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Safety and Efficacy of Linagliptin (BI 1356) Plus Metformin in Type 2 Diabetes, Factorial Design

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00798161
First received: November 24, 2008
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

The objective of the randomised part of the study is to investigate the efficacy and safety of BI 1356 plus metformin compared to BI 1356 or metformin alone given for 24 weeks to drug naive or previously treated (4 weeks wash-out, 2 weeks placebo run-in) type 2 diabetic patients with insufficient glycaemic control. For the open-label part of the study the objective is to estimate the efficacy and safety of BI 1356 and metformin in type 2 diabetic patients with very poor glycaemic control for 24 weeks


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: BI 1356
Drug: BI 1356 + metformin
Drug: Bi 1356 + metformin
Drug: Metformin
Drug: metformin
Drug: matching placebo
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 Phase III Randomised, Double-blind, Placebo-controlled Parallel Group Study to Compare the Efficacy and Safety of Twice Daily Administration of the Free Combination of BI 1356 2.5 mg + Metformin 500 mg, or of BI 1356 2.5 mg + Metformin 1000 mg, With the Individual Components of Metformin (500 mg or 1000 mg Twice Daily), and BI 1356 (5.0 mg Once Daily) Over 24 Weeks in Drug Naive or Previously Treated (4 Weeks Wash-out and 2 Weeks Placebo run-in) Type 2 Diabetic Patients With Insufficient Glycaemic Control

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • HbA1c Change From Baseline at Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.


Secondary Outcome Measures:
  • HbA1c Change From Baseline at Week 6 [ Time Frame: Baseline and week 6 ] [ Designated as safety issue: No ]
    HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

  • HbA1c Change From Baseline at Week 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

  • HbA1c Change From Baseline at Week 18 [ Time Frame: Baseline and week 18 ] [ Designated as safety issue: No ]
    HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

  • FPG Change From Baseline at Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.

  • FPG Change From Baseline at Week 2 [ Time Frame: Baseline and week 2 ] [ Designated as safety issue: No ]
    This change from baseline reflects the Week 2 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.

  • FPG Change From Baseline at Week 6 [ Time Frame: Baseline and week 6 ] [ Designated as safety issue: No ]
    This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.

  • FPG Change From Baseline at Week 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.

  • FPG Change From Baseline at Week 18 [ Time Frame: Baseline and week 18 ] [ Designated as safety issue: No ]
    This change from baseline reflects the Week 18 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.

  • Percentage of Patients With HbA1c <7.0% at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%.

  • Percentage of Patients With HbA1c<7.0 at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%.

  • Percentage of Patients With HbA1c <6.5% at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 6.5%. Only patients with baseline HbA1c =< 6.5%

  • Percentage of Patients With HbA1c < 6.5% at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 6.5%

  • Percentage of Patients With HbA1c Lowering by 0.5% at Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    The percentage of patients with an HbA1c reduction from baseline greater than 0.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c reduction less than 0.5%.

  • Adjusted Means for 2h Post-Prandial Glucose (PPG) Change From Baseline at Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    This change from baseline reflects the Week 24 2h PPG minus the baseline 2h PPG. Means are treatment adjusted for baseline HbA1c, baseline 2h PPG and previous anti-diabetic medication.

  • HbA1c Change From Baseline at Week 24 for Open-label Patients [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percentage. Mean is unadjusted.

  • FPG Change From Baseline at Week 24 for Open-label Patients [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
    This change from baseline reflects the Week 24 FPG minus the baseline FPG. Mean is unadjusted.

  • Use of Rescue Therapy [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    The use of rescue therapy (SUs, thiazolidinediones [TZDs], or insulin) was permitted only during the randomised treatment period of the trial (i.e. Visits 3 to 7), and was to be administered only if a patient had a 'confirmed' glucose level after an overnight fast.


Enrollment: 857
Study Start Date: December 2008
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 1356 + metformin
BI 1356 low dose + metformin 500 mg, twice daily
Drug: BI 1356 + metformin
BI 1356 low dose tablet + Metformin 500 mg tablet, twice daily
Placebo Comparator: matching placebo
matching placebo
Drug: matching placebo
matching placebo
Experimental: BI 1356+ Metformin
BI 1356 low dose + metformin 1000 mg, twice daily
Drug: Bi 1356 + metformin
BI 1356 low dose tablet + Metformin 1000 mg tablet, twice daily
Active Comparator: Metformin
Metformin 500 mg, twice daily
Drug: Metformin
Metformin 500 mg tablet, twice daily
Active Comparator: metformin
Metformin 1000 mg, twice daily
Drug: metformin
metformin 1000 mg tablet, twice daily
Experimental: BI 1356
BI 1356 high dose, once daily
Drug: BI 1356
BI 1356 high dose tablet, once daily

  Eligibility

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

Inclusion criteria:

Patients with type 2 diabetes (drug naive or pre-treated) with insufficient glycaemic control (HbA1c higher or equal than 7.5 to less than 11.0 %), with very poor glycaemic control (HbA1c higher or equal than 11.0 %) who are not eligible for randomisation to be included in the open-label arm

Exclusion criteria:

Myocardial infarction, stroke or transient ischemic attack (TIA), unstable or acute congestive heart failure, impaired hepatic function, treatment with rosiglitazone or pioglitazone, with a GLP1 analogue, with insulin, with anti-obesity drugs, with systemic steroids, renal failure or impairment, gastric bypass

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00798161

  Show 138 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00798161     History of Changes
Other Study ID Numbers: 1218.46, 2008-001640-40
Study First Received: November 24, 2008
Results First Received: May 20, 2011
Last Updated: December 11, 2013
Health Authority: Canada: Health Canada, Therapeutic Products Directorate
Croatia: Croatian Institute for Medicines Control, HR-10000 Zagreb
Estonia: State Agency of Medicines, EE-5041Tartu
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Germany: BfArM-Federal Authorities for Drugs and Medical Devices
India: Drug Control General of India
Lithuania: State Medicines Control Agency, LT-01132 Vilnius
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: Central Committee on Research Involving Human Subjects (CCMO)
Romania: National Medicines Agency, Bucharest
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
Sweden: Medical Products Agency Regional Ethics Committee of Uppsala
Tunisia: Direction de la Pharmacie et du Médicament (DPM) 31, Rue de Khartoum 1002 Tunis - Belvédère
Ukraine: Ministry of Health Care of Ukraine (MoH of Ukraine)

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Linagliptin
Metformin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on November 27, 2014