Phase 2
Completed N=100
A Study in Type 2 Diabetics of Single and Multiple Doses of Orally Administered GSK1292263 to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics
Source: ClinicalTrials.gov NCT01119846 ↗Enrolled (actual)
100
Serious AEs
0.0%
Results posted
Jan 2018
Primary outcomePrimary: Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) — 2; 2; 2; 4 Participants
Summary
The purpose of this study is to see if GSK1292263 is safe and well-tolerated when administered to type 2 diabetics, and to get preliminary information about whether it may be effective in the treatment of type 2 diabetes.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
2; 2; 2; 4; 2; 0 | — |
| PRIMARY Part A: Number of Participants With Abnormal Hematology Parameters of Potential Clinical Importance (PCI) |
0; 0; 1; 0; 1 | — |
| PRIMARY Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI |
0; 1; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings |
0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With Abnormal Vital Signs of PCI |
0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Summary of Maximum Plasma Concentration (Cmax) |
52.04; 165.62; 379.79 | — |
| PRIMARY Part A: Summary of Time to Maximum Concentration (T-max) and Lag Time Before Observation of Drug Concentration in Sampled Matrix (T-lag) |
0.50; 0.00; 0.00; 4.99; 3.00; 3.00 | — |
| PRIMARY Part A: Summary of Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) and Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) |
524.30; 1684.86; 3985.72; 526.88; 1685.44; 3979.35 | — |
| PRIMARY Part C: Number of Participants With AEs and SAEs |
4; 5; 1; 4; 4; 2 | — |
| PRIMARY Part C: Number of Participants With Abnormal Hematology Parameters of PCI |
0; 0; 0; 1; 0; 0 | — |
| PRIMARY Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI |
0; 0; 0; 0; 1; 0 | — |
| PRIMARY Part C: Number of Participants With Significant ECG Abnormalities |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part C: Number of Participants With Abnormal Vital Signs of PCI |
0; 0; 0; 1; 0; 0 | — |
| PRIMARY Part C: Summary of Plasma Cmax |
219.36; 364.73; 584.32; 721.18; 410.98; 715.01 | — |
| PRIMARY Part C: Summary of T-max and T-lag |
0.00; 0.00; 0.00; 0.50; 4.00; 12.00 | — |
| PRIMARY Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 |
1127.45; 1868.87; 3076.52; 4003.80; 3167.19; 5869.82 | — |
| PRIMARY Part C: Summary of Accumulation Ratio (Ro) |
2.22; 2.17; 1.72; 1.29; 2.29; 2.15 | — |
| PRIMARY Part C: Summary of Time Invariance Ratio (Rs) of AUC0-10 for BID Dose of GSK1292263 |
2.8174; 3.0033; 2.4218 | — |
| PRIMARY Part C: Summary of Time Invariance Ratio (Rs) of AUC0-24 for Once Daily Dose of GSK1292263 |
1.2871 | — |
| PRIMARY Part C: Summary of Time Invariance Ratio (Rs) of Cmax |
1.9186; 1.6755; 1.1703 | — |
| PRIMARY Part A: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity |
1.4; 2.1; 2.3; 2.8; 2.7 | — |
| PRIMARY Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity |
6.4; 9.8; 9.2; 8.0; 6.6; 7.0 | — |
| PRIMARY Part A: Summary of Change From Baseline in Fasted Glucose |
0.52; 1.49; 0.53; 0.87; 0.58 | — |
| PRIMARY Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose |
9.42; 9.44; 9.15; 8.64; 9.23; 8.72 | — |
| PRIMARY Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin |
1533.54; 1518.81; 1523.99; 1513.90; 1418.12; 920.62 | — |
| PRIMARY Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose |
12.82; 12.79; 12.12; 11.26; 11.97; 5.55 | — |
| PRIMARY Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin |
1207.17; 1352.32; 1357.81; 1387.78; 1287.66; 563.75 | — |
| PRIMARY Part A: Summary of the OGTT Derived Parameters: Disposition Index |
0.87; 0.76; 1.07; 0.94; 0.86 | — |
| PRIMARY Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio |
0.06; 0.06; 0.05; 0.04; 0.06; 15.98 | — |
| PRIMARY Part A: Summary of the OGTT Derived Parameters: Insulin Glucose Index |
0.23; 0.22; 0.28; 0.26; 0.21 | — |
| PRIMARY Part A: Summary of the OGTT Derived Parameters: Insulin Sensitivity Index |
3.95; 3.47; 3.87; 3.60; 4.01 | — |
| PRIMARY Part C: Summary of Change From Baseline in Fasted Glucose |
4.60; 4.93; 7.39; 5.17; 5.51; 4.09 | — |
| PRIMARY Part C: Summary of Change From Baseline in Fasted Insulin |
158.91; 117.15; 151.56; 129.44; 216.95; 162.83 | — |
| SECONDARY Part B: Number of Participants With AEs and SAEs |
0; 1; 0; 0 | — |
| SECONDARY Part B: Number of Participants With Abnormal Hematology Parameters of PCI |
0; 0 | — |
| SECONDARY Part B: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI |
1; 1 | — |
| SECONDARY Part B: Number of Participants With Significant ECG Abnormalities |
0; 0 | — |
| SECONDARY Part B: Number of Participants With Abnormal Vital Signs of PCI |
0; 0 | — |
| SECONDARY Part B: Summary of Plasma Cmax |
339.52; 944.21 | — |
| SECONDARY Part B: Summary of T-max and T-lag |
2.00; 4.98; 0.00; 0.00 | — |
| SECONDARY Part B: Summary of AUC0-t and AUC0-24 |
3370.43; 12639.84; 3370.43; 12659.88 | — |
| SECONDARY Part B: Summary of Change From Baseline in Fasted Glucose |
0.40; 1.95 | — |
| SECONDARY Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin |
13.44; 55.83; 2.23; 5.40; 0.00; 0.00 | — |
| SECONDARY Part C: Summary of Cmax of GSK1292263 and Sitagliptin When Co-administered |
301.89; 284.59; 458.24; 378.12; 307.45; 360.91 | — |
| SECONDARY Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered |
7.60; 7.24; 7.38; 7.22; 7.85; 7.89 | — |
| SECONDARY Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered |
2701.81; 2585.15; 3338.49; 3012.70; 2437.10; 3027.99 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female subjects, 18 - 60 years of age, inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. FSH and estradiol levels will be checked at Screening for postmenopausal women. Simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol 2 times the upper limit of normal at screening.
- Fasting triglycerides > 450mg/dL at screening.
- Total Bilirubin > 1.5 times the upper limit of normal at screening.
- For females a haemoglobin 2.5; or urine albumin concentration >300mg/g of creatinine).
- Known loss of a kidney either by surgical ablation, injury, or disease.
- Significant ECG abnormalities, defined as follows:
Heart Rate 100bpm PR Interval 220ms QRS duration 120ms QTC Interval (Bazett)* > 450ms
Or, has clinically significant rhythm abnormalities identified during 24-hour Screening Holter assessment. Subjects with Left Bundle Branch Block are excluded from the study. Subjects with partial Right Bundle Branch Block may be considered for inclusion following consultation with the GSK Medical Monitor. Subjects with WPW syndrome are excluded from the study.
*Note that if ECG abnormalities are identified, the ECG should be repeated two more times (with 5 minutes between ECG readings) and the average of the 3 values used to determine eligibility.
- Systolic pressure > 150mmHg or 95mmHg or 2 weeks when used for acute illness in the last 12 months prior to Screening, or if used for more than 1 year when associated with gestational diabetes mellitus.
- Has a history of any of the following conditions:
- Clinically significant symptoms of gastroparesis
- Cholelithiasis or obstructive or inflammatory gallbladder disease within 3 months prior to Screening
- Gastrointestinal disease that could affect fat or bile acid absorption, including inflammatory bowel disease, chronic diarrhea, Crohn's or malabsorption syndromes within the past year
- Gastrointestinal surgery
- Chronic or acute pancreatitis
- History of regular alcohol consumption within 6 months of the study defined as:
- An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360mL) of beer, 5 ounces (150mL) of wine or 1.5 ounces (45mL) of 80 proof distilled spirits.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- Has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Is taking prohibited medications. See Section 9.3 for a detailed list of prohibited medications. Note also:
- The use of anti-diabetic agents other than those listed in Inclusion #7 is reason for exclusion and subjects will not be allowed to wash off of unapproved anti-diabetic medications in order to qualify for participation in this study.
- Subjects must wash out from the following medications during the 7-day period prior to first dose, and must remain off these medications through discharge on post-last-dose of Period 2 (Part B) or Day 15 (Part C): all anti-diabetic medications specified in Inclusion #7, all statin agents, fat absorption blocking agents, bile acid sequestrants. Fibrates must be washed out for a 14-day period prior to first dose.
- Vitamins, herbal and dietary supplements (including St John's Wort) are prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication and through discharge.
- Unwilling to abs
Data sourced from ClinicalTrials.gov (NCT01119846). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.