Efficacy vs Placebo as Initial Combination Therapy With Pioglitazone - Full Text View

Sponsor:	Boehringer Ingelheim Pharmaceuticals
Information provided by:	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00641043

Purpose

The objective of the current study is to investigate the efficacy, safety and tolerability of BI 1356 (Linagliptin) (5 mg / once daily) compared to placebo given for 24 weeks as initial combination therapy with pioglitazone 30 mg in patients with type 2 diabetes mellitus with insufficient glycaemic control.

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: placebo + pioglitazone (30 mg) Drug: Linagliptin + pioglitazone (30 mg)	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Treatment
Official Title:	A Randomised, Double-blind, Placebo Controlled, Parallel Group 24 Week Study to Assess the Efficacy and Safety of BI 1356 (5 mg) in Combination With 30 mg Pioglitazone (Both Administered Orally Once Daily), Compared to 30 mg Pioglitazone Plus Placebo in Drug Naive or Previously Treated Type 2 Diabetic Patients With Insufficient Glycaemic Control.

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: Pioglitazone Pioglitazone hydrochloride

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

HbA1c Change From Baseline to 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 to 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 to 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 to 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 to 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 to 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 to 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 to 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-diabetes 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%. 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% 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 Who Have an 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%.

Enrollment:	389
Study Start Date:	March 2008
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BI 1356 (5 mg) BI 1356 5mg in initial combination therapy with pioglitazone 30 mg	Drug: Linagliptin + pioglitazone (30 mg) 5 mg tablet + overcapsulated 30 mg tablet, once daily
Placebo Comparator: Placebo matching BI 1356 5 mg Placebo in initial combination therapy with pioglitazone 30 mg	Drug: placebo + pioglitazone (30 mg) placebo + overcapsulated 30 mg 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:

Signed and dated written Informed Consent (IC) by date of Visit 1a in accordance with Good Clinical Practice (GCP) and local legislation
Patients with a diagnosis of type 2 diabetes mellitus and treatment naive or previously treated with any oral hypoglycaemic agent; antidiabetic therapy has to be unchanged for ten weeks prior to informed consent.
Glycosylated haemoglobin A1 (HbA1c) 7.5-11% at Visit 2 (Start of Run-in).
Male and female patients aged > or = 18 and < or = to 80 years at Visit 1a (Screening).
Body Mass Index (BMI) < or = 40 kg/m2 at Visit 1a (Screening)
Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation.

Exclusion criteria:

Myocardial infarction, stroke or Transient Isquemic Atack (TIA) within 6 months prior to Inform Consent (IC)
Impaired hepatic function, defined by serum levels of either Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or alkaline phosphatase above 3 x upper limit of normal (ULN) determined at Visit 1a.
Known hypersensitivity or allergy to the investigational product or its excipients and/or to hydrochloride of pioglitazone or its excipients
Treatment with Glucagon-like peptide-1 (GLP-1) analogue / agonist within 3 months prior to IC.
Treatment with insulin within 3 months prior to IC
Treatment with anti-obesity drugs 3 months prior to IC.
Alcohol abuse within the 3 months prior to IC that would interfere with trial participation or drug abuse.
Participation in another trial with an investigational drug within 2 months prior to IC.
Fasting blood glucose > 240 mg/dl (=13.3 mmol/L) at screening (Visit 1).
Pre-menopausal women (last menstruation < or =1 year prior to signing IC) 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. Acceptable methods of birth control include transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner. No exception will be made.
Treatment with systemic steroids or change in the dosage of thyroid hormone within six weeks prior to IC
Heart failure New York Heart Asociation (NYHA) class I-IV, or history of heart failure.
Diabetic ketoacidosis within 6 months prior to IC.
Hemodialyzed patients due to limited experience with Thiazolidinediones (TZDs)
Any other clinical condition wich, in the opinion of the investigator, would not alow safe completion of the protocol and safe administration of BI1356 and pioglitazone.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00641043

Show 43 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

No publications provided

Responsible Party:	Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier:	NCT00641043 History of Changes
Other Study ID Numbers:	1218.15, 2007-002456-41
Study First Received:	February 29, 2008
Results First Received:	May 13, 2011
Last Updated:	August 18, 2011
Health Authority:	Austria: Bundesamt für Sicherheit im Gesundheitswesen, A-1030 Vienna; Greece: National Organization fo Medicines (EOF) National Ethics Committe; Hungary: National Institute of Pharmacy, H-1051 Budapest; Japan: Ministry of Health, Labor and Welfare; Portugal: INFARMED I.P.; Romania: National Medicines Agency, Bucharest; Spain: AEMPS; 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 February 21, 2012