Clinical trial NCT01708902: Study to Compare the Efficacy and Safety of Administration of the Fix Dose Combination of Linagliptin Plus Metformin in Drug naïve Type 2 Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2012-10-17
Enrollment: 876
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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


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 \</= 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

Primary outcomes:
measure: The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group
timeFrame: Baseline and week 24
measure: The Change From Baseline in HbA1c After 24 Weeks of Treatment in Main Group - FAS (OC)
timeFrame: Baseline and week 24
measure: The Change From Baseline in HbA1c After 12 Weeks of Treatment in APG
timeFrame: Baseline and week 12
Secondary outcomes:
measure: The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 24 Weeks of Treatment in Main Group
timeFrame: Week 24 (after first drug administration)
measure: The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 7.0 % After 12 Weeks of Treatment in APG
timeFrame: Week 12 (after first drug administration)
measure: The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 24 Weeks of Treatment in Main Group
timeFrame: Week 24 (after first drug administration)
measure: The Occurrence of Treat to Target Efficacy Response in Terms of HbA1c < 6.5% After 12 Weeks of Treatment in APG
timeFrame: Week 12 (after first drug administration)
measure: The Occurrence of Relative Efficacy Response in Main Group
timeFrame: From baseline until week 24
measure: The Occurrence of Relative Efficacy Response in APG
timeFrame: From baseline until week 12
measure: The Change in Fasting Plasma Glucose (FPG) From Baseline After 24 Weeks of Treatment in Main Group
timeFrame: Baseline and week 24
measure: The Change in Fasting Plasma Glucose (FPG) From Baseline After 12 Weeks of Treatment in APG
timeFrame: Baseline and week 12
measure: The Frequency of Patients With Use of Rescue Therapy During 24 Week Treatment Period in Main Group
timeFrame: From baseline until week 24
measure: The Frequency of Patients With Use of Rescue Therapy During 12 Week Treatment Period in APG
timeFrame: From baseline until week 12
Other outcomes:
Locations:
city: Beijing
country: China
facility: 1288.18.86001 Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: 1288.18.86002 Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: 1288.18.86003 Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: 1288.18.86004 Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: 1288.18.86046 Boehringer Ingelheim Investigational Site
city: Changchun
country: China
facility: 1288.18.86019 Boehringer Ingelheim Investigational Site
city: Changchun
country: China
facility: 1288.18.86020 Boehringer Ingelheim Investigational Site
city: Changsha
country: China
facility: 1288.18.86028 Boehringer Ingelheim Investigational Site
city: Changsha
country: China
facility: 1288.18.86029 Boehringer Ingelheim Investigational Site
city: Changsha
country: China
facility: 1288.18.86050 Boehringer Ingelheim Investigational Site
city: Chengdu
country: China
facility: 1288.18.86045 Boehringer Ingelheim Investigational Site
city: Chongqing
country: China
facility: 1288.18.86042 Boehringer Ingelheim Investigational Site
city: Dalian
country: China
facility: 1288.18.86023 Boehringer Ingelheim Investigational Site
city: Guangzhou
country: China
facility: 1288.18.86009 Boehringer Ingelheim Investigational Site
city: Guangzhou
country: China
facility: 1288.18.86010 Boehringer Ingelheim Investigational Site
city: Guangzhou
country: China
facility: 1288.18.86012 Boehringer Ingelheim Investigational Site
city: Haerbin
country: China
facility: 1288.18.86047 Boehringer Ingelheim Investigational Site
city: Hefei
country: China
facility: 1288.18.86032 Boehringer Ingelheim Investigational Site
city: Hengshui
country: China
facility: 1288.18.86016 Boehringer Ingelheim Investigational Site
city: Jinan
country: China
facility: 1288.18.86017 Boehringer Ingelheim Investigational Site
city: Lanzhou
country: China
facility: 1288.18.86026 Boehringer Ingelheim Investigational Site
city: Nan Ning
country: China
facility: 1288.18.86034 Boehringer Ingelheim Investigational Site
city: Nanchang
country: China
facility: 1288.18.86039 Boehringer Ingelheim Investigational Site
city: Nanjing
country: China
facility: 1288.18.86035 Boehringer Ingelheim Investigational Site
city: Nanjing
country: China
facility: 1288.18.86036 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1288.18.86006 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1288.18.86007 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1288.18.86008 Boehringer Ingelheim Investigational Site
city: Shantou
country: China
facility: 1288.18.86013 Boehringer Ingelheim Investigational Site
city: Shenyang
country: China
facility: 1288.18.86022 Boehringer Ingelheim Investigational Site
city: Shijiazhuang
country: China
facility: 1288.18.86014 Boehringer Ingelheim Investigational Site
city: Shijiazhuang
country: China
facility: 1288.18.86015 Boehringer Ingelheim Investigational Site
city: Suzhou
country: China
facility: 1288.18.86038 Boehringer Ingelheim Investigational Site
city: Wuhan
country: China
facility: 1288.18.86049 Boehringer Ingelheim Investigational Site
city: Wuhu
country: China
facility: 1288.18.86033 Boehringer Ingelheim Investigational Site
city: Xi'An
country: China
facility: 1288.18.86024 Boehringer Ingelheim Investigational Site
city: Xi'An
country: China
facility: 1288.18.86025 Boehringer Ingelheim Investigational Site
city: Yueyang
country: China
facility: 1288.18.86030 Boehringer Ingelheim Investigational Site
city: Kelantan
country: Malaysia
facility: 1288.18.60004 Boehringer Ingelheim Investigational Site
city: Melaka
country: Malaysia
facility: 1288.18.60002 Boehringer Ingelheim Investigational Site
city: Negeri Sembilan
country: Malaysia
facility: 1288.18.60005 Boehringer Ingelheim Investigational Site
city: Negeri Sembilan
country: Malaysia
facility: 1288.18.60007 Boehringer Ingelheim Investigational Site
city: Perak
country: Malaysia
facility: 1288.18.60001 Boehringer Ingelheim Investigational Site
city: Perak
country: Malaysia
facility: 1288.18.60006 Boehringer Ingelheim Investigational Site
city: Putrajaya
country: Malaysia
facility: 1288.18.60008 Boehringer Ingelheim Investigational Site
city: Selangor
country: Malaysia
facility: 1288.18.60003 Boehringer Ingelheim Investigational Site
city: Cebu City
country: Philippines
facility: 1288.18.63003 Boehringer Ingelheim Investigational Site
city: Cebu
country: Philippines
facility: 1288.18.63007 Boehringer Ingelheim Investigational Site
city: Makati City
country: Philippines
facility: 1288.18.63002 Boehringer Ingelheim Investigational Site
city: Manila
country: Philippines
facility: 1288.18.63001 Boehringer Ingelheim Investigational Site
city: Quezon City
country: Philippines
facility: 1288.18.63008 Boehringer Ingelheim Investigational Site
city: Surigao
country: Philippines
facility: 1288.18.63006 Boehringer Ingelheim Investigational Site
city: Tagum City
country: Philippines
facility: 1288.18.63005 Boehringer Ingelheim Investigational Site
city: Hanoi
country: Vietnam
facility: 1288.18.84003 Boehringer Ingelheim Investigational Site
city: Ho Chi Minh City
country: Vietnam
facility: 1288.18.84001 Boehringer Ingelheim Investigational Site
city: Ho Chi Minh City
country: Vietnam
facility: 1288.18.84002 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.