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A Study in Type 2 Diabetic Subjects on Stable Metformin Therapy to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Co-administering Single and Multiple Oral Doses of GSK1292263

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ClinicalTrials.gov Identifier: NCT01128621
Recruitment Status : Completed
First Posted : May 24, 2010
Results First Posted : October 16, 2017
Last Update Posted : October 16, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Single (Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: GSK1292263
Drug: GSK1292263 matching placebo
Drug: Sitagliptin
Enrollment 66
Recruitment Details The study was conducted at two study centers in the United States from 23 November 2009 up to 12 April 2010. The study consisted of open label Part A and single-blind Part B. Total 6 participants were randomized in Part A whereas total 67 participants were randomized in Part B.
Pre-assignment Details  
Arm/Group Title Part A: GSK1292263 300 mg Part B: GSK1292263 75 mg/300 mg/ 600 mg
Hide Arm/Group Description Participants received a single dose of oral 300 milligrams (mg) tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day). Participants received one of three dosing regimens of GSK1292263: 75 mg twice daily (BID) (as 1 x 75 mg tablet GSK1292263 + 2 placebo tablets in morning and evening), 300 mg BID (as 1 x 200 mg tablet + 1 x 75 mg tablet + 1 x 25 mg tablet GSK1292263 in morning and evening) and 600 mg once daily (QD) (as 3 x 200 mg tablets GSK1292263 in morning + 3 x placebo tablets in evening) or matching placebo BID (as 3 x placebo tablets in morning and evening), or open-label sitagliptin 50 mg BID for 14 days. Seven days before enrollment in Part B, participants taking metformin three times daily (TID) or using an extended-release formulation were converted to the equivalent total daily dose of immediate release metformin administered BID.
Period Title: Part A: GSK1292263 300 mg
Started 6 0
Completed 6 0
Not Completed 0 0
Period Title: Part B: GSK1292263 75 mg/300 mg/ 600 mg
Started 0 67
Completed 0 65
Not Completed 0 2
Reason Not Completed
Reached defined stopping criteria             0             2
Arm/Group Title Part A: GSK1292263 300 mg Part B: GSK1292263 75 mg/300 mg/ 600 mg Total
Hide Arm/Group Description Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day). Participants received one of three dosing regimens of GSK1292263: 75 mg twice daily (BID) (as 1 x 75 mg tablet GSK1292263 + 2 placebo tablets in morning and evening), 300 mg BID (as 1 x 200 mg tablet + 1 x 75 mg tablet + 1 x 25 mg tablet GSK1292263 in morning and evening) and 600 mg once daily (QD) (as 3 x 200 mg tablets GSK1292263 in morning + 3 x placebo tablets in evening) or matching placebo BID (as 3 x placebo tablets in morning and evening), or open-label sitagliptin 50 mg BID for 14 days. Seven days before enrollment in Part B, participants taking metformin three times daily (TID) or using an extended-release formulation were converted to the equivalent total daily dose of immediate release metformin administered BID. Total of all reporting groups
Overall Number of Baseline Participants 6 67 73
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
36 to 65 Years Number Analyzed 6 participants 67 participants 73 participants
6
 100.0%
67
 100.0%
73
 100.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 67 participants 73 participants
Female
1
  16.7%
28
  41.8%
29
  39.7%
Male
5
  83.3%
39
  58.2%
44
  60.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 67 participants 73 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  33.3%
6
   9.0%
8
  11.0%
White
4
  66.7%
61
  91.0%
65
  89.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) (Part A)
Hide Description An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.
Time Frame Up to 10 days after discharge (Day 2) in Part A
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
0
   0.0%
Any SAE
0
   0.0%
2.Primary Outcome
Title Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B)
Hide Description An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.
Time Frame Up to 10 days after discharge (Day 15) in Part B
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 15 13
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
2
  14.3%
3
  23.1%
3
  25.0%
4
  26.7%
5
  38.5%
Any SAE
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3.Primary Outcome
Title Number of Participants With Abnormal Hematology Values of Potential Clinical Importance (PCI) (Part A)
Hide Description Blood samples for hematology assessments were collected at screening, fasting (Day -1), at 24hr post- dose (morning of Day 2), and at follow-up. Hematology parameter: Total Neutrophil count was assessed for abnormal value of PCI. The range of PCI value was: <0.83 x lower limit normal (LLN) with unit x10^9 per liter
Time Frame Up to 10 days after discharge (Day 2) in Part A
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
1
  16.7%
4.Primary Outcome
Title Number of Participants With Abnormal Hematology Values of PCI (Part B)
Hide Description Blood samples for hematology assessments were collected at screening, on Day -2 (non-fasting), and prior to breakfast (early in the morning, fasting) on Days 1, 7, and on Day 15 prior to checkout, (=24hrs post-dose), and at follow-up. Hematology parameters: Hematocrit (unit: ratio) and hemoglobin (unit: grams per liter [g/L]), were assessed for abnormal values of PCI. The PCI range for hematocrit was: >0.075 decrease from Baseline (low), >1.02 x upper limit normal (ULN) (high-male), >1.17 x ULN (high-female). The PCI range for hemoglobin was: >25 decrease from Baseline (low), >1.03 x ULN (high-male), >1.13 x ULN (high-female). Data has been presented for the number of participants with hematology data values high from the PCI range in a consolidated format.
Time Frame Up to 10 days after discharge (Day 15) in Part B
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 15 13
Measure Type: Count of Participants
Unit of Measure: Participants
Hematocrit, high
0
   0.0%
1
   7.7%
0
   0.0%
1
   6.7%
0
   0.0%
Hemoglobin, high
0
   0.0%
1
   7.7%
1
   8.3%
1
   6.7%
1
   7.7%
5.Primary Outcome
Title Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part A)
Hide Description

Blood samples for chemistry assessments were collected at screening, fasting (Day -1), at 24hr post- dose (morning of Day 2), and at follow-up.

Clinical chemistry parameter: Glucose (unit: millimoles per liter [mmol/L]) was assessed for abnormal high value of PCI. The normal range was 3.6 to 5.5 mmol/L

Time Frame Up to 10 days after discharge (Day 2) in Part A
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
1
  16.7%
6.Primary Outcome
Title Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B)
Hide Description Blood samples for chemistry assessments were collected at screening, on Day -2 (non-fasting), and prior to breakfast (early in the morning, fasting) on Days 1, 7, and on Day 15 prior to checkout, (=24hrs post-dose), and at follow-up. Clinical chemistry parameters: Aspartate amino transferase (unit: international unit per liter [IU/L]) and Total bilirubin (unit: micromoles per liter (µmol/L) were assessed for abnormal values of PCI. For aspartate aminotransferase the PCI range was >=2 x ULN (high). For total bilirubin the PCI range was >=1.5 x ULN (high).
Time Frame Up to 10 days after discharge (Day 15) in Part B
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 15 13
Measure Type: Count of Participants
Unit of Measure: Participants
Aspartate aminotransferase, high
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
Total bilirubin, high
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
7.Primary Outcome
Title Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A)
Hide Description Urinalysis parameters: Urine occult blood, Urine Glucose, Urine ketones and Urine protein were assessed for abnormal findings by dipstick analysis. The abnormalities were presented as trace, 1+, 2+ and 3+. Trace indicates lowest concentration of the mentioned parameters in urine and 3+ indicates highest concentration. Concentration of 3+ indicates worse outcome.
Time Frame Up to 10 days after discharge (Day 2) in Part A
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
Urine occult blood, Day 1, 24 hours, trace
1
  16.7%
Urine occult blood, follow up, trace
1
  16.7%
Urine glucose, Day 1, 24 hours, 3+
1
  16.7%
Urine glucose, follow up, 3+
1
  16.7%
Urine glucose, follow up, trace
2
  33.3%
Urine ketones, follow up, trace
2
  33.3%
Urine protein, Day 1, 24 hours, trace
1
  16.7%
Urine protein, follow up, trace
2
  33.3%
8.Primary Outcome
Title Number of Participants With Abnormal Urinalysis Data Values (Part B)
Hide Description Urinalysis parameters: Urine occult blood, Urine glucose, Urine ketones, Urine protein, White blood cells were assessed for abnormal findings by dipstick analysis. The abnormal findings were presented as trace, 1+, 2+ and 3+. Trace indicates lowest concentration of the mentioned parameters in urine and 3+ indicates highest concentration. Concentration of 3+ indicates worse outcome.
Time Frame Up to 10 days after discharge (Day 15) in Part B
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 GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 15 13
Measure Type: Count of Participants
Unit of Measure: Participants
Urine occult blood, Day 1, pre-breakfast, 3+ Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
Urine occult blood, Day 1, pre-breakfast, trace Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
2
  15.4%
0
   0.0%
0
   0.0%
0
   0.0%
Urine occult blood, Day 7, pre-breakfast, trace Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
1
   7.7%
1
   8.3%
0
   0.0%
0
   0.0%
Urine occult blood, Day 14, 24 hours, trace Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
2
  14.3%
2
  15.4%
0
   0.0%
2
  14.3%
0
   0.0%
Urine occult blood, follow up, trace Number Analyzed 13 participants 10 participants 12 participants 12 participants 12 participants
0
   0.0%
2
  20.0%
0
   0.0%
1
   8.3%
0
   0.0%
Urine glucose, Day 1, pre-breakfast, 1+ Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine glucose, Day 1, pre-breakfast, 2+ Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine glucose, Day 1, pre-breakfast, 3+ Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
0
   0.0%
1
   8.3%
1
   6.7%
0
   0.0%
Urine glucose, Day 1, pre-breakfast, trace Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
0
   0.0%
2
  15.4%
0
   0.0%
1
   6.7%
1
   7.7%
Urine glucose, Day 7, pre-breakfast, 1+ Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Urine glucose, Day 7, pre-breakfast, 2+ Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
Urine glucose, Day 7, pre-breakfast, trace Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
0
   0.0%
2
  16.7%
0
   0.0%
0
   0.0%
Urine glucose, Day 14, 24 hours, 3+ Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
0
   0.0%
0
   0.0%
1
   8.3%
1
   7.1%
0
   0.0%
Urine glucose, Day 14, 24 hours, trace Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
0
   0.0%
1
   7.7%
1
   8.3%
1
   7.1%
0
   0.0%
Urine glucose, follow up, 1+ Number Analyzed 13 participants 12 participants 12 participants 13 participants 12 participants
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
Urine glucose, follow up, 2+ Number Analyzed 13 participants 12 participants 12 participants 13 participants 12 participants
1
   7.7%
2
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
Urine glucose, follow up, 3+ Number Analyzed 13 participants 12 participants 12 participants 13 participants 12 participants
1
   7.7%
0
   0.0%
4
  33.3%
2
  15.4%
0
   0.0%
Urine glucose, follow up, trace Number Analyzed 13 participants 12 participants 12 participants 13 participants 12 participants
2
  15.4%
2
  16.7%
1
   8.3%
2
  15.4%
1
   8.3%
Urine ketones, Day 1, pre-breakfast, trace Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
0
   0.0%
1
   7.7%
0
   0.0%
1
   6.7%
0
   0.0%
Urine ketones, Day 7, pre-breakfast, trace Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
0
   0.0%
0
   0.0%
1
   8.3%
2
  13.3%
0
   0.0%
Urine ketones, Day 14, 24 hours, trace Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
0
   0.0%
1
   7.7%
2
  16.7%
0
   0.0%
0
   0.0%
Urine ketones, follow up, 1+ Number Analyzed 13 participants 12 participants 12 participants 13 participants 12 participants
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
Urine ketones, follow up, trace Number Analyzed 13 participants 12 participants 12 participants 13 participants 12 participants
0
   0.0%
0
   0.0%
1
   8.3%
4
  30.8%
0
   0.0%
Urine protein, Day 1, pre-breakfast, trace Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
0
   0.0%
2
  15.4%
0
   0.0%
2
  13.3%
1
   7.7%
Urine protein, Day 7, pre-breakfast, 1+ Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
Urine protein, Day 7, pre-breakfast, trace Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
2
  15.4%
1
   8.3%
1
   6.7%
0
   0.0%
Urine protein, Day 14, 24 hours, trace Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
0
   0.0%
2
  15.4%
3
  25.0%
1
   7.1%
0
   0.0%
Urine protein, follow up, 1+ Number Analyzed 13 participants 12 participants 12 participants 13 participants 12 participants
1
   7.7%
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
Urine protein, follow up, 2+ Number Analyzed 13 participants 12 participants 12 participants 13 participants 12 participants
1
   7.7%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
Urine protein, follow up, trace Number Analyzed 13 participants 12 participants 12 participants 13 participants 12 participants
3
  23.1%
3
  25.0%
4
  33.3%
4
  30.8%
1
   8.3%
White blood cells, Day 1, pre-breakfast, 1+ Number Analyzed 13 participants 11 participants 10 participants 9 participants 11 participants
2
  15.4%
1
   9.1%
2
  20.0%
0
   0.0%
0
   0.0%
White blood cells, Day 1, pre-breakfast, trace Number Analyzed 13 participants 11 participants 10 participants 9 participants 11 participants
2
  15.4%
1
   9.1%
1
  10.0%
1
  11.1%
1
   9.1%
White blood cells, Day 7, pre-breakfast, 1+ Number Analyzed 13 participants 11 participants 10 participants 9 participants 11 participants
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
0
   0.0%
White blood cells, Day 7, pre-breakfast, trace Number Analyzed 13 participants 11 participants 10 participants 9 participants 11 participants
1
   7.7%
1
   9.1%
2
  20.0%
0
   0.0%
1
   9.1%
White blood cells, Day 14, 24 hours, 1+ Number Analyzed 13 participants 11 participants 10 participants 9 participants 11 participants
0
   0.0%
1
   9.1%
0
   0.0%
0
   0.0%
1
   9.1%
White blood cells, Day 14, 24 hours, trace Number Analyzed 13 participants 11 participants 10 participants 9 participants 11 participants
5
  38.5%
1
   9.1%
0
   0.0%
1
  11.1%
1
   9.1%
White blood cells, follow up, 1+ Number Analyzed 12 participants 10 participants 10 participants 7 participants 10 participants
0
   0.0%
1
  10.0%
0
   0.0%
0
   0.0%
0
   0.0%
White blood cells, follow up, 2+ Number Analyzed 12 participants 10 participants 10 participants 7 participants 10 participants
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White blood cells, follow up, trace Number Analyzed 12 participants 10 participants 10 participants 7 participants 10 participants
2
  16.7%
0
   0.0%
1
  10.0%
0
   0.0%
0
   0.0%
9.Primary Outcome
Title Mean Value of Urine Albumin at Follow up (Part A)
Hide Description Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urine albumin was assessed using quantitative analysis.
Time Frame Up to 10 days after discharge (Day 2) in Part A
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Arm A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 1
Mean (Standard Deviation)
Unit of Measure: milligrams per liter (mg/L)
6.0 [1]   (NA)
[1]
Not available as only 1 participant was analyzed
10.Primary Outcome
Title Mean Value of Urine Albumin (Part B)
Hide Description Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urine albumin was assessed using quantitative analysis.
Time Frame Up to 10 days after discharge (Day 15) in Part B
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 GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 15 13
Mean (Standard Deviation)
Unit of Measure: mg/L
Day 1, pre-breakfast Number Analyzed 4 participants 3 participants 3 participants 3 participants 5 participants
15.3  (11.30) 17.7  (11.50) 8.7  (5.51) 15.7  (8.33) 6.6  (0.89)
Day 7, pre-breakfast Number Analyzed 3 participants 4 participants 2 participants 6 participants 3 participants
8.0  (1.73) 19.5  (27.67) 24.5  (20.51) 24.0  (22.60) 7.3  (1.53)
Day 14, 24 hours Number Analyzed 4 participants 3 participants 5 participants 4 participants 5 participants
7.8  (2.50) 28.3  (34.53) 11.4  (6.31) 11.0  (3.56) 10.4  (8.88)
Follow up Number Analyzed 6 participants 8 participants 9 participants 2 participants 5 participants
54.0  (78.01) 26.1  (35.34) 17.6  (13.87) 29.5  (34.65) 11.2  (5.17)
11.Primary Outcome
Title Mean Value of Urine pH (Part A)
Hide Description Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urinalysis parameters included urine pH assessed using dipstick analysis. pH is calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral.
Time Frame Up to 10 days after discharge (Day 2) in Part A
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: pH
Day 1, 24 hours 6.17  (0.258)
Follow up 5.92  (0.376)
12.Primary Outcome
Title Mean Value of Urine pH (Part B)
Hide Description Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urinalysis parameters included urine pH assessed using dipstick analysis. pH is calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral.
Time Frame Up to 10 days after discharge (Day 15) in Part B
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 GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 15 13
Mean (Standard Deviation)
Unit of Measure: pH
Day 1, pre-breakfast Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
6.04  (0.499) 6.04  (0.431) 6.04  (0.257) 6.03  (0.399) 5.92  (0.344)
Day 7, pre-breakfast Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
6.11  (0.446) 5.85  (0.240) 6.00  (0.369) 6.07  (0.458) 6.04  (0.380)
Day 14, 24 hours Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
5.96  (0.414) 6.04  (0.247) 6.17  (0.326) 6.07  (0.267) 6.08  (0.277)
Follow up Number Analyzed 13 participants 12 participants 12 participants 13 participants 12 participants
6.15  (0.747) 5.88  (0.483) 5.96  (0.396) 6.08  (0.572) 5.88  (0.311)
13.Primary Outcome
Title Mean Value of Urine Specific Gravity (Part A)
Hide Description Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urinalysis parameter include urine specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine . It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine .
Time Frame Up to 10 days after discharge (Day 2) in Part A
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Arm A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: Ratio
Day 1, 24 hours 1.0150  (0.00500)
Follow up 1.0210  (0.00224)
14.Primary Outcome
Title Mean Value of Urine Specific Gravity (Part B)
Hide Description Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urinalysis parameter include urine specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine . It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine .
Time Frame Up to 10 days after discharge (Day 15) in Part B
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 GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 15 13
Mean (Standard Deviation)
Unit of Measure: Ratio
Day 1, pre-breakfast Number Analyzed 11 participants 8 participants 6 participants 11 participants 10 participants
1.0127  (0.00518) 1.0144  (0.00417) 1.0125  (0.00418) 1.0132  (0.00513) 1.0135  (0.00580)
Day 7, pre-breakfast Number Analyzed 9 participants 11 participants 6 participants 14 participants 11 participants
1.0144  (0.00464) 1.0177  (0.00564) 1.0150  (0.00447) 1.0125  (0.00380) 1.0141  (0.00539)
Day 14, 24 hours Number Analyzed 10 participants 9 participants 7 participants 11 participants 12 participants
1.0170  (0.00587) 1.0161  (0.00651) 1.0143  (0.00607) 1.0127  (0.00410) 1.0138  (0.00433)
Follow up Number Analyzed 9 participants 8 participants 10 participants 9 participants 10 participants
1.0200  (0.00661) 1.0163  (0.00443) 1.0185  (0.00669) 1.0172  (0.00618) 1.0165  (0.00669)
15.Primary Outcome
Title Number of Participants With Abnormal Vital Signs of PCI (Part A)
Hide Description Assessment of vital signs (including systolic, diastolic blood pressure and heart rate) was performed at one time point at Screening, at follow-up and pre-breakfast on Day -1. On Day 1, they were taken at pre-breakfast, 1 hour, 3, 4, 6, 10, 16 and 24 hours post-dose. Assessments were made in triplicate at the pre-breakfast time point, and single assessments were made at all other times. Assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. PCI value of systolic blood pressure: <85 and >160 millimeter of mercury (mmHg). PCI value of diastolic blood pressure: <45 and >100 mmHg. PCI value of heart rate: <40 and >110 beats per minute.
Time Frame Up to 10 days after discharge (Day 2) in Part A
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
Blood pressure (systolic and diastolic)
0
   0.0%
Heart rate, high
1
  16.7%
16.Primary Outcome
Title Number of Participants With Abnormal Vital Signs of PCI (Part B)
Hide Description Assessment of vital signs (including systolic and diastolic blood pressure and heart rate) was performed at Screening, pre-breakfast on Days -1 to 14 in a fasting state early in the morning (prior to morning dosing on Days 1-14), and at Follow-up. On Days 1, 7 and 14, they were taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes.
Time Frame Up to 10 days after discharge (Day 15) in Part B
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population.
Arm/Group Title Placebo GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 15 13
Measure Type: Count of Participants
Unit of Measure: Participants
Systolic blood pressure, high
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
Heart rate
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
17.Primary Outcome
Title Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A)
Hide Description ECGs were taken at Screening, pre-breakfast on Day -1, on Day 1 (pre-breakfast, 1 hour, 2, 3, 4, 6, 8, 13, 24hours post-dose), and at follow-up. Assessments were made in triplicate on Day 1 at the pre-breakfast time point, and single assessments were made at all other times. ECGs were taken in supine position. The data has been presented as abnormal- not clinically significant (NCS) and abnormal-clinically significant (CS).
Time Frame Up to 10 days after discharge (Day 2) in Part A
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population.
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1, pre-breakfast 1, abnormal-NCS
3
  50.0%
Day 1, pre-breakfast 2, abnormal-NCS
2
  33.3%
Day 1, pre-breakfast 3, abnormal-NCS
2
  33.3%
Day 1, 1 hour, abnormal-NCS
1
  16.7%
Day 1, 2 hour, abnormal-NCS
3
  50.0%
Day 1, 3 hour, abnormal-NCS
3
  50.0%
Day 1, 4 hour, abnormal-NCS
2
  33.3%
Day 1, 6 hour, abnormal-NCS
1
  16.7%
Day 1, 8 hour, abnormal-NCS
3
  50.0%
Day 1, 13 hour, abnormal-NCS
1
  16.7%
Day 1, 24 hour, abnormal-NCS
2
  33.3%
18.Primary Outcome
Title Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B)
Hide Description ECGs were taken at Screening, pre-breakfast on Day -1 and at Follow-up. On Days 1, 7 and 14 ECGs were taken pre-breakfast (fasting) and at 1, 2, 4, 6, 8, 12 and 24hours post-dose. Triplicate ECGs were taken at the pre-breakfast time point, and single assessments were taken at all other times. ECGs were taken in supine position. The data has been presented as abnormal- not clinically significant (NCS) and abnormal-clinically significant (CS).
Time Frame Up to 10 days after discharge (Day 15) in Part B
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 GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 15 13
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1, pre-breakfast 1, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
2
  14.3%
2
  15.4%
4
  33.3%
3
  20.0%
3
  23.1%
Day 1, pre-breakfast 2, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
2
  15.4%
5
  41.7%
2
  13.3%
4
  30.8%
Day 1, pre-breakfast 3, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
2
  15.4%
5
  41.7%
2
  13.3%
4
  30.8%
Day 1, 1 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
1
   7.7%
4
  33.3%
6
  40.0%
3
  23.1%
Day 1, 1 hour, abnormal-CS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
0
   0.0%
1
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1, 2 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
1
   7.7%
3
  25.0%
4
  26.7%
2
  15.4%
Day 1, 4 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
2
  15.4%
4
  33.3%
4
  26.7%
2
  15.4%
Day 1, 6 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
2
  14.3%
2
  15.4%
4
  33.3%
4
  26.7%
3
  23.1%
Day 1, 8 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
4
  30.8%
4
  33.3%
4
  26.7%
3
  23.1%
Day 1, 12 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
3
  23.1%
3
  25.0%
3
  20.0%
3
  23.1%
Day 1, 24 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
3
  21.4%
2
  15.4%
3
  25.0%
3
  20.0%
4
  30.8%
Day 7, pre-breakfast 1, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
2
  15.4%
4
  33.3%
3
  20.0%
3
  23.1%
Day 7, pre-breakfast 2, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
2
  14.3%
3
  23.1%
4
  33.3%
3
  20.0%
2
  15.4%
Day 7, pre-breakfast 3, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
3
  23.1%
3
  25.0%
2
  13.3%
3
  23.1%
Day 7, 1 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
0
   0.0%
1
   7.7%
5
  41.7%
2
  14.3%
4
  30.8%
Day 7, 2 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
0
   0.0%
3
  23.1%
5
  41.7%
3
  21.4%
3
  23.1%
Day 7, 4 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
0
   0.0%
2
  15.4%
4
  33.3%
3
  21.4%
4
  30.8%
Day 7, 6 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
0
   0.0%
3
  23.1%
3
  25.0%
2
  14.3%
5
  38.5%
Day 7, 8 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
1
   7.1%
4
  30.8%
4
  33.3%
2
  14.3%
3
  23.1%
Day 7, 12 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
2
  14.3%
2
  15.4%
3
  25.0%
2
  14.3%
3
  23.1%
Day 7, 24 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
1
   7.1%
3
  23.1%
4
  33.3%
3
  21.4%
4
  30.8%
Day 14, pre-breakfast 1, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
1
   7.1%
1
   7.7%
4
  33.3%
3
  21.4%
4
  30.8%
Day 14, pre-breakfast 2, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
1
   7.1%
2
  15.4%
5
  41.7%
3
  21.4%
4
  30.8%
Day 14, pre-breakfast 3, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
1
   7.1%
1
   7.7%
4
  33.3%
3
  21.4%
4
  30.8%
Day 14, 1 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
1
   7.1%
3
  23.1%
5
  41.7%
2
  14.3%
2
  15.4%
Day 14, 2 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
1
   7.1%
2
  15.4%
4
  33.3%
3
  21.4%
2
  15.4%
Day 14, 4 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
0
   0.0%
2
  15.4%
3
  25.0%
3
  21.4%
3
  23.1%
Day 14, 6 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
0
   0.0%
2
  15.4%
4
  33.3%
2
  14.3%
1
   7.7%
Day 14, 8 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 12 participants
1
   7.1%
1
   7.7%
0
   0.0%
1
   7.1%
1
   8.3%
Day 14, 12 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 12 participants
1
   7.1%
2
  15.4%
5
  41.7%
3
  21.4%
2
  16.7%
Day 14, 24 hour, abnormal-NCS Number Analyzed 14 participants 13 participants 12 participants 14 participants 13 participants
1
   7.1%
1
   7.7%
5
  41.7%
3
  21.4%
3
  23.1%
Follow up-NCS Number Analyzed 14 participants 13 participants 12 participants 15 participants 13 participants
1
   7.1%
2
  15.4%
2
  16.7%
3
  20.0%
3
  23.1%
19.Primary Outcome
Title Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours [AUC (0-24)] and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-last)] Following a Single Dose of GSK1292263 (Part A)
Hide Description Blood samples for the determination of pharmacokinetics (PK) were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for 2 participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. AUC (0-last) and AUC (0-24) were determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time Frame On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK Population included participants from the Safety Population who had any PK parameter estimated. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms hour per milliliter (ng*hr/mL)
AUC (0-24)
7046.25
(11.090%)
AUC (0-last)
10099.35
(14.332%)
20.Primary Outcome
Title Maximum Observed Concentration (Cmax) Following a Single Dose of GSK1292263 (Part A)
Hide Description Blood samples for the determination of PK were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. Cmax was determined directly from the raw concentration-time data.
Time Frame On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
582.619
(28.0710%)
21.Primary Outcome
Title Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) and Time of Occurrence of Cmax (Tmax) Following a Single Dose of GSK1292263 (Part A)
Hide Description Blood samples for the determination of PK were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for 2 participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. Tmax was determined directly from the raw concentration-time data. Tlag was determined as the time of the sample preceding the first quantifiable concentration, on Day 1 only.
Time Frame On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 4
Median (Full Range)
Unit of Measure: hour
Tlag
0.000
(0.00 to 0.50)
Tmax
5.00
(4.0 to 13.0)
22.Primary Outcome
Title Apparent Clearance Following Oral Dosing (CL/F) of GSK1292263 (Part A)
Hide Description Outcome measure was added with caveat "as data permits". The data for CL/F was not collected.
Time Frame On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
23.Primary Outcome
Title Volume of Distribution (V/F) (Part A)
Hide Description Outcome measure was added with caveat "as data permits". The data for V/F was not collected.
Time Frame On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
24.Primary Outcome
Title Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-inf]) Following a Single Dose of GSK1292263 (Part A)
Hide Description Outcome measure was added with caveat "as data permits". The data for AUC (0-inf) was not collected.
Time Frame On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
25.Primary Outcome
Title Terminal Phase Half-life (t1/2) Following a Single Dose of GSK1292263 (Part A)
Hide Description Outcome measure was added with caveat "as data permits". The data for t1/2 was not collected.
Time Frame On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
26.Primary Outcome
Title Cmax Following Repeat Dose of GSK1292263 (Part B)
Hide Description Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. Cmax was determined directly from the raw concentration-time data.
Time Frame On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg
Hide Arm/Group Description:
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Overall Number of Participants Analyzed 13 12 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Day 1 Number Analyzed 13 participants 12 participants 15 participants
278.451
(36.5951%)
686.845
(33.1747%)
610.586
(29.2427%)
Day 7 Number Analyzed 13 participants 12 participants 14 participants
416.441
(30.0099%)
872.843
(22.2509%)
738.918
(39.1209%)
Day 14 Number Analyzed 13 participants 12 participants 14 participants
457.716
(20.4386%)
902.325
(30.0011%)
664.505
(37.8497%)
27.Primary Outcome
Title Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B)
Hide Description Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. Tmax was determined directly from the raw concentration-time data. Tlag was determined as the time of the sample preceding the first quantifiable concentration, on Day 1 only.
Time Frame On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg
Hide Arm/Group Description:
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Overall Number of Participants Analyzed 13 12 15
Median (Full Range)
Unit of Measure: hour
Tlag, Day1 Number Analyzed 13 participants 12 participants 15 participants
0.000
(0.00 to 1.00)
0.000
(0.00 to 0.00)
0.000
(0.00 to 1.00)
Tmax, Day 1 Number Analyzed 13 participants 12 participants 15 participants
14.00
(6.0 to 18.0)
14.00
(4.0 to 18.0)
4.0
(4.0 to 12.0)
Tmax, Day 7 Number Analyzed 13 participants 12 participants 14 participants
4.00
(4.0 to 6.0)
4.00
(0.0 to 4.0)
4.00
(2.0 to 10.1)
Tmax, Day 14 Number Analyzed 13 participants 12 participants 15 participants
4.00
(4.0 to 24.0)
13.00
(1.0 to 24.0)
4.0
(1.0 to 10.2)
28.Primary Outcome
Title AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B)
Hide Description Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. AUC (0-10) and AUC (0-24) were determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time Frame On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg
Hide Arm/Group Description:
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Overall Number of Participants Analyzed 13 12 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
AUC (0-10), Day 1 Number Analyzed 13 participants 12 participants 15 participants
1143.35
(36.439%)
3149.94
(38.937%)
NA [1] 
(NA%)
AUC (0-10), Day 7 Number Analyzed 13 participants 12 participants 14 participants
2930.47
(21.366%)
6472.68
(29.790%)
5205.86
(31.529%)
AUC (0-10), Day 14 Number Analyzed 13 participants 12 participants 15 participants
3130.50
(22.430%)
6057.41
(32.784%)
NA [1] 
(NA%)
AUC (0-24), Day 1 Number Analyzed 13 participants 12 participants 15 participants
3775.76
(30.915%)
9968.88
(39.959%)
6791.90
(24.550%)
AUC (0-24), Day 14 Number Analyzed 13 participants 12 participants 14 participants
7785.24
(19.152%)
15479.48
(33.009%)
9391.30
(32.948%)
[1]
Data was not analyzed at this time point
29.Primary Outcome
Title T1/2 Following Repeat Dose of GSK1292263 (Part B)
Hide Description Outcome measure was added with caveat "as data permits". The data for T1/2 was not collected.
Time Frame On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg
Hide Arm/Group Description:
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
30.Primary Outcome
Title Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B)
Hide Description Accumulation ratio (Ro) was derived as: Ro = Day 14 morning AUC(0-10)/Day 1 morning AUC(0-10) (for BID regimens only). Ro = Day 14 AUC(0-24)/Day 1 AUC(0-24) (for both BID and once daily regimens). Accumulation ratio (RCmax)= Day 14 Cmax/Day 1 Cmax. RCmax was not computed for each dosing period (morning and evening).
Time Frame On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg
Hide Arm/Group Description:
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Overall Number of Participants Analyzed 13 12 14
Mean (90% Confidence Interval)
Unit of Measure: Ratio
AUC (0-10)
2.7380
(2.4706 to 3.0344)
1.9230
(1.6883 to 2.1903)
NA [1] 
(NA to NA)
AUC (0-24)
2.0619
(1.8432 to 2.3065)
1.5528
(1.3748 to 1.7538)
1.3730
(1.2219 to 1.5429)
Cmax
1.6438
(1.4256 to 1.8954)
1.3137
(1.2009 to 1.4372)
1.1077
(0.9659 to 1.2704)
[1]
Data was not analyzed at this time point
31.Primary Outcome
Title Change From Baseline in Mean Fasted Glucose Value (Part A)
Hide Description Baseline was considered to be Day 1 pre-breakfast. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.
Time Frame Baseline and at pre-breakfast on Day 1 and 24 h post-dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Pharmacodynamic (PD) Population included participants from the Safety Population who had any PD parameter estimated. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: millimoles per liter (mmol/L)
0.17
(-199.736%)
32.Primary Outcome
Title Change From Baseline in Mean Fasted Insulin Value (Part A)
Hide Description Baseline was considered to be Day 1 pre-breakfast. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.
Time Frame Baseline and at pre-breakfast on Day 1 and 24 hours post-dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Part A
Hide Arm/Group Description:
Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (>=1000 mg per day).
Overall Number of Participants Analyzed 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: picomoles per liter (pmol/L)
3.45
(-187.128%)
33.Primary Outcome
Title Change From Baseline in Mean Fasted Glucose Value (Part B)
Hide Description Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.
Time Frame Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD Population.
Arm/Group Title Placebo GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 14 12
Mean (95% Confidence Interval)
Unit of Measure: mmol/L
Day 7, pre-breakfast
-0.53
(-0.92 to -0.14)
-0.74
(-1.22 to -0.27)
-0.28
(-1.15 to 0.58)
0.21
(-0.53 to 0.95)
-1.75
(-2.20 to -1.29)
Day 14, pre-breakfast
-0.74
(-1.30 to -0.18)
-1.57
(-2.39 to -0.75)
-0.81
(-1.77 to 0.16)
-0.11
(-0.96 to 0.75)
-1.83
(-2.65 to -1.02)
Day 14, 24 hours
-0.01
(-0.94 to 0.92)
-0.57
(-1.49 to 0.36)
0.66
(-0.31 to 1.64)
0.68
(0.09 to 1.27)
-1.06
(-1.87 to -0.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 75 mg
Comments Placebo vs GSK1292263 75 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.216
Confidence Interval (2-Sided) 95%
-1.00 to 0.57
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 300 mg
Comments Placebo vs GSK1292263 300 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.290
Confidence Interval (2-Sided) 95%
-0.53 to 1.11
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 600 mg
Comments Placebo vs GSK1292263 600 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.748
Confidence Interval (2-Sided) 95%
-0.02 to 1.52
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 50 mg
Comments Placebo vs Sitagliptin 50 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.207
Confidence Interval (2-Sided) 95%
-2.01 to -0.41
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection GSK1292263 75 mg, Sitagliptin 50 mg
Comments GSK1292263 75 mg vs Sitagliptin 50 mg: Day 7 , pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.991
Confidence Interval (2-Sided) 95%
0.18 to 1.81
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection GSK1292263 300 mg, Sitagliptin 50 mg
Comments GSK1292263 300 mg vs Sitagliptin 50 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.497
Confidence Interval (2-Sided) 95%
0.66 to 2.34
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection GSK1292263 600 mg, Sitagliptin 50 mg
Comments GSK1292263 600 mg vs Sitagliptin 50 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.955
Confidence Interval (2-Sided) 95%
1.16 to 2.75
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 75 mg
Comments Placebo vs GSK1292263 75 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.780
Confidence Interval (2-Sided) 95%
-1.74 to 0.18
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 300 mg
Comments Placebo vs GSK1292263 300 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.188
Confidence Interval (2-Sided) 95%
-0.81 to 1.19
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 600 mg
Comments Placebo vs GSK1292263 600 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.600
Confidence Interval (2-Sided) 95%
-0.35 to 1.55
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 50 mg
Comments Placebo vs Sitagliptin 50 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.069
Confidence Interval (2-Sided) 95%
-2.05 to -0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection GSK1292263 75 mg, Sitagliptin 50 mg
Comments GSK1292263 75 mg vs Sitagliptin 50 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.289
Confidence Interval (2-Sided) 95%
-0.71 to 1.29
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection GSK1292263 300 mg, Sitagliptin 50 mg
Comments GSK1292263 300 mg vs Sitagliptin 50 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.257
Confidence Interval (2-Sided) 95%
0.22 to 2.29
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection GSK1292263 600 mg, Sitagliptin 50 mg
Comments GSK1292263 600 mg vs Sitagliptin 50 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.669
Confidence Interval (2-Sided) 95%
0.68 to 2.65
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 75 mg
Comments Placebo vs GSK1292263 75 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.556
Confidence Interval (2-Sided) 95%
-1.65 to 0.54
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 300 mg
Comments Placebo vs GSK1292263 300 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.745
Confidence Interval (2-Sided) 95%
-0.40 to 1.89
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 600 mg
Comments Placebo vs GSK1292263 600 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.711
Confidence Interval (2-Sided) 95%
-0.36 to 1.78
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 50 mg
Comments Placebo vs Sitagliptin 50 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.030
Confidence Interval (2-Sided) 95%
-2.15 to 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection GSK1292263 75 mg, Sitagliptin 50 mg
Comments GSK1292263 75 mg vs Sitagliptin 50 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.474
Confidence Interval (2-Sided) 95%
-0.66 to 1.61
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection GSK1292263 300 mg, Sitagliptin 50 mg
Comments GSK1292263 300 mg vs Sitagliptin 50 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.775
Confidence Interval (2-Sided) 95%
0.60 to 2.95
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection GSK1292263 600 mg, Sitagliptin 50 mg
Comments GSK1292263 600 mg vs Sitagliptin 50 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.741
Confidence Interval (2-Sided) 95%
0.63 to 2.86
Estimation Comments [Not Specified]
34.Primary Outcome
Title Change From Baseline in Mean Fasted Insulin Value (Part B)
Hide Description Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.
Time Frame Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD Population.
Arm/Group Title Placebo GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 14 12
Mean (95% Confidence Interval)
Unit of Measure: pmol/L
Day 7, pre-breakfast
-2.74
(-15.26 to 9.77)
-1.84
(-9.22 to 5.53)
-26.34
(-57.25 to 4.57)
-22.99
(-39.68 to -6.31)
2.07
(-15.96 to 20.11)
Day 14, pre-breakfast
4.84
(-8.97 to 18.65)
6.22
(-5.01 to 17.46)
-13.48
(-36.79 to 9.82)
-33.26
(-53.15 to -13.37)
4.43
(-5.65 to 14.50)
Day 14, 24 hours
23.25
(5.53 to 40.96)
4.97
(-19.94 to 29.87)
-12.54
(-40.87 to 15.80)
-17.52
(-41.26 to 6.23)
27.47
(2.50 to 52.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 75 mg
Comments Placebo vs GSK1292263 75 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.195
Confidence Interval (2-Sided) 95%
-17.17 to 17.56
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 300 mg
Comments Placebo vs GSK1292263 300 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -16.863
Confidence Interval (2-Sided) 95%
-34.70 to 0.98
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 600 mg
Comments Placebo vs GSK1292263 600 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.460
Confidence Interval (2-Sided) 95%
-23.04 to 12.12
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 50 mg
Comments Placebo vs Sitagliptin 50 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.850
Confidence Interval (2-Sided) 95%
-13.89 to 21.58
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection GSK1292263 75 mg, Sitagliptin 50 mg
Comments GSK1292263 75 mg vs Sitagliptin 50 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.655
Confidence Interval (2-Sided) 95%
-21.70 to 14.39
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection GSK1292263 300 mg, Sitagliptin 50 mg
Comments GSK1292263 300 mg vs Sitagliptin 50 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -20.712
Confidence Interval (2-Sided) 95%
-39.25 to -2.17
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection GSK1292263 600 mg, Sitagliptin 50 mg
Comments GSK1292263 600 mg vs Sitagliptin 50 mg: Day 7, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -9.310
Confidence Interval (2-Sided) 95%
-27.63 to 9.01
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 75 mg
Comments Placebo vs GSK1292263 75 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.649
Confidence Interval (2-Sided) 95%
-19.43 to 12.14
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 300 mg
Comments Placebo vs GSK1292263 300 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -16.660
Confidence Interval (2-Sided) 95%
-32.72 to -0.60
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 600 mg
Comments Placebo vs GSK1292263 600 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -22.251
Confidence Interval (2-Sided) 95%
-38.34 to -6.16
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 50 mg
Comments Placebo vs Sitagliptin 50 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.590
Confidence Interval (2-Sided) 95%
-20.69 to 11.51
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection GSK1292263 75 mg, Sitagliptin 50 mg
Comments GSK1292263 75 mg vs Sitagliptin 50 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.941
Confidence Interval (2-Sided) 95%
-15.40 to 17.28
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection GSK1292263 300 mg, Sitagliptin 50 mg
Comments GSK1292263 300 mg vs Sitagliptin 50 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -12.070
Confidence Interval (2-Sided) 95%
-28.82 to 4.68
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection GSK1292263 600 mg, Sitagliptin 50 mg
Comments GSK1292263 600 mg vs Sitagliptin 50 mg: Day 14, pre-breakfast
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -17.662
Confidence Interval (2-Sided) 95%
-34.72 to -0.60
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 75 mg
Comments Placebo vs GSK1292263 75 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -19.101
Confidence Interval (2-Sided) 95%
-44.00 to 5.80
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 300 mg
Comments Placebo vs GSK1292263 300 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -27.976
Confidence Interval (2-Sided) 95%
-53.56 to -2.39
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 600 mg
Comments Placebo vs GSK1292263 600 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -23.609
Confidence Interval (2-Sided) 95%
-48.82 to 1.60
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 50 mg
Comments Placebo vs Sitagliptin 50 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.094
Confidence Interval (2-Sided) 95%
-22.34 to 28.53
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection GSK1292263 75 mg, Sitagliptin 50 mg
Comments GSK1292263 75 mg vs Sitagliptin 50 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -22.194
Confidence Interval (2-Sided) 95%
-48.07 to 3.69
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection GSK1292263 300 mg, Sitagliptin 50 mg
Comments GSK1292263 300 mg vs Sitagliptin 50 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -31.070
Confidence Interval (2-Sided) 95%
-57.66 to -4.48
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection GSK1292263 600 mg, Sitagliptin 50 mg
Comments GSK1292263 600 mg vs Sitagliptin 50 mg: Day 14, 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -26.703
Confidence Interval (2-Sided) 95%
-52.98 to -0.42
Estimation Comments [Not Specified]
35.Primary Outcome
Title Mean Post Meal Glucose Value (Part B)
Hide Description Blood samples were collected on Days -1 and 14, post-breakfast at 0.5, 1, 1.5, 2 and 3 hours post dose. For lunch (approximately 4 hours post morning dose) samples were collected at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hours post morning dose), samples were taken at 0.5, 1, 1.5, 2 and 3 hours post dinner.
Time Frame At pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD Population.
Arm/Group Title Placebo GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 14 12
Mean (95% Confidence Interval)
Unit of Measure: mmol/L
Day -1, post-breakfast, 0.5 hour
13.75
(12.80 to 14.70)
13.51
(12.35 to 14.67)
14.68
(13.74 to 15.62)
13.04
(11.67 to 14.42)
13.60
(12.63 to 14.56)
Day -1, post-breakfast, 1 hour
13.62
(12.58 to 14.66)
13.42
(12.39 to 14.45)
14.48
(13.49 to 15.48)
13.43
(12.06 to 14.80)
13.12
(11.88 to 14.37)
Day -1, post-breakfast, 1.5 hour
12.56
(11.41 to 13.71)
12.12
(10.90 to 13.34)
12.94
(11.62 to 14.26)
12.02
(10.24 to 13.80)
11.39
(10.17 to 12.60)
Day -1, post-breakfast, 2 hour
10.71
(9.73 to 11.69)
10.55
(9.03 to 12.06)
11.50
(9.99 to 13.01)
10.67
(9.04 to 12.29)
9.75
(8.46 to 11.03)
Day -1, post-breakfast, 3 hour
7.78
(7.02 to 8.53)
8.48
(6.68 to 10.28)
8.68
(7.02 to 10.33)
8.46
(6.99 to 9.93)
7.73
(6.91 to 8.55)
Day -1, post-lunch, 0.5 hour
7.46
(6.48 to 8.45)
8.90
(7.35 to 10.45)
8.56
(7.54 to 9.58)
8.58
(7.61 to 9.56)
7.93
(7.04 to 8.83)
Day -1, post-lunch, 1 hour
10.31
(9.47 to 11.15)
11.19
(10.09 to 12.29)
10.71
(9.85 to 11.57)
10.12
(8.76 to 11.48)
10.36
(9.34 to 11.39)
Day -1, post-lunch, 1.5 hour
11.07
(9.99 to 12.14)
11.17
(9.75 to 12.58)
11.64
(10.54 to 12.74)
10.45
(9.02 to 11.89)
10.69
(9.51 to 11.87)
Day -1, post-lunch, 2 hour
11.31
(10.11 to 12.51)
10.82
(9.42 to 12.21)
11.75
(10.72 to 12.78)
10.11
(8.82 to 11.39)
10.72
(9.56 to 11.88)
Day -1, post-lunch, 3 hour
11.05
(9.95 to 12.16)
10.05
(8.50 to 11.60)
11.25
(10.08 to 12.43)
10.37
(9.03 to 11.71)
9.92
(8.80 to 11.03)
Day -1, post-dinner, 0.5 hour
9.28
(7.95 to 10.60)
9.19
(8.14 to 10.25)
8.78
(7.85 to 9.71)
8.92
(7.86 to 9.98)
8.39
(7.56 to 9.22)
Day -1, post-dinner, 1 hour
11.15
(9.83 to 12.47)
11.27
(9.88 to 12.67)
11.00
(9.75 to 12.25)
10.77
(9.64 to 11.90)
10.27
(9.33 to 11.22)
Day -1, post-dinner, 1.5 hour
11.45
(10.13 to 12.77)
10.97
(9.46 to 12.49)
10.99
(9.97 to 12.01)
10.94
(9.62 to 12.26)
10.52
(9.47 to 11.58)
Day -1, post-dinner, 2 hour
11.67
(10.15 to 13.20)
10.76
(9.18 to 12.35)
10.81
(9.76 to 11.85)
10.98
(9.57 to 12.39)
10.18
(9.09 to 11.27)
Day -1, post-dinner, 3 hour
11.58
(9.76 to 13.39)
10.41
(8.83 to 11.99)
10.34
(9.45 to 11.23)
10.48
(9.20 to 11.75)
9.66
(8.49 to 10.84)
Day 14, post-breakfast, 0.5 hour
14.16
(12.45 to 15.86)
13.13
(11.86 to 14.41)
14.96
(13.89 to 16.03)
13.83
(12.60 to 15.05)
12.26
(10.53 to 13.98)
Day 14, post-breakfast, 1 hour
14.02
(11.79 to 16.24)
13.32
(11.47 to 15.17)
14.23
(12.91 to 15.55)
14.32
(12.95 to 15.70)
12.03
(10.17 to 13.89)
Day 14, post-breakfast, 1.5 hour
12.69
(11.25 to 14.13)
11.58
(9.63 to 13.52)
12.96
(11.14 to 14.78)
13.07
(11.37 to 14.76)
10.55
(8.66 to 12.43)
Day 14, post-breakfast, 2 hour
11.15
(9.83 to 12.46)
9.98
(8.03 to 11.93)
10.93
(9.10 to 12.76)
11.11
(9.20 to 13.02)
9.10
(7.21 to 11.00)
Day 14, post-breakfast, 3 hour
7.56
(6.14 to 8.98)
6.96
(5.32 to 8.61)
8.20
(6.58 to 9.82)
8.73
(7.04 to 10.43)
6.69
(5.06 to 8.32)
Day 14, post-lunch, 0.5 hour
7.43
(6.43 to 8.44)
8.73
(7.66 to 9.80)
10.07
(8.84 to 11.31)
8.70
(7.76 to 9.63)
7.77
(6.66 to 8.89)
Day 14, post-lunch, 1 hour
9.61
(8.42 to 10.80)
10.59
(9.29 to 11.88)
11.96
(10.62 to 13.29)
10.42
(9.24 to 11.59)
8.38
(7.47 to 9.28)
Day 14, post-lunch, 1.5 hour
10.38
(9.23 to 11.53)
10.80
(9.43 to 12.17)
12.33
(11.25 to 13.41)
11.12
(9.69 to 12.55)
8.83
(7.78 to 9.88)
Day 14, post-lunch, 2 hour
10.83
(9.25 to 12.40)
10.51
(9.15 to 11.88)
12.09
(10.85 to 13.33)
10.87
(9.48 to 12.27)
8.84
(7.78 to 9.91)
Day 14, post-lunch, 3 hour
10.51
(8.71 to 12.30)
9.71
(8.03 to 11.40)
10.57
(9.12 to 12.01)
10.44
(8.91 to 11.96)
8.90
(7.76 to 10.05)
Day 14, post-dinner, 0.5 hour
8.17
(6.86 to 9.47)
7.99
(6.95 to 9.03)
9.37
(8.09 to 10.65)
10.41
(8.96 to 11.86)
7.29
(6.40 to 8.19)
Day 14, post-dinner, 1 hour
11.07
(9.53 to 12.61)
11.20
(10.03 to 12.36)
12.21
(10.72 to 13.70)
12.56
(10.99 to 14.12)
9.43
(8.00 to 10.86)
Day 14, post-dinner, 1.5 hour
11.65
(9.89 to 13.41)
11.81
(10.43 to 13.19)
13.01
(11.38 to 14.64)
13.03
(11.57 to 14.49)
10.41
(8.48 to 12.33)
Day 14, post-dinner, 2 hour
11.42
(9.64 to 13.21)
11.27
(9.62 to 12.93)
12.07
(10.76 to 13.38)
12.60
(11.11 to 14.09)
10.07
(8.11 to 12.03)
Day 14, post-dinner, 3 hour
10.43
(8.77 to 12.10)
9.78
(7.70 to 11.87)
10.69
(9.24 to 12.13)
11.75
(10.17 to 13.32)
8.80
(7.41 to 10.20)
36.Primary Outcome
Title Mean Post Meal Insulin Value (Part B)
Hide Description Blood samples were collected on Days -1 and 14, post-breakfast at 0.5, 1, 1.5, 2 and 3 hours post dose. For lunch (approximately 4 hours post morning dose) samples were collected at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hours post morning dose), samples were taken at 0.5, 1, 1.5, 2 and 3 hours post dinner.
Time Frame At pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD Population.
Arm/Group Title Placebo GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 14 12
Mean (95% Confidence Interval)
Unit of Measure: pmol/L
Day -1, post-breakfast, 0.5 hour
201.81
(120.26 to 283.36)
185.34
(136.03 to 234.64)
270.35
(139.59 to 401.11)
264.15
(183.44 to 344.87)
219.24
(146.34 to 292.15)
Day -1, post-breakfast, 1 hour
222.44
(153.65 to 291.23)
258.37
(176.77 to 339.98)
296.05
(161.61 to 430.50)
338.58
(218.57 to 458.59)
251.79
(167.51 to 336.07)
Day -1, post-breakfast, 1.5 hour
251.01
(161.79 to 340.24)
246.76
(177.95 to 315.57)
318.38
(155.32 to 481.44)
351.10
(239.19 to 463.01)
237.46
(153.03 to 321.90)
Day -1, post-breakfast, 2 hour
233.85
(153.97 to 313.73)
221.27
(147.26 to 295.28)
258.69
(108.85 to 408.52)
304.66
(205.71 to 403.60)
196.53
(154.15 to 238.91)
Day -1, post-breakfast, 3 hour
131.95
(77.37 to 186.53)
114.67
(85.59 to 143.75)
162.58
(89.16 to 235.99)
180.43
(130.54 to 230.32)
106.98
(69.24 to 144.72)
Day -1, post-lunch, 0.5 hour
135.17
(88.11 to 182.22)
115.21
(68.21 to 162.22)
147.60
(80.48 to 214.71)
187.22
(133.25 to 241.19)
109.63
(85.23 to 134.03)
Day -1, post-lunch, 1 hour
193.80
(115.60 to 272.00)
193.65
(127.73 to 259.57)
186.02
(113.55 to 258.49)
246.08
(180.25 to 311.90)
180.49
(128.88 to 232.10)
Day -1, post-lunch, 1.5 hour
188.57
(123.30 to 253.85)
208.37
(138.94 to 277.80)
212.29
(135.68 to 288.90)
289.19
(187.79 to 390.59)
173.21
(124.34 to 222.08)
Day -1, post-lunch, 2 hour
235.41
(106.82 to 363.99)
196.74
(156.56 to 236.93)
218.67
(106.48 to 330.87)
295.21
(185.14 to 405.29)
202.47
(147.19 to 257.74)
Day -1, post-lunch, 3 hour
191.74
(120.96 to 262.51)
171.15
(120.83 to 221.47)
207.00
(98.15 to 315.86)
270.43
(185.95 to 354.91)
167.37
(125.31 to 209.42)
Day -1, post-dinner, 0.5 hour
132.04
(96.91 to 167.16)
131.50
(81.60 to 181.39)
150.10
(90.51 to 209.68)
207.99
(152.25 to 263.72)
104.16
(77.66 to 130.67)
Day -1, post-dinner, 1 hour
199.54
(142.13 to 256.94)
205.59
(142.87 to 268.31)
226.22
(127.02 to 325.41)
274.72
(194.26 to 355.17)
149.94
(122.06 to 177.81)
Day -1, post-dinner, 1.5 hour
195.55
(137.43 to 253.67)
183.16
(135.87 to 230.46)
206.80
(119.94 to 293.65)
275.17
(200.75 to 349.59)
171.08
(131.77 to 210.38)
Day -1, post-dinner, 2 hour
209.64
(130.71 to 288.56)
205.06
(148.39 to 261.73)
206.16
(122.43 to 289.88)
266.34
(184.02 to 348.66)
171.94
(126.51 to 217.36)
Day -1, post-dinner, 3 hour
176.48
(94.31 to 258.66)
164.28
(110.19 to 218.37)
172.36
(102.77 to 241.95)
225.12
(156.84 to 293.39)
155.62
(110.73 to 200.50)
Day 14, post-breakfast, 0.5 hour
258.61
(214.57 to 302.65)
240.43
(163.71 to 317.15)
241.13
(163.33 to 318.93)
259.89
(166.35 to 353.44)
268.74
(202.79 to 334.70)
Day 14, post-breakfast, 1 hour
304.23
(220.12 to 388.34)
280.93
(201.95 to 359.91)
297.58
(188.61 to 406.54)
348.37
(199.81 to 496.92)
354.57
(253.16 to 455.98)
Day 14, post-breakfast, 1.5 hour
297.57
(222.91 to 372.23)
299.22
(183.56 to 414.89)
272.63
(201.63 to 343.64)
409.93
(231.64 to 588.22)
300.33
(203.08 to 397.57)
Day 14, post-breakfast, 2 hour
283.85
(206.65 to 361.06)
234.65
(167.00 to 302.29)
229.72
(135.19 to 324.26)
333.39
(175.19 to 491.60)
246.53
(176.74 to 316.32)
Day 14, post-breakfast, 3 hour
161.67
(91.12 to 232.21)
110.81
(79.94 to 141.68)
122.31
(68.67 to 175.94)
188.31
(120.35 to 256.27)
117.21
(64.59 to 169.83)
Day 14, post-lunch, 0.5 hour
153.65
(104.68 to 202.62)
129.25
(88.96 to 169.54)
126.26
(92.54 to 159.98)
169.17
(122.63 to 215.71)
155.68
(126.09 to 185.26)
Day 14, post-lunch, 1 hour
201.54
(133.12 to 269.95)
169.74
(130.07 to 209.41)
172.43
(128.88 to 215.99)
190.65
(136.34 to 244.96)
164.53
(133.23 to 195.83)
Day 14, post-lunch, 1.5 hour
229.56
(143.82 to 315.30)
194.93
(141.31 to 248.55)
179.44
(128.44 to 230.43)
223.72
(148.81 to 298.63)
184.69
(145.83 to 223.54)
Day 14, post-lunch, 2 hour
237.34
(153.62 to 321.05)
214.66
(152.23 to 277.09)
177.88
(131.02 to 224.73)
227.81
(142.85 to 312.77)
188.61
(140.47 to 236.75)
Day 14, post-lunch, 3 hour
219.31
(111.12 to 327.50)
181.43
(132.84 to 230.02)
137.67
(89.10 to 186.24)
195.64
(140.45 to 250.83)
172.22
(134.89 to 209.55)
Day 14, post-dinner, 0.5 hour
99.41
(60.27 to 138.56)
98.57
(57.19 to 139.96)
75.85
(46.65 to 105.04)
137.16
(100.98 to 173.34)
92.78
(67.46 to 118.09)
Day 14, post-dinner, 1 hour
204.76
(140.32 to 269.19)
178.38
(129.51 to 227.25)
141.59
(96.79 to 186.38)
191.90
(132.03 to 251.77)
156.48
(119.25 to 193.70)
Day 14, post-dinner, 1.5 hour
204.67
(138.63 to 270.71)
210.90
(150.50 to 271.30)
163.94
(111.91 to 215.96)
215.57
(137.16 to 293.98)
179.94
(140.71 to 219.17)
Day 14, post-dinner, 2 hour
237.14
(128.24 to 346.03)
220.97
(159.61 to 282.32)
168.71
(100.05 to 237.38)
223.18
(150.43 to 295.92)
187.66
(130.14 to 245.19)
Day 14, post-dinner, 3 hour
200.85
(106.15 to 295.54)
167.22
(122.78 to 211.66)
134.98
(85.91 to 184.05)
191.01
(133.94 to 248.09)
175.02
(132.20 to 217.83)
37.Primary Outcome
Title Change From Baseline in Weighted Mean for Glucose Value (Part B)
Hide Description Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. Weighted mean were assessed for (0-12) and (0-24). AUC with respect to that time interval was calculated using the linear trapezoidal rule. The weighted mean was determined by dividing the AUC by the observed length of the collection interval (time of last assessment – time of first assessment in hours). In order for the AUC to be calculated, the first and last time points and at least one additional assessment falling between the two must be non-missing.
Time Frame Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD Population.
Arm/Group Title Placebo GSK1292263 75 mg GSK1292263 300 mg GSK1292263 600 mg Sitagliptin 50 mg
Hide Arm/Group Description:
Participants received 3 tablets of matching placebo BID along with metformin for 14 days.
Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.
Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.
Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.
Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Overall Number of Participants Analyzed 14 13 12 14 12
Mean (95% Confidence Interval)
Unit of Measure: mmol/L
Weighted mean (0-12), Day 7
0.064
(-0.629 to 0.756)
-0.432
(-1.123 to 0.259)
0.555
(-0.363 to 1.474)
1.103
(0.424 to 1.781)
-0.862
(-1.812 to 0.089)
Weighted mean (0-12), Day 14
-0.235
(-1.099 to 0.630)
-0.539
(-1.372 to 0.294)
0.123
(-0.806 to 1.052)
0.656
(-0.001 to 1.312)
-1.039
(-1.958 to -0.120)
Weighted mean (0-24), Day 14
-0.414
(-1.134 to 0.306)
-0.555
(-1.463 to 0.352)
0.321
(-0.602 to 1.244)
0.837
(0.126 to 1.548)
-1.025
(-1.889 to -0.161)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 75 mg
Comments Placebo vs GSK1292263 75 mg: Weighted Mean (0-12), Day 7
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.500
Confidence Interval (2-Sided) 95%
-1.50 to 0.50
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK1292263 300 mg
Comments Placebo vs GSK1292263 300 mg: Weighted Mean (0-12), Day 7
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.513
Confidence Interval (2-Sided) 95%