The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00196989




Registration number
NCT00196989
Ethics application status
Date submitted
13/09/2005
Date registered
20/09/2005

Titles & IDs
Public title
Study In People With Type 2 Diabetes
Scientific title
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
Secondary ID [1] 0 0
ADG20001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage change from Baseline (Day 1) in glycated hemoglobin (HbA1c) levels at Week 16 as a measure of improvement in glucose control
Timepoint [1] 0 0
Week (W) 16
Secondary outcome [1] 0 0
Percentage change from Baseline (Day 1) in fasting HbA1c levels at Weeks 4, 8 and 12
Timepoint [1] 0 0
Weeks 4, 8, and 12
Secondary outcome [2] 0 0
Change from Baseline (Day 1) in fasting plasma glucose (FPG) at Weeks 1, 2, 4, 6, 8, 12 and 16
Timepoint [2] 0 0
W1, W2, W4, W6, W8, W12, and W16
Secondary outcome [3] 0 0
Change from Baseline (Day 1) in fasting fructosamine at Weeks 2 and 4
Timepoint [3] 0 0
Baseline (Day 1), W2, W4
Secondary outcome [4] 0 0
Percentage of participants achieving target HbA1c levels at Weeks 4, 8, 12, and 16
Timepoint [4] 0 0
Weeks 4, 8, 12, and 16
Secondary outcome [5] 0 0
Percentage of participants achieving a decrease in HbA1c of >= 0.7% from Baseline (Day 1) at Weeks 4, 8, 12 and 16
Timepoint [5] 0 0
Baseline (Day 1), Weeks 4, 8, 12, and 16
Secondary outcome [6] 0 0
Percentage of participants achieving target range of FPG at Weeks 1, 2, 4, 6, 8, 12 and 16
Timepoint [6] 0 0
Weeks 1,2, 4, 6, 8, 12, and 16
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Weeks 1, 2, 4, 6, 8, 12, and 16
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Baseline (Day 1), Weeks 2, 4, 8, 12, and 16
Secondary outcome [9] 0 0
Percentage change from Baseline (Day 1) in non-HDL-C based on log-transformed data at Week 16
Timepoint [9] 0 0
At Week 16
Secondary outcome [10] 0 0
Percentage change from Baseline (Day 1) in very low density lipoprotein-cholesterol (VLDL-C), apolipoprotein AI (Apo AI), AII, and B at Week 16.
Timepoint [10] 0 0
At Week 16
Secondary outcome [11] 0 0
Change from Baseline (Day 1) in Apo B/TC, TC/HDL-C, and LDL-C/Apo B ratio at Week 16
Timepoint [11] 0 0
At Week 16
Secondary outcome [12] 0 0
Change from Baseline (Day 1) in hemoglobin at Week 16
Timepoint [12] 0 0
At Week 16
Secondary outcome [13] 0 0
Change from Baseline (Day 1) in hematocrit at Week 16
Timepoint [13] 0 0
Wekk 16
Secondary outcome [14] 0 0
Change from Baseline (Day 1) in systolic and diastolic blood pressure (SBP and DBP) at Week 16
Timepoint [14] 0 0
At Week 16
Secondary outcome [15] 0 0
Change from Baseline (Day 1) in heart rate at Week 16
Timepoint [15] 0 0
Week 16
Secondary outcome [16] 0 0
Change from Baseline (Day 1) in body weight at Week 16
Timepoint [16] 0 0
Week 16
Secondary outcome [17] 0 0
Change from Baseline (Day 1) in 12 lead electrocardiogram (ECG) measures including PR interval, QT interval, QTc interval and QRS duration at Week 16
Timepoint [17] 0 0
Week 16
Secondary outcome [18] 0 0
Number of participants with clinical hematology, chemistry, urinalysis, exploratory cardiac parameters of potential clinical concern (PCC) along with serum pregnancy test over period
Timepoint [18] 0 0
Upto 16 weeks
Secondary outcome [19] 0 0
Number of participants with hypoglycemic events as a measure of ophthalmic assessment
Timepoint [19] 0 0
Up to 16 weeks
Secondary outcome [20] 0 0
Number of participants with intensity of hypoglycemic events as a measure of ophthalmic assessment
Timepoint [20] 0 0
Up to 16 weeks
Secondary outcome [21] 0 0
Number of participants with adverse events (AEs) and serious adverse events (SAEs) over period
Timepoint [21] 0 0
Up to 16 weeks
Secondary outcome [22] 0 0
Change from Baseline (Day 1) in phosphocreatine kinase (Creatine kinase-MB) over period
Timepoint [22] 0 0
Up to 16 weeks
Secondary outcome [23] 0 0
Number of participants with absolute Troponin-I (cTnI) levels over period
Timepoint [23] 0 0
Up to 16 weeks
Secondary outcome [24] 0 0
Change from Baseline (Day 1) in fasting insulin at Week 8 and 16
Timepoint [24] 0 0
Week 8 and 16
Secondary outcome [25] 0 0
Change from Baseline (Day 1) in C-peptide at Week 8 and 16
Timepoint [25] 0 0
Week 8 and 16
Secondary outcome [26] 0 0
Change from Baseline (Day 1) in HOMA-S at Week 16
Timepoint [26] 0 0
Week 16
Secondary outcome [27] 0 0
Change from Baseline (Day 1) in QUICKI at Week 16
Timepoint [27] 0 0
Week 16

Eligibility
Key inclusion criteria
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.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 PPAR? or a PPARa/? 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Miranda
Recruitment hospital [2] 0 0
GSK Investigational Site - Carina Heights
Recruitment hospital [3] 0 0
GSK Investigational Site - Spring Hill
Recruitment hospital [4] 0 0
GSK Investigational Site - Adelaide
Recruitment hospital [5] 0 0
GSK Investigational Site - Keswick
Recruitment hospital [6] 0 0
GSK Investigational Site - Port Lincoln
Recruitment hospital [7] 0 0
GSK Investigational Site - Box Hill
Recruitment hospital [8] 0 0
GSK Investigational Site - Ringwood East
Recruitment postcode(s) [1] 0 0
2228 - Miranda
Recruitment postcode(s) [2] 0 0
4152 - Carina Heights
Recruitment postcode(s) [3] 0 0
4000 - Spring Hill
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
5035 - Keswick
Recruitment postcode(s) [6] 0 0
5606 - Port Lincoln
Recruitment postcode(s) [7] 0 0
3128 - Box Hill
Recruitment postcode(s) [8] 0 0
3135 - Ringwood East
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Hawaii
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Indiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
Nevada
Country [14] 0 0
United States of America
State/province [14] 0 0
New Mexico
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Rhode Island
Country [20] 0 0
United States of America
State/province [20] 0 0
South Carolina
Country [21] 0 0
United States of America
State/province [21] 0 0
Tennessee
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Utah
Country [24] 0 0
United States of America
State/province [24] 0 0
Virginia
Country [25] 0 0
United States of America
State/province [25] 0 0
Washington
Country [26] 0 0
United States of America
State/province [26] 0 0
Wisconsin
Country [27] 0 0
Argentina
State/province [27] 0 0
Buenos Aires
Country [28] 0 0
Argentina
State/province [28] 0 0
Córdova
Country [29] 0 0
Argentina
State/province [29] 0 0
San Juan
Country [30] 0 0
Canada
State/province [30] 0 0
British Columbia
Country [31] 0 0
Canada
State/province [31] 0 0
Manitoba
Country [32] 0 0
Canada
State/province [32] 0 0
Newfoundland and Labrador
Country [33] 0 0
Canada
State/province [33] 0 0
Nova Scotia
Country [34] 0 0
Canada
State/province [34] 0 0
Ontario
Country [35] 0 0
Canada
State/province [35] 0 0
Quebec
Country [36] 0 0
Colombia
State/province [36] 0 0
Bogotá
Country [37] 0 0
Costa Rica
State/province [37] 0 0
San José
Country [38] 0 0
Czech Republic
State/province [38] 0 0
Ceske Budejovice
Country [39] 0 0
Czech Republic
State/province [39] 0 0
Cheb
Country [40] 0 0
Czech Republic
State/province [40] 0 0
Olomouc
Country [41] 0 0
Czech Republic
State/province [41] 0 0
Praha 10
Country [42] 0 0
Czech Republic
State/province [42] 0 0
Praha 2
Country [43] 0 0
Czech Republic
State/province [43] 0 0
Praha 5
Country [44] 0 0
Ecuador
State/province [44] 0 0
Quito
Country [45] 0 0
Latvia
State/province [45] 0 0
Cesis
Country [46] 0 0
Latvia
State/province [46] 0 0
Daugavpils
Country [47] 0 0
Latvia
State/province [47] 0 0
Riga
Country [48] 0 0
Latvia
State/province [48] 0 0
Tukums
Country [49] 0 0
Mexico
State/province [49] 0 0
Baja California Norte
Country [50] 0 0
Mexico
State/province [50] 0 0
Hidalgo
Country [51] 0 0
Mexico
State/province [51] 0 0
Morelos
Country [52] 0 0
Mexico
State/province [52] 0 0
Nuevo León
Country [53] 0 0
Mexico
State/province [53] 0 0
Durango
Country [54] 0 0
Mexico
State/province [54] 0 0
Mexico, D.F.
Country [55] 0 0
New Zealand
State/province [55] 0 0
Auckland
Country [56] 0 0
New Zealand
State/province [56] 0 0
Christchurch
Country [57] 0 0
New Zealand
State/province [57] 0 0
Rotorua
Country [58] 0 0
New Zealand
State/province [58] 0 0
Tauranga
Country [59] 0 0
Peru
State/province [59] 0 0
Lima
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Moscow
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Perm
Country [62] 0 0
Russian Federation
State/province [62] 0 0
Samara
Country [63] 0 0
Russian Federation
State/province [63] 0 0
Tumen
Country [64] 0 0
Russian Federation
State/province [64] 0 0
Ufa
Country [65] 0 0
Russian Federation
State/province [65] 0 0
Yaroslavl

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.