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A 24-week, Randomized, Double-blind, Active-controlled, Parallel Group Trial to Assess the Superiority of Oral Linagliptin and Metformin Compared to Linagliptin Monotherapy in Newly Diagnosed, Treatment-naïve, Uncontrolled Type 2 Diabetes Mellitus Patient

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SLCTR Registration Number

SLCTR/2012/004


Date of Registration

18 Apr 2012

The date of last modification

Mar 03, 2019


Trial Status



Application Summary


Scientific Title of Trial

A 24-week, Randomized, Double-blind, Active-controlled, Parallel Group Trial to Assess the Superiority of Oral Linagliptin and Metformin Compared to Linagliptin Monotherapy in Newly Diagnosed, Treatment-naïve, Uncontrolled Type 2 Diabetes Mellitus Patient


Public Title of Trial

Linaglitpin and Metformin Versus Linagliptin in Newly Diagnosed, Untreated Type 2 Diabetes


Disease or Health Condition(s) Studied

Diabetes Mellitus, Type 2


Scientific Acronym

None


Public Acronym

None


Brief title

Linaglitpin and Metformin Versus Linagliptin in Newly Diagnosed, Untreated Type 2 Diabetes


Universal Trial Number

.None


Any other number(s) assigned to the trial and issuing authority

NCT01512979 (clinicaltrials.gov), CTRI – REF/2012/03/003394, Eudra-CT-2011-004158-24


Trial Details


What is the research question being addressed?

To determine whether initial combination of linagliptin and metformin compared to linagliptin alone for 6 months is effective in newly diagnosed, treatment-naïve patients with Type 2 Diabetes. ?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Double blinded


Control

Active


Assignment

Parallel


Purpose

Treatment


Study Phase

Phase 3


Intervention(s) planned

Drug: metformin - 1000 mg to 2000 mg per day, Drug: linagliptin - 5 mg daily, Drug: linagliptin medium dose - 5 mg daily, Drug: metformin placebo - placebo daily, Drug: metformin placebo - 0 to 2 tablets daily


Inclusion criteria

1 Patients must sign and date an Informed Consent consistent with International Conference on Harmonisation / Good Clinical Practice guidelines and local regulations prior to any evaluation and participation in the trial. 2. Male and female patients, 18 years of age or older at Visit 1 (Screen), with newly diagnosed (less than 12 months prior to Screen) Type 2 Diabetes Mellitus. 3. Patients who are treatment-naïve, defined as absence of any oral antidiabetic therapy, injectable glucagon-like peptide-1 agonist/ analogue, or insulin, and uncontrolled for the 12 weeks prior to randomisation. 4. Glycated haemoglobin (HbA1c) between 8.5% and 12.0% at Visit 1 (Screen). 5. Body Mass Index (BMI) of 45 kg/m2 or less at Visit 1 (Screen) 6. In the investigators opinion, patients must be reliable, honest, compliant, and agree to cooperate with all planned future trial evaluations as explained in detail during the informed consent process and to be able to perform them.


Exclusion criteria

Patients with, who are, who have, or who have had: 1.Acute coronary syndrome (NSTEMI, STEMI, and unstable angina), stroke or transient ischemic attack within 3 months prior to informed consent. 2. Liver disease determined during Screen and/or Run-In Period, defined by a serum level above 3 times the upper limit of normal (ULN) in any of the following: alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase. Gilbert-Meulengracht syndrome will be permitted. 3. Impaired renal function, defined as calculated creatinine clearance of less than 60 milliliters per minute (< 60 mL/min), by the Cockcroft-Gault Equation, determined during Screen and/or Run-In Period. 4. Bariatric, gastric bypass, and other gastrointestinal surgeries ((including all types of gastric banding and/or LapBand) within the past two years. 5. Medical History of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years. 6. Medical History of pancreatitis. 7. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells (e.g., malaria, babesiosis, haemolytic anaemia). 8. Any contraindication to metformin and/or linagliptin therapies, according to local labels. 9. Treatment with anti-obesity drugs, including over-the-counter drugs such as Alli (orlistat), 3 months prior to informed consent or any other treatment at the time of screening (i.e., surgery, aggressive diet regimen, etc.) leading to unstable body weight. 10.Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except Type 2 Diabetes Mellitus. 11. Pre-menopausal women (last menstruation of 1 year or less prior to informed consent) who are nursing or pregnant, 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 trial and do not agree to submit to periodic pregnancy testing during participation in the trial. Note: Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems, oral, implantable, intra-vaginal, or injectable contraceptives, Essure micro-inserts placed more than six months prior to Screen Visit, complete sexual abstinence (if acceptable by local authorities), double barrier method (e.g., diaphragm or condom and spermicide), and vasectomised partner. 12. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance to trial procedures or study medication intake in the opinion of the investigator. 13. Participation in another trial with an investigational drug within 2 months prior to informed consent. 14. Any other clinical condition that would jeopardize patient safety while participating in this clinical trial in the opinion of the Investigator. 15. Inability to commit to regular overnight fasting of at least 10 hours duration and attendance to study site visits between 07:00 and 11:00 ante meridiem (a.m.).



Primary outcome(s)

1.

Change from baseline in HbA1c

[

Time Frame: 24 weeks

]

Secondary outcome(s)

1.

Change from baseline in FPG after 24 weeks of treatment

[

Time Frame: 24 weeks

]
2.

Change from baseline in HbA1c by visit over time

[

Time Frame: 6, 12, 18 and 24 weeks

]
3.

Occurrence of relative efficacy response (HbA1c lowering by a least 0.5% after 24 weeks of treatment)

[

Time Frame: 24 weeks

]
4.

Occurrence of relative efficacy response (HbA1c lowering by a least 1.0% after 24 weeks of treatment)

[

Time Frame: 24 weeks

]
5.

Occurrence of treat to target efficacy response (HbA1c <7.0%) after 24 weeks of treatment

[

Time Frame: 24 weeks

]
6.

Change from baseline in FPG by visit over time

[

Time Frame: 6, 12, 18 and 24 weeks

]
7.

Body weight: Change from baseline to Week 24

[

Time Frame: 24 weeks

]
8.

HOMA indices for insulin resistance and insulin secretion (at baseline and Week 24)

[

Time Frame: after 24 weeks

]

Target number/sample size

50


Countries of recruitment

Canada, Estonia, Guatemala, India, Israel, Malaysia, Mexico, Philippines, Poland, Russian Federation, Slovakia, Sri Lanka, Thailand, Ukraine, United States


Anticipated start date

2012-05-04


Anticipated end date

2013-04-30


Date of first enrollment

2012-05-23


Date of study completion


Recruitment status

Complete: follow up complete


Funding source

Boehringer Ingelheim India (Pvt) Ltd


Regulatory approvals



State of Ethics Review Approval


Status

Approved


Date of Approval

2012-01-18


Approval number

Not Available


Details of Ethics Review Committee

Name: Ethics Review Committee, Faculty of Medicine, University of Kelaniya
Institutional Address:PO Box 6, Thalagolla Road, Ragama Sri Lanka
Telephone:+94-11-2961267
Email: erckelaniya@gmail.com

Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Ms. Anjalli Ajgaonke
Team Leader – Clinical Operations
Boehringer Ingelheim India Pvt Ltd, 1102, Hallmark Business Plaza, Near Gurunanak Hospital, Bandra (E), Mumbai 400051

912226456477 912226456163

anjalli.ajgaonker.ext@boehringer-ingelheim.com

Contact Person for Public Queries

Prof. Dr Asita De Silva
Director
Clinical Trials Unit, Faculty of Medicine, University of Kelaniya
94112662166 94112665300


asitades@gmail.com


Primary study sponsor/organization

Boehringer Ingelheim India (Pvt) Ltd

1102, 11th Floor, Hallmark Business Plaza, Near Gurunanak Hospital, Bandra (E), Mumbai 400051, India
912226456477 912226456163

partha.gokhale@boehringer-ingelheim.com
www.boehringer-ingelheim.com

Secondary study sponsor (If any)

None





Trial Completion details


Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?


IPD sharing plan description


Study protocol available


Protocol version and date

Not Available


Protocol URL

Not Available


Results summary available

No


Date of posting results


Date of study completion


Final sample size


Date of first publication


Link to results


Brief summary of results