30 Week Parallel Group Comparison Study of Linagliptin + Pioglitazone (5+15, 5+30 and 5+45 mg) qd Versus Respective Monotherapies, Followed by a Comparison of 5mg+30mg and 5mg+45mg Versus Respective Monotherapies in Type 2 Diabetes for up to 54 Weeks

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01183013
First received: August 16, 2010
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

The primary objective is to demonstrate superior glycaemic control (HbA1c reduction) 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). In addition, durability of treatment effect and safety under chronic treatment conditions will be investigated.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Pioglitazone 15 mg
Drug: Pioglitazone 45 mg
Drug: Pioglitazone 30 mg
Drug: BI 1356 / Pioglitazone 45 mg FDC
Drug: BI 1356 / Pioglitazone 30 mg FDC
Drug: BI 1356
Drug: BI 1356 / Pioglitazone 15 mg FDC
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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 Blinded Trial Period on Linagliptin 5 mg + Pioglitazone 30 or 45 mg Versus Pioglitazone Monotherapy 30 or 45 mg or Linagliptin 5 mg for up to 54 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control on Diet and Exercise

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • The primary endpoint in this study is the change from baseline in HbA1c after 30 weeks of treatment. [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse Events [ Time Frame: Up to 84 weeks ] [ Designated as safety issue: Yes ]
  • Hypoglycaemic events [ Time Frame: Up to 84 weeks ] [ Designated as safety issue: Yes ]
  • Protocol-specified significant adverse events [ Time Frame: Up to 84 weeks ] [ Designated as safety issue: Yes ]
  • Incidence and severity of oedema [ Time Frame: Up to 84 weeks ] [ Designated as safety issue: Yes ]
  • Change in use of diuretics [ Time Frame: Up to 84 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in vital signs (blood pressure and pulse) [ Time Frame: Baseline and up to 84 weeks ] [ Designated as safety issue: Yes ]
  • Changes from baseline in clinical laboratory values, including lipid profiles, bone markers and BNP [ Time Frame: Baseline and up to 84 weeks ] [ Designated as safety issue: Yes ]
  • Changes from baseline in physical examination as reported as adverse event [ Time Frame: Baseline and up to 84 weeks ] [ Designated as safety issue: Yes ]
  • Changes from baseline in 12-lead ECG as reported as adverse event [ Time Frame: Up to 84 weeks ] [ Designated as safety issue: Yes ]
  • Occurrence of cumulative treat to target efficacy response, of HbA1c under treatment of < 7.0% and < 6.5% after 30 weeks of treatment [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • Occurrence of relative efficacy response (HbA1c lowering by at least 0.5% after 30 weeks of treatment) [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • HbA1c reduction from baseline by visit over time [ Time Frame: Baseline and over time ] [ Designated as safety issue: No ]
  • Change from baseline in fasting plasma glucose (FPG) after 30 weeks of treatment [ Time Frame: Baseline and 30 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in fasting plasma glucose (FPG) by visit over time [ Time Frame: Baseline and over time ] [ Designated as safety issue: No ]
  • Meal tolerance test (MTT): two-hour postprandial glucose (2hPPG) at baseline, after 30 weeks of treatment and change from baseline to week 30 (sub-group of patients) [ Time Frame: Baseline and 30 weeks ] [ Designated as safety issue: No ]
  • Incidence of rescue therapy during the first 30 weeks of treatment [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]
  • Meal tolerance test (MTT): area under glucose concentration time curve (AUC; weighted PG) at baseline, after 30 weeks of treatment and change from baseline [ Time Frame: Baseline and 30 weeks ] [ Designated as safety issue: No ]
  • Change in body weight from baseline to week 30 and by visit over time [ Time Frame: Baseline and over time ] [ Designated as safety issue: No ]
  • Change in waist circumference from baseline to week 30. [ Time Frame: Baseline and 30 weeks ] [ Designated as safety issue: No ]

Enrollment: 936
Study Start Date: August 2010
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Pioglitazone 15 mg
Pioglitazone Capsules 15 mg once daily
Drug: Pioglitazone 15 mg
Pioglitazone Capsules 15 mg once daily for 30 weeks followed by Pioglitazone Capsules 30 mg once daily for up to 54 weeks
Active Comparator: Pioglitazone 30 mg
Pioglitazone Capsules 30 mg once daily
Drug: Pioglitazone 30 mg
Pioglitazone Capsules 30 mg once daily for up to 84 weeks
Active Comparator: Pioglitazone 45 mg
Pioglitazone Capsules 45 mg once daily
Drug: Pioglitazone 45 mg
Pioglitazone Capsules 30 mg once daily for 6 weeks followed by Pioglitazone Capsules 45 mg once daily for up to 78 weeks
Experimental: BI 1356
BI 1356 Tablets low dose once daily
Drug: BI 1356
BI 1356 Tablets low dose once daily for 30 weeks followed by BI 1356 low dose / Pioglitazone 30 mg FDC Tablets once daily for up to 54 weeks
Experimental: BI 1356 / Pioglitazone 15 mg
BI 1356 low dose / Pioglitazone 15 mg Tablets once daily
Drug: BI 1356 / Pioglitazone 15 mg FDC
BI 1356 low dose / Pioglitazone 15 mg FDC Tablets once daily for 30 weeks followed by BI 1356 low dose / Pioglitazone 30 mg FDC Tablets once daily for up to 54 weeks
Experimental: BI 1356 / Pioglitazone 30 mg
BI 1356 low dose / Pioglitazone 30 mg Tablets once daily
Drug: BI 1356 / Pioglitazone 30 mg FDC
BI 1356 low dose / Pioglitazone 30 mg FDC Tablets once daily for up to 84 weeks
Experimental: BI 1356 / Pioglitazone 45 mg
BI 1356 low dose / Pioglitazone 45 mg Tablets once daily
Drug: BI 1356 / Pioglitazone 45 mg FDC
BI 1356 low dose / Pioglitazone 30 mg Tablets once daily for 6 weeks followed by BI 1356 low dose / Pioglitazone 45 mg FDC Tablets once daily for up to 78 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Diagnosis of type 2 diabetes mellitus prior to informed consent
  2. 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 (date of Visit 2)
  3. Age >= 18 and <= 80 years at start date of Visit 1 (Screening)
  4. BMI <= 45 kg/m2 (Body Mass Index) at start date of Visit 1 (Screening)
  5. Signed and dated written informed consent by start date of Visit 1 in accordance with GCP and local legislation

Exclusion criteria:

  1. 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 (cf. Section 3.3.4.1)
  2. Myocardial infarction within 6 months, stroke or TIA within 3 months prior to informed consent
  3. 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)
  4. Bariatric surgery, performed within the past 2 years prior to informed consent or planned at the time of informed consent
  5. Gastrointestinal surgeries prior to informed consent that induce chronic malabsorption
  6. Known hypersensitivity or allergy to the investigational products (linagliptin and/or pioglitazone) or their excipients (including matching placebos)
  7. Contraindications to pioglitazone as defined in the local prescribing information (SPC), particularly :

    • Diagnose of heart failure or history of heart failure
    • Haemodialysis patients, due to limited experience with pioglitazone
  8. Treatment with gemfibrozil, montelukast, trimethoprim, or rifampicin - according to pioglitazone label and respective restrictions in Section 4.2.2
  9. Treatment with rosiglitazone, pioglitazone, GLP-1 analogues, or insulin within 3 months prior to informed consent
  10. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to informed consent
  11. Alcohol or drug abuse within the 3 months prior to informed consent or history of alcoholism
  12. Current treatment with systemic corticosteroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent
  13. Participation in another trial with an investigational drug within 30 days prior to informed consent
  14. Any other clinical condition as judged by the investigator that would not allow the safe completion of the protocol, e.g. inability of patients to comply with study procedures
  15. 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, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial.

A highly effective method of birth control is defined - according to the Note for Guidance on non-clinical safety studies for the conduct of human trials for pharmaceuticals (CPMP/ICH/286/95, modification) - as those which result in a low failure rate (i. e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices/systems (IUDs/IUSs), sexual abstinence or vasectomised partner 16) Symptomatic gallbladder disease in the last six months 17) Medical history of pancreatitis. 18) Patients with urinary bladder cancer or a history of urinary bladder cancer or uninvestigated macroscopic haematuria 19) Any other contraindication or restriction for use of pioglitazone in accordance with the local prescribing information for pioglitazone.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01183013

  Show 132 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01183013     History of Changes
Other Study ID Numbers: 1264.3, 2008-008127-15
Study First Received: August 16, 2010
Last Updated: October 30, 2013
Health Authority: Estonia: The State Agency of Medicine
Germany: Federal Institute for Drugs and Medical Devices
Latvia: State Agency of Medicines
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
BI 1356
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014