CTRI/2022/06/043078 [Registered on: 07/06/2022] Trial Registered Prospectively
Last Modified On:
07/01/2026
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioequivalence study of Abacavir, Dolutegravir and Lamivudine tablets for oral suspension 60mg/5mg/30mg in Healthy adult male and female (not of childbearing potential) human volunteers under fed conditions
Scientific Title of Study
Single dose, randomization blinded, two-period, two-treatment, twosequence,
crossover, oral bioequivalence study of Mylan’s Test product Abacavir, Dolutegravir and Lamivudine tablets for oral suspension 60mg/5mg/30mg with Reference Product Triumeq Dispersible Tablets (5mg GSK1349572/60mg Abacavir/30 mg Lamivudine) Manufactured for: ViiV Healthcare UK Limited, 980 Great West Road, Brentford,Middlesex, TW8 9GS, UK, in Healthy adult male and female (not of childbearing potential) human volunteers under fed conditions.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
ABDL-TBP-1003, Version 00, Date: 20 Jan 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Anjum Jabeen MBBS MD
Designation
Manager
Affiliation
Manager - Aizant Drug Research Solutions Private Limited
Address
Aizant Drug Research Solutions Private Limited Clinical Pharmacology Unit-II, St. Theresas Hospital, 2 Floor, Premises No.7-1-645/A,Sanathnagar, Hyderabad Aizant Drug Research Solutions Private Limited Clinical Pharmacology Unit-II, St. Theresas Hospital, 2 Floor, Premises No.7-1-645/A,Sanathnagar, Hyderabad Hyderabad TELANGANA 500018 India
Phone
914023792190
Fax
914023792223
Email
anjum.jabeen@aizant.com
Details of Contact Person Scientific Query
Name
Dr Anjum Jabeen MBBS MD
Designation
Manager
Affiliation
Manager - Aizant Drug Research Solutions Private Limited
Address
Aizant Drug Research Solutions Private Limited Clinical Pharmacology Unit-II, St. Theresas Hospital, 2 Floor, Premises No.7-1-645/A,Sanathnagar, Hyderabad Aizant Drug Research Solutions Private Limited Clinical Pharmacology Unit-II, St. Theresas Hospital, 2 Floor, Premises No.7-1-645/A,Sanathnagar, Hyderabad Medchal TELANGANA 500018 India
Phone
914023792190
Fax
914023792223
Email
anjum.jabeen@aizant.com
Details of Contact Person Public Query
Name
Dr Chakravarthy K MBBS MD
Designation
Deputy Director
Affiliation
Deputy Director - Aizant Drug Research Solutions Private Limited
Address
Aizant Drug Research Solutions Private Limited, Sy.No.172 and 173, Apparel Park road, Dulapally Village, Dundigal gandimaisamma Mandal,Hyderabad Aizant Drug Research Solutions Private Limited, Sy.No.172 and 173, Apparel Park road, Dulapally Village, Dundigal gandimaisamma Mandal,Hyderabad Medchal TELANGANA 500100 India
Phone
914023792190
Fax
914023792223
Email
chakravarthy.k@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, India – 500062.
Primary Sponsor
Name
Mylan Laboratories Limited
Address
Mylan Laboratories Limited,
Clinical Research Centre, Saradhi Chambers Plot No.A 4, Beside Poulomi Hospital, Rukminipuri, Dr. A. S. Rao Nagar,
Hyderabad, India 500062.
Type of Sponsor
Pharmaceutical industry-Global
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 Anjum Jabeen MBBS MD
Aizant Drug Research Solutions Pvt. Ltd., Clinical Pharmacology Unit-II
Abacavir, Dolutegravir and Lamivudine tablets for oral suspension 60mg/5mg/30mg
Single dose, randomization blinded, two-period, two-treatment, twosequence, crossover, oral bioequivalence study of Abacavir, Dolutegravir and Lamivudine tablets for oral suspension 60mg/5mg/30mg in Healthy adult male and female (not of childbearing potential) human volunteers under fed conditions. There will be at least 07 days between dosing times for the treatment periods.
Single dose, randomization blinded, two-period, two-treatment,twosequence,
crossover, oral bioequivalence study in Healthy adult male and female (not of childbearing potential) human volunteers under fed conditions. There will be at least 07 days 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 male and female (not of childbearing potential) human subjects, age
between 18 to 45 years (inclusive of both).
2. A female may be eligible to enter and participate in the study if she is of non-childbearing
potential, defined as either post-menopausal (12 months of spontaneous amenorrhea and
equal to or older than 45 years of age) or physically incapable of becoming pregnant
documented tubal ligation, hysteroctomy or bilateral oophorectomy.
3. Body mass index of ≥ 18.5 kg/m2 and ≤ 24.9 kg/m2 and weight ≥ 50.00 kg.
4. Healthy according to the laboratory results and physical examination, performed within 21
days prior to the commencement of the dosing in Period-1.
5. 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.
6. HLA-B 5701 allele negative subjects.
7. Have normal ECG, Chest X-ray and vital signs.
8. Non-smoker and Non-alcoholic.
9. Subject able to communicate effectively and willing to provide informed consent.
10. Subject willing to adhere to protocol requirements as evidenced by informed consent
approved by an Independent Ethics Committee (IEC).
ExclusionCriteria
Details
A subject will not be eligible for study participation if he/she meets any of the following
criteria:
1. Any history of allergy or hypersensitivity to Abacavir / Dolutegravir / Lamivudine or other related drugs.
2.Positive test result for or HIV-1 antibody or HIV Type 2 (HIV-2) antibody (HIV Ab) or VDRL / syphilis.
3. Positive hepatitis B surface antigen (HBs Ag) and hepatitis C virus antibody (HCV Ab) test results at screening or within 03 months prior to starting the study intervention are excluded
from the study.
4. Any history or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, dermatological, neurological, psychiatric diseases or disorders
and Clinically significant abnormal values of laboratory parameters.
a. Subjects with moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification.
b. Subject has creatinine clearance of <60 mL/min
5. Subject having Modified Patient Health Questionnaire (PHQ)-12 questionnaires >4.
6. Any history of bleeding disorders, peptic ulcer diseases, hemorrhoids, wounds/ ulcers.
7. History or presence of drug abuse in the past one year.
8. Difficulty in swallowing tablets/capsules.
9. Any history of difficulty in donating blood.
10. Resting Blood pressure is < 110/70 and > 129/79 millimeters of mercury (Systolic blood pressure/ Diastolic blood pressure).
11. Resting Pulse rate less than 60 beats / minute and more than 100 beats / minute.
12. Usage of any prescribed medication during last 14 days and for OTC medicinal products, herbal products during the last 07 days preceding the first dosing.
13. Usage of any clinically significant medications last 30 days preceding the first dosing.
14. Any clinically significant illness during 3 months before screening.
15.Participation in a drug research study/donation of blood within past 90 days.
16. ALT > 1.5 xULN or total bilirubin > 1.5 xULN.
17. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilberts syndrome or asymptomatic gallstones).
18. Consideration by the investigator, for any reason that the subject is an unsuitable candidate to receive study drug.
19. Breastfeeding
20. Clinically significant history of psychiatric disease.
21. Female subject demonstrating positive for pregnancy test (performed at the time of each period check-in).
Subject positive for alcohol test (by using urine/ blood), urine screen for drugs of abuse
[Cannabinoids (Marijuana / Tetra Hydro Cannabinoids-THC), Cocaine, Opiates (morphine), Amphetamine, Barbiturates and Benzodiazepines] and pregnancy test (for female subjects only) at the time of each period check-in will be excluded from the study.
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 Abacavir, Dolutegravir and Lamivudine tablets for oral suspension
60mg/5mg/30mg with Reference Product Triumeq Dispersible Tablets (5mg GSK1349572/60mg Abacavir/30 mg Lamivudine) Manufactured for: ViiV Healthcare UK Limited, 980 Great West Road, Brentford, Middlesex, TW8 9GS, UK, following a single oral dose of test product or reference products administration under fed conditions.
The objective of this study is to investigate the comparative relative oral bioavailability of
Mylan’s Test product Abacavir, Dolutegravir and Lamivudine tablets for oral suspension
60mg/5mg/30mg with Reference Product Triumeq Dispersible Tablets (5mg GSK1349572/60mg Abacavir/30 mg Lamivudine) Manufactured for: ViiV Healthcare UK Limited, 980 Great West Road, Brentford, Middlesex, TW8 9GS, UK, following a single oral dose of test product or reference products administration under fed conditions.
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of the subjects.
45 days clinical schedule
Target Sample Size
Total Sample Size="60" Sample Size from India="60" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
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, randomization blinded, two-period, two-treatment, twosequence, crossover, oral bioequivalence study of Mylan’s Test product Abacavir, Dolutegravir and Lamivudine tablets for oral suspension 60mg/5mg/30mg with Reference Product Triumeq Dispersible Tablets (5mg GSK1349572/60mg Abacavir/30 mg Lamivudine) Manufactured for: ViiV Healthcare UK Limited, 980 Great West Road, Brentford,Middlesex, TW8 9GS, UK, in Healthy adult male and female (not of childbearing potential) human volunteers under fed conditions.
Protocol No.
ABDL-TBP-1003
Product
Abacavir, Dolutegravir and Lamivudine tablets for oral suspension 60mg/5mg/30mg
Study Type
Pivotal Fed Bioequivalence
Version
00 Region of Submission PEPFAR
Protocol Date
20 Jan 2022 Revision Date : N/A
General Description
This protocol describes a single-dose, randomization blinded, two-period, two-treatment, two-sequence, crossover study to investigate the bioequivalence of Mylan’s Test product Abacavir, Dolutegravir and Lamivudine tablets for oral suspension 60mg/5mg/30mg with Reference Product Triumeq Dispersible Tablets (5mg GSK1349572/60mg Abacavir/30 mg Lamivudine) Manufactured for: ViiV Healthcare UK Limited, 980 Great West Road, Brentford, Middlesex, TW8 9GS, UK.
Pharmacokinetics will be characterized in Sixty (60) healthy, adult male and female (not of childbearing potential) human volunteers following administration of a Single oral dose of either test product or reference product administration under fed conditions.
28 blood samples of six milliliter (1 × 6 mL) each will be collected in K3 EDTA tubes at pre-dose (0.00) and the following times after dosing: 0.084, 0.17, 0.25, 0.333, 0.5, 0.67, 0.83, 1.0, 1.25, 1.50, 1.75, 2.0, 2.25, 2.50, 2.75, 3.0, 3.50, 4.0, 5.0, 6.0, 8.0, 10, 12, 24, 36, 48 and 72 hours. The collected blood samples will be cooled in an ice bath and centrifuged under refrigeration as soon as possible. Two aliquots 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 -85°C at the clinical site until transferred on dry ice to analytical site.
For the determination of the pharmacokinetic disposition of the formulations, there will be a total of 56 blood samples involving a total of 336 mL of blood collected for pharmacokinetic analysis from each subject provided they complete all blood collections in the study. There will be at least 07 days between dosing times for the treatment periods.
The bioequivalence of Mylan’s Test product Abacavir, Dolutegravir and Lamivudine tablets for oral suspension 60mg/5mg/30mg with Reference Product Triumeq Dispersible Tablets (5mg GSK1349572/60mg Abacavir/30 mg Lamivudine) Manufactured for: ViiV Healthcare UK Limited, 980 Great West Road, Brentford, Middlesex, TW8 9GS, UK will be assessed by a statistical comparison of various pharmacokinetic parameters derived from the plasma concentration-time curves of the drug.
OBJECTIVES
Primary Objective: The objective of this study is to investigate the comparative relative oral bioavailability of Mylan’s Test product Abacavir, Dolutegravir and Lamivudine tablets for oral suspension 60mg/5mg/30mg with Reference Product Triumeq Dispersible Tablets (5mg GSK1349572/60mg Abacavir/30 mg Lamivudine) Manufactured for: ViiV Healthcare UK Limited, 980 Great West Road, Brentford, Middlesex, TW8 9GS, UK, following a single oral dose of test product or reference products administration under fed conditions. Secondary Objective: To monitor the adverse events and to ensure the safety of the subjects.
STUDY DRUG
Investigational Drug: Test Product (T): Abacavir, Dolutegravir and Lamivudine tablets for oral suspension 60mg/5mg/30mg. Manufactured By: Mylan Laboratories Limited., India Reference Product (R): Trimeq Dispersible Tablets (5mg GSK1349572/60mg Abacavir/30 mg Lamivudine) Manufactured by: GlaxoSmithKline Research & Development Limited, Glaxo Operations UK Ltd, Priory Street, Ware, Hertfordshire, SG12 0DG, UK Manufactured for: ViiV Healthcare UK Limited, 980 Great West Road, Brentford, Middlesex, TW8 9GS, UK
Product Description: GSK1349572 5mg/Abacavir 60mg/Lamivudine 30mg pediatric dispersible tablets are pale yellow, biconvex, oval, film-coated, debossed with ‘SV WTU’ on one side and plain on the opposite side. Each tablet contains 70.2 mg abacavir sulfate, which is equivalent to 60 mg of abacavir free base; 5.26 mg dolutegravir sodium, which is equivalent to 5 mg of dolutegravir free acid; and 30 mg of lamivudine. The tablets are packaged in HDPE bottles with child-resistant closures that include an induction seal and a desiccant. Store and dispense in the original package, protect from moisture, and keep bottles tightly closed. Do not remove desiccant. In the study site pharmacy, store up to 30°C (86°F).
The label on each subject’s dispensed drug(s) will include the study code identifier and the randomization number (i.e., subject number). Additional information such as dosing period, route of administration and date, may be appropriate for inclusion on the dispensed drug’s label. The label should include sufficient information to ensure compliance with applicable local/regional regulations and the protocol.
An example of an acceptable label would contain the following: study number, period, subject number, generic drug name, dosage form, route of administration, quantity, clinical site information, and text: for clinical use only.
STUDY CONDUCT
This is a single-dose, randomization blinded, two-period, two-treatment two-sequence crossover study investigating the bioequivalence of Mylan’s Test product Abacavir, Dolutegravir and Lamivudine tablets for oral suspension 60mg/5mg/30mg with Reference Product Triumeq Dispersible Tablets (5mg GSK1349572/60mg Abacavir/30 mg Lamivudine) Manufactured for: ViiV Healthcare UK Limited, 980 Great West Road, Brentford, Middlesex, TW8 9GS, UK, in healthy adult male and female (not of childbearing potential) human volunteers following a single oral dose of test product or reference product in Sixty (60) healthy adult human volunteers under fed conditions.
Subjects will be housed 11.00 hours prior to drug dosing of each period and until at least 72.00 hours after investigational drug administration. Blood samples will be collected prior to dosing and 72.00 hours after each dosing. There will be at least 07 days between dosing times for the 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 12 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 Form (ICF) before any screening procedure is initiated. 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 Principal Investigator or Medical Sub-Investigator will review the inclusion and exclusion criteria to confirm eligibility of each subject prior to enrollment.
Modified Patient Health Questionnaire (PHQ) -12 questionnaires will be evaluated before period-1 check in (Appendix XII). The physician in charge will assess abnormal values to determine if it is clinically significant. Clinical/Laboratory Diagnostic Tests: 1. Hematology: Red blood cell count, White blood cell count, Differential white blood cell count (Neutrophils%, Lymphocytes%, Eosinophils%, Monocytes % and Basophils %), Hemoglobin estimation, Platelet count, Blood grouping and Rh typing 2. Biochemistry: Serum creatinine, Blood urea, SGOT (AST), SGPT (ALT), Serum alkaline phosphatase (ALP), Total bilirubin, Blood sugar/ Plasma Glucose (Random), Serum electrolytes (Sodium, Potassium and Chloride) 3. Serology: HIV (1 & 2) antibodies, Hbs Ag (Hepatitis B surface antigen), HCV antibodies and VDRL/Syphilis. 4. Urine analysis: Color, Appearance/Transparency, pH, Specific gravity, Glucose, Ketones, Bilirubin, Blood, Leucocytes, Proteins, Nitrite, Urobilinogen and Urine microscopic examination (Pus Cells, Red Blood Cells, Epithelial Cells, Casts and Crystals). 5. Additional Tests: Creatinine Clearance (by using Cockroft-Gault method), HLA-B 5701 allele test, Prothrombin Time (PT) and INR. Serum pregnancy test (for women volunteers).
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 to and until at least 72.00 hours after dosing in each period of the study.
Toxicity Management
In the event of a discontinuation of dolutegravir (DTG) containing product for suspected drug induced liver injury, other clinically significant liver chemistry elevations, severe skin reaction or hypersensitivity reaction, subjects should not be rechallenged with a dolutegravir-containing product due to the risk of a recurrent reaction. These subjects should be withdrawn from study. Further details on this are provided in this section as appropriate.
All toxicity related adverse events and gradings will be documented as per the standards mentioned in the information Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events. Refer Section 11 Sr.No 12
Bioanalytical Method
A validated assay method will be employed for the analysis of Abacavir/ Dolutegravir/ Lamivudine 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
Concentration data of subject versus time, which are received after analysis of samples, will be included in the final data analysis. Subjects who complete all periods of the study will be considered for the pharmacokinetic and statistical analysis. Concentration data of subjects who withdrawn from the study due to adverse events will be reported separately and will not be included in the pharmacokinetic and statistical analysis. Data from subjects with missing concentration values (missed blood samples, lost samples, samples unable to be quantified) may be used if pharmacokinetic parameters can be estimated using remaining data points on case to case basis, otherwise data from these subjects will be excluded from the final analysis. All concentration values below the limit of quantification (BLOQ/BLQ) will be set to zero for all pharmacokinetic and statistical calculations. 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 using validated statistical software for Abacavir / Dolutegravir / Lamivudine. Cmax : Maximum observed plasma concentration following each treatment. AUC0-t : AUC is defined as the area under the concentration-time curve. AUC will be estimated using the Linear Up Log Down calculation method i.e. linear trapezoidal for pre-Cmax and log trapezoidal post Cmax. AUC0-inf : The area under the plasma concentration versus time curve from time zero to infinity. Where AUC0-inf = AUC0-t + Ct/ λz, Ct is the last measurable concentration and λz is the terminal elimination rate constant. AUC_%Extr ap_ obs: The residual area in percentage will be determined by the formula, [(AUC0-inf - AUC0-t)/AUC0-inf] x 100. Tmax : Time of the maximum measured plasma concentration t½ : The elimination half-life will be calculated as 0.693/ λz Kel : First order rate constant associated with the terminal (log-linear) 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.
Note: 1. For all the above computations, actual time points of the sample collection will be used in case of sample collection deviations. 2. For an acceptable Kel value, r should not be less than 0.8944 (or r2 not less than 0.80). If r is less than 0.8944, then Kel is set missing. Rarely, under certain special situations, other rules may be used. In these instances (ex. When low % of Kel able to be determined), the statistical programmer or statistician will consult with pharmacokinetics. Any alternative rules used must be documented in a memo to the Trial Master File (TMF). 3. If the pre-dose value is greater than 5% of Cmax, that subject will be dropped from pharmacokinetics and statistical analysis. 4. For any subject having very low plasma concentrations, if its AUC is less than 5% of reference product geometric mean AUC (which should be calculated without inclusion of data from the outlying subject). 5. If any subject experiences emesis at or within two times the median Tmax time following the drug administration in each study period, such subject data will be analysed however data of the subject will not be included in pharmacokinetic and statistical analysis.
Statistical Analysis of the Pharmacokinetic Parameters
Statistical analysis will be performed on the data obtained from the subjects who complete all periods of the study as per IEC approved protocol using appropriate validated statistical software. Descriptive statistics of all the pharmacokinetic parameters will be computed and reported for Abacavir/ Dolutegravir/ Lamivudine. The summary statistics (for relevant pharmacokinetic parameters) will be computed and reported for both test and reference products of Abacavir/ Dolutegravir/ Lamivudine.
The ln-transformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf of Abacavir/ Dolutegravir/ Lamivudine will be subjected to Analysis of Variance (ANOVA). ANOVA model will include Sequence, Formulation, Period and Subject (Sequence) as as fixed effects. Sequence effect will be tested using Subject (Sequence) as 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 period, Treatment and sequence effects will be tested at 5% Level of Significance. Two one-sided test for bioequivalence and 90 % confidence intervals for the ratio of least squares mean between drug formulations will be calculated, for ln-transformed data of Cmax, AUC0-t and AUC0-inf of Abacavir / Dolutegravir / Lamivudine. The power of a test to detect 20% difference between test and reference products will be computed and reported for Abacavir / Dolutegravir / Lamivudine. Ratio of least squares means of test and reference products will be computed for ln-transformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf. Ratio analysis will be reported for ln-transformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf of Abacavir / Dolutegravir / Lamivudine. Intra-Subject variability will be computed for ln-transformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf of Abacavir / Dolutegravir / Lamivudine. Bioequivalence of the test product with that of the reference product under fed conditions will be concluded if the 90% confidence intervals of geometric least square mean ratio of the test and reference product falls within the acceptance range of 80.00 % – 125.00% for lntransformed pharmacokinetic parameters of Cmax, AUC0-t and AUC0-inf for Abacavir / Dolutegravir / Lamivudine reported on normal scale. It is the sponsor’s intent to complete this study in one cohort. In the event that separate enrollments are necessary to complete the intended number of subjects, appropriate adjustments may be made to the statistical model to reflect the multi-cohort nature of the study. a. Additional cohorts will be recruited and dosed under the following conditions: i. Recruiting for additional enrollment(s) begin before the end of the final period of the previous enrollment; ii. Subjects are recruited from the same population, under the same protocol requirements; iii. dosing of additional cohorts began as soon as practical after their recruitment; and iv. no two cohorts are dosed on the same day. b. Appropriate adjustments will be made to the statistical model to reflect the multi-cohort nature of the study if: i. the number of cohorts is less than or equal to 3; and ii. there are at least 6 subjects in each cohort.
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: ABDL-TBP-1003 Protocol Title: Single dose, randomization blinded, two-period, two-treatment, two-sequence, crossover, oral bioequivalence study of Mylan’s Test product Abacavir, Dolutegravir and Lamivudine tablets for oral suspension 60mg/5mg/30mg with Reference Product Triumeq Dispersible Tablets (5mg GSK1349572/60mg Abacavir/30 mg Lamivudine) Manufactured for: ViiV Healthcare UK Limited, 980 Great West Road, Brentford, Middlesex, TW8 9GS, UK, in Healthy adult male and female (not of childbearing potential) human volunteers under fed conditions.
Principal Investigator : Dr. Anjum Jabeen, M.B.B.S., M.D., (please attach curriculum vitae when return to Mylan)
Address of Principal Investigator M/s. Aizant Drug Research Solutions Private Limited Clinical Pharmacology Unit-II St. Theresa’s Hospital, Clinical Pharmacology Department, 02nd Floor, Premises No.7-1-645/A, Sanathnagar, Hyderabad Telangana, India– 500018 Phone Number of Principal Investigator + 91 40 23811981, 91 40 23811982
Clinical Research Facility : Clinical Pharmacology Department,
Address of Clinical Facility M/s. Aizant Drug Research Solutions Private Limited Clinical Pharmacology Unit-II St. Theresa’s Hospital, Clinical Pharmacology Department, 02nd Floor, Premises No.7-1-645/A, Sanathnagar, Hyderabad Telangana, India– 500018. Phone No: + 91 40 23811981, 91 40 23811982
Stastical Investigator : Mr. Uday Kumar Konda M.Sc.,M. Phil 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 23792190/91/92, Fax No: +91 40 23792223
Bioanalytical Investigator : Mr. Amarnath Jaiswal, M Sc. (Tech.), Mylan Laboratories Limited, Clinical Research Centre, Saradhi Chambers, Plot No: A-4, Beside Poulomi Hospital, Rukminipuri, Dr. A. S. Rao Nagar, Hyderabad, India – 500062. Phone No: +91 40 30492901 Fax No: +91 40 27138562
Listing of Sub-Investigator(s) : Dr. K. Suraj Kumar, M.B.B.S., (attach separate sheet, if necessary)