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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01147861
First received: June 17, 2010
Last updated: May 12, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: GSK256073
Other: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Randomized, Single Blind, Placebo-controlled, Three Period Crossover, Dose Selection Study to Evaluate the Effect of GSK256073, an HM74A Receptor Agonist, on Glucose and NEFA 24 Hour Profile in Type 2 Diabetic Patients.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Weighted mean AUC for glucose [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Weighted mean AUC for NEFA, glycerol, triglycerides, insulin, and C-peptide [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Enrollment: 39
Study Start Date: July 2010
Study Completion Date: October 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Subjects will receive 2 placebo tablets in the morning and 2 placebo tablets in the evening on Day 1 and Day 2.
Other: Placebo
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.
Drug: GSK256073
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.
Drug: GSK256073
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.
Drug: GSK256073
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.
Drug: GSK256073
50mg in the AM

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.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01147861

Locations
United States, Alabama
GSK Investigational Site
Anniston, Alabama, United States, 36207
United States, Florida
GSK Investigational Site
Miami, Florida, United States, 33169
GSK Investigational Site
Miami Gardens, Florida, United States, 33169
United States, Texas
GSK Investigational Site
San Antonio, Texas, United States, 78229
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: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01147861     History of Changes
Other Study ID Numbers: 114187
Study First Received: June 17, 2010
Last Updated: May 12, 2011
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
T2DM
Pharmacodynamics
GSK256073

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 11, 2014