Bioequivalence study of Abacavir, Dolutegravir and Lamivudine Tablets for Oral Suspension60mg/5mg/30mg (1 × 5 Tablets) with comparision to the marketed product under fed conditions

Phase 1

Not yet recruiting

• Conditions: Antiretroviral

• Registration Number: CTRI/2022/02/040129
• Lead Sponsor: APL Research Centre Aurobindo Pharma Limited

Brief Summary

This is an openlabel, balanced, randomized, two-treatment, two-sequence, two-period,cross-over, single-dose, oral bioequivalence study of Abacavir, Dolutegravirand Lamivudine Tablets for Oral Suspension 60mg/5mg/30mg (1 × 5 Tablets) (Test)of Aurobindo Pharma Limited, India with Dolutegravir (GSK1349572)/Abacavir/LamivudineDispersible Tablets 5 mg/60 mg/30 mg (1 × 5 Tablets) (Reference) of ViiVHealthcare, UK in 54 healthy, adult, male subjects under fed conditions. There willbe an allowed screening period of 28 days before randomization. The subjectselection will be carried out based on 28 days of screening validity excludingday of screening and check-in. This will be a two-period study and at least 10days washout period will be maintained between each treatment administration.During screening, healthy subjects meeting all inclusion and none of theexclusion criteria will be randomized. If the subject will pass through all thescreening criteria and is willing to participate in the study, the PI willenroll the subjects into the study. After an overnight fast of at least 10.00 hours andexactly 30 minutes after serving of high fat, high calorie breakfast, subjectswill be dosed with either a single oral dose of Test product(T) or Reference product (R) with approximately 240 mL of drinking water atroom temperature under fed conditions as per randomization schedule.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-02-14
• Last Update Posted: 2022-04-02

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: Male
• Target Recruitment: 54

Inclusion Criteria

• 1.Healthy, adult, male subjects within the age range of 18 to 45 years (inclusive of both).
• 2.A body mass index within the range of 18.50-29.99 Kg/m2 (inclusive of both).
• 3.Participation is truly voluntarily.
• 4.Given written informed consent to participate in the study.
• 5.Absence of disease markers of HIV 1 & 2, hepatitis B & C virus and RPR (i.e. Rapid Plasma Reagin).
• 6.Absence of significant diseases and abnormalities in medical history, systemic and physical examination during the screening.
• 7.Absence of clinically significant abnormal laboratory values on laboratory evaluation (any laboratory values which are beyond the normal ranges, have been evaluated with appropriate justification by the investigator/physician) during screening (refer Appendix-V).
• 8.A normal 12-lead ECG.
• 9.The subject is negative for the HLA-B X 5701 allele.
• 10.The subject is negative result for the Hepatitis B core antibody (Anti-HBc (total or immunoglobulin G (IgG))) and HBV DNA (Qualitative) performed on the day of ICF.
• 11.Normal in assessment of Columbia Suicidality Severity Rating Scale (C-SSRS) (refer Appendix-XVI) performed during check-in of each period.
• 12.Normal values in the assessment of depression using depression scale (refer Appendix-XV) during check-in of each period.
• 13.Normal levels of serum amylase test, serum creatine phosphokinase (CPK) test and serum triglycerides test performed during check-in of period-I.
• 14.Having Creatinine clearance (CKD-EPI) test values greater than 90 mL/min performed during period-I check-in.
• 15.A normal chest X-ray (PA view) (done within past 06 months).
• 17.Male subject should be agreed to use contraception during the study including washout period.
• Approved birth control methods (barrier forms) during this period are: •Male latex condom with or without spermicide.
• •Condom with diaphragm.
• •Have undergone vasectomy (vasectomy must have been done more than 06 months prior to first dosing).

Exclusion Criteria

• 1.Institutionalized volunteers.
• 2.History or evidence of known hypersensitivity to Dolutegravir, Abacavir and Lamivudine or any component of the formulations.
• 3.History or evidence of moderate to severe renal impairment or moderate to severe hepatic impairment.
• 4.History or evidence of depression, suicidal ideation or behaviour.
• 5.History or evidence of unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilberts syndrome or asymptomatic gallstones).
• 6.History or evidence of myocardial infarction (MI).
• 7.History or evidence of lactic acidosis and severe hepatomegaly with steatosis.
• 8.History or evidence of general malaise, fatigue, muscle or joint aches, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing.
• 9.History or evidence of Alanine aminotransferase (ALT) greater than 1.5 x ULN and/or total bilirubin greater than 1.5 x ULN at baseline (isolated bilirubin greater than 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
• 10.History or evidence of concomitant use of Dofetilide (or pilsicainide), Etravirine, Trimethoprim, Efavirenz, Nevirapine, Fosamprenavir/ritonavir and Tipranavir/ritonavir, Dalfampridine, Carbamazepine, Oxcarbazepine, Phenytoin, Phenobarbital, St. John’s wort (Hypericum perforatum), medications containing polyvalent cations (Mg or Al) Cation containing antacids or laxatives, Sucralfate buffered medications, oral calcium and iron supplements, including multivitamins containing calcium or iron, Metformin, Rifampin, Methadone, Sorbitol and Riociguat.
• 11.Positive test result for hepatitis B core antibody (Anti HBc (total or immunoglobulin G (IgG)) and HBV DNA (Qualitative) performed on the day of ICF.
• 12.Positive test result for hepatitis B surface antigen (HBs Ag), hepatitis C virus antibody (HCV Ab) performed during screening.
• 13.Positive test result for HIV 1 and HIV Type 2 (HIV 2) antigen or antibody immune assay performed during screening.
• 14.Subjects who are having clinical significant laboratory values in liver function test (LFT) performed during checkin of period II.
• 15.Blood pressure Systolic greater than 140 mm Hg and less than 110 mm Hg 16.Diastolic less than 70 mm Hg and greater than 90 mm Hg 17.History of significant systemic diseases, seizures, psychiatric disorders, neurological disorders, metabolic disorders, nutritional disorders and/or allergic rash.
• 18.Any family history of neurological disorder.
• 19.Habit of consuming high caffeine (more than 5 cups of coffee or tea per day) or tobacco (more than 9 cigarettes or beedies or cigars per day).
• 21.History of difficulty with donating blood or difficulty in accessibility of veins.
• 22.Donation of blood (one unit or 350 mL) within 90 days prior to study checkin.
• 23.History of addiction to any recreational drug or drug dependence.
• 24.Participation in any clinical study within the past 90 days.
• 25.An unusual or abnormal diet, for whatever reason for at least 48.00 hours prior to check-in of each period, fasting due to religious reasons.
• 26.Use of any prescription drugs or over the counter drugs (OTC) (cold preparations, antacid preparations, vitamins or natural products, herbal and dietary supplements (including St Johns wort, calcium and iron supplements) etc)] within 14 days or at least 5 halflives of the compound whichever period is longer prior to checkin of period I and unwilling to refrain from the same till the entire duration of the study.
• 27.Consumed food or beverages containing alcohol or xanthine products (chocolate, tea, coffee, cola or energy drinks), cigarettes or tobacco products for at least 48.00 hours prior to checkin of each period.
• 28.Unwillingness to abstain from excessive consumption of any food or drink containing grapefruit or grapefruit like citrus fruits (mosambi or sweet lime), Seville oranges, blood oranges, or pomelos or their fruit or juice within 7 days prior to the first dose of study interventions and until the end of the study (Excessive consumption is defined as more than one glass of juice or one of these fruits per day, in combination).
• 29.Unwillingness to abstain from chewing or ingesting sugar free gums, candies or other processed food or drink products that contain sugar alcohols (sorbitol, mannitol, xylitol, maltitol, isomalt) for 48.00 hours prior to dosing until the last pharmacokinetic sample is collected.
• 30.History of dehydration from diarrhea, vomiting or any other reason for at least a period of 24.00 hours prior to check-in of each period.
• 31.Use of pharmacological agents known to significantly induce or inhibit drug metabolizing enzymes within 14 days prior to check-in of period-I and unwilling to refrain from the same till the entire duration of the study.
• 32.Positive results for drugs of abuse (benzodiazepines, cocaine, opioids, amphetamines, cannabinoids and barbiturates) in urine performed during the check-in of each period.
• 33.Positive results for urine alcohol test performed at the time of check in of each period.

Study & Design

• Study Type: BA/BE
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To demonstrate the bioequivalence between Test product (T): Abacavir, Dolutegravir and Lamivudine Tablets for Oral Suspension 60mg/5mg/30mg (1 × 5 Tablets) of Aurobindo Pharma Limited, India with that of Reference product (R): Dolutegravir (GSK1349572)/Abacavir/Lamivudine Dispersible Tablets 5 mg/60 mg/30 mg (1 × 5 Tablets) of ViiV Healthcare, UK in 54 healthy, adult, male subjects under fed conditions.	A single pre-dose (00.00 hour) blood sample of 12 mL (2 × 6 mL vacutainers) will be collected in each period. The post-dose blood samples of 6 mL each will be collected at 00.25, 00.50, 00.75, 01.00, 01.33, 01.67, 02.00, 02.33, 02.67, 03.00, 03.50, 04.00, 04.50, 05.00, 05.50, 06.00, 08.00, 12.00, 18.00, 24.00, 36.00, 48.00 and 72.00 hours in each period

Secondary Outcome Measures

Name	Time	Method
To monitor the subjects safety and tolerability of single-dose of investigational products (IPs).	Adverse events and clinically significant deviations from laboratory tests, physical examinations and vital signs will be reported for the evaluation of safety.

Trial Locations

Locations (1)

AXIS Clinicals Limited; 🇮🇳 Hyderabad, TELANGANA, India

AXIS Clinicals Limited

🇮🇳Hyderabad, TELANGANA, India

Dr M Gyaneshwar

Principal investigator

9642990039

Gyaneswar.Mandugula@axisclinicals.com