CTRI/2020/11/028786 [Registered on: 02/11/2020] Trial Registered Prospectively
Last Modified On:
14/09/2021
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A bioequivalence study of Efonidipine 40 mg and S(-)Metoprolol 25 mg tablet combination in healthy adults.
Scientific Title of Study
An open label, balanced, randomized, two-treatment, two-sequence, two-period, single-dose, crossover oral bioequivalence study of test product, fixed dose combination of Efonidipine HCl ethanolate 40 mg and S(-)Metoprolol Succinate Extended Release 25 mg tablets of Zuventus Healthcare Limited, India with reference products, Efnocar 40 (Efonidipine HCl ethanolate 40 mg) tablet, manufactured by Zuventus Healthcare Limited, India and Metpure XL-25 [S(-) Metoprolol Succinate Extended Release 25 mg tablets], manufactured by Emcure Pharmaceuticals Limited, India in normal, healthy, adult, human subjects under fasting conditions.
Clinical Pharmacology Center, Clinical Department, Clinical Research Division, 4th Floor, B-17, TIE, Phase II, Balanagar Hyderabad TELANGANA
4067364700
maheswara.mallu@jeevanscientific.com
Details of Ethics Committee
No of Ethics Committees= 1
Name of Committee
Approval Status
Institutional Ethics Committee Sunshine Hospital
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
Efnocar 40 (Efonidipine HCl ethanolate 40 mg) tablet, manufactured by Zuventus Healthcare Limited, India
Single dose will be administered orally
with 240 ± 2 ml of water in
sitting posture
Intervention
Fixed dose combination of Efonidipine HCl ethanolate 40 mg and S(-)Metoprolol Succinate Extended Release 25 mg tablets of Zuventus Healthcare Limited, India
Single dose will be administered orally
with 240 ± 2 ml of water in
sitting posture
Comparator Agent
Metpure XL-25 [S(-) Metoprolol Succinate Extended Release 25 mg tablets], manufactured by Emcure Pharmaceuticals Limited, India
Single dose will be administered orally
with 240 ± 2 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 to 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 examinations, 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 laboratory 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 caffeine/xanthine containing foods or alcoholic beverages, grapefruit or grapefruit juice from 72.00 hours prior to dosing until the last post dose blood sample collection in each period.
7. Female subjects:
- Postmenopausal for atleast 1 year or
- Surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy has been performed on the subject) or
- 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 exicipients.
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 inflammation, bleeding, ulceration, and perforation of the stomach, small intestine or large intestine.
4. History or evidence of exfoliative dermatitis, Stevens Johnson syndrome, and toxic epidermal necrolysis.
5. Any known enzyme inducing or inhibiting drug taken within 30 days before the study.
6. Participation in 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. Any unusual or abnormal diet for whatever reason within 48.00 hours prior to admission of each period, eg. 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 (benzodiazepine, cocaine, opioids, amphetamine, 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.
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, AUC 0-t and
AUC 0-inf of Efonidipine and S(-)Metoprolol from the test product to
that of reference product will be assessed.
1. Pharmacokinetic parameters Tmax, T1/2, Kel and AUC_%Extrap_ of Efonidipine and S(-)Metoprolol from test products to that of reference product will be assessed.
2. To assess the safety and tolerability of single oral dose of test and reference product.
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 S(-)Metoprolol Succinate extended release 25 mg tablets of Zuventus Healthcare Limited, India with reference products, Efnocar 40 (Efonidipine Ethanolate HCl 40 mg) tablet, manufactured by Zuventus Healthcare Limited, India and Metpure XL-25 [S(-)MEtoprolol Succinate Extended Release 25 mg] tablets, manufactured by Emcure Pharmaceuticals 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 ans S(-)Metoprolol Succinate extended release 25 mg tablets in normal, healthy, adults, human subjects under fasting conditions.