CTRI/2023/04/051711 [Registered on: 18/04/2023] Trial Registered Prospectively
Last Modified On:
28/03/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A clinical study to assess the efficacy and safety of Linagliptin plus Glimepiride Tablets in patients with diabetes.
Scientific Title of Study
“A Phase III, Randomized, Double Blind, Active Controlled, Prospective, Parallel Group, Comparative, Multicentric Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Dose Combination of Linagliptin plus Glimepiride Tablets Versus Linagliptin Tablets in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Monotherapy.â€
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CT/2023/04, Version No.: 00 and Dated Jan 18, 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Rajasekhara Reddy Tamma
Designation
Managing Director
Affiliation
Clinwave Research Pvt. Ltd.
Address
Clinwave Research Pvt. Ltd.,
# H. No.: 4-32-41/13, Plot No.: 38,
Kamala Prasanna Nagar, Near Ramalayam Temple,
Kukatpally.
Hyderabad TELANGANA 500072 India
Phone
7989233379
Fax
Email
dr.sekhar@clinwave.co.in
Details of Contact Person Scientific Query
Name
Dr Rajasekhara Reddy Tamma
Designation
Managing Director
Affiliation
Clinwave Research Pvt. Ltd.
Address
Clinwave Research Pvt. Ltd.,
# H. No.: 4-32-41/13, Plot No.: 38,
Kamala Prasanna Nagar, Near Ramalayam Temple,
Kukatpally.
Institutional Ethics Committee, Visakha Institute of Medical Sciences (VIMS)
Approved
North East Healthcare Private Limited, W Pratiksha Hospital
Approved
Rajarshee Chhatrapati Shahu Maharaj Govt. Medical College and Chhatrapati Pramila Raje General Hospital, Kolhapur Institutional Ethics Committee 2 (RCSMGMCIEC2)
Approved
Redkar Hospital Institutional Ethics Committee (RHIEC), Redkar Hospital and Research Centre
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: E119||Type 2 diabetes mellitus without complications,
Intervention / Comparator Agent
Type
Name
Details
Intervention
FDC of Linagliptin 5 mg plus Glimepiride 1 mg Tablets
One Tablet of FDC of Linagliptin 5 mg plus Glimepiride 1 mg Tablets, once daily 15-30 minutes before meal orally, swallowed with water in the morning preferably same time every day for 16 weeks.
Treatment Period: 16 weeks
Intervention
FDC of Linagliptin 5 mg plus Glimepiride 2 mg Tablets
One Tablet of FDC of Linagliptin 5 mg plus Glimepiride 2 mg Tablets, once daily 15-30 minutes before meal orally, swallowed with water in the morning preferably same time every day for 16 weeks.
Treatment Period: 16 weeks
Comparator Agent
Linagliptin Tablets 5 mg
One Tablet of Linagliptin Tablets 5 mg, once daily 15-30 minutes before meal orally, swallowed with water in the morning preferably same time every day for 16 weeks.
Treatment Period: 16 weeks
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or female patients aged between 18 to 65 years (both inclusive) with diagnosis of type 2 diabetes mellitus.
2. Patients, along with diet and exercise control, additionally on stable total daily dose of Metformin Hydrochloride ≥ 1500 mg for at least 8 weeks prior to screening.
3. Patients having inadequate glycemic control defined as glycosylated hemoglobin (HbA1c) levels of ≥ 8.0% to ≤ 11.0% at screening visit.
4. Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study. WOCBP must have a negative urine pregnancy test at screening / baseline visit.
5. Patients with no abnormality on 12-lead ECG at screening / baseline visit.
6. Patient with ability to understand and provide written informed consent form, which must have been obtained prior to screening.
7. Patients willing to comply with the protocol requirements.
ExclusionCriteria
Details
1. Patients with a history of type 1 diabetes mellitus or secondary diabetes mellitus or diabetes insipidus.
2. Patients with a history of metabolic acidosis or diabetic ketoacidosis.
3. Patients with Fasting Plasma Glucose (FPG) > 270 mg/dL at screening.
4. Patients with the Body Mass Index (BMI) > 45.0 kg/m2 at screening.
5. Patients with Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 [using the Modification of Diet in Renal Disease (MDRD) equation] at screening.
6. Patients with clinically significant impaired hepatic function (SGOT & SGPT more than 3X the ULN and/or Total bilirubin more than 1.5X the ULN) at screening.
7. Patients with a history of congestive heart failure defined as New York Heart Association (NYHA) class III/IV, unstable or acute congestive heart failure.
8. Patients with significant cardiovascular history defined as: myocardial infarction, unstable angina pectoris, transient ischemic attack, unstable or previously undiagnosed arrhythmia, cardiac surgery or revascularization (coronary angioplasty or bypass grafts), or cerebrovascular accident.
9. Patients with history of sustained and clinically relevant ventricular arrhythmia.
10. Patients with history or currently suffering with severe and disabling arthralgia.
11. Patients with history or currently suffering with bullous pemphigoid requiring hospitalization and taking DPP-4 inhibitors.
12. Patients with history of inflammatory bowel disease or intestinal ulcers or chronic enteric diseases related to digestion and absorption.
13. Patients with any condition (e.g., infection, trauma and surgery) which require insulin therapy at the time of screening or during the study period.
14. Patients with uncontrolled hypertension with sitting systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg at screening.
15. Any abnormality on 12-lead ECG at screening that in the opinion of the investigator is clinically significant and is judged as potential risk for patient’s participation in the study.
16. Patients who are accepting treatments of arrhythmias.
17. Patients with a history of anaemia or haemoglobinopathy and/or haemoglobin < 10 g/dL for men; haemoglobin < 9 g/dL for women at screening.
18. Patients with intolerance, contraindication or potential allergy/hypersensitivity to DPP4 inhibitors.
19. Female patients who are pregnant or breast-feeding or expecting to conceive within the projected duration of the study.
20. Female patients who are of childbearing potential and who are neither surgically sterilized nor willing to use reliable contraceptive methods (like hormonal, barrier methods or intrauterine device).
21. Patients with history of any malignancy.
22. Patients with history of infection with hepatitis B, hepatitis C or HIV.
23. Patients with donation or transfusion of blood, plasma, or platelets within the past 3 months prior to screening.
24. Patients with a history of substance abuse or dependence that in the opinion of the Investigator is considered to interfere with the patient’s participation in the study.
25. Patients with concurrent participation in another clinical trial or any investigational therapy within 30 days prior to signing informed consent.
26. Patients currently taking any of the prohibited medications(s) and inability/unwillingness to discontinue them for the entire study period.
27. Suspected inability or unwillingness to comply with the study procedures.
28. Patient with any condition which, in the judgment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk to the patient.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Mean change in glycosylated haemoglobin (HbA1c) from baseline to end of the study visit (week 16).
At Screening or baseline visit (Visit 1),
Visit 5 [Week 12/Day 84(±3)] and
Visit 6 [Week 16/Day 112(±3)].
Secondary Outcome
Outcome
TimePoints
Mean change in fasting plasma glucose (FPG) from baseline to end of the study visit (week 16).
At Screening or baseline visit (Visit 1),
Visit 3 [Week 2/Day 14(±3)],
Visit 4 [Week 6/Day 42(±3)],
Visit 5 [Week 12/Day 84(±3)] and
Visit 6 [Week 16/Day112 (±3)].
Mean change in 2-hr post prandial plasma glucose (2-hr PPG) from baseline to end of the study visit (week 16).
At Screening or baseline visit (Visit 1),
Visit 3 [Week 2/Day 14(±3)],
Visit 4 [Week 6/Day 42(±3)],
Visit 5 [Week 12/Day 84(±3)] and
Visit 6 [Week 16/Day112 (±3)].
Proportion of patients achieving a therapeutic glycemic response, defined as HbA1c 7% at the end of the study visit (week 16).
At Visit 6 [Week 16/Day112 (±3)].
Number of patients requiring hypoglycemia management during the study.
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This
trial is a phase III, randomized, double blind, active controlled, prospective,
parallel group, comparative, multicentric clinical study to evaluate the
efficacy, safety and tolerability of fixed dose combination of Linagliptin plus
Glimepiride Tablets versus Linagliptin Tablets in patients with type 2 diabetes
mellitus inadequately controlled on Metformin monotherapy.
Patients
who are willing and able to participate in the study will sign and date the
Informed Consent Form on the day of screening / baseline visit (Visit 1).
During this screening period, patients who are willing to give consent will be
evaluated for all the eligibility criteria. Eligible patients (male or female) aged
between 18 to 65 years (both inclusive), along with diet and exercise control,
additionally on stable total daily dose of Metformin Hydrochloride ≥ 1500 mg
for at least 8 weeks prior to screening and glycosylated hemoglobin (HbA1c)
levels of ≥ 8.0% to ≤ 11.0% will be considered for the study.
After confirming the inclusion/exclusion criteria the
subject will be randomized and provided with study medication at randomization
visit. Subjects will be provided with patient diary at randomization visit,
which need to be brought along with in each subsequent visit till the last
visit. Follow up visits will be done on week 2/day 14(±3), week 6/day 42(±3), week
12/day 84(±3) and week 16/day 112(±3) (Final Visit) of treatment to assess efficacy
and safety.
Patients will be assigned to either of the three arms
i.e., Arm A or Arm B or Arm C consisting of FDC of Linagliptin 5 mg +
Glimepiride 1 mg Tablets or FDC of Linagliptin 5 mg + Glimepiride 2 mg Tablets
or Linagliptin Tablets 5 mg. Metformin Tablets ≥ 1500 mg/day will be continued throughout the
study period (16 weeks).