Linagliptin in Combination With Metformin in Treatment Naive Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control

NCT01438814 | Completed Phase 4 Results

• 2 other identifiers: 1218.602011-002276-16
• Study Type: interventional
• Target: 689
• Locations: 14 countries
• Sites: 90

Brief Summary

The aim of this study is to investigate the impact of the combination therapy of linagliptin and metformin at submaximal doses in reduction of Glycosylated haemoglobin (HbA1c) and metformin pre-specified gastro-intestinal (GI) side effects in treatment naive patients of with type 2 diabetes mellitus.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) After 14 Weeks Treatment

  Adjusted mean change in HbA1c from baseline at Week 14 was analysed using an ANCOVA model. The Model included treatment and continuous baseline HbA1c.

  Baseline and 14 weeks

Secondary Outcomes (12)

• Composite Endpoint of Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 14 Weeks of Treatment, on no Occurrence of Moderate or Severe Gastrointestinal (GI) Side Effects During 14 Weeks of Treatment

  14 weeks

• Occurence of Metformin Pre-specified Moderate to Severe GI Side Effects Assessed by Investigators During 14 Weeks of Treatment

  14 weeks

• Change From Baseline in Fasting Plasma Glucose (FPG) After 14 Weeks of Treatment

  Baseline and 14 weeks

• Metformin Pre-specified GI Symptom Intensity Score Assessed by Investigators During 14 Weeks of Treatment

  14 weeks

• Metformin Pre-specified GI Symptom Intensity Score Assessed by Patients During 14 Weeks of Treatment

  14 weeks

Study Arms (2)

linagliptin + metformin

EXPERIMENTAL

patients to receive linagliptin +metformin QD

Drug: metformin; Drug: linagliptin

metformin

ACTIVE COMPARATOR

patients to receive metformin BID

Drug: metformin placebo; Drug: linagliptin placebo; Drug: metformin

Interventions

metformin placebo DRUG

metformin placebo tablets 500mg

metformin

linagliptin placebo DRUG

linagliptin placebo tablets 5mg

metformin

metformin DRUG

metformin tablets 500mg

metformin

linagliptin DRUG

linagliptin tablets 5mg

linagliptin + metformin

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 (T2DM) prior to informed consent;
• Male and female patients on diet and exercise regimen who are drug naive, defined as absence of any oral antidiabetic therapy or insulin for 12 weeks prior to randomization
• Glycosylated haemoglobin A1c (HbA1c) \>/= 7.0% (53 mmol/mol) to \</= 10.0% (86 mmol/mol) at visit 1 (screening);
• Age\>/=18 and \</=80 years at visit 1(screening);
• Body Mass Index (BMI)\</= 45kg/m2 at visit 1 (screening);
• Signed and dated written informed consent by date of visit 1 in accordance with Good Clinical Practice (GCP) and local legislation

You may not qualify if:

• Uncontrolled hyperglycaemia with a glucose level \>240 mg/dl (13.3mmol/L) after an overnight fast during screening/placebo run-in and confirmed by a second measurement (Not on the same day);
• Treatment with any oral antidiabetic drug or insulin within 12 weeks prior to randomization
• Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris),stroke or Transient ischemia attack (TIA) within 3 months prior to informed consent;
• Indication of liver disease/Impaired hepatic function, defined by serum levels of either Aspartate aminotransferase (ALT or SGPT), alanine aminotransferase (AST or SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at visit 1 and/or run-in phase,
• Impaired renal function, defined as eGFR\< 60ml/min (moderate or severe renal impairment, modification of diet in renal disease (MDRD) formula) as determined during screening or at run-in phase
• Bariatric surgery within the past two years and other gastrointestinal surgeries that induced chronic malabsorption
• Medical history of Cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
• Blood dyscrasia or any other disorders causing haemolysis or unstable Red Blood Cell (eg. malaria, babesiosis, haemolytic anemia)
• Known history of pancreatitis and chronic pancreatitis
• Contraindications to metformin according to the local label
• Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen etc) leading to unstable body weight
• Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM
• Pre-menopausal women (last menstruation less than 1 year prior to informed consent) 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 or who do not agree to continue contraception for at least 30 days after the last dose of study drug. Acceptable methods of birth control include tubal ligation, transdermal patch, intra-uterine devices/systems(IUDs/IUSs), oral, implantable, or injectable contraceptives, complete sexual abstinence (if acceptable by local authorities), double barrier method and vasectomized partner.

Sponsors & Collaborators

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

Study Sites (90)

1218.60.90001 Boehringer Ingelheim Investigational Site

Dhaka, Bangladesh

Location

1218.60.90002 Boehringer Ingelheim Investigational Site

Dhaka, Bangladesh

Location

1218.60.90003 Boehringer Ingelheim Investigational Site

Dhaka, Bangladesh

Location

1218.60.32001 Boehringer Ingelheim Investigational Site

Genk, Belgium

Location

1218.60.32005 Boehringer Ingelheim Investigational Site

Ham, Belgium

Location

1218.60.32002 Boehringer Ingelheim Investigational Site

Hasselt, Belgium

Location

1218.60.32004 Boehringer Ingelheim Investigational Site

Natoye, Belgium

Location

1218.60.32003 Boehringer Ingelheim Investigational Site

Tremelo, Belgium

Location

1218.60.20009 Boehringer Ingelheim Investigational Site

Calgary, Alberta, Canada

Location

1218.60.20003 Boehringer Ingelheim Investigational Site

Burnaby, British Columbia, Canada

Location

1218.60.20014 Boehringer Ingelheim Investigational Site

Coquitlam, British Columbia, Canada

Location

1218.60.20010 Boehringer Ingelheim Investigational Site

Surrey, British Columbia, Canada

Location

1218.60.20004 Boehringer Ingelheim Investigational Site

Halifax, Nova Scotia, Canada

Location

1218.60.20012 Boehringer Ingelheim Investigational Site

Corunna, Ontario, Canada

Location

1218.60.20015 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

Location

1218.60.20006 Boehringer Ingelheim Investigational Site

London, Ontario, Canada

Location

1218.60.20013 Boehringer Ingelheim Investigational Site

London, Ontario, Canada

Location

1218.60.20002 Boehringer Ingelheim Investigational Site

Sarnia, Ontario, Canada

Location

1218.60.20011 Boehringer Ingelheim Investigational Site

Sarnia, Ontario, Canada

Location

1218.60.20005 Boehringer Ingelheim Investigational Site

Strathroy, Ontario, Canada

Location

1218.60.20007 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1218.60.20016 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1218.60.20001 Boehringer Ingelheim Investigational Site

Saint Romuald, Quebec, Canada

Location

1218.60.86001 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1218.60.86003 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1218.60.86011 Boehringer Ingelheim Investigational Site

Changsha, China

Location

1218.60.86012 Boehringer Ingelheim Investigational Site

Chengdu, China

Location

1218.60.86010 Boehringer Ingelheim Investigational Site

Chongqing, China

Location

1218.60.86013 Boehringer Ingelheim Investigational Site

Hubei, China

Location

1218.60.86014 Boehringer Ingelheim Investigational Site

Hubei, China

Location

1218.60.86006 Boehringer Ingelheim Investigational Site

Nanjing, China

Location

1218.60.86007 Boehringer Ingelheim Investigational Site

Nanjing, China

Location

1218.60.86005 Boehringer Ingelheim Investigational Site

Shanghai, China

Location

1218.60.86009 Boehringer Ingelheim Investigational Site

Shenyang, China

Location

1218.60.86008 Boehringer Ingelheim Investigational Site

Wuxi, China

Location

1218.60.49007 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1218.60.49008 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1218.60.49005 Boehringer Ingelheim Investigational Site

Dresden, Germany

Location

1218.60.49004 Boehringer Ingelheim Investigational Site

Erfurt, Germany

Location

1218.60.49006 Boehringer Ingelheim Investigational Site

Frankfurt, Germany

Location

1218.60.49003 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1218.60.49002 Boehringer Ingelheim Investigational Site

Neuwied, Germany

Location

1218.60.49001 Boehringer Ingelheim Investigational Site

Unterschneidheim, Germany

Location

1218.60.50001 Boehringer Ingelheim Investigational Site

Guatemala City, Guatemala

Location

1218.60.50002 Boehringer Ingelheim Investigational Site

Guatemala City, Guatemala

Location

1218.60.50003 Boehringer Ingelheim Investigational Site

Guatemala City, Guatemala

Location

1218.60.85001 Boehringer Ingelheim Investigational Site

Hong Kong, Hong Kong

Location

1218.60.85002 Boehringer Ingelheim Investigational Site

Hong Kong, Hong Kong

Location

1218.60.91004 Boehringer Ingelheim Investigational Site

Aurangabad, India

Location

1218.60.91010 Boehringer Ingelheim Investigational Site

Bangalore, India

Location

1218.60.91005 Boehringer Ingelheim Investigational Site

Coimbatore, India

Location

1218.60.91008 Boehringer Ingelheim Investigational Site

Kolkata, India

Location

1218.60.91001 Boehringer Ingelheim Investigational Site

Nagpur, India

Location

1218.60.91007 Boehringer Ingelheim Investigational Site

Nagpur, India

Location

1218.60.91003 Boehringer Ingelheim Investigational Site

Pune, India

Location

1218.60.91006 Boehringer Ingelheim Investigational Site

Pune, India

Location

1218.60.96001 Boehringer Ingelheim Investigational Site

Beirut, Lebanon

Location

1218.60.96002 Boehringer Ingelheim Investigational Site

Beirut, Lebanon

Location

1218.60.96004 Boehringer Ingelheim Investigational Site

Byblos, Lebanon

Location

1218.60.96003 Boehringer Ingelheim Investigational Site

Hazmiyeh, Lebanon

Location

1218.60.96005 Boehringer Ingelheim Investigational Site

Saida, Lebanon

Location

1218.60.52005 Boehringer Ingelheim Investigational Site

Aguascalientes, Mexico

Location

1218.60.52003 Boehringer Ingelheim Investigational Site

Cuernavaca, Mexico

Location

1218.60.52001 Boehringer Ingelheim Investigational Site

Durango, Mexico

Location

1218.60.52002 Boehringer Ingelheim Investigational Site

Durango, Mexico

Location

1218.60.52004 Boehringer Ingelheim Investigational Site

Monterrey, Mexico

Location

1218.60.51001 Boehringer Ingelheim Investigational Site

Lima, Peru

Location

1218.60.51002 Boehringer Ingelheim Investigational Site

Lima, Peru

Location

1218.60.51004 Boehringer Ingelheim Investigational Site

Piura, Peru

Location

1218.60.63001 Boehringer Ingelheim Investigational Site

Cebu City, Philippines, Philippines

Location

1218.60.63004 Boehringer Ingelheim Investigational Site

Iloilo City, Philippines, Philippines

Location

1218.60.63003 Boehringer Ingelheim Investigational Site

Manila, Philippines

Location

1218.60.63002 Boehringer Ingelheim Investigational Site

Marikina City, Philippines, Philippines

Location

1218.60.63005 Boehringer Ingelheim Investigational Site

Quezon City, Philippines

Location

1218.60.34001 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1218.60.34002 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1218.60.34003 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1218.60.34004 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1218.60.34006 Boehringer Ingelheim Investigational Site

Borges Del Camp- Tarragona, Spain

Location

1218.60.34005 Boehringer Ingelheim Investigational Site

Centelles, Spain

Location

1218.60.34009 Boehringer Ingelheim Investigational Site

Granada, Spain

Location

1218.60.34008 Boehringer Ingelheim Investigational Site

L'Hospitalet de Llobregat, Spain

Location

1218.60.34007 Boehringer Ingelheim Investigational Site

Mataró, Spain

Location

1218.60.34010 Boehringer Ingelheim Investigational Site

Valencia, Spain

Location

1218.60.88006 Boehringer Ingelheim Investigational Site

Chiayi County, Taiwan

Location

1218.60.88003 Boehringer Ingelheim Investigational Site

Kaohsiung City, Taiwan

Location

1218.60.88001 Boehringer Ingelheim Investigational Site

Taichung, Taiwan

Location

1218.60.88007 Boehringer Ingelheim Investigational Site

Taichung, Taiwan

Location

1218.60.88002 Boehringer Ingelheim Investigational Site

Tainan, Taiwan

Location

1218.60.88004 Boehringer Ingelheim Investigational Site

Taipei County, Taiwan

Location

Related Publications (1)

• Ji L, Zinman B, Patel S, Ji J, Bailes Z, Thiemann S, Seck T. Efficacy and safety of linagliptin co-administered with low-dose metformin once daily versus high-dose metformin twice daily in treatment-naive patients with type 2 diabetes: a double-blind randomized trial. Adv Ther. 2015 Mar;32(3):201-15. doi: 10.1007/s12325-015-0195-3. Epub 2015 Mar 25.

  PMID: 25805187 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin; Linagliptin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

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 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2011
• First Posted: September 22, 2011
• Study Start: November 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: November 25, 2014
• Results First Posted: June 3, 2014

Record last verified: 2014-11

Locations

CN (12); CA (15); BA (3); BE (5); HK (2); LE (5); DE (8); ME (5); PE (3); PH (5); ES (10); GU (3); IN (8); TW (6)