| CTRI Number |
CTRI/2020/03/023708 [Registered on: 02/03/2020] Trial Registered Prospectively |
| Last Modified On: |
12/07/2021 |
| 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 Phase III, Clinical Trial to Evaluate the safety, tolerability and efficacy of 2 Fixed dose combinations of Azelnidipine and Chlorthalidone when compared with fixed dose combination of Amlodipine and Hydrochlorothiazide in patients with Stage II hypertension. |
|
Scientific Title of Study
|
A Phase III Randomized, Double blind, Parallel Group Comparative Clinical Trial to Evaluate the safety, tolerability and efficacy of 2 Fixed dose combinations of Azelnidipine and Chlorthalidone when compared with fixed dose combination of Amlodipine and Hydrochlorothiazide in patients with Stage II hypertension. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Devesh Kumar |
| Designation |
Director |
| Affiliation |
Innovate Research |
| Address |
Basement Office 1, Building D13, Sector 3 Noida
Gautam Buddha Nagar
UTTAR PRADESH
201301
India |
| Phone |
|
| Fax |
|
| Email |
Devesh.kumar@innovate-research.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Devesh Kumar |
| Designation |
Director |
| Affiliation |
Innovate Research |
| Address |
Basement Office 1, Building D13, Sector 3 Noida
Gautam Buddha Nagar
UTTAR PRADESH
201301
India |
| Phone |
|
| Fax |
|
| Email |
Devesh.kumar@innovate-research.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Devesh Kumar |
| Designation |
Director |
| Affiliation |
Innovate Research |
| Address |
Basement Office 1, Building D13, Sector 3 Noida
Gautam Buddha Nagar
UTTAR PRADESH
201301
India |
| Phone |
|
| Fax |
|
| Email |
Devesh.kumar@innovate-research.com |
|
|
Source of Monetary or Material Support
|
| Synokem Pharmaceuticals Ltd |
|
|
Primary Sponsor
|
| Name |
Synokem Pharmaceuticals Ltd |
| Address |
Plot No.35-36, Sector-6A, Integrated Industrial Estate ( SIDCUL ), Ranipur ( BHEL ), Haridwar - 249403. |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 6 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Narendra Deo |
Balrampur Hospital |
Kaiserbagh
Lucknow - 226018
Lucknow
UTTAR PRADESH |
9415059023
drnarendradeo2008@gmail.com |
| Dr Manoj Gupta |
Health Point Hospital |
21 Prannath Pandit Street Kolkata
Kolkata
WEST BENGAL |
0336292206001
manojsrmc@gmail.com |
| Dr Sanjiv Maheshwari |
Jawahar Lal Nehru Medical College & Attached Hospitals |
Kala Bagh, Ajmer - 305001
Ajmer
RAJASTHAN |
9460479888
doctor.sanjiv@gmail.com |
| Dr S Narasinga Rao |
King George Hospital |
Visakhapatnam
Visakhapatnam
ANDHRA PRADESH |
9848136704
drnarasingaraoresearch@gmail.com |
| Dr Vineet Shukla |
Lakshya Cancer Hospital |
Hardoi Road, Sikrauri, Uttar Pradesh 226003
Lucknow
UTTAR PRADESH |
9554540710
lakshya.hospital2015@gmail.com |
| Dr Dipti Gupta |
Panchsheel Hospital Pvt. Ltd. |
C-3/63A, 64A, Yamuna Vihar Opp. Gokulpuri police station, Delhi -110053
North East
DELHI |
011-43541234
dr.dipti16@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 6 |
| Name of Committee |
Approval Status |
| Ethics Committee Panchsheel Hospital |
Approved |
| Healthpoint Ethics Committee |
Approved |
| Institutional Ethics Committee, Balrampur Hospital, Lucknow |
Approved |
| Institutional Ethics Committee, Jawahar Lal Nehru Medical College & Attached Hospital, Ajmer |
Approved |
| Institutional Ethics Committee, King George Hospital, Visakhapatnam |
Approved |
| Institutional Ethics Committee, Lakshya Cancer Hospital, Lucknow |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: I10||Essential (primary) hypertension, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Amlodipine and Hydrochlorothiazide |
A fixed dose combination of Amlodipine 5 mg + Hydrochlorothiazide 12.5 mg
Dosage- 1 tablet to be taken daily, orally with plain water after meal, daily for 84 days.
|
| Intervention |
Azelnidipine and Chlorthalidone |
A) Azelnidipine 8mg + Chlorthalidone 6.25 mg and
B) Azelnidipine 8mg + Chlorthalidone 12.5 mg
Dosage- 1 tablet to be taken daily, orally with plain water after meal, daily for 84 days.
|
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
Male or female subjects aged between 18 and 65 years (both inclusive).
2. Treatment naïve subjects diagnosed with stage 2 hypertension having mean seated SBP of ≥160 to ≤180 mmHg and mean seated DBP ≥100 to ≤110 mmHg (3 readings will be taken by validated automated blood pressure machine in sitting position, first reading will be taken after 15 min. rest and subsequent two readings will be recorded at the interval of 2 min. each).
3. Subjects with ability to understand and provide written informed consent form, which must have been obtained prior to screening.
4. Subjects willing to comply with the protocol requirements.
|
|
| ExclusionCriteria |
| Details |
1. Suspected hypersensitivity to either of the study medications or any of the ingredients of the formulation.
2. Has clinical laboratory evaluations (including biochemistry and hematology) are not within the reference range for the testing laboratory and the results are deemed clinically significant by the investigator.
3. Subjects with known case of Secondary or Malignant Hypertension.
4. Subjects with evidence of postural hypotension (defined as drop in >20 mmHg for systolic blood pressure and >10 mmHg for diastolic blood pressure after assuming the standing posture from supine or sitting position).
5. Subjects with known case of symptomatic congestive heart failure, unstable angina pectoris, sinus node dysfunction and any clinically significant cardiac arrhythmias.
6. Subject who has had myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery in last 1 year.
7. Subjects with known case of Stroke.
8. Subjects with abnormal eGFR (<60 mL/min/1.73 m2).
9. Subjects with known case of bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, post-renal transplant or with only one functioning kidney. 1
10. Subjects with hyponatremia as per blood biochemistry results at screening.
11. Subjects with hyperkalemia and hypokalemia as per blood biochemistry results at screening.
12. Subjects with abnormal Liver Function Tests (Total bilirubin, SGOT & SGPT) with values more than 2.5 times the upper limit of normal.
13. Subjects with abnormal Thyroid Function Test (TSH).
14. Subjects with Type 1 diabetes & Type 2 diabetes mellitus whose diabetes has not been stable and controlled for the previous three months and with HbA1c value greater than 8%.
15. Subjects with medical history of Oncological Conditions since last 5 years.
16. Subjects with known case of Epileptic seizures.
17. Subjects with clinical history of bipolar disorder.
18. Subjects with known case of HIV, Hepatitis B & C.
19. Female subjects who are pregnant or lactating or planning to become pregnant during the study period.
20. Females who are not ready to use acceptable contraceptive methods during the course of study.
21. Concurrent participation in another clinical trial or any investigational therapy within 90 days prior to signing informed consent.
22. Currently taking prohibited medications(s) listed and inability/unwillingness to discontinue them for the entire study period.
23. Suspected inability or unwillingness to comply with the study procedures. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
On-site computer system |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| The safety and tolerability of the FDCs will be assessed by the Clinical AEs, including laboratory abnormalities |
Day 1, Week 2, Week 4, Week 8 and Week 12 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1. Difference in mean change in SBP from baseline at the end of 12 weeks between each FDC group
2. Difference in mean change in DBP from baseline at the end of 12 weeks between each FDC group
|
Testing Intervals: Day 1, Week 2, Week 4, Week 8 and Week 12 |
|
|
Target Sample Size
|
Total Sample Size="210"
Sample Size from India="210"
Final Enrollment numbers achieved (Total)= "210"
Final Enrollment numbers achieved (India)="210" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
05/03/2020 |
| Date of Study Completion (India) |
12/12/2020 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="0"
Months="9"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
Not Applicable |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Hypertension (HTN) is a public health menace contributing up to 45% of cardiovascular diseases (CVD) deaths and 51% of stroke deaths. [1] In India up to 33% of urban and 25% of the rural population are afflicted with the disease. [2] Attainment of blood pressure (BP) goals in the population at large is a major challenge and area of focus of health systems worldwide. Over the years, BP targets have been continuously redefined as the armamentarium of drugs has expanded. The recently published the American College of Cardiology/American Heart Association (ACC/AHA) 2017 HTN guidelines advocate a paradigm shift in the way we manage abnormal BP. |