Clinical trial NCT00641043: Efficacy vs Placebo as Initial Combination Therapy With Pioglitazone
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-03-21
Enrollment: 389
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion criteria:

1. Signed and dated written Informed Consent (IC) by date of Visit 1a in accordance with Good Clinical Practice (GCP) and local legislation
2. 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.
3. Glycosylated haemoglobin A1 (HbA1c) 7.5-11% at Visit 2 (Start of Run-in).
4. Male and female patients aged \> or = 18 and \< or = to 80 years at Visit 1a (Screening).
5. Body Mass Index (BMI) \< or = 40 kg/m2 at Visit 1a (Screening)
6. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation.

Exclusion criteria:

1. Myocardial infarction, stroke or Transient Isquemic Atack (TIA) within 6 months prior to Inform Consent (IC)
2. 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.
3. Known hypersensitivity or allergy to the investigational product or its excipients and/or to hydrochloride of pioglitazone or its excipients
4. Treatment with Glucagon-like peptide-1 (GLP-1) analogue / agonist within 3 months prior to IC.
5. Treatment with insulin within 3 months prior to IC
6. Treatment with anti-obesity drugs 3 months prior to IC.
7. Alcohol abuse within the 3 months prior to IC that would interfere with trial participation or drug abuse.
8. Participation in another trial with an investigational drug within 2 months prior to IC.
9. Fasting blood glucose \> 240 mg/dl (=13.3 mmol/L) at screening (Visit 1).
10. 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.
11. Treatment with systemic steroids or change in the dosage of thyroid hormone within six weeks prior to IC
12. Heart failure New York Heart Asociation (NYHA) class I-IV, or history of heart failure.
13. Diabetic ketoacidosis within 6 months prior to IC.
14. Hemodialyzed patients due to limited experience with Thiazolidinediones (TZDs)
15. 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.

Primary outcomes:
measure: HbA1c Change From Baseline to Week 24
timeFrame: Baseline and week 24
Secondary outcomes:
measure: HbA1c Change From Baseline to Week 6
timeFrame: Baseline and week 6
measure: HbA1c Change From Baseline to Week 12
timeFrame: Baseline and week 12
measure: HbA1c Change From Baseline to Week 18
timeFrame: Baseline and week 18
measure: FPG Change From Baseline to Week 24
timeFrame: Baseline and week 24
measure: FPG Change From Baseline to Week 6
timeFrame: Baseline and week 6
measure: FPG Change From Baseline to Week 12
timeFrame: Baseline and week 12
measure: FPG Change From Baseline to Week 18
timeFrame: Baseline and week 18
measure: Percentage of Patients With HbA1c <7.0% at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Patients With HbA1c<7.0 at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Patients With HbA1c <6.5% at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Patients With HbA1c<6.5% at Week 24
timeFrame: Baseline and week 24
measure: Percentage of Patients Who Have an HbA1c Lowering by 0.5% at Week 24
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Feldkirch
country: Austria
facility: 1218.15.43004 Boehringer Ingelheim Investigational Site
city: Graz
country: Austria
facility: 1218.15.43001 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1218.15.43003 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1218.15.43005 Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: 1218.15.30004 Boehringer Ingelheim Investigational Site
city: Athens
country: Greece
facility: 1218.15.30007 Boehringer Ingelheim Investigational Site
city: Ioannina
country: Greece
facility: 1218.15.30017 Boehringer Ingelheim Investigational Site
city: Melissia-Athens
country: Greece
facility: 1218.15.30002 Boehringer Ingelheim Investigational Site
city: Nikaia
country: Greece
facility: 1218.15.30003 Boehringer Ingelheim Investigational Site
city: Thessaloniki
country: Greece
facility: 1218.15.30006 Boehringer Ingelheim Investigational Site
city: Thessaloniki
country: Greece
facility: 1218.15.30014 Boehringer Ingelheim Investigational Site
city: Thessaloniki
country: Greece
facility: 1218.15.30016 Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: 1218.15.36003 Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: 1218.15.36004 Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: 1218.15.36006 Boehringer Ingelheim Investigational Site
city: Debrecen
country: Hungary
facility: 1218.15.36008 Boehringer Ingelheim Investigational Site
city: Györ
country: Hungary
facility: 1218.15.36005 Boehringer Ingelheim Investigational Site
city: Szombathely
country: Hungary
facility: 1218.15.36002 Boehringer Ingelheim Investigational Site
city: Amagasaki, Hyogo
country: Japan
facility: 1218.15.81001 Boehringer Ingelheim Investigational Site
city: Koganei, Tokyo
country: Japan
facility: 1218.15.81005 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1218.15.81002 Boehringer Ingelheim Investigational Site
city: Shinjyuku-ku,Tokyo
country: Japan
facility: 1218.15.81004 Boehringer Ingelheim Investigational Site
city: Suita, Osaka,
country: Japan
facility: 1218.15.81003 Boehringer Ingelheim Investigational Site
city: Aveiro
country: Portugal
facility: 1218.15.35007 Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: 1218.15.35001 Boehringer Ingelheim Investigational Site
city: Alba Iulia
country: Romania
facility: 1218.15.40504 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1218.15.40501 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1218.15.40502 Boehringer Ingelheim Investigational Site
city: Sibiu
country: Romania
facility: 1218.15.40503 Boehringer Ingelheim Investigational Site
city: Targu-Mures
country: Romania
facility: 1218.15.40505 Boehringer Ingelheim Investigational Site
city: Badalona
country: Spain
facility: 1218.15.34002 Boehringer Ingelheim Investigational Site
city: Badia del Vallés
country: Spain
facility: 1218.15.34011 Boehringer Ingelheim Investigational Site
city: Bercelona
country: Spain
facility: 1218.15.34001 Boehringer Ingelheim Investigational Site
city: Borges del Camp
country: Spain
facility: 1218.15.34012 Boehringer Ingelheim Investigational Site
city: Centelles
country: Spain
facility: 1218.15.34013 Boehringer Ingelheim Investigational Site
city: Granada
country: Spain
facility: 1218.15.34007 Boehringer Ingelheim Investigational Site
city: L'Hospitalet de Llobregat (Barcelona)
country: Spain
facility: 1218.15.34008 Boehringer Ingelheim Investigational Site
city: L'Hospitalet de Llobregat (Barcelona)
country: Spain
facility: 1218.15.34009 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1218.15.34004 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1218.15.34006 Boehringer Ingelheim Investigational Site
city: Sant Adrià del Besós (Barcelona)
country: Spain
facility: 1218.15.34010 Boehringer Ingelheim Investigational Site
city: Sevilla
country: Spain
facility: 1218.15.34005 Boehringer Ingelheim Investigational Site
city: Vic (Barcelona)
country: Spain
facility: 1218.15.34014 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Johansen OE, Neubacher D, von Eynatten M, Patel S, Woerle HJ. Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme. Cardiovasc Diabetol. 2012 Jan 10;11:3. doi: 10.1186/1475-2840-11-3.