Efficacy and Safety of B I1356 (Linagliptin) vs. Placebo Added to Metformin Background Therapy in Patients With Type 2 Diabetes - Full Text View

Sponsor:	Boehringer Ingelheim Pharmaceuticals
Information provided by:	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00601250

Purpose

The objective of the current study is to investigate the efficacy, safety and tolerability of BI 1356 (5 mg once daily) compared to placebo given for 24 weeks as add-on therapy to metformin in patients with type 2 diabetes mellitus with insufficient glycaemic control

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: linagliptin	Phase III

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, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 1356 (One Dose, e.g. 5 mg), Administered Orally Once Daily Over 24 Weeks, With an Open Label Extension to 80 Weeks (Placebo Patients Switched to BI 1356), in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite Metformin Therapy

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

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 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 7.0% 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 >= 7.0%. Only patients with baseline HbA1c >= 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 7.0% 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 >= 7.0%.
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 >= 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 >= 6.5%.
Percentage of Patients Who Have a 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 >= 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 Blood 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 PPG and previous anti-diabetic medication.

Enrollment:	701
Study Start Date:	January 2008
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Linagliptin Patients receive linagliptin 5 mg tablets once daily	Drug: linagliptin Patients receive linagliptin 5 mg tablets once daily
Placebo Comparator: Placebo Patients receive placebo tablets maching linagliptin 5 mg tablets once daily	Drug: linagliptin Patients receive linagliptin 5 mg tablets once daily

Eligibility

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

Criteria

Inclusion criteria:

Male and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with metformin alone, or with metformin and not more than one other oral antidiabetic drug
Diagnosis of type 2 diabetes prior to informed consent
Glycosylated haemoglobin A1 (HbA1c)at screening:

For patients undergoing wash out of previous medication: HbA1c 6.5 - 9.0% For patients not undergoing wash-out of previous medication: HbA1c 7.0 - 10.0%
Glycosylated haemoglobin A1 (HbA1c) 7.0 - 10.0% at the beginning of Placebo Run-in
Age 18 -80 years
BMI (Body Mass Index) less than 40 kg/m2
Signed and dated written informed consent by date of Visit 1a in accordance with GCP and local legislation

Exclusion criteria:

Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months prior to informed consent
Impaired hepatic function
Known hypersensitivity or allergy to the investigational product or its excipients or metformin or placebo
Treatment with rosiglitazone or pioglitazone within 3 months prior to informed consent
Treatment with an injectable GLP-1 analogue (e.g. exenatide) within 3 months prior to informed consent
Treatment with insulin within 3 months prior to informed consent
Treatment with anti-obesity drugs (e.g. sibutramine, orlistat, rimonabant) within 3 months prior to informed consent
Alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation or drug abuse
Participation in another trial with an investigational drug within 2 months prior to informed consent
Pre-menopausal women who:
- are nursing or pregnant,
- or are of child-bearing potential and are not practicing an acceptable 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.
Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent.
Renal failure or renal impairment
Unstable or acute congestive heart failure
Acute or chronic metabolic acidosis (present in patient history)
Hereditary galactose intolerance

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00601250

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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

No publications provided

Responsible Party:	Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier:	NCT00601250 History of Changes
Other Study ID Numbers:	1218.17, 2007-002457-24
Study First Received:	January 15, 2008
Results First Received:	May 13, 2011
Last Updated:	July 5, 2011
Health Authority:	Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10; Finland: Finnish Medicines Agency; Greece: National Organization of Medicines (EOF) National Ethics Committee; India: Ministry of Health and Family Welfare; Israel: Ministry of Health; Mexico: Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS); New Zealand: Multicentre Ethics Committee/Medsafe; Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow; 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
BI 1356
Metformin

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 February 21, 2012