| CTRI Number |
CTRI/2022/02/040081 [Registered on: 07/02/2022] Trial Registered Prospectively |
| Last Modified On: |
06/10/2022 |
| 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 combination of Azilsartan and Amlodipine Tablets in patients with hypertension." |
|
Scientific Title of Study
|
“A Multicentric, Randomized, Double Blind, Parallel Group, Comparative, Phase III Clinical Study to Evaluate the Efficacy, Safety and Tolerability of FDC of Azilsartan Medoxomil 40 mg plus Amlodipine 5 mg Tablets and FDC of Azilsartan Medoxomil 80 mg plus Amlodipine 5 mg Tablets Versus FDC of Telmisartan 40 mg plus Amlodipine 5 mg Tablets in Patients with Stage 2 Hypertension.†|
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| CR/CT/18/001, Version No.: 02 & Dated Apr 08, 2020 |
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.I.G: 19, H. No. 1-9-25/19,
4th Floor, Above Karur Vysya Bank,
Dr. A.S. Rao Nagar, Hyderabad - 500062,
Telangana, India.
Hyderabad
TELANGANA
500062
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.I.G: 19, H. No. 1-9-25/19,
4th Floor, Above Karur Vysya Bank,
Dr. A.S. Rao Nagar, Hyderabad - 500062,
Telangana, India.
TELANGANA
500062
India |
| Phone |
7989233379 |
| Fax |
|
| Email |
dr.sekhar@clinwave.co.in |
|
Details of Contact Person
Public Query
|
| Name |
Dr Prashant Shirode |
| Designation |
Head - PKPD |
| Affiliation |
Inventia Healthcare Ltd. |
| Address |
Inventia Healthcare Ltd.,
A-214, Road No. 30,
Wagle Industrial Estate,
Thane - 400604, Mumbai,
Maharashtra, India.
Thane
MAHARASHTRA
400604
India |
| Phone |
9916866001 |
| Fax |
|
| Email |
prashant.shirode@inventiahealthcare.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
Inventia Healthcare Ltd |
| Address |
A-214, Road No. 30,
Wagle Industrial Estate,
Thane - 400604, Mumbai,
Maharashtra, India. |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 12 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Hemali Ashish Jha |
Charak Hospital and Research Centre |
Department of Medicine, Ground Floor OPD, Hardoi Road, Dubagga, Lucknow-226003.
Lucknow
UTTAR PRADESH |
8808835455
dr_hemali@yahoo.co.in |
| Dr Peddi Sirisha |
Gandhi Medical College and Hospital |
In Patient Block, 3rd Floor, Department of General Medicine, Gandhi Hospital, Musheerabad, Secunderabd-500003.
Hyderabad
TELANGANA |
9701859566
sirishabhaskar.sirisha@gmail.com |
| Dr Richa Giri |
GSVM Medical College |
Post Graduate Department of Medicine, Kanpur-208002.
Kanpur Nagar
UTTAR PRADESH |
8400331045
krricha227@gmail.com |
| Dr Praphull Deepankar |
Indira Gandhi Institute of Medical Sciences (IGIMS) |
Department of General Medicine,
Sheikhpura, Patna-800014.
Patna
BIHAR |
7011196234
drprafsjh@gmail.com |
| Dr Sanjiv Maheshwari |
Jawahar Lal Nehru (J.L.N) Medical College |
Department of Medicine, Kala Bagh, Ajmer-305001.
Ajmer
RAJASTHAN |
9460479888
doctor.sanjiv@gmail.com |
| Dr Prabhat Kumar Sharma |
Maharaja Agrasen Superspeciality Hospital |
Room No. 109, Basement, Central Spine, Agrasen Aspatal Marg, Sector 7, Vidyadhar Nagar, Jaipur-302039.
Jaipur
RAJASTHAN |
9983995050
pksharma.clinical@gmail.com |
| Dr Raja Bhattacharya |
Medical College and Hospital, Kolkata |
Department of Medicine, MCH Building, 4th Floor, 88
College Street, Kolkata-700073.
Kolkata
WEST BENGAL |
9477305539
rbrbhattacharya@gmail.com |
| Dr M Saitej Reddy |
Osmania Medical College and General Hospital |
Department of Cardiology,
Afzalgunj, Hyderabad-500012.
Hyderabad
TELANGANA |
8555956810
saitejreddy17@gmail.com |
| Dr Vijaykumar Shivajirao Patil |
Prakash Institute of Medical Sciences & Research, Urun-Islampur (PIMS&R) |
Research Room, Islampur Sangli Road, Islampur, Tal-Walwa, Dist.Sangli-415409.
Sangli
MAHARASHTRA |
9371877555
prakashmc.research@gmail.com |
| Dr Vijaykumar Bhagwan Barge |
Rajarshee Chhatrapati Shahu Maharaj GMC and Chhatrapati Pramila Raje General Hospital |
Department of Medicine, Dasara Chowk, Town Hall, Bhausingji Road, Kolhapur-416002.
Kolhapur
MAHARASHTRA |
8080328480
rcsmgmc.research@gmail.com |
| Dr Sagar Vivek Redkar |
Redkar Hospital and Research Centre |
Research Room, Mumbai-Goa Highway, Oshalbag, Village-Dhargal, Tal-Pernem, Goa-403513.
North Goa
GOA |
9158592177
redkar.research@gmail.com |
| Dr Gaurav Singh |
Vatsalya Hospital Multispeciality Center |
Research Room,
S-2/656, C4A Sikraul, Varanasi-221002.
Varanasi
UTTAR PRADESH |
9555112643
drgauravsingh371@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 12 |
| Name of Committee |
Approval Status |
| Ethics Committee, GSVM Medical College |
Approved |
| Institutional Ethics Committee for Human Research Medical College |
Approved |
| Institutional Ethics Committee, Charak Hospital & Research Centre |
Approved |
| Institutional Ethics Committee, Gandhi Medical College/Gandhi Hospital |
Approved |
| Institutional Ethics Committee, Indira Gandhi Institute of Medical Sciences (IGIMS) |
Approved |
| Institutional Ethics Committee, Jawahar Lal Nehru Medical College |
Approved |
| Institutional Ethics Committee, Maharaja Agrasen Superspeciality Hospital |
Approved |
| Institutional Ethics Committee, Osmania Medical College and General Hospital |
Approved |
| Prakash Medical College Institutional Ethics Committee |
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 |
| Vatsalya Ethics Committee |
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 |
| Intervention |
FDC of Azilsartan Medoxomil 40 mg plus Amlodipine 5 mg Tablets |
One tablet once a day orally in the morning after breakfast around same time every day for 12 weeks. |
| Intervention |
FDC of Azilsartan Medoxomil 80 mg plus Amlodipine 5 mg Tablets |
One tablet once a day orally in the morning after breakfast around same time every day for 12 weeks. |
| Comparator Agent |
FDC of Telmisartan 40 mg plus Amlodipine 5 mg Tablets |
One tablet once a day orally in the morning after breakfast around same time every day for 12 weeks. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Male or Female patients between 18 to 65 years of age (both inclusive).
2. Treatment-Naïve patients who are suffering from Stage 2 Hypertension.
3. Patients diagnosed with mean sitting SBP of ≥160 to ≤180 mmHg and mean sitting 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).
4. Patients who are willing to sign informed consent for participation in the study and willing to adhere to all protocol procedures. |
|
| 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. Patients with known case of secondary or malignant hypertension.
4. Patients with evidence of postural hypotension (defined as drop in >20 mg of Hg for systolic blood pressure and >10 mm of Hg for diastolic blood pressure after assuming the standing posture from supine or sitting position).
5. Patients with known case of symptomatic congestive heart failure, unstable angina pectoris, sinus node dysfunction and any clinically significant cardiac arrhythmias.
6. Patient who has had myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery in last 1 year.
7. Patients with known case of stroke.
8. Patients with abnormal eGFR (<60 mL/min/1.73 m2).
9. Patients with known case of bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, post-renal transplant or with only one functioning kidney.
10. Patients with hyponatremia as per blood biochemistry results at screening.
11. Patients with hyperkalemia and hypokalemia as per blood biochemistry results at screening.
12. Patients with clinically significant impaired hepatic function [SGOT & SGPT more than 2.5X the UNL and Total bilirubin more than 1.5X the UNL].
13. Patients with abnormal thyroid function test (TSH).
14. Patients with known case of type 1 diabetes and 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. Patients with medical history of any oncological conditions.
16. Patients with known case of epileptic seizures.
17. Patients with clinical history of bipolar disorder.
18. Patients with known case of HIV, hepatitis B & C.
19. Pregnant or lactating women.
20. Women of child bearing potential who do not agree to remain abstinent or use medically acceptable methods of contraception [which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, some IUDs, sexual abstinence or vasectomised partner, during the study therapy.
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
|
Pre-numbered or coded identical Containers |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Change from baseline in mean sitting systolic blood pressure (MSSBP) at the end of study (12 weeks). |
At Screening Visit (Visit 1),
Visit 3 / Day 14,
Visit 4 / Day 28,
Visit 5 / Day 56 and
Visit 6 / Day 84 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Change from baseline in mean sitting diastolic blood pressure (MSDBP) at the end of study (12 weeks). |
At Screening Visit (Visit 1),
Visit 3 / Day 14,
Visit 4 / Day 28,
Visit 5 / Day 56 and
Visit 6 / Day 84 |
| Mean change in Ambulatory Blood Pressure (Mean 24 hour SBP and DBP) from baseline to the end of study (12 weeks). |
At Screening Visit (Visit 1) and
Visit 6 / Day 84 |
| The assessment of safety of Patients (comparison of incidence of treatment emergent adverse event (TEAE)). |
At Visit 3 / Day 14,
Visit 4 / Day 28,
Visit 5 / Day 56 and
Visit 6 / Day 84 |
| The assessment of tolerability of Investigational Product will be based on incidence of AEs and SAEs and Changes in laboratory values. |
At Visit 3 / Day 14,
Visit 4 / Day 28,
Visit 5 / Day 56 and
Visit 6 / Day 84 |
|
|
Target Sample Size
|
Total Sample Size="246"
Sample Size from India="246"
Final Enrollment numbers achieved (Total)= "309"
Final Enrollment numbers achieved (India)="309" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
10/02/2022 |
| Date of Study Completion (India) |
19/07/2022 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
NIL |
|
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 multicentric, randomized, double blind, parallel group, comparative,
phase III clinical study to evaluate the efficacy, safety and tolerability of fixed
dose combination of Azilsartan Medoxomil 40 mg plus Amlodipine 5 mg Tablets and
fixed dose combination of Azilsartan Medoxomil 80 mg plus Amlodipine 5 mg
Tablets versus fixed dose combination of Telmisartan 40 mg plus Amlodipine 5 mg
Tablets in patients with stage 2 hypertension.
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). The
purpose of screening is to obtain informed consent and to establish protocol
eligibility. Informed consent will be obtained after the study has been fully
explained to each patient and before the conduct of any screening procedures or
assessments. During this screening period, patients who are willing to give
consent will be evaluated for all the eligibility criteria.
Eligible
patients clinically diagnosed with stage 2 hypertension and who are between 18
to 65 years of age will be considered for the study. Patients fulfilling all
the inclusion criteria and none of the exclusion criteria will be confirmed and
randomized on randomization visit/visit 2 and that day will be considered as
day 1.
After confirming the inclusion/exclusion criteria the patient
will be provided with study medication and drug dosing card at randomization
visit. Blood pressure measurement will be standardized at all sites by
providing validated automated blood pressure machine.
Patients
will be assigned either of the three treatment arms i.e., Arm A or Arm B or Arm
C consisting of FDC of Azilsartan Medoxomil 40 mg plus Amlodipine 5 mg Tablets or
FDC of Azilsartan Medoxomil 80 mg plus Amlodipine 5 mg Tablets or FDC of
Telmisartan 40 mg plus Amlodipine 5 mg Tablets in a ratio of 1:1:1.
The
recommended dose of test product is one tablet once a day in the morning after
breakfast for 12 weeks. Each tablet is to be taken orally with water around
same time every day during entire clinical trial period.
All patients will be
assessed for primary efficacy endpoint and secondary efficacy end points. For patients
who are discontinued due to lack of efficacy last SBP & DBP reading at the
time of discontinuation will be considered as end point. Patients will be
assessed for the safety and tolerability of the study medications. |