CTRI/2025/07/090166 [Registered on: 04/07/2025] Trial Registered Prospectively
Last Modified On:
07/01/2026
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Other
Public Title of Study
Bioequivalence study of Emtricitabine, Tenofovir Alafenamide and Dolutegravir 15 mg/1.88 mg/5 mg Tablets for Oral Suspension healthy adult males and non-pregnant, non-lactating females under Fed condition
Scientific Title of Study
Single dose Fed oral bioequivalence study of Emtricitabine, Tenofovir
Alafenamide and Dolutegravir 15 mg/1.88 mg/5 mg Tablets for Oral
Suspension (T) of Mylan Laboratories Limited, India with that of Reference product (R=R1+R2) R1: TIVICAY PD (Dolutegravir) 5 mg Tablets for oral suspension of ViiV healthcare, Durham, NC27701 and R2: DESCOVY® (emtricitabine and tenofovir alafenamide) 15 mg and 1.88 mg Tablets for oral suspension of Gilead Sciences, Inc. Foster City, CA 94404 in healthy adult males and non-pregnant, non-lactating females under fed conditions.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
TAED-TBP-1003 Version No. 03 Dated: 07 May 2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Anjum Jabeen MBBS MD
Designation
Prinicipal Investigator
Affiliation
Aizant Drug Research Solutions Pvt. Ltd.,
Address
Aizant Drug Research Solutions Pvt. Ltd.,
Clinical Pharmacology Unit-II, Maitrivihar Commercial Complex, Block No. 101-107 and 201-206, Ameerpet
Hyderabad, Telangana, India - 500016. Aizant Drug Research Solutions Pvt. Ltd.,
Clinical Pharmacology Unit-II, Maitrivihar Commercial Complex, Block No 101-107 and 201-206, Ameerpet
Hyderabad, Telangana, India - 500016. Hyderabad TELANGANA 500016 India
Phone
04023811981
Fax
04023811982
Email
anjum.jabeen@aizant.com
Details of Contact Person Scientific Query
Name
Anjum Jabeen MBBS MD
Designation
Prinicipal Investigator
Affiliation
Aizant Drug Research Solutions Pvt. Ltd.,
Address
Aizant Drug Research Solutions Pvt. Ltd.,
Clinical Pharmacology Unit-II, Maitrivihar Commercial Complex, Block No. 101-107 and 201-206, Ameerpet
Hyderabad, Telangana, India - 500016. Aizant Drug Research Solutions Pvt. Ltd.,
Clinical Pharmacology Unit-II, Maitrivihar Commercial Complex, Block No 101-107 and 201-206, Ameerpet
Hyderabad, Telangana, India - 500016.
TELANGANA 500016 India
Phone
04023811981
Fax
04023811982
Email
anjum.jabeen@aizant.com
Details of Contact Person Public Query
Name
Anjum Jabeen MBBS MD
Designation
Prinicipal Investigator
Affiliation
Aizant Drug Research Solutions Pvt. Ltd.,
Address
Aizant Drug Research Solutions Pvt. Ltd.,
Clinical Pharmacology Unit-II, Maitrivihar Commercial Complex, Block No. 101-107 and 201-206, Ameerpet
Hyderabad, Telangana, India - 500016. Aizant Drug Research Solutions Pvt. Ltd.,
Clinical Pharmacology Unit-II, Maitrivihar Commercial Complex, Block No 101-107 and 201-206, Ameerpet
Hyderabad, Telangana, India - 500016.
TELANGANA 500016 India
Phone
04023811981
Fax
04023811982
Email
anjum.jabeen@aizant.com
Source of Monetary or Material Support
Mylan Laboratories Limited, Clinical Research Centre, Saradhi Chambers, Plot No. A-4, Beside Poulomi Hospital,Rukminipuri, Dr. A. S. Rao Nagar,Hyderabad– 500062, India.
Primary Sponsor
Name
Mylan Laboratories Limited
Address
Clinical Research Centre, Saradhi Chambers, Plot No. A-4, Beside Poulomi Hospital,Rukminipuri, Dr. A. S. Rao Nagar,Hyderabad– 500062, India.
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
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 Anjum Jabeen MBBS MD
Aizant Drug Research Solutions Pvt. Ltd.,
Clinical Pharmacology Unit-II,
Maitrivihar Commercial Complex,
Block No.: 101-107 and 201-206, Ameerpet
Hyderabad, Telangana, India - 500016. Hyderabad TELANGANA
04023811981 04023811982 anjum.jabeen@aizant.com
Details of Ethics Committee
No of Ethics Committees= 1
Name of Committee
Approval Status
Maarg Independent Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Healthy Human Volunteers
Fed
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
(R=R1+R2) R1: TIVICAY PD (Dolutegravir) 5 mg Tablets for oral suspension of and DESCOVY® (emtricitabine and tenofovir alafenamide) 15 mg and 1.88 mg Tablets for oral suspension
Single dose Fed oral bioequivalence study of in healthy adult males and non-pregnant, non-lactating females under fed condition. There will be at least 07 days between
dosing times for the treatment periods.
Intervention
Emtricitabine, Tenofovir Alafenamide and Dolutegravir 15 mg/1.88 mg/5 mg Tablets for Oral Suspension
Single dose Fed oral bioequivalence study of Emtricitabine, Tenofovir Alafenamide and Dolutegravir 15 mg/1.88 mg/5 mg Tablets for Oral Suspension in healthy adult males and non-pregnant, non-lactating females.under fed conditions. There will be at least 07 days gap between dosing times for the treatment periods.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
45.00 Year(s)
Gender
Both
Details
Subjects must fulfill all of the following criteria to be considered for inclusion into this study. 1. Normal healthy adult males and non-pregnant, non-lactating females, age between 18 to 45 years (inclusive of both). 2. Body mass index of (greater than or equal to) 18.5 kg/m2 and (less than and equal to) 30.0 kg/m2 and weight (greater than or equal to) 50.00 kg. 3. Healthy according to the laboratory results and physical examination, performed within 21 days prior to the commencement of the dosing in Period-1. 4. Subject whose clinical laboratory values are within normal limits or clinically insignificant as determined by physician or principal investigator to be of no clinical significance. 5. Have normal ECG, Chest X-ray and vital signs. 6. Non-smoker and Non-alcoholic. 7. Subject creatinine clearance (CrCl) should be more than 60 mL/min. 8. Willing to not to participate in clinical research study or blood donations till 90 days after the study completion. 9. Subject able to communicate effectively and provide written informed consent. 10. Subject willing to adhere to protocol requirements as evidenced by written informed consent approved by an Independent Ethics Committee (IEC). 11. If study subject is a female and is of child bearing 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, intrauterine device (IUD), or abstinence. Or is postmenopausal for at least 1 year Or is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy or tubectomy has been performed on the study subject).
ExclusionCriteria
Details
Subject candidates must not be enrolled in the study if they meet any of the following criteria. 1. Any history of allergy or hypersensitivity to Emtricitabine, Tenofovir Alafenamide and Dolutegravir or other related drugs. 2. Positive test result for hepatitis B surface antigen (HBs Ag), hepatitis C virus antibody (HCV Ab) or HIV-1 antibody or HIV Type 2 (HIV-2) antibody (HIV Ab) and VDRL / syphilis. 3. The study drug is contraindicated for medical reasons. 4. Any history or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, dermatological, neurological, psychiatric diseases or disorders. 5. History or presence of drug abuse in the past one year. 6. Difficulty in swallowing tablets or suspension. 7. Any history of difficulty in donating blood. 8. Had clinically significant abnormal values of laboratory parameters. 9. Blood pressure is (less than) 90/60 and (greater than) 129/79 millimeters of mercury (Systolic blood pressure/ Diastolic blood pressure). 10. Pulse rate less than 60 beats / minute and more than 100 beats / minute. 11. Any history or presence of fractures or decreases in bone density. 12. Any history evidence of Lactic acidosis and severe hepatomegaly. 13. Use of any prescription or over the counter (OTC) medications other than hormonal contraceptive or hormone replacement therapy within the 14 days prior to the initial administration of study medication. 14. A depot injection or implant of any drug within 3 months prior to initial administration of study medication. 15. Use of any medication, herbal supplement, or vitamin known to induce or inhibit hepatic enzyme activity within 28 days prior to the initial administration of study medication. 15. Liver function tests (ALT, AST and bilirubin) 1.1 times the upper limit of normal. 16. Amenorrhea or irregular menstrual periods (defined unable to predict within 7 days) during past 6 months for females. 17. Female subject who is currently breast feeding or a female study subject who is pregnant or who is likely to become pregnant during the study. 18. Female subject demonstrating positive for pregnancy test (performed at the time of each period check-in). 19. Consideration by the investigator, for any reason that the subject is an unsuitable candidate to receive study drug. 20. Subject positive for urine or breath alcohol test, urine screen for drugs of abuse [Cannabinoids (Marijuana / Tetra Hydro Cannabinoids-THC), Cocaine, Opiates (morphine), Amphetamine, Barbiturates and Benzodiazepines] at the time of each period check-in will be excluded from the study. 21. Any clinically significant illness during 3 months before screening. 22. Participation in a drug research study/donation of blood within past 90 days.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Protocol Title
Single dose Fed oral bioequivalence study of
Emtricitabine, Tenofovir Alafenamide and Dolutegravir 15 mg/1.88 mg/5 mg
Tablets for Oral Suspension (T) of Mylan Laboratories Limited, India with
that of Reference product (R=R1+R2) R1: TIVICAY PD (Dolutegravir) 5 mg
Tablets for oral suspension of ViiV healthcare, Durham, NC27701 and R2:
DESCOVY® (emtricitabine and tenofovir alafenamide) 15 mg and 1.88 mg Tablets
for oral suspension of Gilead Sciences, Inc. Foster City, CA 94404 in healthy
adult males and non-pregnant, non-lactating females under fed conditions.
Protocol No.
TAED-TBP-1003 Version No:03 Dated: 07 May
2025
Product
Emtricitabine, Tenofovir Alafenamide and
Dolutegravir 15 mg/1.88 mg/5 mg Tablets for Oral Suspension
Study Type
Pilot Fed Bioequivalence
Version
03
Protocol Date
07 May 2025
General Description
This protocol describes an open
labelled, balanced, single dose, randomized, two-treatment, four-period,
two-sequence, crossover, full replicate study to investigate the
bioequivalence of Emtricitabine, Tenofovir Alafenamide and Dolutegravir 15
mg/1.88 mg/5 mg Tablets for Oral Suspension (T) of Mylan Laboratories
Limited, India with that of Reference product (R=R1+R2) R1: TIVICAY PD
(Dolutegravir) 5 mg Tablets for oral suspension of ViiV healthcare, Durham,
NC27701 and R2: DESCOVY® (emtricitabine and tenofovir alafenamide) 15 mg and
1.88 mg Tablets for oral suspension of Gilead Sciences, Inc. Foster City, CA
94404.
Single dose fed
pharmacokinetics will be characterized in Twenty-four (24) healthy adult
males and non-pregnant, non-lactating females following administration of a
single oral dose of either test product (T) or reference product (R=R1+R2) as
per randomization schedule. The detailed administration process is given in
the section 7.5. Treatment procedure of the protocol.
For Period 01 & 02: For
Emtricitabine, Tenofovir Alafenamide, Tenofovir and Dolutegravir:
In each study period, Six
milliliter (1 × 6 mL) blood samples (23) will be collected in K3EDTA
Vacutainers at pre-dose (0.00 hour) and the following times after dosing:
0.083, 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00,
3.50, 4.00, 6.00, 8.00, 10.00, 12.00, 24.00, 36.00, 48.00 and 72.00 hours.
For Period 03 & 04: For
Tenofovir Alafenamide:
In each study period, four
milliliter (1 × 4 mL) blood samples (15) will becollected
in K3EDTA Vacutainers at pre-dose (0.00 hour) and the following times after
dosing: 0.083, 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50,
3.00, 3.50, 4.00 hours.
The Collected blood samples
will be placed in an ice batch and centrifuged under refrigeration as soon as
possible. Two aliquots (Aliquot 1 of 2, & Aliquot 2 of 2) of plasma will
be extracted and stored in suitably labeled tubes at -70°C or colder with an
acceptable operating range within -55°C to -90°C at the clinical site until
transferred on dry ice to analytical site (refer Appendix-I: Bioanalytical
sample handling instruction of the protocol).
For the determination of the
pharmacokinetic disposition of the formulations, there will be a total of 76
(46 blood samples from period-1 & 2 and and 30 samples from period -3
& 4) blood samples involving a total of 396 mL of blood collected for
pharmacokinetic analysis from each subject in the study. There will be at
least 07 days gap between dosing times for the treatment periods.
The bioequivalence of
Emtricitabine, Tenofovir Alafenamide and Dolutegravir 15 mg/1.88 mg/5 mg
Tablets for Oral Suspension (T) of Mylan Laboratories Limited, India with
that of Reference product (R=R1+R2) R1: TIVICAY PD (Dolutegravir) 5 mg
Tablets for oral suspension of ViiV healthcare, Durham, NC27701 and R2:
DESCOVY® (emtricitabine and tenofovir alafenamide) 15 mg and 1.88 mg Tablets
for oral suspension of: Gilead Sciences, Inc. Foster City, CA 94404 will be
assessed by a statistical comparison of various pharmacokinetic parameters
derived from the plasma concentration-time curves of the drug.
OBJECTIVES
Primary Objective: To investigate the bioequivalence of
Emtricitabine, Tenofovir Alafenamide and Dolutegravir 15 mg/1.88 mg/5 mg
Tablets for Oral Suspension (T) of Mylan Laboratories Limited, India with
that of Reference product (R=R1+R2) R1: TIVICAY PD (Dolutegravir) 5 mg
Tablets for oral suspension of ViiV healthcare, Durham, NC27701 and R2:
DESCOVY® (emtricitabine and tenofovir alafenamide) 15 mg and 1.88 mg Tablets
for oral suspension of Gilead Sciences, Inc. Foster City, CA 94404 in healthy
adult males and non-pregnant, nonlactating females.
Secondary Objective: To evaluate the safety of the subjects (i.e.
monitor adverse events) under fed conditions.
STUDY DRUG
Test product (T): Emtricitabine, Tenofovir Alafenamide and
Dolutegravir 15 mg/1.88 mg/5 mg Tablets for Oral Suspension.
Manufactured by: Mylan Laboratories Limited, India.
Distributed by: Gilead Sciences, Inc. Foster City, CA
94404.
STUDY CONDUCT
This is an open labelled,
balanced, single-dose, randomized, two-treatment, four-period, two sequence, crossover,
full replicate study to investigate the bioequivalence of Emtricitabine, Tenofovir
Alafenamide and Dolutegravir 15 mg/1.88 mg/5 mg Tablets for Oral Suspension
(T) of Mylan Laboratories Limited, India with that of Reference product
(R=R1+R2) R1: TIVICAY PD (Dolutegravir) 5 mg Tablets for oral suspension of
ViiV healthcare, Durham, NC27701 and R2: DESCOVY® (emtricitabine and
tenofovir alafenamide) 15 g and 1.88 mg Tablets for oral suspension of Gilead
Sciences, Inc. Foster City, CA 94404 in healthy adult males and nonpregnant, non-lactating
females.
Single dose fed
pharmacokinetics will be characterized in Twenty-four (24) healthy adult
males and non-pregnant, non-lactating females following administration of a
single oral dose of either test product (T) or reference product (R=R1+R2).
Subjects will be housed the
evening prior to drug dosing of period-1, period-2 and until at least 72.00
hours after investigational drug administration. Blood samples will be
collected prior to dosing and for up to 72.00 hours after period-1 and
period-2 dosing. Subjects will be housed the evening prior to drug dosing of
period-3, period-4 and until at least 24.00 hours after investigational drug
administration. Blood samples will be collected prior to dosing and for up to
4.00 hours after period-3 and period-4 dosing. There will be at least 07 days
gap between dosing times of each treatment periods. Individual subjects
should be dosed at approximately the same time of day in each dosing period.
It is the sponsor’s intent to complete all subjects simultaneously. Thus, it
is anticipated that all subjects will be completed in a single cohort within
approximately 24 days following the initiation of dosing. If multiple cohorts
are necessary to enroll the required number of subjects, no two cohorts can
be dosed on the same day.
Screening Procedures
Each prospective subject must
agree to participate in screening procedures by signing the most recent
Institutional Review Board/Independent Ethics Committee approved Informed
Consent Document (ICD) before any screening procedure is initiated. The
Principal Investigator or Medical Sub-Investigator will review the inclusion
and exclusion criteria to confirm eligibility of each subject prior to
enrollment.
Each subject will undergo a
screening procedure for health assessment, which consists of a complete
medical history, physical examination with vital signs, clinical laboratory
evaluations, 12-lead ECG and Chest X-ray PA view. The physical examination
findings, ECG, and the laboratory tests can be considered as valid for
maximum of 21 days prior to the dosing (drug administration) in first period
of the study. Chest X-ray PA view will be taken within 6 months prior to
dosing (drug administration) of period-1.
The physician in charge will
assess abnormal values to determine if it is clinically significant.
Housing
Enough subjects from the general population
will be available in the clinic for Period-1 dosing in order to dose the
required number of subjects. Subjects will be housed 11.00 hours prior until
at least 72.00 hours after dosing for period-1 & period-2. Subjects will
be housed 11.00 hours prior to dosing until at least 24.00 hours after dosing
for period-3 and period-4. There will be at least 07 days gap between dosing
times for the treatment periods.
Toxicity Management
Bioanalytical Method
A validated assay method will
be employed for the analysis of Emtricitabine, Tenofovir Alafenamide,
Tenofovir and Dolutegravir in plasma samples. Full validation of the method, including
precision, accuracy and reproducibility will be included in the final report,
along with a statement regarding the stability of frozen samples.
Pharmacokinetic Parameter Determination
All concentration values below the lower
limit of quantification (BLOQ) will be set to zero. Any missing samples will
be reported as ‘M’ and will
not be included for pharmacokinetic and statistical analysis.
The following pharmacokinetic parameters will
be computed by using Phoenix® WinNonlin® version 8.0 or higher for
Emtricitabine, Tenofovir Alafenamide, Tenofovir and Dolutegravir through non
compartmental method. Pharmacokinetic data from tenofovir will be provided as
supportive evidence of comparable therapeutic outcome. Subjects concentration
data from the first two periods will be considered for the pharmacokinetic parameters
estimation of Emtricitabine, Tenofovir & Dolutegravir:
For TAF: The pharmacokinetic parameters will be estimated by using the
concentration data up to 04.00 hrs post dose.
Statistical Analysis of the Pharmacokinetic
Parameters
Subjects who completed all
periods of the study will be included in scaled average BE and with in
reference variability estimation. All other scenarios where the subject didn’t completed all periods of the study will be considered in
average bioequivalence evaluation as per IEC approved protocol using SAS
version 9.4 or higher version. Descriptive statistics of all the
pharmacokinetic parameters will be computed and reported for Emtricitabine,
Tenofovir Alafenamide, Tenofovir and Dolutegravir. The below will be
calculated and reported for Emtricitabine, Tenofovir Alafenamide, Tenofovir and
Dolutegravir:
APPENDIX VI: STUDY CONDUCT
INFORMATION
The clinical research organization conducting
this study on behalf of Mylan Laboratories Ltd., India is required to
complete this sheet and forward to Mylan prior to the enrollment of any subjects
into the study. Any updates throughout the study conduct period must be
reported on this sheet.
Protocol Number: TAED-TBP-1003
Protocol Title: Single dose Fed oral bioequivalence study of
Emtricitabine, Tenofovir Alafenamide and Dolutegravir 15 mg/1.88 mg/5 mg
Tablets for Oral
Suspension (T) of Mylan Laboratories Limited,
India with that of Reference
product (R=R1+R2) R1: TIVICAY PD
(Dolutegravir) 5 mg Tablets for oral suspension of ViiV healthcare, Durham,
NC27701 and R2: DESCOVY® (emtricitabine and tenofovir alafenamide) 15 mg and
1.88 mg Tablets for oral suspension of Gilead Sciences, Inc. Foster City, CA
94404 in healthy adult males and non-pregnant, non-lactating females.
Principal Investigator: Dr. Anjum Jabeen, M.B.B.S., M.D.,
Address: Aizant Drug Research Solutions Pvt.
Ltd., Clinical Pharmacology Unit-II,