| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045242 |
| E.1.2 | Term | Type II diabetes mellitus |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The present study is a dose-ranging study that will evaluate the efficacy, safety and
tolerability of a range of doses of GSK189075 and pioglitazone 30mg, compared to
placebo, administered as monotherapy over 12 weeks in treatment naïve subjects with Type 2 Diabetes Mellitus.
|
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of a range of doses of GSK189075 and 30mg
pioglitazone.
• To evaluate the effect of a range of doses of GSK189075 and 30mg pioglitazone,
compared to placebo, on additional glycemic/pharmacodynamic parameters in a
fasted state [plasma glucose, serum insulin, serum fructosamine, serum lipid profiles]
• To evaluate the effect of a range of doses of GSK189075 and 30mg pioglitazone,
compared to placebo, on glycemic/pharmacodynamic profiles during a 50g oral
glucose tolerance test (plasma glucose/insulin over a 2-hour period) in a sub-group
of subjects.
• To evaluate the effect of a range of doses of GSK189075 and 30mg pioglitazone,
compared to placebo, on body weight and waist circumference.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact subject eligibility is provided in the Investigator’s Brochure.
Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Subjects with a documented diagnosis of T2DM and have an HbA1c level at Visits 1
and 2 of ≥7.5% and ≤9.5% as measured by a central laboratory.
2. Subjects who are treatment naïve, or who may have taken insulin or any oral
antidiabetic medications for a total of no more than 2 and 4 weeks respectively
within the previous 12 months, but not at all within the 3 months prior to screening,
or subjects who are newly diagnosed and treated with diet and exercise for a minimum of 8 weeks.
3. Subjects who are 18 to 70 years of age inclusive at the time of Screening.
|
|
| E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Metabolic Disease
• Diagnosis of Type 1 diabetes mellitus.
• History of ketoacidosis which has required hospitalization.
• Thyroid disorder [TSH below the lower limit of the reference range (LLRR) of 0.4mIU/L or above the upper limit of the reference range (ULRR) of >5.5 mIU/L at Screening]. Hypothyroidism treated with the same dose and regimen of thyroid hormone replacement for at least 3 months prior to Screening is allowed.
• BMI of <25 or >40 kg/m2.
• Significant weight gain or loss (as defined as >5% of total body weight) in the 3
months prior to Screening.
2. Diabetic Medication
• Has taken insulin for more than 2 weeks in the 12 months prior to screening or
at any time within the 3 months prior to screening.
• Has taken any oral anti-diabetic medication for more than 4 weeks in the 12
months prior to screening or at anytime within the 3 months prior to screening.
3. Cardiovascular Disease
• Recent history or presence of clinically significant acute cardiovascular disease
including:
- Documented myocardial infarction in the 6 months prior to Screening.
- Coronary revascularization including percutaneous transluminal coronary
angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery either
planned and/or occurred in the 6 months prior to Screening.
- Unstable angina in the 6 months prior to Screening.
- Clinically significant supraventricular arrhythmias requiring medical therapy,
or history of nonsustained or sustained ventricular tachycardia. Symptomatic
valvular heart disease or valvular heart disease requiring therapy other than
endocarditis prophylaxis.
- Congestive heart failure (CHF, New York Heart Association (NYHA) Class II
to IV) requiring pharmacologic treatment. NYHA Class I may be included in
accordance with the local prescribing information for pioglitazone.
- Blood pressure (BP) >150/100mmHg. If a subject is receiving permitted
antihypertensive therapy, then they must be on stable dose(s) of therapy for at
least 3 month prior to Screening.
- Has a QTc interval (Bazett’s) ≥450msec at Screening on a single ECG or an
average value from 3 ECGs taken 5 minutes apart (on local reading of ECG).
- Other clinically significant ECG abnormalities which, in the opinion of the
investigator, may affect the interpretation of efficacy and safety data, or which
otherwise contraindicates participation in a clinical trial with a new chemical
entity.
• Fasting plasma triglycerides ≥400mg/dL (4.56mmol/L) at Screening. If a
subject is receiving permitted lipid-lowering therapy, then they must be on a
stable dose(s) of therapy for at least 3 months prior to Screening. Niacin and
bile acid sequestrants are prohibited.
4. Hepatic Disease
Has a diagnosis of active hepatitis (hepatitis B surface antigen or hepatitis C
antibody), or clinically significant hepatic enzyme elevation including:
Any one of the following enzymes greater than 2 times the upper limit of the
reference range (ULRR) value at Screening.
- alanine transaminase (ALT).
- aspartate transaminase (AST).
- alkaline phosphatase (AP).
Has a total bilirubin level that is >1.5 times the ULRR at Screening with the
exception of suspected or confirmed Gilbert’s disease.
5. Pancreatic Disease
• Secondary causes of diabetes:
- history of chronic or acute pancreatitis
6. Renal Disease
• Significant renal disease at Screening as manifested by:
- Glomerular filtration rate (GFR) <60mL/min (as estimated from serum creatinine at Visit 1 and demographic data using the MDRD equation).
For the MDRD equation, please refer to the study procedures manual.
- Proteinuria of ≥1+ by urinary dipstick
• Recurrent genitourinary tract infections defined as ≥2 episodes of complicated
or uncomplicated cystitis or pyelonephritis in the 6 months prior to Screening
• A positive qualitative urinary dipstick for leukocytes, red blood cells (RBC) or
nitrites at Screening.
7. Concurrent Disease
• Has any concurrent condition or any clinically significant abnormality identified
on the screening physical examination, laboratory tests (including blood electrolytes), electrocardiogram, including pulmonary, neurological or inflammatory diseases, which, in the opinion of the investigator, may affect the interpretation of efficacy and safety data, or which otherwise contraindicates participation in a clinical trial with a new chemical entity
• History of significant co-morbid diseases active in the 6 months prior to Screening (e.g., cholecystitis, acute pancreatitis, gastrointestinal disease, chronic
diarrhea, etc.)
• Has a history of malignancy within the past five years [other than superficial squamous cell carcinoma which is non-invasive on pathology or basal cell carcinoma which is successfully treated with local excision] and cervical cancer in situ treated definitively at least 6 months prior to Screening |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary objective is to determine the dose response and efficacy of a range of doses of GSK189075 and 30mg of pioglitazone versus placebo on the reduction of HbA1c.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 32 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| last visit of the last subject undergoing the trial |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 6 |
Print
