A randomised, double-blind parallel group study to compare the efficacy and safety of initial combination therapy with linagliptin 5 mg + pioglitazone 15 mg, 30 mg, or 45 mg, vs. monotherapy with pioglitazone (15 mg, 30 mg, or 45 mg) or linagliptin 5 mg once daily for 30 weeks, followed by a 54 week blinded trial period on linagliptin 5 mg + pioglitazone 30 or 45 mg versus pioglitazone monotherapy 30 or 45 mg or linagliptin 5 mg in type 2 diabetic patients with insufficient glycaemic control on diet and exercise
- Conditions
- type 2 diabetes mellitusMedDRA version: 14.0Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2008-008127-15-LV
- Lead Sponsor
- Boehringer Ingelheim RCV Gmbh
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1811
- Diagnosis of type 2 diabetes mellitus prior to informed consent
- Male and female patients with insufficient glycaemic control (HbA1c = 7.0 to =
10.5% at Visit 2) on diet and exercise alone, without oral antidiabetic drug therapy
within 10 weeks prior to start of the run-in period
- Age = 18 and = 80 years at start of screening
- BMI = 45 kg/m2 (Body Mass Index) at start of screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
- Uncontrolled hyperglycaemia with a confirmed glucose level > 240 mg/dl (> 13.3
mmol/l) after an overnight fast during screening or placebo run-in period
- Myocardial infarction within 6 months, stroke or TIA within 3 months prior to
informed consent
- Clinical evidence of active liver disease (e.g. jaundice) or the ALT level > 2.5 times
the upper limit of normal (according to pioglitazone label)
- Bariatric surgery, performed within the past 2 years prior to informed consent or
planned at the time of informed consent
- Gastrointestinal surgeries prior to informed consent that induce chronic
malabsorption
- Known hypersensitivity or allergy to the investigational products (linagliptin and/or
pioglitazone) or their excipients (including matching placebos)
- Contraindications to pioglitazone as defined in the local prescribing information (
- Treatment with gemfibrozil, montelukast, trimethoprim, or rifampicin
- Treatment with rosiglitazone, pioglitazone, GLP-1 analogues, or insulin within 3
months prior to informed consent
- Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to
informed consent
- Alcohol or drug abuse within the 3 months prior to informed consent or documented history of alcoholism
- Current treatment with systemic corticosteroids at time of informed consent or
change in dosage of thyroid hormones within 6 weeks prior to informed consent
- Participation in another trial with an investigational drug within 30 days prior to
informed consent
- Pre-menopausal women (last menstruation < 1 year prior to informed consent)
who are nursing or pregnant or are of child-bearing potential (i.e. not permanently
sterilised) and are not practicing a highly effective method of birth control
- Symptomatic gallbladder disease in the last six months
- Medical history of pancreatitis
- Patients with urinary bladder cancer or a history of urinary bladder cancer or uninvestigated macroscopic haematuria
- Any other contraindication or restriction for use of pioglitazone in accordance with the local prescribing information for pioglitazone
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Demonstration of superior glycaemic control (HbA1c reduction) of the fixed combination of linagliptin/pioglitazone (5/15, 5/30 and 5/45 mg) versus the respective individual monotherapies of pioglitazone (15 mg, 30 mg, or 45 mg, administered orally once daily), and linagliptin (5 mg, administered orally once daily) after 30 weeks of treatment ;Secondary Objective: Investigation of both durability of treatment and safety of the linagliptin/pioglitazone FDC under chronic treatment conditions (84 weeks of treatment);Primary end point(s): Change in HbA1c from baseline at 30 weeks of treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Cumulative treat to target efficacy response (HbA1c<br>under treatment of < 7.0% and < 6.5%), relative efficacy response (HbA1c lowering<br>by a least 0.5%), HbA1c reduction from baseline by visit over time up to completion<br>of study Part B, change from baseline in fasting plasma glucose (FPG, after 30 weeks<br>of treatment and by visit over time up to completion of study Part B), two-hour<br>postprandial glucose (2hPPG) at baseline, after 30 weeks of treatment and change<br>from baseline to week 30 (meal tolerance test (MTT): sub-group of patients)