Study to Compare the Efficacy and Safety of Administration of the Fix Dose Combination of Linagliptin Plus Metformin in Drug naïve Type 2 Patients

NCT01708902 | Completed Phase 3 Results

• 1 other identifier: 1288.18
• Study Type: interventional
• Target: 876
• Locations: 4 countries
• Sites: 56

Brief Summary

Reduced factorial design study with 24 week randomized treatment of initial combination therapy with linagliptin and metformin in T2DM patients

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (3)

• The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group

  The change from baseline in HbA1c after 24 weeks of treatment in main group. The mean was adjusted by baseline HbA1c and treatment group.

  Baseline and week 24

• The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group - FAS (OC)

  The change from baseline in HbA1c after 24 weeks of treatment in main group. Only subjects from the FAS with measured HbA1c values (observed cases \[OC\]) were considered. The mean was adjusted by treatment, baseline HbA1c, week and treatment\*week. The sensitivity analysis was added as the primary analysis failed with borderline results.

  Baseline and week 24

• The Change From Baseline in HbA1c After 12 Weeks of Treatment in APG

  The change from baseline in HbA1c after 12 weeks of treatment in additional parallel group (APG) The mean was adjusted by baseline HbA1c and treatment group.

  Baseline and week 12

Secondary Outcomes (10)

• The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 24 Weeks of Treatment in Main Group

  Week 24 (after first drug administration)

• The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 12 Weeks of Treatment in APG

  Week 12 (after first drug administration)

• The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 24 Weeks of Treatment in Main Group

  Week 24 (after first drug administration)

• The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 12 Weeks of Treatment in APG

  Week 12 (after first drug administration)

• The Occurrence of Relative Efficacy Response in Main Group

  From baseline until week 24

Study Arms (5)

linagliptin2.5mg / metformin500mg BID

EXPERIMENTAL

patient to receive a tablet containing linagliptin 2.5mg and metformin 500mg BID

Drug: linagliptin 5mg; Drug: Metformin 500mg

linagliptin2.5mg / metformin1000mg BID

EXPERIMENTAL

patient to receive a tablet containing linagliptin 2.5mg and metformin 1000mg BID

Drug: linagliptin 5mg; Drug: Metformin 1000mg

metformin 500mg BID

ACTIVE COMPARATOR

patient to receive a tablet containing metformin 500mg BID

Drug: linagliptin2.5mg/metformin500mg

metformin 1000mg BID

ACTIVE COMPARATOR

patient to receive a tablet containing metformin 1000mg BID

Drug: linagliptin2.5mg/metformin1000mg

linagliptin 5 mg QD

ACTIVE COMPARATOR

patient to receive a tablet containing linagliptin 5mg once daily

Drug: linagliptin2.5mg/metformin1000mg; Drug: linagliptin2.5mg/metformin500mg

Interventions

linagliptin2.5mg/metformin1000mg DRUG

linagliptin2.5mg/metformin1000mg BID

metformin 1000mg BID

linagliptin 5mg DRUG

linagliptin 5mg once daily

linagliptin2.5mg / metformin500mg BID

Metformin 500mg DRUG

Metformin 500mg BID

linagliptin2.5mg / metformin500mg BID

linagliptin2.5mg/metformin500mg DRUG

linagliptin2.5mg/metformin500mg BID

metformin 500mg BID

Metformin 1000mg DRUG

Metformin 1000mg BID

linagliptin2.5mg / metformin1000mg BID

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-naïve
• Glycosylated haemoglobin A1c (HbA1c) at V1a \>/=7.5 %\<11% for main group and HbA1c \>/= 11.0 % for the additional parallel group
• Age \>/= 18 and \</= 80 years at Visit 1a (Screening)
• Body Mass Index(BMI)\</ = 40 kg/m2 at Visit 1a (Screening)
• Signed and dated written informed consent by date of Visit 1a in accordance with good clinical practice(GCP) and local legislation

You may not qualify if:

• Uncontrolled hyperglycaemia required for rescue medication during placebo run-in phase
• In main group, the patients with investigational medicinal product(IMP) compliance \< 80 % or \>120 % during 2 weeks placebo run in period
• Acute coronary syndrome stroke or Transient ischaemic attack (TIA) within 3 months prior to randomisation
• Impaired hepatic function, defined by serum levels of either Alanine aminotransferase(ALT) ,Aspartate aminotransferase(AST), or alkaline phosphatase (AP) above 3 x upper limit of normal (ULN) ,or total bilirubin above 1.5 x ULN as determined at Visit 1a
• Known hypersensitivity or allergy to linagliptin or its excipients or metformin or placebo
• Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at the time of screening
• Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake in the opinion of the investigator.
• Concurrent participation in another clinical trial or any investigational therapy within thirty days prior to signing the consent form or during the trial.
• Pre-menopausal women (last menstruation \</= 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
• 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 at Visit 1a (screening) with an Estimated Glomerular Filtration Rate(eGFR) \< 60 ml/min
• Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
• Dehydration by clinical judgement of the investigator
• Clinical detected unstable or acute congestive heart failure
• Acute or chronic metabolic acidosis (present in patient history)

Sponsors & Collaborators

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

Study Sites (56)

1288.18.86001 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1288.18.86002 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1288.18.86003 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1288.18.86004 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1288.18.86046 Boehringer Ingelheim Investigational Site

Beijing, China

Location

1288.18.86019 Boehringer Ingelheim Investigational Site

Changchun, China

Location

1288.18.86020 Boehringer Ingelheim Investigational Site

Changchun, China

Location

1288.18.86028 Boehringer Ingelheim Investigational Site

Changsha, China

Location

1288.18.86029 Boehringer Ingelheim Investigational Site

Changsha, China

Location

1288.18.86050 Boehringer Ingelheim Investigational Site

Changsha, China

Location

1288.18.86045 Boehringer Ingelheim Investigational Site

Chengdu, China

Location

1288.18.86042 Boehringer Ingelheim Investigational Site

Chongqing, China

Location

1288.18.86023 Boehringer Ingelheim Investigational Site

Dalian, China

Location

1288.18.86009 Boehringer Ingelheim Investigational Site

Guangzhou, China

Location

1288.18.86010 Boehringer Ingelheim Investigational Site

Guangzhou, China

Location

1288.18.86012 Boehringer Ingelheim Investigational Site

Guangzhou, China

Location

1288.18.86047 Boehringer Ingelheim Investigational Site

Haerbin, China

Location

1288.18.86032 Boehringer Ingelheim Investigational Site

Hefei, China

Location

1288.18.86016 Boehringer Ingelheim Investigational Site

Hengshui, China

Location

1288.18.86017 Boehringer Ingelheim Investigational Site

Jinan, China

Location

1288.18.86026 Boehringer Ingelheim Investigational Site

Lanzhou, China

Location

1288.18.86039 Boehringer Ingelheim Investigational Site

Nanchang, China

Location

1288.18.86035 Boehringer Ingelheim Investigational Site

Nanjing, China

Location

1288.18.86036 Boehringer Ingelheim Investigational Site

Nanjing, China

Location

1288.18.86034 Boehringer Ingelheim Investigational Site

Nanning, China

Location

1288.18.86006 Boehringer Ingelheim Investigational Site

Shanghai, China

Location

1288.18.86007 Boehringer Ingelheim Investigational Site

Shanghai, China

Location

1288.18.86008 Boehringer Ingelheim Investigational Site

Shanghai, China

Location

1288.18.86013 Boehringer Ingelheim Investigational Site

Shantou, China

Location

1288.18.86022 Boehringer Ingelheim Investigational Site

Shenyang, China

Location

1288.18.86014 Boehringer Ingelheim Investigational Site

Shijiazhuang, China

Location

1288.18.86015 Boehringer Ingelheim Investigational Site

Shijiazhuang, China

Location

1288.18.86038 Boehringer Ingelheim Investigational Site

Suzhou, China

Location

1288.18.86049 Boehringer Ingelheim Investigational Site

Wuhan, China

Location

1288.18.86033 Boehringer Ingelheim Investigational Site

Wuhu, China

Location

1288.18.86024 Boehringer Ingelheim Investigational Site

Xi'an, China

Location

1288.18.86025 Boehringer Ingelheim Investigational Site

Xi'an, China

Location

1288.18.86030 Boehringer Ingelheim Investigational Site

Yueyang, China

Location

1288.18.60004 Boehringer Ingelheim Investigational Site

Kelantan, Malaysia

Location

1288.18.60003 Boehringer Ingelheim Investigational Site

Kuala Selangor, Malaysia

Location

1288.18.60002 Boehringer Ingelheim Investigational Site

Malacca, Malaysia

Location

1288.18.60005 Boehringer Ingelheim Investigational Site

Negeri Sembilan, Malaysia

Location

1288.18.60007 Boehringer Ingelheim Investigational Site

Negeri Sembilan, Malaysia

Location

1288.18.60001 Boehringer Ingelheim Investigational Site

Perak, Malaysia

Location

1288.18.60006 Boehringer Ingelheim Investigational Site

Perak, Malaysia

Location

1288.18.60008 Boehringer Ingelheim Investigational Site

Putrajaya, Malaysia

Location

1288.18.63007 Boehringer Ingelheim Investigational Site

Cebu, Philippines

Location

1288.18.63003 Boehringer Ingelheim Investigational Site

Cebu City, Philippines

Location

1288.18.63002 Boehringer Ingelheim Investigational Site

Makati City, Philippines

Location

1288.18.63001 Boehringer Ingelheim Investigational Site

Manila, Philippines

Location

1288.18.63008 Boehringer Ingelheim Investigational Site

Quezon City, Philippines

Location

1288.18.63006 Boehringer Ingelheim Investigational Site

Surigao City, Philippines

Location

1288.18.63005 Boehringer Ingelheim Investigational Site

Tagum, Philippines

Location

1288.18.84003 Boehringer Ingelheim Investigational Site

Hanoi, Vietnam

Location

1288.18.84001 Boehringer Ingelheim Investigational Site

Ho Chi Minh City, Vietnam

Location

1288.18.84002 Boehringer Ingelheim Investigational Site

Ho Chi Minh City, Vietnam

Location

Related Publications (1)

• Lv Q, Shen J, Miao L, Ye B, Schepers C, Plat A, Shi Y. Early Combination Therapy with Linagliptin and Metformin in People with Type 2 Diabetes Improves Glycemic Control to HbA1c </= 6.5% without Increasing Hypoglycemia: Pooled Analysis of Two Randomized Clinical Trials. Diabetes Ther. 2020 Jun;11(6):1317-1330. doi: 10.1007/s13300-020-00819-9. Epub 2020 Apr 23.

  PMID: 32328953 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Linagliptin; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

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: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2012
• First Posted: October 17, 2012
• Study Start: October 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 24, 2015
• Results First Posted: April 24, 2015

Record last verified: 2015-04

Locations

VN (3); PH (7); CN (38); MY (8)