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Efficacy and Safety of BI 1356 in Combination With Metformin in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00622284
First received: February 13, 2008
Last updated: November 30, 2012
Last verified: November 2012
History of Changes
  Purpose

The objective of the current study is to investigate the efficacy, safety and tolerability of BI 1356 (5.0 mg daily) compared to glimepiride given for 104 weeks as add-on therapy to preferably > 1500 mg metformin in patients with type 2 diabetes mellitus with insufficient glycaemic control


Condition Intervention Phase
Diabetes Mellitus, Type 2
 Drug: Placebo identical to BI 1356 5mg
Drug: Placebo identical to Glimepiride 1mg or 2mg or 3mg or 4 mg
Drug: BI 1356
Drug: Glimepiride
 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, Active-controlled Parallel Group Efficacy and Safety Study of BI 1356 ( 5.0 mg, Administered Orally Once Daily) Compared to Glimepiride Over Two Years in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite Metformin Therapy

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:
  • HbA1c Change From Baseline at Week 52 [ Time Frame: Baseline and week 52 ] [ Designated as safety issue: No ]
    This co-primary endpoint, change from baseline, reflects the Week 52 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and the number of previous anti-diabetic medications.

  • HbA1c Change From Baseline at Week 104 [ Time Frame: Baseline and week 104 ] [ Designated as safety issue: No ]
    This co-primary endpoint, change from baseline, reflects the Week 104 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and the number of previous anti-diabetic medications.


Secondary Outcome Measures:
  • Body Weight Change From Baseline at Week 52 [ Time Frame: Baseline and week 52 ] [ Designated as safety issue: No ]
    This key secondary endpoint, change from baseline, reflects the Week 52 body weight minus the baseline body weight. Means are treatment adjusted for baseline HbA1c, baseline weight and the number of previous antidiabetic-medications.

  • Body Weight Change From Baseline at Week 104 [ Time Frame: Baseline and week 104 ] [ Designated as safety issue: No ]
    This key secondary endpoint, change from baseline, reflects the Week 104 body weight minus the baseline body weight. Means are treatment adjusted for baseline HbA1c, baseline weight and the number of previous antidiabetic-medications.

  • Incidence of Hypoglycaemic Events up to 52 Weeks [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    A hypoglycaemic event is defined as patient showing clinical signs suggestive of low blood glucose confirmed by a home blood glucose monitoring (HBGM) of below 55 mg/dl (3.1 mmol/L)

  • Incidence of Hypoglycaemic Events up to 104 Weeks [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
    A hypoglycaemic event is defined as patient showing clinical signs suggestive of low blood glucose confirmed by a HBGM of below 55 mg/dl (3.1 mmol/L)

  • Fasting Plasma Glucose (FPG) Change From Baseline at Week 52 [ Time Frame: Baseline and week 52 ] [ Designated as safety issue: No ]
    This change from baseline reflects the Week 52 FPG minus the Baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and the number of previous anti-diabetic medications.

  • Fasting Plasma Glucose (FPG) Change From Baseline at Week 104 [ Time Frame: Baseline and week 104 ] [ Designated as safety issue: No ]
    This change from baseline reflects the Week 104 FPG minus the Baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and number of previous anti-diabetic medications.

  • Percentage of Patients With HbA1c <7.0% at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    The percentage of patients with an HbA1c value below 7.0% at week 52, based upon patients with baseline HbA1c >= 7%. If a patient did not have an HbA1c value at week 52 they were considered a failure, so HbA1c >= 7.0%. The logistic regression is treatment adjusted for baseline HbA1c and number of previous anti-diabetic medications.

  • Percentage of Patients With HbA1c <7.0% at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
    The percentage of patients with an HbA1c value below 7.0% at week 104, based upon patients with baseline HbA1c >= 7%. If a patient did not have an HbA1c value at week 104 they were considered a failure, so HbA1c >= 7.0%. The logistic regression is treatment adjusted for baseline HbA1c and number of previous anti-diabetic medications.

  • Percentage of Patients With HbA1c <6.5% at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    The percentage of patients with an HbA1c value below 6.5% at week 52, based upon patients with baseline HbA1c >= 6.5%. If a patient did not have an HbA1c value at week 52 they were considered a failure, so HbA1c >= 6.5%. The logistic regression is treatment adjusted for baseline HbA1c and number of previous anti-diabetic medications.

  • Percentage of Patients With HbA1c <6.5% at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
    The percentage of patients with an HbA1c value below 6.5% at week 104, based upon patients with baseline HbA1c >= 6.5%. If a patient did not have an HbA1c value at week 104 they were considered a failure, so HbA1c >= 6.5%. The logistic regression is treatment adjusted for baseline HbA1c and number of previous anti-diabetic medications.

  • Percentage of Patients With HbA1c Lowering by 0.5% at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
    Occurrence of relative efficacy response, defined as a lowering of 0.5% HbA1c at week 104

  • 2 hr Postprandial Glucose (PPG) Change From Baseline at Week 104 [ Time Frame: Baseline and week 104 ] [ Designated as safety issue: No ]
    This change from baseline reflects the Week 104 2 hr PPG minus the Baseline 2hr PPG. Means are treatment adjusted for baseline HbA1c, baseline 2hr PPG and number of previous anti-diabetic medications.

  • HbA1c Change at Week 4 [ Time Frame: Baseline and week 4 ] [ Designated as safety issue: No ]
    Difference of base percent value [Week x(%) - baseline (%)]

  • HbA1c Change at Week 8 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
  • HbA1c Change at Week 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
  • HbA1c Change at Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
  • HbA1c Change at Week 28 [ Time Frame: Baseline and week 28 ] [ Designated as safety issue: No ]
  • HbA1c Change at Week 40 [ Time Frame: Baseline and week 40 ] [ Designated as safety issue: No ]
  • HbA1c Change at Week 52 [ Time Frame: Baseline and week 52 ] [ Designated as safety issue: No ]
  • HbA1c Change at Week 65 [ Time Frame: Baseline and week 65 ] [ Designated as safety issue: No ]
  • HbA1c Change at Week 78 [ Time Frame: Baseline and week 78 ] [ Designated as safety issue: No ]
  • HbA1c Change at Week 91 [ Time Frame: Baseline and week 91 ] [ Designated as safety issue: No ]
  • HbA1c Change at Week 104 [ Time Frame: Baseline and week 104 ] [ Designated as safety issue: No ]
    The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement available during the first phase of the study. Last observation carried forward (LOCF) was used as imputation rule.

  • Change in Baseline Lipid Parameter Cholesterol at Week 104 [ Time Frame: Baseline and week 104 ] [ Designated as safety issue: No ]
  • Change in Baseline Lipid Parameter HDL at Week 104 [ Time Frame: Baseline and week 104 ] [ Designated as safety issue: No ]
  • Change in Baseline Lipid Parameter Low Density Lipoprotein (LDL) at Week 104 [ Time Frame: Baseline and week 104 ] [ Designated as safety issue: No ]
  • Change in Baseline Lipid Parameter Triglyceride at Week 104 [ Time Frame: Baseline and week 104 ] [ Designated as safety issue: No ]

Enrollment: 1560
Study Start Date: February 2008
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 1356 5mg, once daily
patient to receive a tablet containing 5mg BI 1356 plus one (two in US) inactive placebo capsule matching Glimepiride
 Drug: Placebo identical to Glimepiride 1mg or 2mg or 3mg or 4 mg
Placebo tablets once daily
Drug: BI 1356
5mg, once daily in the morning for 104 weeks
Active Comparator: Glimepiride
patient to receive 1mg or 2mg or 3mg (not in US) or 4mg Glimepiride capsule plus one inactive placebo tablet matching BI 1356 (plus one inactive placebo capsule in US)
 Drug: Placebo identical to BI 1356 5mg
Placebo tablet once daily
Drug: Glimepiride
1mg or 2mg or 3mg or 4mg in the morning for 104 weeks

  Eligibility

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

Inclusion criteria:

  1. Male and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with metformin alone or with metformin and one other oral antidiabetic drug
  2. Glycosylated haemoglobin (HbA1c) 6.0 - 9.0% at screening for patients treated with metformin and one other oral antidiabetic drug
  3. HbA1c 6.5 - 10.0% at screening for patients treated with metformin alone
  4. HbA1c 6.5 - 10.0% at beginning of the placebo run-in phase

Exclusion criteria:

  1. Myocardial infarction, stroke or transient ischemic attack (TIA)
  2. Impaired hepatic function
  3. Renal failure or renal impairment
  4. Treatment with rosiglitazone or pioglitazone within 6 months prior to screening
  5. Treatment with insulin or glucagon-like peptide 1 (GLP-1) analogue/antagonists within 3 months prior to screening
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00622284

  Show 221 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim Pharmaceuticals
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim Pharmaceuticals
  More Information

Additional Information:
Related Info  This link exits the ClinicalTrials.gov site
Related Info  This link exits the ClinicalTrials.gov site

No publications provided by Boehringer Ingelheim Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00622284     History of Changes
Other Study ID Numbers: 1218.20, 2007-004585-40
Study First Received: February 13, 2008
Results First Received: November 30, 2011
Last Updated: November 30, 2012
Health Authority: Bulgaria: Bulgarian Drug Agency, BG-1504 Sofia
Denmark: Danish Medicines Agency
France: AFSSAPS 143/147, bld Anatole France 93285 Saint-Denis Cedex FRANCE
Germany: Federal Institute for Drugs and Medical Devices
Great Britain: MHRA
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy, H-1051 Budapest
India: Drugs Controller General of India
Ireland: Irish Medicines Board
Italy: Comitato Etico Locale per la Sperimentazione Clinica dei Medicinali A.O. Universitaria Senese - Località Le Scotte - SIENA
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Norway: Norwegian Medicines Agency (Statens Legemiddelverk)
Poland: Registration Medicinal Product Medical Device Biocidal Product
South Africa: Medicines Control Council
Sweden: Sweden; Läkemedelsverket (Medical Product 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
Glimepiride
BI 1356
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
 Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 17, 2013