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

Overview[ - collapse ][ - ]

Purpose Reduced factorial design study with 24 week randomized treatment of initial combination therapy with linagliptin and metformin in T2DM patients
ConditionDiabetes Mellitus, Type 2
InterventionDrug: linagliptin2.5mg/metformin1000mg
Drug: linagliptin2.5mg/metformin1000mg
Drug: linagliptin 5mg
Drug: Metformin 500mg
Drug: linagliptin2.5mg/metformin500mg
Drug: linagliptin2.5mg/metformin500mg
Drug: linagliptin 5mg
Drug: Metformin 1000mg
PhasePhase 3
SponsorBoehringer Ingelheim
Responsible PartyBoehringer Ingelheim
ClinicalTrials.gov IdentifierNCT01708902
First ReceivedOctober 16, 2012
Last UpdatedApril 16, 2014
Last verifiedApril 2014

Tracking Information[ + expand ][ + ]

First Received DateOctober 16, 2012
Last Updated DateApril 16, 2014
Start DateOctober 2012
Estimated Primary Completion DateApril 2014
Current Primary Outcome MeasuresThe change from baseline in HbA1c after 24 weeks of treatment (for both in main group and additional parallel group). [Time Frame: 24 weeks] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • The occurrence of treat to target efficacy response in terms of HbA1c < 7.0 % and < 6.5% after 24 weeks of treatment [Time Frame: 24 weeks] [Designated as safety issue: No]
  • The occurrence of relative efficacy response (HbA1c lowering by at least 0.5% after 24 weeks of treatment) [Time Frame: 24 weeks] [Designated as safety issue: No]
  • The change in FPG from baseline after 24 weeks of treatment [Time Frame: 24 weeks] [Designated as safety issue: No]
  • The change of Fasting Plasma Glucose(FPG) by visit over time [Time Frame: 24 weeks] [Designated as safety issue: No]
  • The use of rescue therapy [Time Frame: 24 weeks] [Designated as safety issue: No]
  • The change of Postprandial Glucose(PPG) from baseline after 24 weeks of treatment (substudy in main group) [Time Frame: 24 weeks] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleStudy to Compare the Efficacy and Safety of Administration of the Fix Dose Combination of Linagliptin Plus Metformin in Drug naïve Type 2 Patients
Official TitleA Phase III Randomised, Double-blind, Double-dummy, Parallel Group Study to Compare the Efficacy and Safety of Twice Daily Administration of the Fix Dose Combination of Linagliptin 2.5 mg + Metformin 500 mg, or of Linagliptin 2.5 mg + Metformin 1000 mg, With the Individual Components of Metformin (500 mg or 1000 mg, Twice Daily), and Linagliptin (5.0 mg, Once Daily) Over 24 Weeks in Treatment naïve Type 2 Diabetic Patients With Insufficient Glycaemic Control
Brief Summary
Reduced factorial design study with 24 week randomized treatment of initial combination
therapy with linagliptin and metformin in T2DM patients
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double-Blind, Primary Purpose: Treatment
ConditionDiabetes Mellitus, Type 2
InterventionDrug: linagliptin2.5mg/metformin1000mg
linagliptin2.5mg/metformin1000mg BID
Drug: linagliptin2.5mg/metformin1000mg
linagliptin2.5mg/metformin1000mg BID
Drug: linagliptin 5mg
linagliptin 5mg once daily
Drug: Metformin 500mg
Metformin 500mg BID
Drug: linagliptin2.5mg/metformin500mg
linagliptin2.5mg/metformin500mg BID
Drug: linagliptin2.5mg/metformin500mg
linagliptin2.5mg/metformin500mg BID
Drug: linagliptin 5mg
linagliptin 5mg once daily
Drug: Metformin 1000mg
Metformin 1000mg BID
Study Arm (s)
  • Experimental: linagliptin2.5mg / metformin1000mg BID
    patient to receive a tablet containing linagliptin 2.5mg and metformin 1000mg BID
  • Active Comparator: metformin 500mg BID
    patient to receive a tablet containing metformin 500mg BID
  • Active Comparator: metformin 1000mg BID
    patient to receive a tablet containing metformin 1000mg BID
  • Active Comparator: linagliptin 5 mg QD
    patient to receive a tablet containing linagliptin 5mg once daily
  • Experimental: linagliptin2.5mg / metformin500mg BID
    patient to receive a tablet containing linagliptin 2.5mg and metformin 500mg BID

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment876
Estimated Completion DateApril 2014
Estimated Primary Completion DateApril 2014
Eligibility Criteria
Inclusion criteria:

1. Diagnosis of Type 2 diabetes mellitus(T2DM) prior to informed consent

2. Male and female patients on diet and exercise regimen who are drug-naïve

3. Glycosylated haemoglobin A1c (HbA1c) at V1a >/=7.5 %<11% for main group and HbA1c >/=
11.0 % for the additional parallel group

4. Age >/= 18 and
5. Body Mass Index(BMI)
6. Signed and dated written informed consent by date of Visit 1a in accordance with good
clinical practice(GCP) and local legislation

Exclusion criteria:

1. Uncontrolled hyperglycaemia required for rescue medication during placebo run-in
phase

2. In main group, the patients with investigational medicinal product(IMP) compliance <
80 % or >120 % during 2 weeks placebo run in period

3. Acute coronary syndrome stroke or Transient ischaemic attack (TIA) within 3 months
prior to randomisation

4. 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

5. Known hypersensitivity or allergy to linagliptin or its excipients or metformin or
placebo

6. Treatment with anti-obesity drugs 3 months prior to informed consent or any other
treatment at the time of screening

7. 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.

8. Concurrent participation in another clinical trial or any investigational therapy
within thirty days prior to signing the consent form or during the trial.

9. Pre-menopausal women (last menstruation 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

10. Current treatment with systemic steroids at time of informed consent or change in
dosage of thyroid hormones within 6 weeks prior to informed consent.

11. Renal failure or renal impairment at Visit 1a (screening) with an Estimated
Glomerular Filtration Rate(eGFR) < 60 ml/min

12. Bariatric surgery within the past two years and other gastrointestinal surgeries that
induce chronic malabsorption

13. Dehydration by clinical judgement of the investigator

14. Clinical detected unstable or acute congestive heart failure

15. Acute or chronic metabolic acidosis (present in patient history)

16. Hereditary galactose intolerance

17. Known history of pancreatitis and chronic pancreatitis

18. Medical history of cancer (except for basal cell carcinoma) and/or treatment for
cancer within last 5 years.

19. Any other clinical condition that would jeopardize patients safety while
participating in this clinical trial at the discretion of investigator
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesChina, Malaysia, Philippines, Vietnam

Administrative Information[ + expand ][ + ]

NCT Number NCT01708902
Other Study ID Numbers1288.18
Has Data Monitoring CommitteeNot Provided
Information Provided ByBoehringer Ingelheim
Study SponsorBoehringer Ingelheim
CollaboratorsEli Lilly and Company
Investigators Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Verification DateApril 2014

Locations[ + expand ][ + ]

1288.18.86001 Boehringer Ingelheim Investigational Site
Beijing, China
1288.18.86002 Boehringer Ingelheim Investigational Site
Beijing, China
1288.18.86003 Boehringer Ingelheim Investigational Site
Beijing, China
1288.18.86046 Boehringer Ingelheim Investigational Site
Beijing, China
1288.18.86004 Boehringer Ingelheim Investigational Site
Beijing, China
1288.18.86019 Boehringer Ingelheim Investigational Site
Changchun, China
1288.18.86020 Boehringer Ingelheim Investigational Site
Changchun, China
1288.18.86050 Boehringer Ingelheim Investigational Site
Changsha, China
1288.18.86029 Boehringer Ingelheim Investigational Site
Changsha, China
1288.18.86028 Boehringer Ingelheim Investigational Site
Changsha, China
1288.18.86045 Boehringer Ingelheim Investigational Site
Chengdu, China
1288.18.86042 Boehringer Ingelheim Investigational Site
Chongqing, China
1288.18.86023 Boehringer Ingelheim Investigational Site
Dalian, China
1288.18.86009 Boehringer Ingelheim Investigational Site
Guangzhou, China
1288.18.86010 Boehringer Ingelheim Investigational Site
Guangzhou, China
1288.18.86012 Boehringer Ingelheim Investigational Site
Guangzhou, China
1288.18.86047 Boehringer Ingelheim Investigational Site
Haerbin, China
1288.18.86032 Boehringer Ingelheim Investigational Site
Hefei, China
1288.18.86016 Boehringer Ingelheim Investigational Site
Hengshui, China
1288.18.86017 Boehringer Ingelheim Investigational Site
Jinan, China
1288.18.86026 Boehringer Ingelheim Investigational Site
Lanzhou, China
1288.18.86034 Boehringer Ingelheim Investigational Site
Nan Ning, China
1288.18.86039 Boehringer Ingelheim Investigational Site
Nanchang, China
1288.18.86035 Boehringer Ingelheim Investigational Site
Nanjing, China
1288.18.86036 Boehringer Ingelheim Investigational Site
Nanjing, China
1288.18.86008 Boehringer Ingelheim Investigational Site
Shanghai, China
1288.18.86006 Boehringer Ingelheim Investigational Site
Shanghai, China
1288.18.86007 Boehringer Ingelheim Investigational Site
Shanghai, China
1288.18.86013 Boehringer Ingelheim Investigational Site
Shantou, China
1288.18.86022 Boehringer Ingelheim Investigational Site
Shenyang, China
1288.18.86014 Boehringer Ingelheim Investigational Site
Shijiazhuang, China
1288.18.86015 Boehringer Ingelheim Investigational Site
Shijiazhuang, China
1288.18.86038 Boehringer Ingelheim Investigational Site
Suzhou, China
1288.18.86049 Boehringer Ingelheim Investigational Site
Wuhan, China
1288.18.86033 Boehringer Ingelheim Investigational Site
Wuhu, China
1288.18.86024 Boehringer Ingelheim Investigational Site
Xi'An, China
1288.18.86025 Boehringer Ingelheim Investigational Site
Xi'An, China
1288.18.86030 Boehringer Ingelheim Investigational Site
Yueyang, China
1288.18.60004 Boehringer Ingelheim Investigational Site
Kelantan, Malaysia
1288.18.60002 Boehringer Ingelheim Investigational Site
Melaka, Malaysia
1288.18.60007 Boehringer Ingelheim Investigational Site
Negeri Sembilan, Malaysia
1288.18.60005 Boehringer Ingelheim Investigational Site
Negeri Sembilan, Malaysia
1288.18.60006 Boehringer Ingelheim Investigational Site
Perak, Malaysia
1288.18.60001 Boehringer Ingelheim Investigational Site
Perak, Malaysia
1288.18.60008 Boehringer Ingelheim Investigational Site
Putrajaya, Malaysia
1288.18.60003 Boehringer Ingelheim Investigational Site
Selangor, Malaysia
1288.18.63007 Boehringer Ingelheim Investigational Site
Cebu, Philippines
1288.18.63003 Boehringer Ingelheim Investigational Site
Cebu City, Philippines
1288.18.63002 Boehringer Ingelheim Investigational Site
Makati City, Philippines
1288.18.63001 Boehringer Ingelheim Investigational Site
Manila, Philippines
1288.18.63008 Boehringer Ingelheim Investigational Site
Quezon City, Philippines
1288.18.63006 Boehringer Ingelheim Investigational Site
Surigao, Philippines
1288.18.63005 Boehringer Ingelheim Investigational Site
Tagum City, Philippines
1288.18.84003 Boehringer Ingelheim Investigational Site
Hanoi, Vietnam
1288.18.84002 Boehringer Ingelheim Investigational Site
Ho Chi Minh City, Vietnam
1288.18.84001 Boehringer Ingelheim Investigational Site
Ho Chi Minh City, Vietnam