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

Primary Purpose

Infection, Human Immunodeficiency Virus

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Dolutegravir

Lamivudine

Dolutegravir + Lamivudine FDC Formulation 1

Dolutegravir + Lamivudine FDC Formulation 2

About this trial

This is an interventional treatment trial for Infection, Human Immunodeficiency Virus focused on measuring FDC, Lamivudine, Bio-equivalence, Dolutegravir, HIV

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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]).
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
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.

Exclusion Criteria:

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.

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Treatment sequence A/B: Part 1

Treatment sequence B/A: Part 1

Subjects receiving high fat meal: Part 1

Treatment sequence A/C: Part 2

Treatment sequence C/A: Part 2

Subjects receiving high fat meal: Part 2

Arm Description

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity [AUC (0-Inf)] of Plasma DTG and 3TC in the Fasted State: Part 1

Blood samples were collected at indicated time points to study the pharmacokinetic (PK) profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of monolayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 1.

AUC (0-Inf) of Plasma DTG and 3TC in the Fasted State: Part 2

Blood samples were collected at given time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted conditions in Periods 1 and 2 of Part 2.

Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Time Point (AUC[0-t]) of Plasma DTG and 3TC in the Fasted State: Part 1

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of monolayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 1.

AUC(0-t) of Plasma DTG and 3TC in the Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2.

Maximum Observed Concentration (Cmax) of Plasma DTG and 3TC in the Fasted State: Part 1

Cmax of Plasma DTG and 3TC in the Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2.

Secondary Outcome Measures

Absorption Lag Time (Tlag) of DTG and 3TC in Fasted State: Part 1

Tlag of DTG and 3TC in Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2.

Time to Reach Maximum Plasma Concentration (Tmax) of DTG and 3TC in the Fasted State: Part 1

Tmax of DTG and 3TC in the Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2

Time of the Last Quantifiable Concentration (Tlast) of DTG and 3TC in the Fasted State: Part 1

Tlast of DTG and 3TC in the Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2

Time to Reach Half the Maximum Plasma Concentration (t1/2) of DTG and 3TC in the Fasted State: Part 1

t1/2 of DTG and 3TC in the Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2

Apparent Elimination Rate Constant (Lambda z) of DTG and 3TC in the Fasted State: Part 1

Lambda z of DTG and 3TC in in the Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2.

Percentage of Extrapolated AUC (0 to Inf) of DTG and 3TC in the Fasted State: Part 1

Percentage of Extrapolated AUC(0 to Inf) of DTG and 3TC in the Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2.

AUC of 0 to 24 Hours (AUC[0-24]) of DTG and 3TC in the Fasted State: Part 1

AUC(0-24) of DTG and 3TC in the Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2.

Apparent Oral Clearance (CL/F) of DTG and 3TC in the Fasted State: Part 1

CL/F of DTG and 3TC in the Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2.

Apparent Oral Volume of Distribution (Vz/F) of DTG and 3TC in the Fasted State: Part 1

Vz/F of DTG and 3TC in the Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2.

Concentration at 24 Hours Post-dose (C24) of DTG and 3TC in the Fasted State: Part 1

C24 of DTG and 3TC in the Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2.

Last Quantifiable Concentration (Clast) of DTG and 3TC in the Fasted State: Part 1

Clast of DTG and 3TC in the Fasted State: Part 2

Blood samples were collected at indicated time points to study the PK profile of DTG and 3TC when administered as FDC tablet compared to co-administration of separate tablet formulations of DTG and 3TC in fasted state. The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. PK parameters of bilayer FDC tablet formulation of DTG and 3TC was evaluated under fasted condition in Periods 1 and 2 of Part 2.

AUC (0-Inf) of Plasma DTG and 3TC in the Fed State: Part 1

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC monolayer FDC tablet formulations was assessed in Period 3 of Part 1.

AUC (0-Inf) of Plasma DTG and 3TC in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

AUC (0-t) of Plasma DTG and 3TC in the Fed State: Part 1

AUC (0-t) of Plasma DTG and 3TC in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

Cmax of Plasma DTG and 3TC in the Fed State: Part 1

Cmax of Plasma DTG and 3TC in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

Tlag of DTG and 3TC in Fed State: Part 1

Tlag of DTG and 3TC in Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

Tmax of DTG and 3TC in the Fed State: Part 1

Tmax of DTG and 3TC in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

T1/2 of DTG and 3TC in the Fed State: Part 1

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood. The effect of food on DTG and 3TC monolayer FDC tablet formulations was assessed in Period 3 of Part 1.

T1/2 of DTG and 3TC in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

Lambda z of DTG and 3TC in in the Fed State: Part 1

Lambda z of DTG and 3TC in in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

Clast of DTG and 3TC in in the Fed State: Part 1

Clast of DTG and 3TC in in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

Percentage of Extrapolated AUC (0-inf) in the Fed State: Part 1

Percentage of Extrapolated AUC (0-inf) in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

AUC(0-24) of DTG and 3TC in the Fed State: Part 1

AUC(0-24) of DTG and 3TC in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

CL/F of DTG and 3TC in the Fed State: Part 1

CL/F of DTG and 3TC in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

Tlast of DTG and 3TC in the Fed State: Part 1

Tlast of DTG and 3TC in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

Vz/F of DTG and 3TC in the Fed State: Part 1

Vz/F of DTG and 3TC in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

C24 of DTG and 3TC in the Fed State: Part 1

C24 of DTG and 3TC in the Fed State: Part 2

Blood samples for PK analysis of DTG and 3TC were collected at given time points to study the PK profile of DTG and 3TC FDC tablet(s). The 4-hour post-dose sample was drawn prior to the participant's first post-dose meal. At each time point, 2 mL of blood was collected. The effect of food on DTG and 3TC bilayer FDC tablet formulations was assessed in Period 3 of Part 2.

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Part 1 and 2

SBP and DBP were measured in the supine or semi-supine position after 5 minutes rest. The Baseline value was considered to be the participant's last available assessment prior to time of the first dose. Change from Baseline was defined as post dose visit value minus Baseline value. Data for SBP and DBP for Part 1 and 2 is presented.

Change From Baseline in Heart Rate (HR): Part 1 and 2

HR was measured in the supine or semi-supine position after 5 minutes rest. The Baseline value was considered to be the participant's last available assessment prior to time of the first dose. Change from Baseline was defined as post dose visit value minus Baseline value. Data for HR for Part 1 and 2 is presented.

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 and 2

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Participants having any AE or SAE are presented.

Full Information

NCT ID

NCT03078556

First Posted

March 8, 2017

Last Updated

October 10, 2018

Sponsor

ViiV Healthcare

Collaborators

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT03078556

Brief Title

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

Official Title

An Open-label, Randomized, Single Dose, Crossover, Pivotal Bioequivalence Study of Fixed-dose Combination Tablets of Dolutegravir and Lamivudine Versus Dolutegravir and Lamivudine Single Entities and Food Effect Assessment in Healthy Volunteers

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

March 27, 2017 (Actual)

Primary Completion Date

August 18, 2017 (Actual)

Study Completion Date

August 18, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ViiV Healthcare

Collaborators

GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Infection, Human Immunodeficiency Virus

Keywords

FDC, Lamivudine, Bio-equivalence, Dolutegravir, HIV

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

154 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment sequence A/B: Part 1

Arm Type

Experimental

Arm Description

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.

Arm Title

Treatment sequence B/A: Part 1

Arm Type

Experimental

Arm Description

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.

Arm Title

Subjects receiving high fat meal: Part 1

Arm Type

Experimental

Arm Description

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.

Arm Title

Treatment sequence A/C: Part 2

Arm Type

Experimental

Arm Description

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.

Arm Title

Treatment sequence C/A: Part 2

Arm Type

Experimental

Arm Description

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.

Arm Title

Subjects receiving high fat meal: Part 2

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Dolutegravir

Intervention Description

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

Intervention Name(s)

Lamivudine

Intervention Description

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

Intervention Name(s)

Dolutegravir + Lamivudine FDC Formulation 1

Intervention Description

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. <br>FDC formulation 1 tablets will be oval, biconvex, white, film coated tablet engraved 'SV H7I' on one face.

Intervention Type

Drug

Intervention Name(s)

Dolutegravir + Lamivudine FDC Formulation 2

Intervention Description

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. <br>FDC formulation 2 tablets will be oval, biconvex, white, film coated tablet engraved 'SV 13N' on one face.

Primary Outcome Measure Information:

Title

Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity [AUC (0-Inf)] of Plasma DTG and 3TC in the Fasted State: Part 1

Description

Time Frame