A Phase 1 Study to Evaluate the Effect of GSK256073, an HM74A Receptor Agonist, on Glucose and NEFA Levels in Type 2 Diabetics

NCT ID: NCT01147861

Last Updated: 2017-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-01
• Study Completion Date: 2010-09-07

Brief Summary

The aim of this study is to verify whether a significant decrease in glucose levels can be achieved with the HM74A agonist GSK256073 in type 2 diabetic patients. Several dose levels and a placebo will be evaluated in a three period crossover study with two active doses and one placebo dose per subject, in order to determine whether there is a dose that produces glucose lowering in the target population. In addition, this study will investigate the optimal dosing regimen for full manifestation of any metabolic effect of GSK256073 by comparing once a day versus twice a day regimens.

Detailed Description

This is a multi-center study that will enroll approximately 36 subjects. The study consists of three periods of two days of dosing each. The study will evaluate 5 potential dose regimens. Each subject will receive a randomized sequence of treatments over three periods, with placebo treatment in one period and two different active dose regimens in the other two periods. There will be 5 to 12 days of outpatient washout between treatment periods. Subjects will continue their current treatment on metformin throughout the study. Subjects will monitor blood glucose levels daily via glucometer during oupatient washout periods. A follow-up visit will occur between 5 and 10 days after the last period of the study.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Placebo

Subjects will receive 2 placebo tablets in the morning and 2 placebo tablets in the evening on Day 1 and Day 2.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

2 placebo tablets in the AM and 2 placebo tablets in the PM

5mg BID

Subjects will receive 1 x 5mg tablet and 1 placebo tablet in the morning, and 1 x 5mg tablet and 1 placebo tablet in the evening on Day 1 and Day 2.

Group Type: OTHER

GSK256073

Intervention Type: DRUG

5mg in the AM and 5mg in the PM

10mg QD

Subjects will receive 2 x 5mg tablets in the morning and 2 placebo tablets in the evening on Day 1 and Day 2.

Group Type: OTHER

GSK256073

Intervention Type: DRUG

10mg in the AM

25mg BID

Subjects will receive 1 x 25mg tablet and 1 placebo tablet in the morning, and 1 x 25mg tablet and 1 placebo tablet in the evening on Day 1 and Day 2.

Group Type: OTHER

GSK256073

Intervention Type: DRUG

25mg in the AM and 25mg in the PM

50mg QD

Subjects will receive 2 x 25mg tablets in the morning and 2 placebo tablets in the evening on Day 1 and Day 2.

Group Type: OTHER

GSK256073

Intervention Type: DRUG

50mg in the AM

Interventions

GSK256073

5mg in the AM and 5mg in the PM

Intervention Type: DRUG

GSK256073

10mg in the AM

Intervention Type: DRUG

GSK256073

50mg in the AM

Intervention Type: DRUG

GSK256073

25mg in the AM and 25mg in the PM

Intervention Type: DRUG

Placebo

2 placebo tablets in the AM and 2 placebo tablets in the PM

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Subjects with documented (not less than 6 months prior to screening) type 2 diabetes mellitus diagnosis with:
• HbA1c levels greater than 6.5 percent and less than or equal to 9.5 percent at screening,
• On monotherapy with metformin at the time of screening, and at a todal daily dose greater than or equal to 1000 mg at the time of dosing,
• Fasting plasma glucose level less than 270 mg/dl at screening
• Male or female between 20 and 70 years of age inclusive, at the time of signing the informed consent
• Waist circumference above 102cm (40 inches) for men, and 88cm (35 inches) for women
• Fasting triglycerides between 150 mg/dl and 500 mg/dl, inclusive
• BMI within the range of 22-37 kg/meter squared, inclusive

Exclusion Criteria

A subject will not eligible for inclusion in this study if any of the following criteria apply:

• Requiring insulin therapy or use of combination oral antidiabetic medications or use of monotherapy other than metformin within the 3 months prior to screening
• Past or present disease (other than type 2 diabetes mellitus) that in the opinion of the Investigator may affect the outcome of this study. These diseases include the following but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, gastrointestinal disease and endocrine disease
• A positive pre-study Hepatitis B surface antigen, or positive Hepatitis C or HIV antibody result within 3 months of screening
• Renal impairment as defined by a calculated GFR less than 60 ml/min
• Any concurrent serious illness (e.g., severe COPD, history of malignancy other than skin cancer within 5 years of initial diagnosis or with evidence of recurrence) that may interfere with a subject completing the study
• Clinical laboratory values as defined per protocol
• ECG parameters as defined per protocol
• History of gout and/or hyperuricemia/uric acid kidney stone or treated with drugs for hyperuricemia: allopurinol and/or probenecid
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Use of the following blood pressure medications or other medications renally excreted via OAT is prohibited: Enalapril (at any dose), Losartan (at any dose), Captopril (at any dose)
• Pregnant females as determined by positive serum hCG test at screening or positive urine hCG test prior to dosing
• Lactating females

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Anniston, Alabama, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Miami Gardens, Florida, United States

GSK Investigational Site

San Antonio, Texas, United States

Countries

United States

References

Dobbins RL, Shearn SP, Byerly RL, Gao FF, Mahar KM, Napolitano A, Nachbaur GJ, Le Monnier de Gouville AC. GSK256073, a selective agonist of G-protein coupled receptor 109A (GPR109A) reduces serum glucose in subjects with type 2 diabetes mellitus. Diabetes Obes Metab. 2013 Nov;15(11):1013-21. doi: 10.1111/dom.12132. Epub 2013 Jun 12.

Reference Type: BACKGROUND

PMID: 23701262 (View on PubMed)

Study Documents

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

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Other Identifiers

114187

Identifier Type: -

Identifier Source: org_study_id