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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00575159
First Posted: December 18, 2007
Last Update Posted: October 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
The purpose of this research study is to look at concentrations of GSK189075 in blood when single doses of the drug are taken by mouth in combination with basal insulin. The clinical effects of the drug in combination with insulin on the body will also be studied. The results will help determine doses of GSK189075 can be studied in the future in the type I diabetes mellitus population.

Condition Intervention Phase
Diabetes Mellitus, Type 1 Drug: GSK189075 Drug: placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Single Ascending Dose Escalation, Placebo-controlled, Crossover Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK189075 Administered to Subjects With Type 1 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: Up to 6 months ]
    Data for number of participants who presented one or more adverse events (serious or non serious) was reported. An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.

  • Number of Participants With Hypoglycemia Episodes/Events [ Time Frame: Day 1 of each treatment period ]
    A hypoglycemic event was defined as symptoms of hypoglycemia confirmed by a blood glucose value below normal limits [less than 3.89 millimoles per liter (mmol/L)] or 70 milligrams per deciliter (mg/dL). Symptoms of hypoglycemia without confirmed blood glucose values were reported as AEs instead of hypoglycemic events. Number of participants with hypoglycemic events were reported.

  • Change From Baseline Vital Signs: Systolic and Diastolic Blood Pressure (SBP and DBP) [ Time Frame: Day 1 of each treatment period ]
    SBP and DBP were obtained during each treatment period at the indicated time points. Measurements were made with the participant lying semi-recumbent having rested in this position for at least 10 minute before the initial reading.

  • Change From Baseline Vital Signs: Heart Rate [ Time Frame: Day 1 of each treatment period ]
    Heart rate was obtained during each treatment period at indicated time points. Measurements were made with the participants lying semi-recumbent having rested in this position for at least 10 minutes before the initial reading.

  • Number of Participants With Abnormal Electrocardiogram (ECG) Findings [ Time Frame: Day 1 of each treatment period ]
    Standard semi-recumbent 12-lead ECG was obtained after the participant rested for a minimum of 10 minutes (If questionable abnormality was noted on the ECG, 2 more measurements were allowed to provide an average of 3 measurements). Number of participants with abnormal ECG were reported.

  • Number of Participants With Abnormal Clinical Chemistry Data [ Time Frame: Day 1 of each treatment period ]
    Clinical Chemistry data for parameters: Alanine Amino Transferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Bicarbonate, Calcium, Chloride, Creatine Kinase, Creatinine, Gamma Glutamyl Transferase (GGT), Glucose, Lactate Dehydrogenase, Magnesium, Phosphorus, Potassium, Total Bilirubin, Sodium, Total protein, triglycerides and urea/BUN was reported. Data for number of participants with abnormal clinical Chemistry data was presented.

  • Number of Participants With Abnormal Hematology Data [ Time Frame: Day 1 of each treatment period ]
    Data for abnormal Hematology parameters: Basophils, Eosinophils, Hematocrit, Hemoglobin, Lymphocytes, Mean Corpuscle Hemoglobin (MCH), Mean Corpuscle Volume (MCV), Monocytes, Platelet count, Red Blood Cell (RBC), Reticulocytes, Total Neutrophils, White Blood Cell (WBC) were reported. Data for number of participants with abnormal Hematology were reported.

  • Summary of Urine Osmolality [ Time Frame: Day 1 (pre dose) of each treatment period ]
    Urine sample was collected at screening, Day -2 (18:00h) and Day 1 (7:45h) for determination of urine osmolality which was measured in Millimole per kilogram (mmol/kg).

  • Mean Creatinine Clearance [ Time Frame: Up to 24 hours post dose of each treatment period. ]
    Creatinine clearance was calculated and reported in Milliliters per minute (mL/min) on Day 1 of each period for each collection interval 0-4, 4-8, 8-12, 12-16 and 16-24 hour, as well as the combined intervals of 0-12 and 0-24 hour. For urine measurements, participants were instructed to void within 30 minutes before administration of study medication.

  • Summary of Fluid Balance [ Time Frame: Up to 24 hours post dose of each treatment period. ]
    On Day 1, fluid intake, urine volume and number of micturations were recorded over the intervals for each of the following dosing periods: 0-4h, 4-8h, 8-12h, 12-16h and 16-24h. From these measures, fluid balance was calculated over the 24-hour period. Fluid Balance=total fluid intake minus total urine volume. The 0-24h amounts of total Fluid Intake, total urine output, and fluid balance were calculated by adding the amounts collected during these time intervals.

  • Mean of Derived Plasma Glucose Parameters [ Time Frame: Up to 24 hours post dose of each treatment period. ]
    The plasma measurements at specified time points on Day 1 were collected. Derived plasma glucose parameters were presented.


Secondary Outcome Measures:
  • Incremental Adjusted Weighted Means of Plasma Glucose AUC(0-4) and AUC(0-10) on Day 1 [ Time Frame: Up to 24 hours post dose of each treatment period. ]
    AUC(0-10) was the plasma glucose weighted mean AUC for 0 to 10 h post-dosing and AUC(0-4) was the plasma glucose weighted mean AUC for 0 to 4 h post-dosing. Incremental Adjusted Weighted Means were presented.

  • Urinary Glucose Excretion (UGE) for Timed Subintervals up to 24 Hours Post Dose (0-24 H) [ Time Frame: Up to 24 hours post dose of each treatment period ]
    UGE was assessed for timed subintervals up to 24h post-dose. Urine samples were collected at intervals: 0-4h, 4-8h, 8-12h, 12-16h and 16-24h on study days. The 0-24h amounts excreted in urine were calculated by adding the amounts collected during these time intervals.

  • Percent of Filtered Glucose in the Urine. [ Time Frame: Up to 24 hours post dose of each treatment period. ]
    Filtered glucose in the urine was assessed at indicated time points and was presented as Percentage. The 0-12h and 0-24h amounts Percent of filtered glucose in the urine were calculated by adding the amounts collected during these time intervals.

  • Mean Total Urine Volume 0-24 H [ Time Frame: Day 1 of each treatment period ]
    Urine volume was recorded over intervals : 0-4h, 4-8h, 8-12h, 12-16h and 16- 24h on Day 1 for each dosing period. Mean total Urine volume over 24 hours was presented.

  • Mean Creatinine Clearance 0-24 H [ Time Frame: Day 1 of each treatment period ]
    Urine samples for calculating creatinine clearance were obtained over the intervals: 0-4h, 4-8h, 8-12h, 12-16h and 16-24h. Mean creatinine clearance over 0-24 H was presented.

  • Area Under the Plasma Concentration vs. Time Curve (AUC) From Time Zero (Time of Dosing) to the Last Time Point With Measurable Analyte Concentration, AUC(0-last), AUC From Time Zero to Infinite Time, AUC(0-inf) of GSK189075 Over Period [ Time Frame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period ]
    AUC(0-last) was defined as area under the plasma concentration vs. time curve from time zero (time of dosing) to the last time point with measurable analyte concentration and AUC(0-inf) was defined as area under the plasma concentration vs. time curve from time zero to infinite time. Blood samples were collected on time points: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period.

  • Maximum Observed Plasma Concentration (Cmax) of GSK189075 Over Period [ Time Frame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period ]
    Plasma samples for pharmacokinetic analysis were drawn at indicated time points of each treatment period. Cmax was defined as maximal measured plasma concentration over the time span specified. Values were reported as Geometric Means with respective Geometric Coefficient of Variation (% CV).

  • Time to Maximum Observed Plasma Concentration (Tmax) and Terminal Half Life, (T1/2) of GSK189075 Over Period [ Time Frame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period ]
    Tmax was defined as the time to the maximum or "peak" concentration of a drug observed after multiple administration. T1/2 was defined as the time to when half of the total amount of a particular substance is eliminated from the body. Blood samples obtained during indicated time points. T1/2 was calculated as t1/2 = ln2/λz, with λz (the terminal elimination rate-constant) estimated from log-linear regression analysis of the terminal phase of the plasma concentration-time profile.Tmax and t1/2 values for GSK189075 were presented.

  • AUC From Time Zero to 4 Hours Post Dose, AUC(0-4) for GSK189074 Over Period [ Time Frame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period ]
    AUC(0-4) was defined as AUC from time zero to 4 hours post dose. Blood samples were collected on time points: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period.

  • Oral Clearance (CL/F) Over Period [ Time Frame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period ]
    Oral clearance is a measure of the rate at which the drug is cleared from the body via metabolism. Blood samples were collected on time points: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period

  • The Metabolite to Parent AUC Ratio, AUCmetabolite/AUCparent Ratio for GSK189074 Over Period [ Time Frame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period ]
    Blood samples were collected on time points: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period to obtain the metabolite to parent AUC ratio for GSK189074

  • The Metabolite to Parent AUC Ratio, AUCmetabolite/AUCparent Ratio for GSK279782 Over Period [ Time Frame: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period ]
    Blood samples were collected on time points: Pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 16 h of each treatment period to obtain the metabolite to parent AUC ratio for GSK279782


Enrollment: 10
Actual Study Start Date: March 31, 2008
Study Completion Date: December 18, 2008
Primary Completion Date: December 18, 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm a
GSK189075
Drug: GSK189075
investigational drug
Placebo Comparator: Arm b
Placebo
Drug: placebo
placebo comparator
Other Name: GSK189075

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult male/female, 18 to 55 years old
  • Diagnosis of type 1 diabetes mellitus for at least 6 months; and using a continuous insulin pump
  • Willing and able to follow all study-related instructions provided by the site staff.
  • Willing to provide signed informed consent.

Exclusion Criteria:

  • Pregnant or a nursing female.
  • Have a past or current disease such as heart, liver, kidney, blood, brain, or other disease.
  • Have HIV or hepatitis, or have alcohol or drugs in your system at the screening visit.
  • Have a history of alcohol abuse or have an eating disorder
  • Have been in another research study in the last month or have taken certain medications in the 1 week before study drug would be taken.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00575159


Locations
United States, California
GSK Investigational Site
San Diego, California, United States, 92161
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00575159     History of Changes
Other Study ID Numbers: KGI107465
First Submitted: December 14, 2007
First Posted: December 18, 2007
Results First Submitted: August 1, 2017
Results First Posted: October 9, 2017
Last Update Posted: October 9, 2017
Last Verified: August 2017

Keywords provided by GlaxoSmithKline:
type 1 Diabetes mellitus, pharmacokinetics,
pharmacodynamics
Adult male and females,

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases