Bioequivalence Study of Fixed Dose Versus Single Entities of Dolutegravir and Lamivudine

NCT ID: NCT03078556

Last Updated: 2019-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-27
• Study Completion Date: 2017-08-18

Brief Summary

This study aims to compare the bioequivalence of two experimental fixed dose combination (FDC) tablets versus single entity products of dolutegravir (DTG) and lamivudine (3TC) in healthy adult subjects. The study will be carried out in two parts. Part 1 of the study will be open label, up to 3 periods design with a wash out period of at least 7 days between treatment periods. Subjects will be randomized to receive either single entities or formulation 1 FDC of DTG and 3TC in a crossover manner in first 2 periods. The first 16 subjects who complete the first two treatment periods and consent to continue will receive a single dose of FDC formulation 1 tablet administered with a high fat meal for a third treatment period. In Part 2 of the study, subjects will be randomized to receive either single entities or formulation 2 FDC of DTG and 3TC in a crossover manner in first 2 periods. Similarly the first 16 subjects will then receive FDC formulation 2 tablets with high fat meal in treatment period 3. Subjects will have a follow-up visit within 7-14 days after the last dose of study drug. Approximately 76 healthy subjects will be included in Part 1 of the study and if Part 2 of the study is conducted, another 76 healthy subjects will be included. The total duration will be approximately 11 weeks.

Conditions

Infection, Human Immunodeficiency Virus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment sequence A/B: Part 1

Eligible subjects will be randomized in sequence A/B and will receive A: DTG 50 milligram (mg) and 3TC 300 mg single entities in Period 1, B: DTG 3TC FDC formulation 1 tablet in Period 2.

Group Type: EXPERIMENTAL

Dolutegravir

Intervention Type: DRUG

Single dose of DTG 50 mg tablet along with 3TC (EPIVIR) tablet will be given to randomized subjects in parts 1 and 2 with 240 mL of room temperature water. DTG will be a white, film coated, round tablet engraved with SV 572 on one side and 50 on the other side.

Lamivudine

Intervention Type: DRUG

Single dose 3TC (commercial name: EPIVIR) 300 mg tablet along with DTG tablet will be given to randomized subjects in parts 1 and 2 with 240 mL of room temperature water.\<br\>3TC will be gray, diamond shaped tablet, engraved "GX EJ7" on one side and plain on the other side.

Dolutegravir + Lamivudine FDC Formulation 1

Intervention Type: DRUG

Single dose of DTG 50 mg combined with 3TC 300 mg in a FDC formulation 1 tablet will be administered to randomized subjects in treatment periods 1 and 2 (under fasted state) of Part 1 and the first 16 subjects in treatment period 3 (under fed) of Part 1 with 240 mL of room temperature water. \&lt;br\&gt;FDC formulation 1 tablets will be oval, biconvex, white, film coated tablet engraved 'SV H7I' on one face.

Treatment sequence B/A: Part 1

Eligible subjects will be randomized in sequence B/A and will receive B: DTG 3TC FDC formulation 1 tablet in Period 1 and A: DTG 50 mg and 3TC 300 mg single entities in Period 2.

Group Type: EXPERIMENTAL

Dolutegravir

Intervention Type: DRUG

Single dose of DTG 50 mg tablet along with 3TC (EPIVIR) tablet will be given to randomized subjects in parts 1 and 2 with 240 mL of room temperature water. DTG will be a white, film coated, round tablet engraved with SV 572 on one side and 50 on the other side.

Lamivudine

Intervention Type: DRUG

Single dose 3TC (commercial name: EPIVIR) 300 mg tablet along with DTG tablet will be given to randomized subjects in parts 1 and 2 with 240 mL of room temperature water.\<br\>3TC will be gray, diamond shaped tablet, engraved "GX EJ7" on one side and plain on the other side.

Dolutegravir + Lamivudine FDC Formulation 1

Intervention Type: DRUG

Single dose of DTG 50 mg combined with 3TC 300 mg in a FDC formulation 1 tablet will be administered to randomized subjects in treatment periods 1 and 2 (under fasted state) of Part 1 and the first 16 subjects in treatment period 3 (under fed) of Part 1 with 240 mL of room temperature water. \&lt;br\&gt;FDC formulation 1 tablets will be oval, biconvex, white, film coated tablet engraved 'SV H7I' on one face.

Subjects receiving high fat meal: Part 1

Eligible subjects will be administered single dose of DTG 3TC FDC formulation 1 tablet with high fat meal in Period 3 to study the effect of food on tablet.

Group Type: EXPERIMENTAL

Dolutegravir + Lamivudine FDC Formulation 1

Intervention Type: DRUG

Single dose of DTG 50 mg combined with 3TC 300 mg in a FDC formulation 1 tablet will be administered to randomized subjects in treatment periods 1 and 2 (under fasted state) of Part 1 and the first 16 subjects in treatment period 3 (under fed) of Part 1 with 240 mL of room temperature water. \&lt;br\&gt;FDC formulation 1 tablets will be oval, biconvex, white, film coated tablet engraved 'SV H7I' on one face.

Treatment sequence A/C: Part 2

Eligible subjects will be randomized in sequence A/B and will receive A: DTG 50 mg and 3TC 300 mg single entities in Period 1 and C: DTG 3TC FDC formulation 2 tablet in Period 2.

Group Type: EXPERIMENTAL

Dolutegravir

Intervention Type: DRUG

Single dose of DTG 50 mg tablet along with 3TC (EPIVIR) tablet will be given to randomized subjects in parts 1 and 2 with 240 mL of room temperature water. DTG will be a white, film coated, round tablet engraved with SV 572 on one side and 50 on the other side.

Lamivudine

Intervention Type: DRUG

Single dose 3TC (commercial name: EPIVIR) 300 mg tablet along with DTG tablet will be given to randomized subjects in parts 1 and 2 with 240 mL of room temperature water.\<br\>3TC will be gray, diamond shaped tablet, engraved "GX EJ7" on one side and plain on the other side.

Dolutegravir + Lamivudine FDC Formulation 2

Intervention Type: DRUG

Single dose of DTG 50 mg combined with 3TC 300 mg in a FDC formulation 2 tablet will be administered to randomized subjects in treatment periods 1 and 2 (under fasted state) and the first 16 subjects in treatment period 3 (under fed) of Part 2 with 240 mL of room temperature water. \&lt;br\&gt;FDC formulation 2 tablets will be oval, biconvex, white, film coated tablet engraved 'SV 13N' on one face.

Treatment sequence C/A: Part 2

Eligible subjects will be randomized in sequence C/A and will receive C: DTG 3TC FDC formulation 2 tablet in Period 1 and A: DTG 50 milligram (mg) and 3TC 300 mg single entities in Period 2.

Group Type: EXPERIMENTAL

Dolutegravir

Intervention Type: DRUG

Single dose of DTG 50 mg tablet along with 3TC (EPIVIR) tablet will be given to randomized subjects in parts 1 and 2 with 240 mL of room temperature water. DTG will be a white, film coated, round tablet engraved with SV 572 on one side and 50 on the other side.

Lamivudine

Intervention Type: DRUG

Single dose 3TC (commercial name: EPIVIR) 300 mg tablet along with DTG tablet will be given to randomized subjects in parts 1 and 2 with 240 mL of room temperature water.\<br\>3TC will be gray, diamond shaped tablet, engraved "GX EJ7" on one side and plain on the other side.

Dolutegravir + Lamivudine FDC Formulation 2

Intervention Type: DRUG

Single dose of DTG 50 mg combined with 3TC 300 mg in a FDC formulation 2 tablet will be administered to randomized subjects in treatment periods 1 and 2 (under fasted state) and the first 16 subjects in treatment period 3 (under fed) of Part 2 with 240 mL of room temperature water. \&lt;br\&gt;FDC formulation 2 tablets will be oval, biconvex, white, film coated tablet engraved 'SV 13N' on one face.

Subjects receiving high fat meal: Part 2

Eligible subjects will be administered single dose of DTG 3TC FDC formulation 2 tablet with high fat meal in Period 3 to study the effect of food on tablet.

Group Type: EXPERIMENTAL

Dolutegravir + Lamivudine FDC Formulation 2

Intervention Type: DRUG

Single dose of DTG 50 mg combined with 3TC 300 mg in a FDC formulation 2 tablet will be administered to randomized subjects in treatment periods 1 and 2 (under fasted state) and the first 16 subjects in treatment period 3 (under fed) of Part 2 with 240 mL of room temperature water. \&lt;br\&gt;FDC formulation 2 tablets will be oval, biconvex, white, film coated tablet engraved 'SV 13N' on one face.

Interventions

Dolutegravir

Single dose of DTG 50 mg tablet along with 3TC (EPIVIR) tablet will be given to randomized subjects in parts 1 and 2 with 240 mL of room temperature water. DTG will be a white, film coated, round tablet engraved with SV 572 on one side and 50 on the other side.

Intervention Type: DRUG

Lamivudine

Single dose 3TC (commercial name: EPIVIR) 300 mg tablet along with DTG tablet will be given to randomized subjects in parts 1 and 2 with 240 mL of room temperature water.\<br\>3TC will be gray, diamond shaped tablet, engraved "GX EJ7" on one side and plain on the other side.

Intervention Type: DRUG

Dolutegravir + Lamivudine FDC Formulation 1

Single dose of DTG 50 mg combined with 3TC 300 mg in a FDC formulation 1 tablet will be administered to randomized subjects in treatment periods 1 and 2 (under fasted state) of Part 1 and the first 16 subjects in treatment period 3 (under fed) of Part 1 with 240 mL of room temperature water. \&lt;br\&gt;FDC formulation 1 tablets will be oval, biconvex, white, film coated tablet engraved 'SV H7I' on one face.

Intervention Type: DRUG

Dolutegravir + Lamivudine FDC Formulation 2

Single dose of DTG 50 mg combined with 3TC 300 mg in a FDC formulation 2 tablet will be administered to randomized subjects in treatment periods 1 and 2 (under fasted state) and the first 16 subjects in treatment period 3 (under fed) of Part 2 with 240 mL of room temperature water. \&lt;br\&gt;FDC formulation 2 tablets will be oval, biconvex, white, film coated tablet engraved 'SV 13N' on one face.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
• Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac evaluation (history, electrocardiogram [ECG]).

Exclusion Criteria

• Subject must be able to swallow 2 tablets at the same time (Reference tablets only).
• Body weight >=50 kilogram (kg) for men and >=45 kg for women and body mass index (BMI) within the range 18.5-31.0 kg per meter square (kg/m^2).
• Male or Female. Female subject: is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies: 1. non-reproductive potential defined as: pre-menopausal females with one of the following: documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea; in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. 2. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until at least five terminal half-lives OR until any continuing pharmacologic effect has ended, whichever is longer after the last dose of study medication and completion of the follow-up visit.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions.

• Alanine aminotransferase (ALT) and bilirubin >1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percentage).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• QT interval corrected for heart rate according to Fridericia's formula (QTcF) > 450 milliseconds (msec).
• Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and ViiV Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram (g) of alcohol: 12 ounces [360 milliliter (mL)] of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 1 month prior to screening.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
• Creatinine clearance (CrCL) <90 mL/minute.
• A positive hepatitis B surface antigen (HBsAg) or a positive hepatitis B core antibody with a negative hepatitis B surface antibody, positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
• A positive pre-study drug/alcohol screen.
• A positive test for HIV antibody.
• Where participation in the study would result in donation of blood or blood product in excess of 500 mL within 56 days.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Overland Park, Kansas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

204994

Identifier Type: -

Identifier Source: org_study_id