Efficacy and Safety Study of Linagliptin (5 mg Administered Orally Once Daily) Over 24 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite Metformin Therapy

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 1356 Over 24 Weeks in T2D Patients With Insufficient Glycaemic Control Despite Metformin Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01215097
• Other study ID #: 1218.65
• Status: Completed
• Phase: Phase 3
• First received: September 28, 2010
• Last updated: December 5, 2013
• Start date: October 2010
• Est. completion date: April 2012

Study information

• Verified date: June 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug AdministrationMalaysia: Ministry of HealthPhilippines: Bureau of Food and Drugs
• Study type: Interventional

Clinical Trial Summary

In this randomised, double-blind, parallel group trial, the safety and efficacy of 5 mg of Linagliptin administered orally once daily will be compared with a placebo after 24 weeks of treatment as add-on therapy to metformin in patients with type 2 diabetes and insufficient glycaemic control.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 306
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion criteria:

1. Male and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with metformin alone, or with metformin and not more than one other oral antidiabetic drug (antidiabetic therapy has to be unchanged for 6 weeks prior to informed consent and patients should receive standard diet and exercise counseling) A dose of >/=1500 mg/day metformin is required for inclusion into the trial. The dosage needs to be stable for at least 8 weeks before randomisation. Patients with a total daily dose of less than 1500 mg metformin will only be included; if the investigator has documented them to be on their maximum tolerated dose (also in this case the 8 week time interval will apply for a stable dose).

2. Diagnosis of type 2 diabetes prior to informed consent

3. Glycosylated haemoglobin A1 (HbA1c) at Visit 1a (Screening):

For patients undergoing wash out of previous medication: HbA1c =7.0 to =9.5% For patients not undergoing wash-out of previous medication: HbA1c =7.0 to =10.0%

4. Glycosylated haemoglobin A1 (HbA1c) =7.0 to =10.0% at Visit 2 (Start of Run-in)

5. Age = 18 and < 80 years at Visit 1a (Screening)

6. BMI (Body Mass Index) = 45 kg/m2 at Visit 1a (Screening)

7. Signed and dated written informed consent by date of Visit 1a in accordance with GCP and local legislation

Exclusion criteria:

1. Myocardial infarction, stroke or TIA within 6 months prior to informed consent

2. Impaired hepatic function, defined by serum levels of either Alanine transaminase,Aspartate transaminase, or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at Visit 1a

3. Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast during wash-out / placebo run-in and confirmed by a second measurement (not on the same day).

4. Known hypersensitivity or allergy to the investigational product or its excipients or metformin or placebo

5. Treatment with rosiglitazone or pioglitazone within 3 months prior to informed consent

6. Treatment with an injectable Glucagon-like peptide- 1 (GLP-1) analogue (e.g. exenatide) , Dipeptidyl-Peptidase 4 (DPP-IV) inhibitor within 3 months prior to informed consent

7. Treatment with insulin within 3 months prior to informed consent

8. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat, rimonabant) within 3 months prior to informed consent.

9. Alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation or drug abuse

10. Participation in another trial with an investigational drug within 2 months prior to informed consent

11. 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 and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include transdermal patch, intra-uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner. No exception will be made.

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

13. Renal failure or renal impairment (serum creatinine =1.5 mg/dl as determined at Visit 1a)

14. Dehydration by clinical judgement of the investigator

15. Unstable or acute congestive heart failure

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

17. Hereditary galactose intolerance

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• Linagliptin
once a day
• placebo
once a day

Locations

Country	Name	City	State
China	1218.65.86007 Boehringer Ingelheim Investigational Site	Beijing
China	1218.65.86011 Boehringer Ingelheim Investigational Site	Chongqing
China	1218.65.86008 Boehringer Ingelheim Investigational Site	Dalian
China	1218.65.86010 Boehringer Ingelheim Investigational Site	Fuzhou
China	1218.65.86014 Boehringer Ingelheim Investigational Site	Hangzhou
China	1218.65.86005 Boehringer Ingelheim Investigational Site	Hefei
China	1218.65.86006 Boehringer Ingelheim Investigational Site	Hefei
China	1218.65.86012 Boehringer Ingelheim Investigational Site	Nanjing
China	1218.65.86001 Boehringer Ingelheim Investigational Site	Shanghai
China	1218.65.86002 Boehringer Ingelheim Investigational Site	Shanghai
China	1218.65.86003 Boehringer Ingelheim Investigational Site	Shanghai
China	1218.65.86004 Boehringer Ingelheim Investigational Site	Suzhou
China	1218.65.86015 Boehringer Ingelheim Investigational Site	Wenzhou
China	1218.65.86009 Boehringer Ingelheim Investigational Site	Wuhan
China	1218.65.86013 Boehringer Ingelheim Investigational Site	Yangzhou
Malaysia	1218.65.60002 Boehringer Ingelheim Investigational Site	Johor Bahru,
Malaysia	1218.65.60001 Boehringer Ingelheim Investigational Site	Kelantan
Philippines	1218.65.63001 Boehringer Ingelheim Investigational Site	Marikina
Philippines	1218.65.63002 Boehringer Ingelheim Investigational Site	San Juan

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Eli Lilly and Company

Countries where clinical trial is conducted

China,  Malaysia,  Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c Change From Baseline at Week 24	Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and at week 24	No
Secondary	HbA1c Change From Baseline at Week 6	Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and at week 6	No
Secondary	HbA1c Change From Baseline at Week 12	Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and at week 12	No
Secondary	HbA1c Change From Baseline at Week 18	Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and at week 18	No
Secondary	HbA1c Change From Baseline at Week 24(Chinese Only)	Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.	Baseline and at 24 weeks	No
Secondary	FPG Change From Baseline at Week 24	Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.	Baseline and at week 24	No
Secondary	FPG Change From Baseline at Week 6	Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.	Baseline and at week 6	No
Secondary	FPG Change From Baseline at Week 12	Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.	Baseline and at week 12	No
Secondary	FPG Change From Baseline at Week 18	Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.	Baseline and at week 18	No
Secondary	Number of Patients With HbA1c < 7.0%	Number of patients with HbA1c < 7.0% at week 24	baseline and at week 24	No
Secondary	Number of Patients With HbA1c < 7.0% at Week 24 With Baseline HbA1c >= 7.0%.	Number of patients with HbA1c < 7.0% at week 24 with baseline HbA1c >= 7.0%.	baseline and at week 24	No
Secondary	Number of Patients With HbA1c < 6.5%	Number of patients with HbA1c < 6.5% at week 24	baseline and at week 24	No
Secondary	Number of Patients With HbA1c < 6.5% at Week 24 With Baseline HbA1c >= 6.5%.	Number of patients with HbA1c < 6.5% at week 24 with baseline HbA1c >= 6.5%.	baseline and at week 24	No
Secondary	Number With HbA1c at Least Lowering 0.5%	Number with HbA1c at least 0.5% lowering from baseline at week 24	baseline and at week 24	No

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