| CTRI Number |
CTRI/2009/091/000824 [Registered on: 23/11/2009] |
| Last Modified On: |
01/09/2014 |
| Post Graduate Thesis |
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| Type of Trial |
Interventional |
Type of Study
Modification(s)
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Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
Public Title of Study
Modification(s)
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To compare the effects & safety of linagliptin 2.5mg twice daily dose vs linagliptin 5mg OD dose for 12weeks with background therapy of metformin,in subjects who are not exposed to linagliptin or previously treated with other OHG drugs in patients with type-2DM & insufficient blood glucose control |
Scientific Title of Study
Modification(s)
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A randomised, double-blind, placebo-controlled, 3 parallel group efficacy and safety study of linagliptin 2.5 mg twice daily versus 5 mg once daily over 12 weeks as add-on therapy to a twice daily dosing regimen of metformin in patients with type 2 diabetes mellitus and insufficient glycaemic control |
| Trial Acronym |
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Secondary IDs if Any
Modification(s)
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| Secondary ID |
Identifier |
| 1218.62 |
Protocol Number |
| 2009-013549-27 |
EudraCT |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
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| Name |
Dr Nagendra N |
| Designation |
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| Affiliation |
Manipal AcuNova Ltd |
| Address |
Mobius Towers, SJR - I park
EPIP Zone, Whitefield
Bangalore
KARNATAKA
560066
India |
| Phone |
91-80-66915780 |
| Fax |
91-80-66915719 |
| Email |
nagendra.n@ecronacunova.com |
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Details of Contact Person
Public Query
Modification(s)
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| Name |
Rakesh Dadhania |
| Designation |
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| Affiliation |
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| Address |
Manipal Acunova Limited.,Mobius, SJR i-Park
EPIP, Whitefield
Bangalore
KARNATAKA
560066
India |
| Phone |
91-80-66915757 |
| Fax |
91-80-66915719 |
| Email |
rakesh.dadhania@ecronacunova.com |
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Source of Monetary or Material Support
Modification(s)
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| Boehringer Ingelheim Korea Ltd., Korea |
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Primary Sponsor
Modification(s)
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| Name |
Boehringer Ingelheim Korea Ltd |
| Address |
16F, Yonsei severance Bldg, 84-11Namdaemunro-5Ka, Chung-Ku, Seoul, Korea |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
Modification(s)
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Countries of Recruitment
Modification(s)
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India |
Sites of Study
Modification(s)
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| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr.Padmalatha Devi |
Diabetomics |
Manduva Diabetomics India, 6-3-349/17B Hindi Nagar,Behind Panjagutta Sai Baba Temple Banjara Hills PO-500 034
Hyderabad
ANDHRA PRADESH |
91-40-65503111
91-40-23357111
drpadmalatha@gmail.com |
| Dr. S. R. Aravind |
DIACON Hospital & Research Center |
Centre 359/360, 19th Main 1st Block,Rajaji Nagar -560 010
Bangalore
KARNATAKA |
91-80-23323560
91-80-23130553
diacon90@hotmail.com |
| Dr. Rajendran K |
Health & Research Center |
T.C. 1/907, 1st Floor- Devi Scans Buildin,Kumarapuram Medical College P.O-695011
|
91-471-2554911
91-471-2554913
healthtrials@gmail.com |
| DrSanjay Reddy AC |
Medisys Clinisearch India Pvt. Ltd |
Diabetes Centre, No: 426,4th Cross,2nd Block. Kalyan Nagar-560043
Bangalore
KARNATAKA |
91-80-25457022
91-80-25425396
drsanjaycreddy@yahoo.com |
| Dr Sunil Surajprasad Gupta |
Sunil?s Diabetes Care n? Research Centre |
42, Lendra Park,Ramdaspeth-440010
Nagpur
MAHARASHTRA |
91-712-2428111
91-712-2428555
drsgupta_ngp@rediffmail.com |
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Details of Ethics Committee
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| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| ? Ethics Committee of Diabetes Care n? Research Centre, Nagpur |
Approved |
| Clinicom, Malleshwaram west, Bangalore |
Approved |
| Diacon Hospital Ethics Committee,Bangalore |
Approved |
| INDEPENDENT HUMAN ETHICS COMMITTEE, Trivandrum, Kerala |
Approved |
| Medisys Clinisearch Ethical Review Board |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
Modification(s)
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| Health Type |
Condition |
| Patients |
Type 2 Diabetes Mellitus , |
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Intervention / Comparator Agent
Modification(s)
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| Type |
Name |
Details |
| Intervention |
Linagliptin 2.5mg + Metformin |
Linagliptin 2.5 mg Bid + Metformin 1500 mg /day for 12 weeks |
| Intervention |
Linagliptin 5mg + Metformin |
Linagliptin 5 mg OD + Metformin >1500 mg/day for 12 weeks |
| Comparator Agent |
Metformin |
Metformin >1500 mg /day for 12 weeks |
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Inclusion Criteria
Modification(s)
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| Age From |
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| Age To |
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| Gender |
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| Details |
1. Diagnosis of type 2 diabetes mellitus prior to informed consent.
2. Male and female patients, currently treated with metformin alone, or with metformin and not more than one other oral antidiabetic drug (antidiabetic therapy may be a sulphonylurea, meglitinide, DPP-4 inhibitor or α-glucosidase inhibitor and its dose has to be unchanged for 12 weeks prior to informed consent).
A total daily dose of ≥1500 mg/day metformin divided into twice daily administration (e.g., 850 mg bid, 1000 mg bid, 850/1000 mg bid or 500/1000 mg bid) is required for inclusion into the trial. A patient taking metformin tid can be included if switched to a bid dosing regimen at the time of informed consent. In this case, the total daily dose must be maintained (e.g., 500 mg tid to 1000/500 mg bid, 1000/500/500 mg tid to 1000 bid, 500/500/850 mg tid to 1000/850 mg bid). Patients treated with a total daily dose of metformin of less than 1500 mg (e.g., 500 mg bid) can be included in the trial only if the Investigator has documented that the dose is the maximum tolerated dose for that patient.
The total daily dosage of metformin needs to be stable for at least 12 weeks prior to randomisation and throughout the duration of the study.
3. Glycosylated haemoglobin A1 (HbA1c) at Visit 1a (Screening) fulfils the following
criteria:
- For patients undergoing wash out of previous medication: ≥7.0 % to ≤9.5 %..
- For patients not undergoing wash-out of previous medication: ≥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 ≤45 kg/m2 (Body Mass Index) at Visit 1a (Screening).
7. Signed and dated written informed consent by date of Visit 1a in accordance with
GCP and local legislation. |
|
| ExclusionCriteria |
| Details |
1. Treatment with extended release formulations of metformin within 12 weeks prior to consent.
2. 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).
3. Myocardial infarction, stroke or TIA within 6 months prior to informed consent.
4. Impaired hepatic function, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at Visit 1a.
5. Gastric bypass surgery.
6. Known hypersensitivity or allergy to the investigational product or its excipients or to the trial background therapy (i.e., metformin).
7. Contraindication to metformin therapy according to local label, for example:
? Renal disease or renal dysfunction (e.g., as specified by product information
of locally approved metformin)
? Dehydration by clinical judgement of the investigator
? Acute or chronic metabolic acidosis (present condition in patient history)
? Hereditary galactose intolerance.
8. Renal failure or renal impairment (serum creatinine ≥1.5 mg/dL [132 μmol/L]) as
determined at Visit 1a (Screening).
9. Treatment with rosiglitazone, pioglitazone, GLP-1 analogues/mimetics or insulin
within 3 months prior to informed consent.
10. Treatment with anti-obesity drugs (e.g., sibutramine, orlistat, rimonabant) 3 months
prior to informed consent.
11. Alcohol or drug abuse within the 3 months prior to informed consent that would
interfere with trial participation.
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. However, the
use of inhaled steroids (e.g., for asthma, COPD) is not an exclusion as these do not
cause systemic steroid action.
13. Participation in another trial with an investigational drug within 2 months prior to
informed consent.
14. 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. |
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Method of Generating Random Sequence
Modification(s)
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Computer generated randomization |
Method of Concealment
Modification(s)
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Centralized |
Blinding/Masking
Modification(s)
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Participant, Investigator and Outcome Assessor Blinded |
Primary Outcome
Modification(s)
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| Outcome |
TimePoints |
| change in HbA1c from baseline |
6 week and 12 week (visit 4 & 5) |
|
Secondary Outcome
Modification(s)
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| Outcome |
TimePoints |
? Occurrence of relative efficacy response (HbA1c lowering by at least 0.5% after 12 weeks of treatment)
? Change from baseline in HbA1c by visit over time
? Change from baseline in fasting plasma glucose (FPG) after 12 weeks of
treatment
? Change from baseline in FPG by visit over time
? Use of rescue therapy. |
12 weeks |
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Target Sample Size
Modification(s)
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Total Sample Size="451"
Sample Size from India="451"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
Phase of Trial
Modification(s)
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Phase 2 |
Date of First Enrollment (India)
Modification(s)
|
12/11/2009 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
Estimated Duration of Trial
Modification(s)
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Years="1"
Months="0"
Days="0" |
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Recruitment Status of Trial (Global)
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Completed |
| Recruitment Status of Trial (India) |
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Publication Details
Modification(s)
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NONE YET |
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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Brief Summary
Modification(s)
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This is a global trial (France, Morrocco, Italy, Spain, Belgium, Canada, Republic of Korea, Malaysia, India, Netherlands) with Indian traget for 80 patient recruitment. Anticipated first date of enrollement in India is 7 Dec 2009. This randomised, double-blind, multi-national, and placebo-controlled, three parallel groups study will compare linagliptin 2.5 mg twice daily versus 5 mg once daily as add-on to a background therapy of metformin. In total, 451 patients with type 2 diabetes who meet the entry criteria are planned for inclusion in this trial. The randomised treatment will be double-blind within the dose groups of linagliptin (i.e., each patient will receive one active treatment and one placebo to match the alternative active treatment) and placebo (i.e., each patient will receive placebos to match each of the active treatments). Patients with previous oral antidiabetic therapy (e.g., sulphonylureas, meglitinides, DPP-4 inhibitors, α-glucosidase inhibitors) will stop this current antidiabetic therapy (background therapy of metformin will continue) and enter a six-week wash-out phase (4 weeks, followed by a two week open-label placebo run-in phase). Patients pre-treated with metformin alone will undergo a 2-week open-label placebo run-in phase before randomisation. Patients who successfully complete the placebo run-in phase and who still meet the inclusion/exclusion criteria will be randomised to the 12-week treatment phase of the study in which they will receive either 1 of the 2 doses of linagliptin or placebo in addition to background therapy of metformin. |