Study In People With Type 2 Diabetes

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study of Oral GW677954 as a Monotherapy for 12 Weeks Duration in Patients With Type 2 Diabetes Mellitus

This Phase 2 dose-ranging study will evaluate the efficacy, safety and tolerability of a range of doses of GW677954 compared with placebo over sixteen weeks of treatment in subjects with T2DM (Type 2 Diabetes Mellitus).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Pioglitazone; Drug: GW677954

Detailed Description

A Multicenter, Randomized, Double-Blind, Double-Dummy, Parallel-Group, Placebo-Controlled, Study To Evaluate Efficacy, Safety And Tolerability Of Oral GW677954 Capsules (2.5, 5, 10, 15 And 20 Mg Once A Day) As A Monotherapy (Diet and/or exercise treated) Or As An Add-On To Metformin For 16 Weeks Duration In Subjects With Type 2 Diabetes Mellitus

• Study Type: Interventional
• Enrollment (Actual): 448
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1425
    • GSK Investigational Site
  • San Juan, Argentina, 5400
    • GSK Investigational Site
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1181
      • GSK Investigational Site
    • Capital Federal, Buenos Aires, Argentina, C1221ACI
      • GSK Investigational Site
  • Córdova
    • Cordoba, Córdova, Argentina, 5000
      • GSK Investigational Site
• Australia
  • New South Wales
    • Miranda, New South Wales, Australia, 2228
      • GSK Investigational Site
  • Queensland
    • Carina Heights, Queensland, Australia, 4152
      • GSK Investigational Site
    • Spring Hill, Queensland, Australia, 4000
      • GSK Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • GSK Investigational Site
    • Keswick, South Australia, Australia, 5035
      • GSK Investigational Site
    • Port Lincoln, South Australia, Australia, 5606
      • GSK Investigational Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • GSK Investigational Site
    • Ringwood East, Victoria, Australia, 3135
      • GSK Investigational Site
• Canada
  • Quebec, Canada, G1W 4R4
    • GSK Investigational Site
  • British Columbia
    • Langley, British Columbia, Canada, V3A 4H9
      • GSK Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
      • GSK Investigational Site
  • Newfoundland and Labrador
    • Saint John's, Newfoundland and Labrador, Canada, A1E 2C2
      • GSK Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 5R3
      • GSK Investigational Site
  • Ontario
    • Brampton, Ontario, Canada, L6T 3J1
      • GSK Investigational Site
    • London, Ontario, Canada, N5W 6A2
      • GSK Investigational Site
    • Mississauga, Ontario, Canada, L5A 1N1
      • GSK Investigational Site
    • Ottawa, Ontario, Canada, K1H 1A2
      • GSK Investigational Site
    • Smiths Falls, Ontario, Canada, K7A 4W8
      • GSK Investigational Site
    • Sudbury, Ontario, Canada, P3A 1Y8
      • GSK Investigational Site
    • Thornhill, Ontario, Canada, L4J 8L7
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M9W 4L6
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M4R 2G4
      • GSK Investigational Site
    • Waterloo, Ontario, Canada, N2J 1C4
      • GSK Investigational Site
  • Quebec
    • Bonaventure, Quebec, Canada, G0C 1E0
      • GSK Investigational Site
    • Granby, Quebec, Canada, J2G 8Z9
      • GSK Investigational Site
    • Laval, Quebec, Canada, H7T 2P5
      • GSK Investigational Site
    • Longueuil, Quebec, Canada, J4N 1L6
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H4N 2W2
      • GSK Investigational Site
    • Saint Marc Des Carrieres, Quebec, Canada, G0A 4B0
      • GSK Investigational Site
    • Sainte-Foy, Quebec, Canada, G1V 4G5
      • GSK Investigational Site
    • Sainte-Foy, Quebec, Canada, G1V 4G2
      • GSK Investigational Site
    • Sainte-Foy, Quebec, Canada, G1V 1V6
      • GSK Investigational Site
    • Sherbrooke, Quebec, Canada, J1G 5K2
      • GSK Investigational Site
• Colombia
  • Bogotá, Colombia
    • GSK Investigational Site
• Costa Rica
  • San José, Costa Rica
    • GSK Investigational Site
• Czech Republic
  • Ceske Budejovice, Czech Republic, 370 87
    • GSK Investigational Site
  • Cheb, Czech Republic, 350 02
    • GSK Investigational Site
  • Olomouc, Czech Republic, 779 00
    • GSK Investigational Site
  • Praha 10, Czech Republic, 10000
    • GSK Investigational Site
  • Praha 2, Czech Republic, 128 08
    • GSK Investigational Site
  • Praha 5, Czech Republic, 15030
    • GSK Investigational Site
  • Praha 5, Czech Republic, 158 00
    • GSK Investigational Site
• Ecuador
  • Quito, Ecuador
    • GSK Investigational Site
• Latvia
  • Cesis, Latvia, LV4100
    • GSK Investigational Site
  • Daugavpils, Latvia, LV5417
    • GSK Investigational Site
  • Riga, Latvia, LV 1002
    • GSK Investigational Site
  • Riga, Latvia, LV1024
    • GSK Investigational Site
  • Tukums, Latvia, LV 3100
    • GSK Investigational Site
• Mexico
  • Durango, Mexico, 3400
    • GSK Investigational Site
  • Mexico, D.F., Mexico, 11650
    • GSK Investigational Site
  • Baja California Norte
    • Tijuana, Baja California Norte, Mexico, 22320
      • GSK Investigational Site
  • Hidalgo
    • Pachuca, Hidalgo, Mexico, 42039
      • GSK Investigational Site
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62420
      • GSK Investigational Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64570
      • GSK Investigational Site
• New Zealand
  • Auckland, New Zealand, 1309
    • GSK Investigational Site
  • Auckland, New Zealand, 1311
    • GSK Investigational Site
  • Christchurch, New Zealand, 8001
    • GSK Investigational Site
  • Rotorua, New Zealand, 3201
    • GSK Investigational Site
  • Tauranga, New Zealand, 3001
    • GSK Investigational Site
• Peru
  • Lima, Peru, Lima 1
    • GSK Investigational Site
  • Lima, Peru, Lima 27
    • GSK Investigational Site
  • Lima, Peru, Lima 14
    • GSK Investigational Site
  • Lima
    • San Isidro, Lima, Peru, Lima 27
      • GSK Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 117 036
    • GSK Investigational Site
  • Perm, Russian Federation, 614600
    • GSK Investigational Site
  • Samara, Russian Federation, 443067
    • GSK Investigational Site
  • Tumen, Russian Federation, 625023
    • GSK Investigational Site
  • Ufa, Russian Federation, 450000
    • GSK Investigational Site
  • Yaroslavl, Russian Federation, 150062
    • GSK Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • GSK Investigational Site
    • Northport, Alabama, United States, 35476
      • GSK Investigational Site
  • Arizona
    • Chandler, Arizona, United States, 85224
      • GSK Investigational Site
    • Phoenix, Arizona, United States, 85006
      • GSK Investigational Site
    • Phoenix, Arizona, United States, 85032
      • GSK Investigational Site
  • California
    • Alhambra, California, United States, 91801
      • GSK Investigational Site
    • Artesia, California, United States, 90701
      • GSK Investigational Site
    • Huntington Beach, California, United States, 92648
      • GSK Investigational Site
    • Inglewood, California, United States, 90301
      • GSK Investigational Site
    • Irvine, California, United States, 92618
      • GSK Investigational Site
    • LaJolla, California, United States, 92037
      • GSK Investigational Site
    • Long Beach, California, United States, 90806
      • GSK Investigational Site
    • Los Angeles, California, United States, 90095
      • GSK Investigational Site
    • Los Angeles, California, United States, 90057
      • GSK Investigational Site
    • Northridge, California, United States, 91325
      • GSK Investigational Site
    • Norwalk, California, United States, 90650
      • GSK Investigational Site
    • Pasadena, California, United States, 91105
      • GSK Investigational Site
    • Sacramento, California, United States, 95825
      • GSK Investigational Site
    • San Diego, California, United States, 92128
      • GSK Investigational Site
    • San Diego, California, United States, 92177
      • GSK Investigational Site
    • Santa Monica, California, United States, 90404
      • GSK Investigational Site
    • Tustin, California, United States, 92780
      • GSK Investigational Site
    • Vista, California, United States, 92084
      • GSK Investigational Site
    • West Hills, California, United States, 91307
      • GSK Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80220
      • GSK Investigational Site
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • GSK Investigational Site
  • Florida
    • Hollywood, Florida, United States, 33021
      • GSK Investigational Site
    • Hollywood, Florida, United States, 33023
      • GSK Investigational Site
    • Largo, Florida, United States, 33773
      • GSK Investigational Site
    • Miami, Florida, United States, 33156
      • GSK Investigational Site
    • Sarasota, Florida, United States, 34239
      • GSK Investigational Site
    • St. Cloud, Florida, United States, 34769
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • GSK Investigational Site
    • Duluth, Georgia, United States, 30097
      • GSK Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • GSK Investigational Site
  • Illinois
    • Springfield, Illinois, United States, 62701
      • GSK Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • GSK Investigational Site
  • Massachusetts
    • West Yarmouth, Massachusetts, United States, 02673
      • GSK Investigational Site
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • GSK Investigational Site
    • St. Louis, Missouri, United States, 63110
      • GSK Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89014
      • GSK Investigational Site
    • Henderson, Nevada, United States, 89015
      • GSK Investigational Site
    • Las Vegas, Nevada, United States, 89119
      • GSK Investigational Site
    • Las Vegas, Nevada, United States, 89106
      • GSK Investigational Site
    • Las Vegas, Nevada, United States, 89128
      • GSK Investigational Site
    • Pahrump, Nevada, United States, 89048
      • GSK Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • GSK Investigational Site
    • Santa Fe, New Mexico, United States, 87505
      • GSK Investigational Site
  • New York
    • New York, New York, United States, 10032
      • GSK Investigational Site
    • New York, New York, United States, 10024
      • GSK Investigational Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
      • GSK Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • GSK Investigational Site
    • Franklin, Ohio, United States, 45005
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • GSK Investigational Site
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • GSK Investigational Site
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • GSK Investigational Site
    • Simpsonville, South Carolina, United States, 29681
      • GSK Investigational Site
  • Tennessee
    • Cite, Tennessee, United States, 37604
      • GSK Investigational Site
    • Kingsport, Tennessee, United States, 37660
      • GSK Investigational Site
  • Texas
    • Dallas, Texas, United States, 75246
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
    • Tyler, Texas, United States, 75708
      • GSK Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • GSK Investigational Site
    • West Jordan, Utah, United States, 84084
      • GSK Investigational Site
  • Virginia
    • Virginia Beach, Virginia, United States, 23451
      • GSK Investigational Site
  • Washington
    • Edmonds, Washington, United States, 98026
      • GSK Investigational Site
    • Everett, Washington, United States, 98208
      • GSK Investigational Site
    • Monroe, Washington, United States, 98272
      • GSK Investigational Site
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Subjects with T2DM as defined by the criteria of the ADA and/or recognized by WHO Expert Committee on the Diagnosis and Classification of Diabetes Mellitus [American Diabetes Association, 2004], for at least 3 months preceding screening (see Section 15.3, Appendix 3:, "Diagnosis and Classification of Diabetes Mellitus").

• To be eligible for Randomization into the trial, a subject must satisfy all of the following glycemic criteria:

  • HbA1c level via central laboratory at the pre-screening visit
  • If HbA1c ≥ 8.0% but ≤ 10.0%: subject may proceed to Randomization;
  • If HbA1c ≥ 7.8% but < 8.0%, subject not eligible to proceed, but may be retested once to establish eligibility (or lack thereof). If HbA1c level ≥ 8.0% upon retest, subject is eligible to proceed; otherwise they should be withdrawn.
  • If HbA1c < 7.8%, subject not eligible to proceed (no retest allowed).
  • FPG level via central laboratory at the pre-screening visit must be < 270 mg/dL (15.0 mmol/L). FPG may be retested within a week to confirm eligibility (or lack thereof).

• Concurrent T2DM therapy:

  • Diet and/or exercise treated: Must not have taken antidiabetic medication for at least 2 months prior to the pre-screening visit, OR
  • Metformin monotherapy: Subjects entering the study on metformin must be on the same dose, formulation and regimen of metformin for at least 2 months prior to the pre-screening visit, AND
  • TZDs and insulin are excluded in the 3 months prior to the Screening visit for all subjects.
• Males and females who are 18 to 70 years of age inclusive at the time of Screening.

• If female, eligible to enter and participate in this study:

  • If of non-childbearing potential (i.e., physiologically incapable of becoming pregnant (tubal ligation), including any female who is post-menopausal [>1 year without menstrual period]); or,

  • If of child-bearing potential, has a negative pregnancy test at Screening (serum), at Randomization (urine) and:

    • Has a male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject, or
    • Uses double-barrier methods of contraception; condoms with the use of caps (with spermicide) and IUDs are acceptable, or
    • Uses hormonal contraceptives (oral, depots, patches etc) with double- barrier methods of contraception as outlined above, or
    • Abstains from sexual intercourse, or
    • Is with a same sex partner and does not participate in bisexual activities where there is any risk of pregnancy.
• Body Mass Index (BMI): ≥25 and ≤40 kg/m² and weigh at least 50 kg at Screening.
• If subject is a smoker, must be able to abstain while in clinic at each visit.
• Subject has given full written informed consent prior to any study related procedures are performed.

Exclusion criteria:

Exclusion Criteria:

• Metabolic Disease including:

  • Diagnosis of Type 1 diabetes mellitus
  • Uncorrected thyroid dysfunction. (NOTE: subjects with hypothyroidism on a stable dose of thyroid replacement therapy for at least 1 month prior to Screening, and who have a screening thyroid stimulating hormone (TSH) within the upper limit of normal may participate).
  • Significant weight gain or loss (defined as > 5% of total body weight) within the 3 months prior to Screening.
• Previous use of insulin for treatment of hyperglycemia within 3 months of Screening.

• History of recent clinically significant cardiovascular disease including:

  • History or ECG evidence of prior myocardial infarction within 6 months prior to Screening.
  • Current unstable angina or history of unstable angina in past 6 months.
  • Coronary revascularization including percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery that is either planned or occurred in the 6 months prior to Screening.
  • Clinically significant arrhythmia or valvular heart disease.
  • Congestive heart failure (CHF) with New York Heart Association (NYHA) Class II-IV symptoms (see Section 15.4, Appendix 4).
  • Blood pressure > 160/100 mmHg or resting heart rate > 100 bpm. Note: subjects using antihypertensives [e.g., beta blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II antagonists, calcium channel blockers and diuretics] must be on stable doses during the 30 days prior to Screening and during the trial.
  • Has a QTc interval (Bazett's) > 440 msec in males and > 450 msec in females at Screening.
  • Clinically significant ECG abnormalities which, in the opinion of the Investigator, may affect the interpretation of safety data, or which otherwise, contraindicates participation in a clinical trial with a new chemical entity.
• History of chronic pancreatitis.
• Familial hypercholesterolemia.
• TGs ≥800 mg/dL (8.96 mmol/L) at Screening.
• Serum creatinine at screening > 1.4 mg/dL (124 µmol/L) for women, or > 1.5 mg/dL (133 µmol/L) for men.
• Clinically significant anemia defined by hemoglobin concentrations <12.0 g/dL or < 120.0 g/L for males and < 11.0 g/dL or < 110.0 g/L for females.
• History of significant co-morbid diseases (e.g., cholelithiasis, gastrointestinal disease, etc.) that would preclude participation in the study.

• Documented history of hepato-biliary disease including a history of, or positive laboratory results for hepatitis (hepatitis B surface antigen and/or hepatitis C antibody) at Screening, and/or clinically significant hepatic enzyme elevation including:

  •Any one of the following enzymes greater than 2.5 times the upper limit of normal (ULN) value at Screening:

  • Alanine aminotransferase (ALT)
  • Aspartate aminotransferase (AST)
  • Alkaline phosphatase (ALP)
  • Total or direct bilirubin > 1.5 times the ULN at Screening, unless consistent with presumed or diagnosed Gilbert's disease.
• History of metabolic acidosis, rhabdomyolysis, myalgia, myositis or myopathy after taking statins or fibrates.
• Any subject who has withdrawn therapy due to AEs after taking a PPARγ or a PPARα/γ dual agonist, either marketed (e.g., troglitazone, rosiglitazone or pioglitazone) or under current or previous clinical investigation.
• Signs or symptoms of myositis at Screening (or upon 1 repeat test), and/or creatinine phosphokinase (CPK)≥3.0 times ULN

• Is currently taking or has taken any of the following medications in the 3 months prior to the pre-screening visit:

  • Anti-obesity agents (including fat absorption blocking agents)
  • St. John's Wort
  • Warfarin and other oral anticoagulants (excluding aspirin and non-steroidal anti-inflammatory drugs)
  • Digoxin
  • Oral or injectable corticosteroids (inhaled and intranasal steroids are acceptable)
  • Use of antidiabetic agents (other than metformin) in the 2 months prior to the pre-screening visit.
  • Use of TZDs in the 3 months prior to the pre-screening visit.
  • Methotrexate, cyclosporine or monoclonal antibodies (e.g., alemtuzumab, gemtuzumab ozogamicin, rituximab, trastuzumab, ibritumomab, tiuxetan) for rheumatoid arthritis or psoriasis.
  • Atypical antipsychotic medications [e.g., aripiprazole (Abilify), risperidone (Risperdal), clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), and ziprasidone (Geodon)].
  • Antiretroviral drugs
  • Use of lipid lowering agents within 3 months prior to the pre-screening visit. This includes statins, fibrates, ezetimibe (Zetia), niacin and bile acid sequestrants.
  • Monoamine oxidase inhibitors

• History of cancer except for the following:

  • Basal cell carcinoma or superficial squamous cell carcinoma treated by local excision.
  • Cervical cancer in situ treated definitively more than 6 months prior to screening.
• Women who are lactating, pregnant, or planning to become pregnant.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to any drug chemically related to the study drug.
• Known allergy to any of the capsule excipients, or history of drug or other allergy, which, in the opinion of the responsible study physician, contradicts participation. Hypersensitivity to metformin or any of its components (for subjects entering on metformin).

• Has a history of substance and/or alcohol abuse within the past year as determined by the Investigator at screening or during treatment:

  • Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated restrictions while participating in the study.
  • History of alcohol abuse defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint of beer or 1 measure of spirits or 1 glass of wine.
• Received treatment with a new molecular entity (investigational drug) during the previous 4 months or participated in any other trial during the previous 3 months, or has participated in a previous study with GW677954. A new molecular entity is defined as any compound not in Phase 3. (The washout is from last dose of investigational product in the previous study until the first dose of investigational product.)
• Likely to be non-compliant, in the investigator's opinion, with respect to the protocol and related scheduled visits.
• Subject has any concomitant medical condition which in the opinion of the investigator makes them unsuitable to participate in the study.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change from Baseline (Day 1) in glycated hemoglobin (HbA1c) levels at Week 16 as a measure of improvement in glucose control	Improvement in glucose control was measured by means of reduction in glycated hemoglobin (Hb) levels in blood.	Week (W) 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change from Baseline (Day 1) in fasting HbA1c levels at Weeks 4, 8 and 12	Improvement in glucose control was measured by means of reduction in glycated hemoglobin (HbA1c) levels in blood. Change from Baseline is the value at indicated time point minus the value at Baseline.	Weeks 4, 8, and 12
Change from Baseline (Day 1) in fasting plasma glucose (FPG) at Weeks 1, 2, 4, 6, 8, 12 and 16	Change from Baseline is the value at indicated time point minus the value at Baseline.	W1, W2, W4, W6, W8, W12, and W16
Change from Baseline (Day 1) in fasting fructosamine at Weeks 2 and 4	Change from Baseline is the value at indicated time point minus the value at Baseline.	Baseline (Day 1), W2, W4
Percentage of participants achieving target HbA1c levels at Weeks 4, 8, 12, and 16	Improvement in glucose control was measured by means of reduction in glycated hemoglobin (HbA1c) levels in blood. The ideal concentration of HbA1c was desired to be less than or equal to 7%.	Weeks 4, 8, 12, and 16
Percentage of participants achieving a decrease in HbA1c of >= 0.7% from Baseline (Day 1) at Weeks 4, 8, 12 and 16	Improvement in glucose control was measured by means of reduction in glycated hemoglobin (HbA1c) levels in blood.	Baseline (Day 1), Weeks 4, 8, 12, and 16
Percentage of participants achieving target range of FPG at Weeks 1, 2, 4, 6, 8, 12 and 16	The target range for FPG was <=126 milligrams per deciliter (mg/dL) or 7.0 millimoles per liter (mmol/L) to <=140 mg/dL or 7.8 mmol/L	Weeks 1,2, 4, 6, 8, 12, and 16
Percentage of participants achieving a decrease from Baseline (Day 1) of >=30 mg/dL [1.66 mmol/L] in FPG at Weeks 1, 2, 4, 6, 8, 12 and 16	Change from Baseline is the value at indicated time point minus the value at Baseline.	Weeks 1, 2, 4, 6, 8, 12, and 16
Ratio to the Baseline (percentage change) of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and free fatty acids (FFA) at Weeks 2, 4, 8, 12, and 16	This data analysis was based on log-transformed data.	Baseline (Day 1), Weeks 2, 4, 8, 12, and 16
Percentage change from Baseline (Day 1) in non-HDL-C based on log-transformed data at Week 16	Change from Baseline is the value at indicated time point minus the value at Baseline.	At Week 16
Percentage change from Baseline (Day 1) in very low density lipoprotein-cholesterol (VLDL-C), apolipoprotein AI (Apo AI), AII, and B at Week 16.	Change from Baseline is the value at indicated time point minus the value at Baseline.	At Week 16
Change from Baseline (Day 1) in Apo B/TC, TC/HDL-C, and LDL-C/Apo B ratio at Week 16	Change from Baseline is the value at indicated time point minus the value at Baseline.	At Week 16
Change from Baseline (Day 1) in hemoglobin at Week 16	This analysis was performed in sitting position. Change from Baseline is the value at indicated time point minus the value at Baseline.	At Week 16
Change from Baseline (Day 1) in hematocrit at Week 16	Change from Baseline is the value at indicated time point minus the value at Baseline.	Wekk 16
Change from Baseline (Day 1) in systolic and diastolic blood pressure (SBP and DBP) at Week 16	Systolic blood pressure )SBP) and diastolic blood pressure (DBP) were measured in sitting position. Change from Baseline is the value at indicated time point minus the value at Baseline.	At Week 16
Change from Baseline (Day 1) in heart rate at Week 16	Heart rate was measured in sitting position. Change from Baseline is the value at indicated time point minus the value at Baseline.	Week 16
Change from Baseline (Day 1) in body weight at Week 16	Change from Baseline is the value at indicated time point minus the value at Baseline.	Week 16
Change from Baseline (Day 1) in 12 lead electrocardiogram (ECG) measures including PR interval, QT interval, QTc interval and QRS duration at Week 16	QT(c) interval calculations were done by Bazett's method (QTc[B]) as well as by Fridericia's correction (QTc[F]). Change from Baseline is the value at indicated time point minus the Baseline value.	Week 16
Number of participants with clinical hematology, chemistry, urinalysis, exploratory cardiac parameters of potential clinical concern (PCC) along with serum pregnancy test over period	Participants were analyzed for any abnormality for laboratory parameters either higher or lower than the potential clinical concern range.	Upto 16 weeks
Number of participants with hypoglycemic events as a measure of ophthalmic assessment	Participants received a glucose log for reading for routine recording of glucometer readings. Glucose values were recorded on timely basis.	Up to 16 weeks
Number of participants with intensity of hypoglycemic events as a measure of ophthalmic assessment	Participants received a glucose log for reading for routine recording of glucometer readings. Glucose values were recorded on timely basis.	Up to 16 weeks
Number of participants with adverse events (AEs) and serious adverse events (SAEs) over period	Adverse event (AE) is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. Serious adverse event (SAE) is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above.	Up to 16 weeks
Change from Baseline (Day 1) in phosphocreatine kinase (Creatine kinase-MB) over period	CK-MB is a cardiac biomarker.	Up to 16 weeks
Number of participants with absolute Troponin-I (cTnI) levels over period	Troponin-I (cTnI) is a cardiac biomarker.	Up to 16 weeks
Change from Baseline (Day 1) in fasting insulin at Week 8 and 16	Change from Baseline is the value at indicated time point minus the value at Baseline.	Week 8 and 16
Change from Baseline (Day 1) in C-peptide at Week 8 and 16		Week 8 and 16
Change from Baseline (Day 1) in HOMA-S at Week 16		Week 16
Change from Baseline (Day 1) in QUICKI at Week 16		Week 16

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): April 1, 2007
• Study Completion (Actual): April 1, 2007

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 20, 2005

Study Record Updates

• Last Update Posted (Actual): March 23, 2017
• Last Update Submitted That Met QC Criteria: March 21, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Pharmacokinetics; Tolerability; Pharmacodynamics; Type 2 Diabetes Mellitus; PPARpan; Phase IIb; GW677954; Dose-Ranging
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: ADG20001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Clinical Study Report
   Information identifier: ADG20001
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: ADG20001
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: ADG20001
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: ADG20001
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: ADG20001
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: ADG20001
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: ADG20001
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register