CTRI/2020/09/027593 [Registered on: 04/09/2020] Trial Registered Prospectively
Last Modified On:
23/11/2020
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Comaparing the two different treatments of Darunavir and Ritonavir Tablet 800 mg/100 mg of Emcure Pharmaceuticals Ltd., India with DANAVIR R (Darunavir & Ritonavir Tablet 800 mg/100 mg) of Hetero Healthcare Limited, India in healthy, adult, human subjects under fed conditions
Scientific Title of Study
An open label, balanced, randomized, single oral dose, two treatment, two sequence, two period, crossover bioequivalence study of test product, Darunavir and Ritonavir Tablet 800mg 100mg of Emcure Pharmaceuticals Ltd, India and reference product, DANAVIR R Darunavir & Ritonavir Tablet 800mg 100mg of Hetero Healthcare Limited, India in healthy, adult, human subjects under fed conditions
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
051-20, Version 01, date: 09 Jul 2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Neel Lahoti
Designation
PRINCIPAL INVESTIGATOR
Affiliation
Synergen Bio Private Limited
Address
Synergen Bio Private Limited
Unit Nos. 101 to 104, Sai Chambers,
302, Old Mumbai - Pune Highway,
Wakadewadi, Shivajinagar,
Pune, Maharashtra - 411003, India
Pune MAHARASHTRA 411003 India
Phone
020-25540555
Fax
Email
neel@synergenbio.com
Details of Contact Person Scientific Query
Name
Dr Neel Lahoti
Designation
PRINCIPAL INVESTIGATOR
Affiliation
Synergen Bio Private Limited
Address
Synergen Bio Private Limited
Unit Nos. 101 to 104, Sai Chambers,
302, Old Mumbai - Pune Highway,
Wakadewadi, Shivajinagar,
Pune, Maharashtra - 411003, India
MAHARASHTRA 411003 India
Phone
020-25540555
Fax
Email
neel@synergenbio.com
Details of Contact Person Public Query
Name
Tarak Desai
Designation
Manager
Affiliation
Emcure Pharmaceuticals Limited
Address
Emcure Pharmaceutical Ltd,
R&D Center, Uvarsad Square,
Sarkhej Gandhinagar, Adalaj,
District Gandhinagar.
Gandhinagar GUJARAT 382421 India
Phone
07930640179
Fax
Email
tarak.desai@emcure.co.in
Source of Monetary or Material Support
Emcure Pharmaceuticals Limited
Primary Sponsor
Name
Emcure Pharmaceuticals Limited
Address
Plot No P1 and P2, ITBT Park, MIDC,
Phase II, Hinjwadi, Pune 411057, India
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 1
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Neel Lahoti
Synergen Bio Private Limited
Unit Nos 101 to 104, Sai Chambers,
302, Old Mumbai - Pune Highway,
Wakadewadi, Shivajinagar,
Pune, Maharashtra - 411003, India Pune MAHARASHTRA
020-25540555 020-25540444 neel@synergenbio.com
Details of Ethics Committee
No of Ethics Committees= 1
Name of Committee
Approval Status
Royal Pune Independent Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Healthy Human Volunteers
Adult healthy subjects of age between 18 and 45 years
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
DANAVIR R (Darunavir & Ritonavir Tablet 800mg/100mg)
Marketed by: Hetero Healthcare Limited, 7-2-A 2, Hetero Corporate, Industrial Estate, Sanath Nagar, Hyderabad - 500018
Manufactured by: Hetero Labs Limited (Unit III), Village: Kalyanpur, Chakkan Road, Tehsil: Baddi, District: Solan, Himachal Pradesh - 173205
Dose: DANAVIR R (Darunavir & Ritonavir Tablet 800mg/100mg)
Frequency: single dose
Route of Adminsitration: Oral
Duration of therapy: Single dose, two period study, in one period test and other period reference drug will be administered
Intervention
Darunavir and Ritonavir Tablet 800mg/100mg
Manufactured by: Emcure Pharmaceuticals Ltd., India
Dose: Darunavir and Ritonavir Tablet 800mg/100mg
Frequency: single dose
Route of Adminsitration: Oral
Duration of therapy: Single dose, two period study, in one period test and other period reference drug will be administered
Inclusion Criteria
Age From
18.00 Year(s)
Age To
45.00 Year(s)
Gender
Both
Details
1.0 Healthy, human subjects (Male and/or non-pregnant, non-lactating female) aged between 18 and 45 years (inclusive of both).
2.0 Female of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test performed within 21 days prior to initiation of the study. Female subject must have a negative urine pregnancy test prior to check-in of each period. They must be using an acceptable form of contraception.
3.0 For female of childbearing potential, acceptable forms of contraception include the following:
I. Non hormonal intrauterine device in place for at least 3 months prior to the start of the study and remaining in place during the study period and for 07 days following last dose of the study medication, or
II. Barrier methods containing or used in conjunction with a spermicidal agent, or
III. Surgical sterilization or
IV. Practicing sexual abstinence throughout the course of the study.
4.0 Female will not be considered of childbearing potential if one of the following is reported and documented on the medical history:
I. Postmenopausal with spontaneous amenorrhea for at least one year, or
II. Bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or
III. Total hysterectomy and an absence of bleeding for at least 3 months.
5.0 Male agreeing to use appropriate contraceptive measures like Double Barrier method (Condom), and should not donate sperm etc. during study and 07 days after completion of study.
6.0 Subjects with a BMI between 18.50-25.00 kg/m2 (inclusive of both) and body mass not less than 50.00 kg.
7.0 Subjects in normal health as determined by personal medical history, clinical examination including vital signs and clinically acceptable results of laboratory examinations (including serological tests).
8.0 Subjects having a normal or clinically not significant 12-lead electrocardiogram (ECG) recording
9.0 Subjects having a normal or clinically not significant chest X-Ray (P/A view).
10.0 A negative urine screen result for drugs of abuse (including amphetamines, barbiturates, benzodiazepines, marijuana, cocaine and morphine).
11.0 A negative alcohol breath test result.
12.0 A negative urine screen result for cotinine during screening.
13.0 Subject able to communicate effectively and provide written informed consent.
14.0 Subjects willing to adhere to the protocol requirements as evidenced by written informed consent approved by ethics committee.
15.0 Subjects that can provide adequate evidence of their identity.
16.0 Availability of volunteer for the entire study duration.
17.0 Ability to fast for at least 10.00 hours and consume high-fat high-calorie non veg breakfast and standard meals.
ExclusionCriteria
Details
The subjects will be excluded from the study if they meet any of the following criteria:
1.0 Known hypersensitivity to Darunavir and Ritonavir or any component of this medication.
2.0 Incapable of understanding the informed consent information.
3.0 History or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological or psychiatric disease or disorder.
4.0 Any treatment which could bring about induction or inhibition of hepatic microsomal enzyme system within one month of starting the study.
5.0 History or presence of alcoholism or drug abuse.
6.0 History or presence of asthma, urticaria or other allergic reactions.
7.0 History or presence of gastric and/or duodenal ulceration.
8.0 History or presence of thyroid disease, adrenal dysfunction, organic intracranial lesion.
9.0 History or presence of cancer.
10.0 Difficulty with donating blood.
11.0 Difficulty in swallowing solids like tablets or capsules.
12.0 Use of any prescribed medication (including herbal remedies) during the two weeks before the start of the study or OTC medicinal products (including herbal remedies) during the week prior to study initiation and throughout the study.
13.0 Consumption of alcohol and/or smoking or consumption of tobacco products within 48.00 hours prior to dosing.
14.0 Subject consumed tobacco/ tobacco containing products, pan or pan masala, gutkha, masala (containing beetle nut and tobacco) for at least 48.00 hours prior to initiation of the study and throughout the study.
15.0 Subject consumed caffeine and /or xanthine-containing foods or beverages (i.e. coffee, tea, chocolate, and caffeine-containing sodas, colas, etc.) and grapefruit or grapefruit juice and poppy containing foods for at least 48.00 hours prior to initiation of the study and throughout the study.
16.0 Major illness during the 90 days before screening.
17.0 Participation in a drug research study within 90 days of screening.
18.0 Donation of blood within 90 days of screening.
19.0 Positive screening test result for any one or more of the following: HIV, Hepatitis B, Hepatitis C and VDRL.
20.0 History or presence of easy bruising or bleeding.
21.0 Abnormal diet pattern for whatever reason (e.g. low sodium, fasting, and high protein diets) during the four weeks preceding the study.
22.0 Pregnant woman and nursing mothers.
23.0 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.
24.0 Woman of child bearing age who do not agree to follow a reliable method of contraception during study period.
25.0 Male volunteer unwilling to employ appropriate contraceptive measures to ensure that his partner will not get pregnant during the study till 07 days after the completion of study.
26.0 Male volunteer willing to donate sperms during the study till 07 days after the completion of study.
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To compare the rate and extent of absorption of Darunavir and Ritonavir from Darunavir and Ritonavir Tablet 800mg/100mg of Emcure Pharmaceuticals Ltd., India (Test Product) and DANAVIR R (Darunavir & Ritonavir Tablet 800mg/100mg) of Hetero Healthcare Limited, India (Reference product) in healthy, adult, human subjects under fed conditions.
Twenty- four (24) blood samples will be collected from each subject in each period.
The pre-dose (0.00 hours) blood sample of 05 mL will be taken not more than one hour prior to dosing in each period. Further samples of 05 mL each will be collected at 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 10.00, 14.00, 18.00, 24.00, 36.00, 48.00 and 72.00 hours post-dose.
Secondary Outcome
Outcome
TimePoints
To monitor the safety and tolerability of a single oral dose of Darunavir and Ritonavir Tablet 800mg/100mg in healthy, adult, human subjects under fed conditions.
Vital signs (axillary temperature, radial pulse rate and sitting blood pressure) and questioning for well-being will be recorded within 2.50 hours prior to dosing in each period.
Vital signs (sitting blood pressure and radial pulse rate) and questioning for well-being will also be recorded at approximately: -
• at 3.00, 06.00, 12.00, 24.00, 36.00, 48.00 and 72.00 hours after dosing in each period (within ± 40 minutes of the scheduled time, referring to the last recording).
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
Open-label, balanced, randomized, single oral dose, two-treatment, two-sequence, two-period, crossover bioequivalence study. To compare the rate and extent of absorption of Darunavir and Ritonavir from Darunavir and Ritonavir Tablet 800mg/100mg of Emcure Pharmaceuticals Ltd., India (Test Product) and DANAVIR R (Darunavir & Ritonavir Tablet 800mg/100mg) of Hetero Healthcare Limited, India (Reference product) in healthy, adult, human subjects under fed conditions.
To monitor the safety and tolerability of a single dose of Darunavir and Ritonavir Tablet 800mg/100mg in healthy, adult, human subjects under fed conditions.
The sponsor aims to market the test product as a pharmaceutical equivalent of the reference product, provided the test and reference products are bioequivalent. Twenty- eight (28) healthy, adult, human subjects will be dosed in the study.
A sufficient number of healthy adult volunteers will be asked to report on the day of check-in, in order to ensure that at least 28 subjects will be administered the investigational product at the beginning of the study. Subsequent dropouts/ withdrawals (after dosing) will not be replaced.