Clinical trial NCT01376323: A Study of GSK256073 in Subjects With Type 2 Diabetes Mellitus Who Are Being Treated With Metformin
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Keywords: Safety
Dose Ranging
Efficacy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-06-20
Enrollment: 92
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to Week 12
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Baseline (pre-dose Day 1) and up to Week 12
measure: Change From Baseline in Heart Rate
timeFrame: Baseline (pre-dose Day 1) and up to Week 12
measure: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings
timeFrame: Up to Week 20
measure: Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance (PCI)
timeFrame: Up to Week 12
measure: Number of Participants With Hematology Abnormalities of Potential Clinical Importance (PCI)
timeFrame: Up to Week 12
measure: Number of Participants With Abnormal Urinalysis: Glucose, Protein, Blood and Ketones by Dipstick
timeFrame: Up to Week 12
measure: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12
timeFrame: Baseline (Day -1) and up to Week 12
Secondary outcomes:
measure: Change From Baseline in 12 Hour Non-esterified Fatty Acids (NEFA) and Glucose Weighted Mean Concentration Value at Day 2 and at Week 6
timeFrame: Baseline (Day 1) and up to Week 6
measure: GSK256073 AUC and HbA1c at Week 12 Was Evaluated to Establish the Exposure-response Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship
timeFrame: Up to Week 12
measure: Change From Baseline in Fasting Plasma Glucose at Week 12
timeFrame: Baseline (Day 1) and up to Week 12
measure: Change From Baseline in Fasting Insulin at Week 12
timeFrame: Baseline (Day 1) and up to Week 12
measure: Summary of Homeostatic Model Assessment (HOMA) Index Calculated From Change From Baseline in Fasting Insulin and Fasting Glucose at Week 12
timeFrame: Baseline (Day 1) and up to Week 12
measure: Change From Baseline in Fructosamine at Week 6 and Week 12
timeFrame: Baseline (Day -1) and Week 12
measure: Number of Participants With HbA1c < 7.0% and < 6.5%
timeFrame: Up to Week 12
Other outcomes:
Locations:
city: Anniston
country: United States
facility: GSK Investigational Site
state: Alabama
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miramar
country: United States
facility: GSK Investigational Site
state: Florida
city: Nantes cedex 01
country: France
facility: GSK Investigational Site
city: Pierre-Bénite Cedex
country: France
facility: GSK Investigational Site
city: Rennes Cedex
country: France
facility: GSK Investigational Site
city: Rueil-Malmaison
country: France
facility: GSK Investigational Site
city: Alicante
country: Spain
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Edinburgh
country: United Kingdom
facility: GSK Investigational Site
state: Midlothian
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
city: Coventry
country: United Kingdom
facility: GSK Investigational Site
city: Newcastle upon Tyne
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: