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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01708902
• Other study ID #: 1288.18
• Status: Completed
• Phase: Phase 3
• First received: October 16, 2012
• Last updated: April 8, 2015
• Start date: October 2012
• Est. completion date: April 2014

Study information

• Verified date: April 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug AdministrationMalaysia: Ministry of HealthPhilippines: Bureau of Food and DrugsVietnam: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 876
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 </= 80 years at Visit 1a (Screening)

5. Body Mass Index(BMI)</ = 40 kg/m2 at Visit 1a (Screening)

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 </= 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

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• linagliptin2.5mg/metformin1000mg
linagliptin2.5mg/metformin1000mg BID
• linagliptin2.5mg/metformin1000mg
linagliptin2.5mg/metformin1000mg BID
• linagliptin 5mg
linagliptin 5mg once daily
• Metformin 500mg
Metformin 500mg BID
• linagliptin2.5mg/metformin500mg
linagliptin2.5mg/metformin500mg BID
• linagliptin2.5mg/metformin500mg
linagliptin2.5mg/metformin500mg BID
• linagliptin 5mg
linagliptin 5mg once daily
• Metformin 1000mg
Metformin 1000mg BID

Locations

Country	Name	City	State
China	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	1288.18.86004 Boehringer Ingelheim Investigational Site	Beijing
China	1288.18.86046 Boehringer Ingelheim Investigational Site	Beijing
China	1288.18.86019 Boehringer Ingelheim Investigational Site	Changchun
China	1288.18.86020 Boehringer Ingelheim Investigational Site	Changchun
China	1288.18.86028 Boehringer Ingelheim Investigational Site	Changsha
China	1288.18.86029 Boehringer Ingelheim Investigational Site	Changsha
China	1288.18.86050 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	1288.18.86006 Boehringer Ingelheim Investigational Site	Shanghai
China	1288.18.86007 Boehringer Ingelheim Investigational Site	Shanghai
China	1288.18.86008 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
Malaysia	1288.18.60004 Boehringer Ingelheim Investigational Site	Kelantan
Malaysia	1288.18.60002 Boehringer Ingelheim Investigational Site	Melaka
Malaysia	1288.18.60005 Boehringer Ingelheim Investigational Site	Negeri Sembilan
Malaysia	1288.18.60007 Boehringer Ingelheim Investigational Site	Negeri Sembilan
Malaysia	1288.18.60001 Boehringer Ingelheim Investigational Site	Perak
Malaysia	1288.18.60006 Boehringer Ingelheim Investigational Site	Perak
Malaysia	1288.18.60008 Boehringer Ingelheim Investigational Site	Putrajaya
Malaysia	1288.18.60003 Boehringer Ingelheim Investigational Site	Selangor
Philippines	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
Vietnam	1288.18.84003 Boehringer Ingelheim Investigational Site	Hanoi
Vietnam	1288.18.84001 Boehringer Ingelheim Investigational Site	Ho Chi Minh City
Vietnam	1288.18.84002 Boehringer Ingelheim Investigational Site	Ho Chi Minh City

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Eli Lilly and Company

Countries where clinical trial is conducted

China,  Malaysia,  Philippines,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 24 Weeks of Treatment in Main Group	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)	No
Secondary	The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 12 Weeks of Treatment in APG	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)	No
Secondary	The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 24 Weeks of Treatment in Main Group	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)	No
Secondary	The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 12 Weeks of Treatment in APG	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)	No
Secondary	The Occurrence of Relative Efficacy Response in Main Group	The occurrence of relative efficacy response (HbA1c lowering by at least 0.5% after 24 weeks of treatment) in main group	From baseline until week 24	No
Secondary	The Occurrence of Relative Efficacy Response in APG	The Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 12 Weeks of Treatment) in APG	From baseline until week 12	No
Secondary	The Change in Fasting Plasma Glucose (FPG) From Baseline After 24 Weeks of Treatment in Main Group	The change in fasting plasma glucose (FPG) from baseline after 24 weeks of treatment in main group.; Adjusted mean: The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.	Baseline and week 24	No
Secondary	The Change in Fasting Plasma Glucose (FPG) From Baseline After 12 Weeks of Treatment in APG	The Change in Fasting Plasma Glucose (FPG) From Baseline After 12 Weeks of Treatment in APG.; Adjusted mean: The model includes continuous baseline HbA1c, continuous baseline FPG and treatment group.	Baseline and week 12	No
Secondary	The Frequency of Patients With Use of Rescue Therapy During 24 Week Treatment Period in Main Group	The frequency of patients with use of rescue therapy during 24 week treatment period in main group.; For this analysis the main group contrast 'Metformin 1000mg BID, Linagliptin 2.5mg / Metformin 1000mg BID' could not be analysed due to lack of events in the Metformin 1000mg BID group.	From baseline until week 24	No
Secondary	The Frequency of Patients With Use of Rescue Therapy During 12 Week Treatment Period in APG	The Frequency of Patients With Use of Rescue Therapy During 12 Week Treatment Period in APG.	From baseline until week 12	No

External Links

•   Related Info