A Study of GSK256073 in Subjects With Type 2 Diabetes Mellitus Who Are Being Treated With Metformin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01376323
First received: June 16, 2011
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

The aim of this combined, two part study is to evaluate the safety and glucose lowering effects of GSK256073 when administered to diabetic subjects for 12 weeks.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: GSK256073 1mg
Drug: GSK256073 5mg
Drug: GSK256073 10mg
Drug: GSK256073 25mg
Drug: Placebo
Drug: Sitagliptin 100mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Two Part, Randomized, Parallel Group, Placebo and Sitagliptin Controlled Study to Evaluate the Safety and Efficacy of GSK256073 Administered Once or Twice Daily for 12 Weeks in Subjects With Type 2 Diabetes Mellitus Who Are Being Treated With Metformin

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Adverse events, clinical laboratory tests, electrocardiograms (ECGs), and vital signs

  • Efficacy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change from baseline in HbA1c at week 12


Secondary Outcome Measures:
  • Pk/Pd relationship [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    GSK256073 AUC and HbA1c at week 12 will be evaluated to establish the exposure-response (PK/PD) relationship

  • Biomarkers [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change from baseline in glucose, insulin, and fructosamine at week 12

  • Sustainability of effect [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Change from baseline in 12 hour NEFA and glucose AUC on Day 2 and at Week 6

  • Number of subjects achieving HbA1c treatment targets [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Percentage of subjects with HbA1c less than 7% and less than 6.5%


Enrollment: 92
Study Start Date: July 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK256073 1mg bid
GSK256073 1mg capsule taken orally twice a day
Drug: GSK256073 1mg
GSK256073 1mg capsule
Experimental: GSK256073 2mg qd
GSK256073 2 x 1mg capsule taken orally once a day
Drug: GSK256073 1mg
GSK256073 1mg capsule
Experimental: GSK256073 5mg bid
GSK256073 5mg capsule taken orally twice a day
Drug: GSK256073 5mg
GSK256073 5mg capsule
Experimental: GSK256073 10mg qd
GSK256073 2 x 5mg capsule taken orally once a day
Drug: GSK256073 5mg
GSK256073 5mg capsule
Experimental: GSK256073 10mg bid
GSK256073 10mg capsule taken orally twice a day
Drug: GSK256073 10mg
GSK256073 10mg capsule
Experimental: GSK256073 20mg qd
GSK256073 2x 10mg capsule taken orally once a day
Drug: GSK256073 10mg
GSK256073 10mg capsule
Experimental: GSK256073 25mg bid
GSK256073 25mg capsule taken orally twice a day
Drug: GSK256073 25mg
GSK256073 25mg capsule
Experimental: GSK256073 50mg qd
GSK256073 2x 25mg capsule taken orally once a day
Drug: GSK256073 25mg
GSK256073 25mg capsule
Placebo Comparator: Placebo
Matching placebo capsules taken orally either once a day or twice a day
Drug: Placebo
placebo capsule
Active Comparator: Sitagliptin 100mg qd
Commercially available Sitagliptin 100mg capsules taken once a day
Drug: Sitagliptin 100mg
Sitagliptin 100mg capsule

Detailed Description:

The study will be conducted at centers in Europe and the United States. The study is being conducted in two parts. Part A (n = 90 subjects) will provide a preliminary evaluation of 12 weeks of treatment. Initiation of part B (n = 210 additional subjects) will be dependent on the results observed in part A. The emerging data from part A will be used to guide selection of the doses in Part B. Up to 8 dose levels of GSK256073 may be included in part B. The emerging exposure response relationships from the part A interim analysis will be used to guide dose selection.

Each subject enrolled in the study will undergo screening procedures, a 2 week placebo run-in period, baseline assessments, randomization, a twelve week treatment period, and a 2 week follow-up period. Following completion of the baseline visit and randomization into the study, subjects will return to the clinic for safety and efficacy assessments at Weeks 3, 6, 9, and 12. A subject's total participation in the study will last up to approximately 20 weeks. Subjects will continue their current prescribed regimen of metformin (glucophage) monotherapy and will monitor fasting blood glucose levels daily using a glucometer.

  Eligibility

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

Inclusion Criteria:

  • A diagnosis of T2DM as determined by a responsible physician based on a medical evaluation including medical history, physical examination, and laboratory tests, with onset at least 6 months prior to Screening. Subjects may be entered if they have stable hypertension or dyslipidemia on therapy. Subjects with other conditions except as noted in the Exclusion criteria may be included only if the investigator and GSK medical monitor agree that the condition is unlikely to introduce additional risk factors and will not interfere with study procedures
  • HbA1c levels greater than or equal to 7.0 % and less than or equal to 9.5% at Screening
  • On monotherapy with metformin at the time of screening, and at a maximum tolerated dose greater than or equal to 1000 mg for at least 2 months prior to dosing.
  • Fasting plasma glucose level less than 13.3 mmol/L (240 mg/dL) at Screening
  • Male or female between 20 and 70 years of age, inclusive, at the time of signing the informed consent
  • Fasting Triglycerides lower than 4.52 mmol/L (400 mg/dL)
  • A female subject is able to participate is she if of non-child bearing potential
  • Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until 3 days after last dose of the study medication
  • Overweight with BMI greater than or equal to 25 kg/m2 for non-Asian Indians and greater than or equal to 24 kg/m2 for Asian-Indian, and less than 40 kg/m2
  • The subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
  • Subjects in France will be eligible only if they are affiliated to or a beneficiary of a social security category
  • Subjects in other countries must meet all local and/or country-specific requirements for registration and reimbursement, as applicable

Exclusion Criteria:

  • 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
  • A positive pre-study Hepatitis B surface antigen, or positive Hepatitis C 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
  • Laboratory values as defined per protocol
  • ECG criteria as defined per protocol
  • Systolic blood pressure greater than 160 mmHg, or diastolic blood pressure greater than 100 mmHg at Screening
  • History of uric acid kidney stone, and being treated with drugs for hyperuricemia including Allopurinol or Probenecid
  • History of peptic ulcer disease (PUD) and/or other gastrointestinal bleeding within the 12 months prior to screening
  • Use of certain blood pressure medications or certain other medications that are renally excreted as defined per protocol
  • History of myopathy or CPK value greater than 3 times upper limit of normal at screening
  • The subject has participated in a clinical trial and has received an investigational product within 30 days or 5 half-lives or twice the biological effect (whichever is longer)
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day
  • Any change in diet, exercise habits or smoking status within six weeks prior to screening. Any subject that cannot refrain from smoking while in the unit must be excluded
  • History of sensitivity to any of the study medications, including sitagliptin or metformin, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation
  • The subject has a positive pre-study drug screen
  • History of regular alcohol consumption within 6 months of the study as defined per protocol
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
  • Pregnant females as determined by positive serum and/or urine hCG test at screening and prior to dosing
  • Lactating females
  • Subjects who are unwilling or unable 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: NCT01376323

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
Miramar, Florida, United States, 33025
France
GSK Investigational Site
Nantes cedex 01, France, 44093
GSK Investigational Site
Pierre-Bénite Cedex, France, 69495
GSK Investigational Site
Rennes Cedex, France, 35046
GSK Investigational Site
Rueil-Malmaison, France, 92502
Spain
GSK Investigational Site
Alicante, Spain, 03114
GSK Investigational Site
Badalona, Spain, 08916
GSK Investigational Site
Granada, Spain, 18004
GSK Investigational Site
Madrid, Spain, 28046
United Kingdom
GSK Investigational Site
Edinburgh, Midlothian, United Kingdom, EH4 2XU
GSK Investigational Site
Cambridge, United Kingdom, CB2 0GG
GSK Investigational Site
Coventry, United Kingdom, CV2 2DX
GSK Investigational Site
Newcastle upon Tyne, United Kingdom, NE1 4LP
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01376323     History of Changes
Other Study ID Numbers: 114728
Study First Received: June 16, 2011
Last Updated: May 29, 2014
Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Safety
Dose Ranging
Efficacy

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
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014