30 Week Parallel Group Comparison Study of Linagliptin + Pioglitazone (5+15, 5+30 and 5+45 mg) qd Versus Respective Monotherapies, Followed by a Comparison of 5mg+30mg and 5mg+45mg Versus Respective Monotherapies in Type 2 Diabetes for up to 54 Weeks

NCT01183013 | Completed Phase 3 Results

• 2 other identifiers: 1264.32008-008127-15
• Study Type: interventional
• Target: 936
• Locations: 5 countries
• Sites: 120

Brief Summary

The primary objective is to demonstrate superior glycaemic control (HbA1c reduction) after 30 weeks of linagliptin/pioglitazone (5/15, 5/30 and 5/45 mg) versus the respective individual monotherapies of pioglitazone (15 mg, 30 mg, or 45 mg, administered orally once daily), and linagliptin (5 mg, administered orally once daily). In addition, durability of treatment effect and safety under chronic treatment conditions will be investigated.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in HbA1c After 30 Weeks of Treatment.

  HbA1c is measured as a percentage. The change from baseline is the Week 30 HbA1c minus the baseline HbA1c.

  Baseline and 30 weeks

Secondary Outcomes (9)

• Occurrence of Cumulative Treat to Target Efficacy Response, of HbA1c Under Treatment of < 7.0% After 30 Weeks of Treatment

  Baseline and 30 weeks

• Occurrence of Cumulative Treat to Target Efficacy Response, of HbA1c Under Treatment of < 6.5% After 30 Weeks of Treatment

  Baseline and 30 weeks

• Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 30 Weeks of Treatment)

  Baseline and 30 weeks

• HbA1c Change From Baseline by Visit Over Time

  Baseline, week 6, week 12, week 18, week 24, week 30

• Fasting Plasma Glucose (FPG) Change From Baseline After 30 Weeks of Treatment

  Baseline and 30 weeks

Study Arms (7)

Pioglitazone 15 mg

ACTIVE COMPARATOR

Pioglitazone Capsules 15 mg once daily

Drug: Pioglitazone 15 mg

Pioglitazone 30 mg

ACTIVE COMPARATOR

Pioglitazone Capsules 30 mg once daily

Drug: Pioglitazone 30 mg

Pioglitazone 45 mg

ACTIVE COMPARATOR

Pioglitazone Capsules 45 mg once daily

Drug: Pioglitazone 45 mg

Linagliptin 5mg

ACTIVE COMPARATOR

Linagliptin 5mg Tablets once daily

Drug: Linagliptin 5mg

Linagliptin 5mg / Pioglitazone 15 mg

EXPERIMENTAL

Linagliptin 5mg / Pioglitazone 15 mg Tablets once daily

Drug: Linagliptin 5mg / Pioglitazone 15 mg FDC

Linagliptin 5mg / Pioglitazone 30 mg

EXPERIMENTAL

Linagliptin 5mg / Pioglitazone 30 mg Tablets once daily

Drug: Linagliptin 5mg / Pioglitazone 30 mg FDC

Linagliptin 5mg / Pioglitazone 45 mg

EXPERIMENTAL

Linagliptin 5mg / Pioglitazone 45 mg Tablets once daily

Drug: Linagliptin 5mg / Pioglitazone 45 mg FDC

Interventions

Pioglitazone 15 mg DRUG

Pioglitazone Capsules 15 mg once daily for 30 weeks followed by Pioglitazone Capsules 30 mg once daily for up to 54 weeks

Pioglitazone 15 mg

Pioglitazone 45 mg DRUG

Pioglitazone Capsules 30 mg once daily for 6 weeks followed by Pioglitazone Capsules 45 mg once daily for up to 78 weeks

Pioglitazone 45 mg

Pioglitazone 30 mg DRUG

Pioglitazone Capsules 30 mg once daily for up to 84 weeks

Pioglitazone 30 mg

Linagliptin 5mg / Pioglitazone 45 mg FDC DRUG

Linagliptin 5mg low dose / Pioglitazone 30 mg Tablets once daily for 6 weeks followed by Linagliptin 5mg low dose / Pioglitazone 45 mg FDC Tablets once daily for up to 78 weeks

Linagliptin 5mg / Pioglitazone 45 mg

Linagliptin 5mg / Pioglitazone 30 mg FDC DRUG

Linagliptin 5mg low dose / Pioglitazone 30 mg FDC Tablets once daily for up to 84 weeks

Linagliptin 5mg / Pioglitazone 30 mg

Linagliptin 5mg DRUG

Linagliptin 5mg Tablets low dose once daily for 30 weeks followed by Linagliptin 5mg low dose / Pioglitazone 30 mg FDC Tablets once daily for up to 54 weeks

Linagliptin 5mg

Linagliptin 5mg / Pioglitazone 15 mg FDC DRUG

Linagliptin 5mg low dose / Pioglitazone 15 mg FDC Tablets once daily for 30 weeks followed by Linagliptin 5mg low dose / Pioglitazone 30 mg FDC Tablets once daily for up to 54 weeks

Linagliptin 5mg / Pioglitazone 15 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of type 2 diabetes mellitus prior to informed consent
• Male and female patients with insufficient glycaemic control (HbA1c \>= 7.0 to \<= 10.5% at Visit 2) on diet and exercise alone, without oral antidiabetic drug therapy within 10 weeks prior to start of the run-in period (date of Visit 2)
• Age \>= 18 and \<= 80 years at start date of Visit 1 (Screening)
• BMI \<= 45 kg/m2 (Body Mass Index) at start date of Visit 1 (Screening)
• Signed and dated written informed consent by start date of Visit 1 in accordance with GCP and local legislation

You may not qualify if:

• Uncontrolled hyperglycaemia with a confirmed glucose level \> 240 mg/dl (\> 13.3 mmol/l) after an overnight fast during screening or placebo run-in period (cf. Section 3.3.4.1)
• Myocardial infarction within 6 months, stroke or TIA within 3 months prior to informed consent
• Clinical evidence of active liver disease (e.g. jaundice) or the ALT level \> 2.5 times the upper limit of normal (according to pioglitazone label)
• Bariatric surgery, performed within the past 2 years prior to informed consent or planned at the time of informed consent
• Gastrointestinal surgeries prior to informed consent that induce chronic malabsorption
• Known hypersensitivity or allergy to the investigational products (linagliptin and/or pioglitazone) or their excipients (including matching placebos)
• Contraindications to pioglitazone as defined in the local prescribing information (SPC), particularly :
• Diagnose of heart failure or history of heart failure
• Haemodialysis patients, due to limited experience with pioglitazone
• Treatment with gemfibrozil, montelukast, trimethoprim, or rifampicin - according to pioglitazone label and respective restrictions in Section 4.2.2
• Treatment with rosiglitazone, pioglitazone, GLP-1 analogues, or insulin within 3 months prior to informed consent
• Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to informed consent
• Alcohol or drug abuse within the 3 months prior to informed consent or history of alcoholism
• Current treatment with systemic corticosteroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent
• Participation in another trial with an investigational drug within 30 days prior to informed consent

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Eli Lilly and Company: collaborator

Study Sites (132)

1264.3.01026 Boehringer Ingelheim Investigational Site

Birmingham, Alabama, United States

Location

1264.3.01021 Boehringer Ingelheim Investigational Site

Montgomery, Alabama, United States

Location

1264.3.01020 Boehringer Ingelheim Investigational Site

Muscle Shoals, Alabama, United States

Location

1264.3.01062 Boehringer Ingelheim Investigational Site

Chandler, Arizona, United States

Location

1264.3.01064 Boehringer Ingelheim Investigational Site

Mesa, Arizona, United States

Location

1264.3.01049 Boehringer Ingelheim Investigational Site

Carmichael, California, United States

Location

1264.3.01078 Boehringer Ingelheim Investigational Site

Chino, California, United States

Location

1264.3.01031 Boehringer Ingelheim Investigational Site

Concord, California, United States

Location

1264.3.01037 Boehringer Ingelheim Investigational Site

Lakewood, California, United States

Location

1264.3.01065 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

Location

1264.3.01006 Boehringer Ingelheim Investigational Site

Norwalk, California, United States

Location

1264.3.01001 Boehringer Ingelheim Investigational Site

Rancho Cucamonga, California, United States

Location

1264.3.01059 Boehringer Ingelheim Investigational Site

San Diego, California, United States

Location

1264.3.01023 Boehringer Ingelheim Investigational Site

Tarzana, California, United States

Location

1264.3.01016 Boehringer Ingelheim Investigational Site

Tustin, California, United States

Location

1264.3.01058 Boehringer Ingelheim Investigational Site

Valencia, California, United States

Location

1264.3.01083 Boehringer Ingelheim Investigational Site

Westlake Village, California, United States

Location

1264.3.01027 Boehringer Ingelheim Investigational Site

Denver, Colorado, United States

Location

1264.3.01033 Boehringer Ingelheim Investigational Site

Norwalk, Connecticut, United States

Location

1264.3.01035 Boehringer Ingelheim Investigational Site

Boca Raton, Florida, United States

Location

1264.3.01015 Boehringer Ingelheim Investigational Site

Clearwater, Florida, United States

Location

1264.3.01082 Boehringer Ingelheim Investigational Site

Hialeah, Florida, United States

Location

1264.3.01036 Boehringer Ingelheim Investigational Site

Jacksonville, Florida, United States

Location

1264.3.01013 Boehringer Ingelheim Investigational Site

Longwood, Florida, United States

Location

1264.3.01038 Boehringer Ingelheim Investigational Site

Miami, Florida, United States

Location

1264.3.01042 Boehringer Ingelheim Investigational Site

Miami, Florida, United States

Location

1264.3.01079 Boehringer Ingelheim Investigational Site

Miami, Florida, United States

Location

1264.3.01019 Boehringer Ingelheim Investigational Site

Port Orange, Florida, United States

Location

1264.3.01018 Boehringer Ingelheim Investigational Site

Saint Cloud, Florida, United States

Location

1264.3.01009 Boehringer Ingelheim Investigational Site

Tampa, Florida, United States

Location

1264.3.01012 Boehringer Ingelheim Investigational Site

Tampa, Florida, United States

Location

1264.3.01008 Boehringer Ingelheim Investigational Site

Atlanta, Georgia, United States

Location

1264.3.01055 Boehringer Ingelheim Investigational Site

Atlanta, Georgia, United States

Location

1264.3.01061 Boehringer Ingelheim Investigational Site

Atlanta, Georgia, United States

Location

1264.3.01074 Boehringer Ingelheim Investigational Site

Blue Ridge, Georgia, United States

Location

1264.3.01084 Boehringer Ingelheim Investigational Site

Cartersville, Georgia, United States

Location

1264.3.01060 Boehringer Ingelheim Investigational Site

Perry, Georgia, United States

Location

1264.3.01050 Boehringer Ingelheim Investigational Site

Savannah, Georgia, United States

Location

1264.3.01077 Boehringer Ingelheim Investigational Site

Chicago, Illinois, United States

Location

1264.3.01052 Boehringer Ingelheim Investigational Site

Brownsburg, Indiana, United States

Location

1264.3.01075 Boehringer Ingelheim Investigational Site

Evansville, Indiana, United States

Location

1264.3.01076 Boehringer Ingelheim Investigational Site

Evansville, Indiana, United States

Location

1264.3.01073 Boehringer Ingelheim Investigational Site

Franklin, Indiana, United States

Location

1264.3.01002 Boehringer Ingelheim Investigational Site

Wichita, Kansas, United States

Location

1264.3.01007 Boehringer Ingelheim Investigational Site

Wichita, Kansas, United States

Location

1264.3.01010 Boehringer Ingelheim Investigational Site

Lexington, Kentucky, United States

Location

1264.3.01028 Boehringer Ingelheim Investigational Site

New Orleans, Louisiana, United States

Location

1264.3.01029 Boehringer Ingelheim Investigational Site

Sunset, Louisiana, United States

Location

1264.3.01069 Boehringer Ingelheim Investigational Site

Hyattsville, Maryland, United States

Location

1264.3.01066 Boehringer Ingelheim Investigational Site

Southfield, Michigan, United States

Location

1264.3.01057 Boehringer Ingelheim Investigational Site

Great Falls, Montana, United States

Location

1264.3.01045 Boehringer Ingelheim Investigational Site

Burlington, North Carolina, United States

Location

1264.3.01044 Boehringer Ingelheim Investigational Site

Charlotte, North Carolina, United States

Location

1264.3.01022 Boehringer Ingelheim Investigational Site

Zanesville, Ohio, United States

Location

1264.3.01032 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

Location

1264.3.01051 Boehringer Ingelheim Investigational Site

Fleetwood, Pennsylvania, United States

Location

1264.3.01025 Boehringer Ingelheim Investigational Site

Pittsburgh, Pennsylvania, United States

Location

1264.3.01081 Boehringer Ingelheim Investigational Site

Columbia, South Carolina, United States

Location

1264.3.01003 Boehringer Ingelheim Investigational Site

Greer, South Carolina, United States

Location

1264.3.01011 Boehringer Ingelheim Investigational Site

Kingsport, Tennessee, United States

Location

1264.3.01017 Boehringer Ingelheim Investigational Site

Corpus Christi, Texas, United States

Location

1264.3.01067 Boehringer Ingelheim Investigational Site

Dallas, Texas, United States

Location

1264.3.01004 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Location

1264.3.01039 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Location

1264.3.01041 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Location

1264.3.01047 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Location

1264.3.01070 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Location

1264.3.01040 Boehringer Ingelheim Investigational Site

Killeen, Texas, United States

Location

1264.3.01048 Boehringer Ingelheim Investigational Site

Midland, Texas, United States

Location

1264.3.01030 Boehringer Ingelheim Investigational Site

New Braunfels, Texas, United States

Location

1264.3.01071 Boehringer Ingelheim Investigational Site

North Richland Hills, Texas, United States

Location

1264.3.01085 Boehringer Ingelheim Investigational Site

Plano, Texas, United States

Location

1264.3.01046 Boehringer Ingelheim Investigational Site

San Antonio, Texas, United States

Location

1264.3.01056 Boehringer Ingelheim Investigational Site

Norfolk, Virginia, United States

Location

1264.3.37207 Boehringer Ingelheim Investigational Site

Harju, Estonia

Location

1264.3.37209 Boehringer Ingelheim Investigational Site

Pärnu, Estonia

Location

1264.3.37201 Boehringer Ingelheim Investigational Site

Tallinn, Estonia

Location

1264.3.37202 Boehringer Ingelheim Investigational Site

Tallinn, Estonia

Location

1264.3.37203 Boehringer Ingelheim Investigational Site

Tallinn, Estonia

Location

1264.3.37204 Boehringer Ingelheim Investigational Site

Tallinn, Estonia

Location

1264.3.37205 Boehringer Ingelheim Investigational Site

Tallinn, Estonia

Location

1264.3.37208 Boehringer Ingelheim Investigational Site

Tallinn, Estonia

Location

1264.3.37206 Boehringer Ingelheim Investigational Site

Tartu, Estonia

Location

1264.3.37210 Boehringer Ingelheim Investigational Site

Viljandi County, Estonia

Location

1264.3.49001 Boehringer Ingelheim Investigational Site

Bad Lauterberg / Harz, Germany

Location

1264.3.49007 Boehringer Ingelheim Investigational Site

Dietzenbach, Germany

Location

1264.3.49002 Boehringer Ingelheim Investigational Site

Dortmund, Germany

Location

1264.3.49009 Boehringer Ingelheim Investigational Site

Essen, Germany

Location

1264.3.49003 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1264.3.49012 Boehringer Ingelheim Investigational Site

Ingelheim, Germany

Location

1264.3.49008 Boehringer Ingelheim Investigational Site

Leipzig, Germany

Location

1264.3.49005 Boehringer Ingelheim Investigational Site

Mainz, Germany

Location

1264.3.49010 Boehringer Ingelheim Investigational Site

Offenbach, Germany

Location

1264.3.49004 Boehringer Ingelheim Investigational Site

Stuhr, Germany

Location

1264.3.37105 Boehringer Ingelheim Investigational Site

Daugavpils, Latvia

Location

1264.3.37112 Boehringer Ingelheim Investigational Site

Daugavpils, Latvia

Location

1264.3.37113 Boehringer Ingelheim Investigational Site

Daugavpils, Latvia

Location

1264.3.37110 Boehringer Ingelheim Investigational Site

Jelgava, Latvia

Location

1264.3.37101 Boehringer Ingelheim Investigational Site

Liepāja, Latvia

Location

1264.3.37106 Boehringer Ingelheim Investigational Site

Ogre, Latvia

Location

1264.3.37104 Boehringer Ingelheim Investigational Site

Riga, Latvia

Location

1264.3.37108 Boehringer Ingelheim Investigational Site

Riga, Latvia

Location

1264.3.37109 Boehringer Ingelheim Investigational Site

Riga, Latvia

Location

1264.3.37111 Boehringer Ingelheim Investigational Site

Riga, Latvia

Location

1264.3.37107 Boehringer Ingelheim Investigational Site

Talsi, Latvia

Location

1264.3.37102 Boehringer Ingelheim Investigational Site

Tukums, Latvia

Location

1264.3.37103 Boehringer Ingelheim Investigational Site

Valmiera, Latvia

Location

1264.3.34013 Boehringer Ingelheim Investigational Site

Badía Del Vallès - Barcelona, Spain

Location

1264.3.34001 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1264.3.34008 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1264.3.34005 Boehringer Ingelheim Investigational Site

Borges Del Camp- Tarragona, Spain

Location

1264.3.34006 Boehringer Ingelheim Investigational Site

Canet de Mar - Barcelona, Spain

Location

1264.3.34010 Boehringer Ingelheim Investigational Site

Centelles - Barcelona, Spain

Location

1264.3.34009 Boehringer Ingelheim Investigational Site

L'Hospitalet de Llobregat, Spain

Location

1264.3.34004 Boehringer Ingelheim Investigational Site

L'Hospitalet de Llobregat - Barcelona, Spain

Location

1264.3.34002 Boehringer Ingelheim Investigational Site

Sant Adrià Del Besós- Barcelona, Spain

Location

1264.3.34007 Boehringer Ingelheim Investigational Site

Tarrega - Lleida, Spain

Location

1264.3.34012 Boehringer Ingelheim Investigational Site

Valencia, Spain

Location

1264.3.34011 Boehringer Ingelheim Investigational Site

Vic - Barcelona, Spain

Location

1264.3.44032 Boehringer Ingelheim Investigational Site

Annan, United Kingdom

Location

1264.3.44028 Boehringer Ingelheim Investigational Site

Ash Vale, Aldershot, United Kingdom

Location

1264.3.44029 Boehringer Ingelheim Investigational Site

Baillieston, Glasgow, United Kingdom

Location

1264.3.44008 Boehringer Ingelheim Investigational Site

Balham, United Kingdom

Location

1264.3.44021 Boehringer Ingelheim Investigational Site

Bradford-on-Avon, United Kingdom

Location

1264.3.44019 Boehringer Ingelheim Investigational Site

Burbage, United Kingdom

Location

1264.3.44012 Boehringer Ingelheim Investigational Site

Chesterfield, United Kingdom

Location

1264.3.44027 Boehringer Ingelheim Investigational Site

Chestfield, Whitstable, United Kingdom

Location

1264.3.44011 Boehringer Ingelheim Investigational Site

Chippenham, United Kingdom

Location

1264.3.44033 Boehringer Ingelheim Investigational Site

Johnstone, United Kingdom

Location

1264.3.44007 Boehringer Ingelheim Investigational Site

Midsomer Norton, United Kingdom

Location

1264.3.44034 Boehringer Ingelheim Investigational Site

Paisley, United Kingdom

Location

1264.3.44031 Boehringer Ingelheim Investigational Site

Warminster, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Pioglitazone; Linagliptin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinazolines

Limitations and Caveats

The study (Part B treatment only) was stopped early by protocol amendment #5, although Part A (time frame for all efficacy outcomes) proceeded to completion

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2010
• First Posted: August 17, 2010
• Study Start: August 1, 2010
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: October 20, 2014
• Results First Posted: April 21, 2014

Record last verified: 2014-10

Locations

GB (13); US (74); LA (13); ES (10); DE (10)