.00%) 
Respiratory, thoracic and mediastinal disorders           
Dry throat  1  0/10 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/10 (0.00%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00575159     History of Changes
Other Study ID Numbers: KGI107465
First Submitted: December 14, 2007
First Posted: December 18, 2007
Results First Submitted: August 1, 2017
Results First Posted: October 9, 2017
Last Update Posted: October 9, 2017