CTRI/2021/03/032140 [Registered on: 19/03/2021] Trial Registered Prospectively
Last Modified On:
20/07/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Crossover Trial
Public Title of Study
A bioequivalence study of Efonidipine 40 mg and Chlorthalidone 12.5 mg tablet combination in
healthy adults.
Scientific Title of Study
An open label, balanced, randomized, two-treatment, two-sequence, two-period, single-dose, truncated (only for chlorthalidone) crossover oral bioequivalence study of test product, fixed dose combination of Efonidipine HCl ethanolate 40 mg and Chlorthalidone 12.5 mg tablets of Zuventus Healthcare Limited, India with reference products, Efnocar 40 (Efonidipine HCl ethanolate 40 mg) tablets, manufactured by Zuventus Healthcare Limited, India and CTD®-12.5 (Chlorthalidone 12.5 mg) tablets, manufactured by Ipca Laboratories Limited, India in normal, healthy, adult, human subjects under fasting conditions.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
20-242 (Ver No. 01, dated: 03.11.2020)
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Bhupesh Dewan
Designation
Director- Medical Services
Affiliation
Zuventus Healthcare Limited
Address
3101, Department of Medical Services, C wing, Oberoi Garden
Estate, Chandivali, Andheri (E), Mumbai
Mumbai
MAHARASHTRA
400072
India
Mumbai MAHARASHTRA 400072 India
Phone
022-30610000
Fax
Email
Bhupesh.Dewan@zuventus.com
Details of Contact Person Scientific Query
Name
Dr Suraj Kumar K
Designation
Principal Investigator
Affiliation
Jeevan Scientific Technology Ltd
Address
Clinical Pharmacology Center, Clinical Department, Clinical
Research Division, 4th Floor, B-17, TIE, Phase II, Balanagar,
Hyderabad
Hyderabad TELANGANA 500037 India
Phone
040-67364700
Fax
Email
suraj.katpali@jeevanscientific.com
Details of Contact Person Public Query
Name
Dr Bhupesh Dewan
Designation
Director- Medical Services
Affiliation
Zuventus Healthcare Limited
Address
3101, Department of Medical Services, C wing, Oberoi Garden
Estate, Chandivali, Andheri (E), Mumbai
Mumbai
MAHARASHTRA
400072
India
Clinical Pharmacology Center, Clinical Department, Clinical Research Division, 4th Floor, B-17, TIE, Phase II, Balanagar Hyderabad Hyderabad TELANGANA
4067364700
suraj.katpali@jeevanscientific.com
Details of Ethics Committee
No of Ethics Committees= 1
Name of Committee
Approval Status
Vasavi Medical & Research Centre
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Healthy Human Volunteers
Normal, healthy, adult, human subjects under fasting conditions.
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
CTD®-12.5 (Chlorthalidone 12.5 mg) tablets, manufactured by Ipca Laboratories Limited, India
1 tablet as a single oral dose of reference product will be administered (as per randomization) with 240 ml of water in sitting posture.
Comparator Agent
Efnocar 40 (efonidipine HCl ethanolate 40 mg) tablet manufactured by Zuventus
Healthcare Limited, India
1 tablet as a single oral dose of reference product will be administered (as per randomization) with 240 ml of water in sitting posture.
Intervention
Fixed dose combination of Efonidipine HCl ethanolate 40 mg and Chlorthalidone 12.5 mg tablets of Zuventus Healthcare Limited, India
1 tablet as a single oral dose of intervention product will be administered (as per randomization) with 240 ml of water in sitting posture.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
45.00 Year(s)
Gender
Both
Details
1. Healthy human subjects between 18-45 years of age (including both) and weight ≥ 50 Kg (BMI 18.5 to 24.9 kg/m² (including both)).
2. Acceptable findings during registration and screening including, medical history, physical examination, laboratory evaluations, 12- lead ECG and Chest X-Ray (postero-anterior view).
3. Values within normal ranges for laboratory parameters upon evaluation by the Investigator or Physician for any of the following tests.
4. Subjects able to communicate effectively.
5. Subjects willing to give written informed consent and adhere to all the requirements of this protocol.
6. Subject willing to abstain from all kinds of alcoholic beverages, grapefruit/caffeine/xanthine containing foods or juices from at least 72.00 hours prior to admission until the last blood sample collection in each study period.
7. Must be non-smokers or ex-smokers: An ex-smoker is defined as someone who completely stopped smoking for at least 6 months before Day 1 (first dosing) of Period-I of this study.
8. Female subjects:
ï‚· Postmenopausal for at least 1 year or
ï‚· Surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy has been performed on the subject) or
ï‚· Female of childbearing potential practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as condoms, foams, jellies, diaphragm, and intrauterine device (IUD) or abstinence.
ExclusionCriteria
Details
1. Subjects having contraindication or hypersensitivity (e.g., anaphylaxis) to Efonidipine and Chlorthalidone or related group of drugs or any of its excipients.
2. A history or presence of significant asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs, seizures, diabetes, migraine, hypertension, cardiovascular, pulmonary, neurological or psychiatric disease/disorder, dermatological, endocrine, immunological, hepatic, renal, hematopoietic, gastrointestinal, ongoing infectious diseases, or any other significant abnormality as evidenced by medical history and physical examination or according to the opinion of the physician.
3. History or presence of gastrointestinal (GI) inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine.
4. History or evidence of exfoliative dermatitis, Stevens - Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).
5. Any known enzyme inducing or inhibiting drug taken within 30 days before the study.
6. Participation in a drug research study within 90 days prior to dosing of this study.
7. Blood loss or whole blood donation within 90 days prior to drug administration.
8. Consumption of high caffeine (more than 5 cups of coffee or tea/day).
9. History of addiction to any recreational drug or drug dependence.
10. An unusual or abnormal diet, for whatever reason within 48.00 hours prior to admission of each period, e.g. fasting due to religious reasons.
11. History of dehydration from diarrhea, vomiting or any other reason within a period of 72.00 hours prior to study admission of each period.
12. Positive results for drugs of abuse (benzodiazepines, cocaine, opioids, amphetamines, cannabinoids and barbiturates) in urine during the study admission of each period.
13. Positive results for alcohol breathe analysis during the study admission of each period.
14. History of pre-existing bleeding disorder.
15. Difficulty in swallowing solids like tablets.
16. Difficulty with donating blood.
17. Systolic blood pressure less than 120 mm Hg or more than 140 mm Hg.
18. Diastolic blood pressure less than 70 mm Hg or more than 90 mm Hg.
19. Pulse rate less than 60 beats/minute or more than 100 beats/minute.
20. Use of any prescribed medication or OTC medicinal products during last two weeks preceding the first dosing.
21. Female subjects demonstrating a positive pregnancy screen.
22. Female volunteer who is pregnant, currently breast-feeding.
23. Female volunteer who has used implanted or injected hormonal contraceptives anytime during the 6 months prior to study or used hormonal contraceptives within 14 days before dosing.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pharmacy-controlled Randomization
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Pharmacokinetic parameters Cmax, AUC0-72hr/AUC0-t and AUC0-inf of Efonidipine and Chlorthalidone from the test product to that of reference product will be assessed.
Pre-dose (00.00 hour) and 00.50, 01.00, 01.25, 01.50, 01.75, 02.00, 02.50, 03.00, 03.50, 04.00, 04.50, 05.00, 06.00, 08.00, 12.00, 24.00, 36.00, 48.00 and 72.00 hours post dose.
Secondary Outcome
Outcome
TimePoints
Pharmacokinetic parameters Tmax, T1/2, Kel and AUC_%Extrap_ of Efonidipine and
Chlorthalidone from test products to that of reference product will be assessed.
Pre-dose (00.00 hour) and 00.50, 01.00, 01.25, 01.50, 01.75, 02.00, 02.50, 03.00, 03.50, 04.00, 04.50, 05.00, 06.00, 08.00, 12.00, 24.00, 36.00, 48.00 and 72.00 hours post dose.
Assessment of safety and tolerability of single oral dose of test and reference product.
Through-out the study period
Target Sample Size
Total Sample Size="28" Sample Size from India="28" Final Enrollment numbers achieved (Total)= "28" Final Enrollment numbers achieved (India)="28"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
STUDY OBJECTIVES
-Primary Objective
To compare the rate and extent of absorption of test product, fixed-dose combination of Efonidipine HCl ethanolate 40 mg and Chlorthalidone 12.5 mg tablets of Zuventus Healthcare Limited, India with Reference products, Efnocar 40 (efonidipine HCl ethanolate 40 mg) tablets, manufactured by Zuventus Healthcare Limited, India and CTD®-12.5 (Chlorthalidone 12.5 mg) tablets, manufactured by Ipca Laboratories Limited, India in normal, healthy, adult, human subjects under fasting conditions.
-Secondary Objective
To assess the safety and tolerability of single oral dose of Efonidipine HCl ethanolate 40 mg and Chlorthalidone 12.5 mg tablets in normal, healthy, adult, human subjects under fasting conditions.