A 12-week multi-center, randomized, double-blind, placebo-controlled, parallel-group adaptive design study to evaluate the efficacy on blood glucose control and safety of five doses of LCQ908 (2, 5, 10, 15 and 20 mg) or sitagliptin 100 mg on a background therapy of metformin in obese patients with type 2 diabetes
- Conditions
- Type II DiabetesMedDRA version: 9.1Level: LLTClassification code 10012601Term: Diabetes mellitus
- Registration Number
- EUCTR2009-009888-60-BE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 720
1.Written informed consent to participate in the study, before any study related activities are performed, and is likely to comply with all study requirements, including dietary guidelines.
2.Age 18-75 years, inclusive.
3.Males, non-fertile females, and females of non-childbearing potential. Women must be (a) postmenopausal, defined as age >48 with 12 months of natural (i.e. spontaneous) amenorrhea or age >42 with >6 months of spontaneous amenorrhea with serum FSH levels > 30 mIU/mL and estradiol <30 pg/ml ; (b) 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy; or (c) have a documented history of tubal ligation at least 1 year prior to screening.
4.Patients with T2DM with HbA1c 7.0 to 10.0%, inclusive, at Visit 1.
5.Fasting plasma glucose =250mg/dL (13.9 mmol/L) at Visit 1 assessed by the central laboratory
6.Patients treated with metformin for at least three months prior to Visit 1 (screening) and on a stable dose =1500 mg for 4 weeks prior to Visit 3 (randomization). Patients must agree to maintain the same dose of metformin from 4 weeks before Visit 3 to the end of the study.
7.Body mass index (BMI) of 28 to 42 kg/m2 inclusive
8.Body weight at Visit 1 within 5% of their self-reported weight over the past three months and agreement to maintain the study-recommended diet (counseled during screening) and usual exercise habits during the full course of the study.
9.Patients on stable doses of statins or fibrates for 6 weeks prior to Visit 1 must agree to maintain those doses during the study period.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.A history of type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g. Cushing’s syndrome and acromegaly
2.A history of acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months.
3.Evidence of significant diabetic complications, e.g., symptomatic autonomic neuropathy, severe diabetic retinopathy (e.g. associated with retinal hemorrhages or repeated photocoagulation therapy), diabetic gastroparesis or enteropathy.
4.Treatment with any oral antidiabetic agent other than metformin within 12 weeks prior to Visit 1.
5.Chronic insulin treatment (> 1 week of treatment in the absence of concurrent illness) within the 6 months prior to Visit 1.
6.Acute infections which may affect blood glucose control 4 weeks prior to Visit 1 and other concurrent medical conditions that may interfere with the interpretation of efficacy and safety during the study.
7.Donation of one unit (500 ml) or more of blood, significant blood loss equaling at least one unit of blood within 2 weeks, or a blood transfusion within 8 weeks prior to Visit 1
8.Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
9.Severe illness, trauma, or major surgery within 3 months prior to Visit 1.
10.Mean (of the last 2 of 3 consecutive determinations) sitting diastolic blood pressure >100 mmHg and/or mean sitting systolic blood pressure >150 mmHg. (patients may be re-screened on one occasion only no sooner than 4 weeks after adjustment of antihypertensive medications)
11.History of Congestive Heart Failure (New York Heart Association (NYHA) Class III-IV) or pacemaker use within the past 5 years.
12.Any of the following within the past 12 months:
a.Myocardial infarction (MI). If the Visit 1 ECG reveals patterns consistent with a MI in the absence of clinical signs and symptoms of acute MI and in the absence of elevated troponin and CK-MB enzymes and the date of the event can not be determined, then the patient can enter the trial at the discretion of the investigator and/or local medical monitor
b.Unstable angina
c.Arterial revascularization, coronary artery bypass graft surgery, or percutaneous coronary intervention
d.Cerebrovascular accident or recurrent transient ischemic attacks
13.Any of the following ECG abnormalities:
a.Torsades de pointes, sustained and clinically relevant atrial or ventricular tachycardia, or atrial or ventricular fibrillation
b.Second degree AV block (Mobitz 1 and 2)
c.Third degree AV block
d.Prolonged QTc (>450 ms for males and >470 ms for females) at screening confirmed by visual inspection of the electrocardiogram
14.Liver disease such as cirrhosis or chronic active hepatitis B and C
15.Impaired renal function including a history of dialysis or of nephrotic syndrome and/or estimated creatinine clearance less than 50 ml/min (using the Modification of Diet in Renal Disease (MDRD) formula). Proteinuria <300 mg/gram creatinine will be allowed.
16.Any of the following significant laboratory abnormalities at Visit 1:
a.Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN), confirmed by a repeat measurement within 3 working days
b.Total bilirubin >2 times ULN and/or direct bilirubin greater than the ULN, confirmed by a repeat measurement within 3
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method