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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01128621
First received: February 12, 2010
Last updated: March 29, 2012
Last verified: March 2012
  Purpose

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


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: GSK1292263
Drug: GSK1292263 matching placebo
Drug: Sitagliptin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number and frequency of adverse events and abnormal lab values [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic measures (e.g., AUC, t1/2, tmax) [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  • Changes in glucose and insulin [ Time Frame: 5 months ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: November 2009
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Part A
Part A is open label, in T2DM subjects on established metformin monotherapy. Subjects will receive a single dose of GSK1292263 with food. This will permit a comparison of GSK1292263 exposures in this cohort with those observed in study GPR111598 in which T2DM subjects were drug naïve or washed off prior anti-diabetic medications.
Drug: GSK1292263
Tablet
Placebo Comparator: Part B - PLA
Part B is a single-blind, randomized, placebo-controlled, 4-arm cohort of 48 subjects dosed for 14 days with one of two doses of GSK1292263 BID, placebo BID or open-label sitagliptin 50mg BID. It is being conducted to assess safety, tolerability, PK and PD of GSK1292263 and open-label sitagliptin after 14-days of dosing in T2DM subjects already taking metformin monotherapy.
Drug: GSK1292263 matching placebo
Tablet
Active Comparator: Part B - Active
Part B is a single-blind, randomized, placebo-controlled, 4-arm cohort of 48 subjects dosed for 14 days with one of two doses of GSK1292263 BID, placebo BID or open-label sitagliptin 50mg BID. It is being conducted to assess safety, tolerability, PK and PD of GSK1292263 and open-label sitagliptin after 14-days of dosing in T2DM subjects already taking metformin monotherapy.
Drug: GSK1292263
Tablet
Active Comparator: Part B - Sitagliptin
Part B is a single-blind, randomized, placebo-controlled, 4-arm cohort of 48 subjects dosed for 14 days with one of two doses of GSK1292263 BID, placebo BID or open-label sitagliptin 50mg BID. It is being conducted to assess safety, tolerability, PK and PD of GSK1292263 and open-label sitagliptin after 14-days of dosing in T2DM subjects already taking metformin monotherapy.
Drug: Sitagliptin
Tablet

Detailed Description:

This study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of GSK1292263 when co-administered with metformin. The study will be in 2 parts. Part A will determine the PK of GSK1292263 following single day dosing of type 2 diabetes (T2DM) subjects on metformin. Part B will investigate the effects of 14d of co-dosing of GSK1292263 BID, 50mg BID of sitagliptin or placebo to 48 T2DM subjects taking metformin.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects, 18 - 65 years of age, inclusive.
  • Females of non-childbearing potential.
  • Male subjects willing to employ appropriate contraception.
  • Except as noted elsewhere, subjects should have no significant known medical conditions other than T2DM that would affect the safety of the subject or the objectives of the study.
  • BMI (body mass index) within the range 21.8-37.5 kg/m2.
  • T2DM diagnosed by American Diabetes Association criteria for at least 3 month prior to screening.
  • Currently on stable metformin therapy.
  • Fasting plasma glucose <= 250mg/dL.
  • HbA1c between 6.5 and 11.0%.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Average QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with right bundle branch block. Subjects with left bundle branch block are not eligible.
  • AST and ALT < 2xULN; alkaline phosphatase and bilirubin <=1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). Subjects with Gilbert's syndrome are allowed to participate in the study.

Exclusion Criteria:

  • Positive for Hepatitis B or C, or HIV.
  • History of uncorrected thyroid dysfunction or an abnormal thyroid function test.
  • History of ketoacidosis or lactic acidosis.
  • Fasting triglycerides > 450mg/dL.
  • For females a hemoglobin < 11.5g/dL, and for males a hemoglobin < 12.5g/dL.
  • Positive drug/alcohol screen.
  • Smoking.
  • If female is pregnant or has a positive pregnancy test or is lactating.
  • Significant renal disease.
  • Significant ECG abnormalities.
  • Systolic blood pressure > 150mmHg or <80mmHg or diastolic blood pressure > 95mmHg or <60mmHg at screening.
  • Previous use of insulin as a treatment within 3 months of screening, or for >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.
  • History of: clinically significant symptoms of gastroparesis; symptomatic cholelithiasis or obstructive or inflammatory gallbladder disease within 3 months prior to screening; gastrointestinal disease that could affect fat or bile acid absorption, or the pharmacokinetics or pharmacodynamics of the study drugs, including inflammatory bowel disease, chronic diarrhea, Crohn's or malabsorption syndromes within the past year; gastrointestinal surgery that may affect the pharmacokinetics or pharmacodynamics of the study drugs; or, chronic or acute pancreatitis.
  • History of regular alcohol consumption within 6 months.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months.
  • 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. In Parts A and B, 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 Day 2 (Part A) or Day 15 (Part B): all statin agents, fat absorption blocking agents, bile acid sequestrants. Fibrates must be washed out for a 14-day period prior to first dose. • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication.
  • Unwilling to abstain from: Caffeine-or xanthine-containing products from Day -7 until D2 (Part A) or Day -7 through Day 15 (Part B); use of illicit drugs or nicotine-containing products; alcohol from Day -7 prior to dosing until D2 (Part A) or Day -7 through Day 15 (Part B); Consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication until collection of the final pharmacokinetic blood samples.
  • History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. This includes sensitivity to heparin or heparin-induced thrombocytopenia, if heparin will be used to maintain catheter patency.
  • Where participation in the study would result in donation of blood in excess of approximately 500mL within a 56 day period.
  • Subject is either an immediate family member of a participating investigator, study coordinator, employee of an investigator; or is a member of the staff conducting the study.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subject is mentally or legally incapacitated.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01128621

Locations
United States, California
GSK Investigational Site
Chula Vista, California, United States, 91910
United States, Florida
GSK Investigational Site
Miami, Florida, United States, 33169
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01128621     History of Changes
Other Study ID Numbers: 113132
Study First Received: February 12, 2010
Last Updated: March 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Pharmacokinetics
Glucose
Safety
Male
Female
Metformin
Pharmacodynamics
Tolerability
Type II Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014