CTRI/2026/03/105236 [Registered on: 02/03/2026] Trial Registered Prospectively
Last Modified On:
02/03/2026
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public 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
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, NC 27701 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.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
TAED-TBP-1005, Version: 00, Date: 10 Sep 2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Nikhil Kumar Kursam MBBS MD
Designation
Principal Investigator
Affiliation
Aizant Drug Research Solutions Pvt. Ltd.
Address
Aizant Drug Research Solutions Pvt. Ltd., Survey No.172 and 173, Apparel Park Road, Dulapally Village, Dundigal Gandimaisamma Mandal, Medchal- Malkhajgiri District-500100 Telangana, India.
Medchal TELANGANA 500100 India
Phone
04023792190
Fax
Email
nikhil.kursam@aizant.com
Details of Contact Person Scientific Query
Name
Dr Nikhil Kumar Kursam MBBS MD
Designation
Principal Investigator
Affiliation
Aizant Drug Research Solutions Pvt. Ltd.
Address
Aizant Drug Research Solutions Pvt. Ltd., Survey No.172 and 173, Apparel Park Road, Dulapally Village, Dundigal Gandimaisamma Mandal, Medchal- Malkhajgiri District-500100 Telangana, India.
TELANGANA 500100 India
Phone
04023792190
Fax
Email
nikhil.kursam@aizant.com
Details of Contact Person Public Query
Name
Dr Nikhil Kumar Kursam MBBS MD
Designation
Principal Investigator
Affiliation
Aizant Drug Research Solutions Pvt. Ltd.
Address
Aizant Drug Research Solutions Pvt. Ltd., Survey No.172 and 173, Apparel Park Road, Dulapally Village, Dundigal Gandimaisamma Mandal, Medchal- Malkhajgiri District-500100 Telangana, India.
TELANGANA 500100 India
Phone
04023792190
Fax
Email
nikhil.kursam@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.
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 Nikhil Kumar Kursam MBBS MD
Aizant Drug Research Solutions Pvt. Ltd.
Survey No.172 and 173, Apparel Park Road, Dulapally Village, Dundigal Gandimaisamma Mandal, Medchal Malkhajgiri District-500100 Telangana, India.Medchal TELANGANA. Medchal TELANGANA
04023792190
nikhil.kursam@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 and R2:
DESCOVY® (emtricitabine
and tenofovir alafenamide) 15
mg and 1.88 mg Tablets for
oral suspension.
Single dose Fasting oral
bioequivalence study of
(R=R1+R2) R1: TIVICAY PD
(Dolutegravir) 5 mg Tablets for
oral suspension and R2:
DESCOVY® (emtricitabine
and tenofovir alafenamide) 15
mg and 1.88 mg Tablets for
oral suspension. in healthy
adult males and non-pregnant,
non-lactating females, under
Fasting condition. There will be
at least 07 days gap 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 condition. 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 fulfil 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 any clinical research study
or blood donations till 90 days after the study completion. 9. Willing
to avoid or take parecautions while performing the skilled tasks like
driving, operating machinery, while working at high elevations etc.,
but not limited to. 10. Subject able to communicate effectively and
provide written informed consent. 11. Subject willing to adhere to
protocol requirements as evidenced by written informed consent
approved by an Independent Ethics Committee (IEC). 12. Male
subjects willing to follow acceptable barrier method of
contraception during the study and till 07 days after completion of
the study. 13. If study subject is a female and is of childbearing
potential practicing an acceptable method of birth control for the
duration of the study and till 07 days after completion 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/capsules 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 (greeter than) 129/79 millimeters
of mercury (Systolic blood pressure/Diastolic blood pressure).
Pulse rate less than 60 beats / minute and more than 100 beats
/minute. 10.Any history or presence of fractures or decreases in
bone density. 11. Any history/evidence of Lactic acidosis and
severe hepatomegaly. 12. 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. 13. A depot injection or implant
of any drug within 3 months prior to initial administration of study
medication. 14. 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) 1.5 times the upper limit of
normal. 16. Any clinically significant illness during 3 months before
screening. 17.Participation in a drug research study/donation of
blood within past 90 days. 18. Amenorrhea or irregular menstrual
periods (defined unable to predict within 7 days) during past 6
months for females. 19.Female subject who is currently breast
feeding or a female study subject who is pregnant or who may wish
to become pregnant during the study. 20. Female subject
demonstrating positive for pregnancy test (performed at the time of
each period check-in). 21. Consideration by the investigator, for
any reason that the subject is an unsuitable candidate to receive
study drug. 22. 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/period as per
PI discretion.
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
Primary Outcome
Outcome
TimePoints
The objective of this study is to investigate the
comparative relative oral bioavailability of
Mylan’s Test product Emtricitabine, Tenofovir
Alafenamide and Dolutegravir 15 mg/1.88 mg/5
mg Tablets for OralSuspension with Reference
product (R=R1+R2) R1: TIVICAY PD
(Dolutegravir) 5 mg Tablets for oral suspension
of ViiV healthcare, Durham, NC 27701 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 following a single oral dose of
test product or reference products administration under Fed conditions
2 Months clinical schedule
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events & to ensure
the safety of the subjects.
at baseline, 4 weeks & 8 weeks
Target Sample Size
Total Sample Size="48" Sample Size from India="48" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
N/A
Date of First Enrollment (India)
03/06/2026
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="0" Months="2" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
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, NC 27701 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.
Protocol No.
TAED-TBP-1005
Product
Emtricitabine, Tenofovir Alafenamide and Dolutegravir 15 mg/1.88 mg/5 mg Tablets for Oral Suspension
Study Type
Pivotal Fed Bioequivalence
Version
00
Protocol Date
10 Sep 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 Fourty-eight (48) 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, seven milliliter (1 × 7 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, three milliliter (1 × 3 mL) blood samples (15) 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 hours post dose.
The Collected blood samples will be placed in an ice batch and centrifuged under refrigeration as soon as possible. All aliquots (Four aliquots of period-1 & 2 and two aliquots of period-3 & 4) 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 30 blood samples from period-3 & 4) blood samples involving a total of 412 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 for the pharmacokinetic parameters Cmax, AUC0-t 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.
Reference Product (R2): DESCOVY® (emtricitabine and tenofovir alafenamide) 15 mg and 1.88 mg Tablets for oral suspension.
Note: The intended commercial product name for emtricitabine/tenofovir 15/1 .88 mg tablets for oral suspension is Descovy; however, that name is not approved for this product. For the purposes of these clinical studies, the labels will contain "emtricitabine/tenofovir 15/1.88 mg tablets for oral suspension instead of DESCOVY®.
Manufactured for: 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 Fourty-eight (48) 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) under fed conditions. 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.
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, urine pregnancy test (for female subjects only) 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
Serum creatinine, Blood urea, SGOT (AST), SGPT (ALT), Serum alkaline phosphatase (ALP), Total bilirubin, Blood sugar / Plasma Glucose (Random) and Serum electrolytes (Sodium, Potassium and Chloride)Creatinine clearance (CrCl) test will be done by using Cockcroft-Gault method will be performed during screening and post study.
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 8.5.2 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.
Primary Pharmacokinetic Parameters:
Cmax: Maximum observed plasma concentration
AUC0 t: The area under the plasma concentration versus time curve from time zero to the last measurable concentration
Secondary Pharmacokinetic Parameters:
Tmax: Time of the maximum measured plasma concentration
AUC0 inf: The area under the plasma concentration versus time curve from time zero to infinity. Where AUC0-inf = AUC0 t Ct/ Kel, Ct is the last measurable concentration and z is the terminal elimination rate constant
t½: The elimination half-life will be calculated as 0.693/ Kel
Kel: First order elimination rate constant associated with the terminal (loglinear) portion of the curve. This is estimated via linear regression of time vs. log concentration. This parameter will be calculated by linear least squares regression analysis using at least last three or more non-zero plasma concentration values.
For Tenofovir: [Considering the half life > 24hrs]
Primary Pharmacokinetic Parameters:
Cmax: Maximum observed plasma concentration
AUC0-72: The area under the plasma concentration versus time curve from time zero to the last measurable concentration
Secondary Pharmacokinetic Parameters:
Tmax: Time of the maximum measured plasma concentration
Statistical Analysis of the Pharmacokinetic Parameters
Pharmacokinetic parameters data obtained for the analytes Emtricitabine, Tenofovir Alafenamide, Tenofovir and Dolutegravir will be included in the statistical analysis as per the criteria mentioned below by using SAS version 9.4 or higher. For Emtricitabine, Dolutegravir, Tenofovir:
Pharmacokientic parammeters data of the subjects who completes the first two periods of the study will be considered for statistical analysis.
For Tenofovir Alafenamide:
• Subjects who completed all periods of the study will be included in scaled average BE and within reference variability estimation.
• All other scenarios where the subject didn’t complete all periods of the study will be considered in average bioequivalence evaluation as per IEC approved protocol using SAS version 9.4 or higher.
Descriptive statistics of all the pharmacokinetic parameters will be computed and reported for Emtricitabine, Tenofovir Alafenamide, Tenofovir and Dolutegravir.
The summary statistics (for relevant pharmacokinetic parameters) will be computed and reported for both test and reference products.
The 90% confidence intervals for the ratio of least squares mean between drug formulations will be calculated, for ln-transformed data of Cmax and AUC0-t.
Ratio of least squares means of test and reference products will be computed for ln-transformed pharmacokinetic parameters Cmax and AUC0-t.
Ratio summarizations will be reported for all non-transformed pharmacokinetic parameters.
Intra-Subject variability will be computed for ln-transformed pharmacokinetic parameters Cmax, and AUC0-t.
Statistical analysis plan for Emtricitabine, Tenofovir and Dolutegravir:
The ln-transformed pharmacokinetic parameters Cmax and AUC0-t.of Emtricitabine, Tenofovir (Cmax, AUC0-72) and Dolutegravir will be subjected to Analysis of Variance (ANOVA) by usingPROC GLM procedure of SAS version 9.4 or higher. ANOVA model will include Sequence, Formulation, Period and Subject (Sequence) as fixed effects.
Sequence effect will be tested using Subject (Sequence) as an error term.
An F-test will be performed to determine the statistical significance of the effects involved in the model at a significance level of 5% (alpha =0.05).
All the main effects will be tested at 5% Level of Significance.
Bioequivalence evaluation:
BE criteria For Emtricitabine, Tenofovir and Dolutegravir: 90% CI should fall between 80 to125% for all primary pharmacokinetics for Emtricitabine & Dolutegravir.
Note: Pharmacokinetic data from tenofovir will be provided as supportive evidence of comparable therapeutic outcome.
Bioequivalence evaluation:
BE criteria for Tenofovir Alafenamide:
1. If within-subject standard deviation of the reference product SWR 0.294 then assessment of bioequivalence will be determined using scaled average bioequivalence criteria.
a. The point estimates (Geometric Least Squares mean of test/reference ratios) must fall within the bioequivalent limits 80.00% 125.00%.
b. The 95% upper confidence bound for (T- R)2- S2 WR must be 0.0000, where = (ln (1.25)/ W0)2 andW0 = 0.25.
2. If within-subject standard deviation of the reference product SWR < 0.294 then assessment of bioequivalence will be determined using average bioequivalence criteria
APPENDIX VI: STUDY CONDUCT INFORMATION
Dr. Nikhil Kumar Kursam., M.B.B.S., M.D.,
CLINICAL DEVELOPMENT DIVISION,
Aizant Drug Research Solutions private limited.,
Survey No.: 172 &173, Apparel Park Road, Dulapally Village,
Dundigal Gandimaisamma Mandal,
Medchal-Malkhajgiri District - 500100,
Phone No.: +91 40 23792190/91/92;
Fax No.: +91 40 23792223.
Clinical Research Facility:
Clinical Pharmacology Unit-I,
CLINICAL DEVELOPMENT DIVISION
Aizant Drug Research Solutions private limited.,
Survey No.: 172 &173, Apparel Park Road, Dulapally Village,
Dundigal Gandimaisamma Mandal,
Medchal-Malkhajgiri District - 500100,
Phone No.: +91 40 2379219
Stastical Investigator and Randomization Facility:
Mr. Udaya Kumar Konda
Pharmacokinetic & Statistical analysis
Aizant Drug Research Solutions Pvt. Ltd.,
Survey No.: 172 &173, Apparel Park Road,
Dulapally Village, Dundigal Gandimaisamma Mandal, Medchal-
Malkhajgiri District - 500100, Telangana, India. Phone No.: +91 40