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Bioavailability Study of 10 Milligram (mg) and 5 mg Tablets Versus Conventional Tablets of Dolutegravir

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Conventional dolutegravir 10 mg tablet

Conventional dolutegravir 50 mg tablet

Dispersible dolutegravir 5 mg tablet

Conventional dolutegravir 25 mg tablet

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Dispersible tablets, Bioavailability, Dolutegravir, Healthy, Conventional tablets

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Between 18 and 65 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 and 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 agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Body weight >= 50 kilogram (kg) for males and >= 45 kg for females and body mass index (BMI) within the range 18.5 - 31.0 kg per meter square (kg/m^2) (inclusive).
Male or female. 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. 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 2 weeks after dosing with 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 amino transferase (ALT) and bilirubin >1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
QT correction using Fridericia Formula (QTcF) >450 Milliseconds (msec).
Unable to refrain from the use of prescription [that is (i.e. 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 milliliters [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 Human Immuno-deficiency Virus (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 7

Arm 8

Arm Type

Experimental

Arm Label

Treatment sequence A/B: Part 1

Treatment sequence B/A: Part 1

Treatment sequence C/D/E: Part 2

Treatment sequence D/E/C: Part 2

Treatment sequence E/C/D: Part 2

Treatment sequence C/E/D: Part 2

Treatment sequence D/C/E: Part 2

Treatment sequence E/D/C: Part 2

Arm Description

Eligible subjects will be randomized in sequence A/B in Part 1 and will receive A: conventional 10 mg DTG tablet (5 tablets) in Period 1 and B: conventional 50 mg DTG tablet in Period 2, administered directly to mouth.

Eligible subjects will be randomized in sequence B/A in Part 1 and will receive B: conventional 50 mg DTG tablet in Period 1 and A: conventional 10 mg DTG tablet (5 tablets) in Period 2, administered directly to mouth.

Eligible subjects will be randomized in sequence C/D/E in Part 2 and will receive C: 5 mg dispersible DTG tablet (5 tablets) administered as a dispersion and immediately taken in Period 1, D: 5 mg dispersible DTG tablet (5 tablets) administered as direct to mouth in Period 2 and E: conventional 25 mg DTG tablet administered as direct to mouth in Period 3.

Eligible subjects will be randomized in sequence D/E/C in Part 2 and will receive D: 5 mg dispersible DTG tablet (5 tablets) administered as direct to mouth in Period 1, E: conventional 25 mg DTG tablet administered as direct to mouth in Period 2 and C: 5 mg dispersible DTG tablet (5 tablets) administered as a dispersion and immediately taken in Period 3.

Eligible subjects will be randomized in sequence E/C/D in Part 2 and will receive E: conventional 25 mg DTG tablet administered as direct to mouth in Period 1, C: 5 mg dispersible DTG tablet (5 tablets) administered as a dispersion and immediately taken in Period 2 and D: 5 mg dispersible DTG tablet (5 tablets) administered as direct to mouth in Period 3.

Eligible subjects will be randomized in sequence C/E/D in Part 2 and will receive C: 5 mg dispersible DTG tablet (5 tablets) administered as a dispersion and immediately taken in Period 1, E: conventional 25 mg DTG tablet administered as direct to mouth in Period 2 and D: 5 mg dispersible DTG tablet (5 tablets) administered as direct to mouth in Period 3.

Eligible subjects will be randomized in sequence D/C/E in Part 2 and will receive D: 5 mg dispersible DTG tablet (5 tablets) administered as direct to mouth in Period 1, C: 5 mg dispersible DTG tablet (5 tablets) administered as a dispersion and immediately taken in Period 2 and E: conventional 25 mg DTG tablet administered as direct to mouth in Period 3.

Eligible subjects will be randomized in sequence E/D/C in Part 2 and will receive E: conventional 25 mg DTG tablet administered as direct to mouth in Period 1, D: 5 mg dispersible DTG tablet (5 tablets) administered as direct to mouth in Period 2 and C: 5 mg dispersible DTG tablet (5 tablets) administered as a dispersion and immediately taken in Period 3.

Outcomes

Primary Outcome Measures

Area Under the Plasma Concentration-time Curve From Time of Dose Extrapolated to Infinite Time (AUC[0-infinity]) of DTG for Part 1

Blood samples were collected at the indicated time points after administration of study treatment to investigate the pharmacokinetic (PK) profile of DTG tablets in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times. The PK Population was defined as participants in the All Subjects Population for whom a PK sample was obtained and that had evaluable PK assay results.

Area Under the Plasma Concentration-time Curve From Time of Dose to Last Measurable Concentration AUC [0-t] of DTG for Part 1

Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of DTG tablets in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times..

Maximum Observed Concentration (Cmax) of DTG for Part 1

AUC (0-infinity) of DTG for Part 2

Secondary Outcome Measures

AUC (0-t) of DTG for Part 2

Cmax of DTG for Part 2

Plasma DTG Lag Time Before Observation of Drug Concentrations (Tlag) for Part 1

Time to First Occurrence of Cmax (Tmax) of DTG for Part 1

Terminal Phase Half-life (t1/2) of DTG for Part 1

Terminal-phase Rate Constant (Lambda z) of DTG for Part 1

Percentage of AUC (0-infinity) Obtained by Extrapolation (%AUCex) of DTG for Part 1

Area Under the Concentration-time Curve Over Time Zero (Pre-dose) to 24 Hours After Dose Administration (AUC[0-24]) of DTG for Part 1

Apparent Oral Clearance (CL/F) of DTG for Part 1

Apparent Volume of Distribution During the Terminal Phase (Vz/F) of DTG for Part 1

Last Observed Quantifiable Concentration (Ct) of DTG for Part 1

Observed Concentration at 24 Hours After Dose Administration (C24) of DTG for Part 1

Plasma DTG Tlag for Part 2

Tmax of DTG for Part 2

Blood sample were collected at the indicated time points after administration of study treatment to investigate the pharmacokinetic profile of DTG tablets in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

t1/2 of DTG for Part 2

Lambda Z of DTG for Part 2

%AUCex of DTG for Part 2

AUC (0-24) of DTG for Part 2

DTG CL/F for Part 2

Vz/F of DTG for Part 2

Ct of DTG for Part 2

C24 of DTG for Part 2

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

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Data has been presented for AEs and SAEs up-to follow-up (25 days) in Part 1. All Subjects Population was defined as all participants who received at least 1 dose of study medication.

Number of Participants With Adverse Events AEs and Serious Adverse Events SAEs for Part 2

Change From Baseline in Clinical Laboratory Parameters Serum Glucose, Serum Calcium, Serum Potassium, Serum Sodium, Serum Urea for Part 1

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum glucose, serum calcium, serum potassium, serum sodium, serum urea results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Change From Baseline in Clinical Chemistry Parameters Serum Alanine Amino Transferase (ALT), Serum Alkaline Phosphatase, Serum Aspartate Amino Transferase (AST), Serum Creatine Kinase for Part 1

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum ALT, serum alkaline phosphatase, serum AST, serum creatine kinase results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Change From Baseline in Clinical Chemistry Parameters Serum Albumin and Serum Protein for Part 1

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum albumin and serum protein results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Change From Baseline in Clinical Chemistry Parameters Serum Bilirubin, Serum Creatinine and Serum Direct Bilirubin for Part 1

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum bilirubin, serum creatinine and serum direct bilirubin results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Change From Baseline in Clinical Chemistry Parameters Serum Glucose, Serum Calcium, Serum Potassium, Serum Sodium, Serum Urea for Part 2

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum glucose, serum calcium, serum potassium, serum sodium, serum urea results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Change From Baseline in Clinical Chemistry Parameters Serum ALT, Serum Alkaline Phosphate, Serum AST, Serum Creatine Kinase for Part 2

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum ALT, serum alkaline phosphatase, serum AST, serum creatine kinase results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Change From Baseline in Clinical Chemistry Parameters Serum Albumin and Serum Protein for Part 2

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum albumin and serum protein results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Change From Baseline in Clinical Chemistry Parameters Serum Bilirubin, Serum Creatine and Serum Direct Bilirubin for Part 2

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum bilirubin, serum creatine and serum direct bilirubin results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Change From Baseline in Hematology Parameter Blood Erythrocyte Mean Corpuscular Hemoglobin (MCH) for Part 1

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood erythrocyte MCH results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Change From Baseline in Hematology Parameter Blood Erythrocyte Mean Corpuscular Volume (MCV) for Part 1

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood erythrocyte MCV results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x,x in the category titles).

Change From Baseline in Hematology Parameters Blood Basophils, Blood Eosinophils, Blood Leukocytes, Blood Lymphocytes, Blood Monocytes, Blood Neutrophils, Blood Platelets for Part 1

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood basophils, blood eosinophils, blood leukocytes, blood lymphocytes, blood monocytes, blood neutrophils, blood platelets results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x,x in the category titles)

Change From Baseline in Hematology Parameter Blood Hemoglobin for Part 1

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood hemoglobin results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x,x in the category titles)

Change From Baseline in Hematology Parameter Blood Hematocrit for Part 1

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood hematocrit results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x,x in the category titles).

Change From Baseline in Hematology Parameter Blood Erythrocytes for Part 1

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood erythrocyte results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x,x in the category titles).

Change From Baseline in Hematology Parameter Blood Erythrocyte MCH for Part 2

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood erythrocyte MCH results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles).

Change From Baseline in Hematology Parameter Blood Erythrocyte MCV for Part 2

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood erythrocyte MCV results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles).

Change From Baseline in Hematology Parameters Blood Basophils, Blood Eosinophils,, Blood Leukocytes, Blood Lymphocytes, Blood Monocytes, Blood Neutrophils, Blood Platelets for Part 2

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood basophils, blood eosinophils, blood leukocytes, blood lymphocytes, blood monocytes, blood neutrophils, blood platelets results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles)

Change From Baseline in Hematology Parameter Blood Hemoglobin for Part 2

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood hemoglobin results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles)

Change From Baseline in Hematology Parameter Blood Hematocrit for Part 2

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood hematocrit results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles)

Change From Baseline in Hematology Parameter Blood Erythrocytes for Part 2

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood erythrocytes results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles).

Number of Participants With Abnormal Values on Urinalysis by Dipstick Method for Part 1

Urinalysis parameters assessed were urine ketones, urine glucose, urine occult blood and urine protein. In this dipstick test, the level of ketones, glucose, occult blood and protein in urine samples was recorded as negative trace, 1+, 2+, and 3+ (the plus sign increases with a higher level of glucose, ketones, or proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive). Urine samples were collected for the measurement of urinalysis parameters by dipstick method up-to follow-up (Day 25) in Part 1. Only categories with significant values have been presented.

Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part 1

Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by dipstick method up-to follow-up (Day 25) in Part 1. Only categories with significant values have been presented. Only those participants with data available at the specified time were analyzed (represented by n=x,x in the category titles).

Urine Specific Gravity Analysis by Dipstick Method for Part 1

Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected for the measurement of urine specific gravity by dipstick method up-to follow-up (Day 25) in Part 1. Only categories with significant values have been presented. Only those participants with data available at the specified time were analyzed (represented by n=x,x in the category titles).

Number of Participants With Abnormal Values on Urinalysis by Dipstick Method for Part 2

Urinalysis parameters assessed were urine ketones, urine glucose, urine occult blood and urine protein. In this dipstick test, the level of ketones, glucose, occult blood and protein in urine samples was recorded as negative trace, 1+, 2+, and 3+ (the plus sign increases with a higher level of glucose, ketones, or proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive). Urine samples were collected for the measurement of urinalysis parameters by dipstick method up-to follow-up (Day 36) in Part 2. Only categories with significant values have been presented.

Urine pH Analysis by Dipstick Method for Part 2

Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by dipstick method up-to follow-up (Day 36) in Part 2. Only categories with significant values have been presented. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles).

Urine Specific Gravity Analysis by Dipstick Method for Part 2

Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected for the measurement of urine specific gravity by dipstick method up-to follow-up (Day 36) in Part 2. Only categories with significant values have been presented. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Number of Participants With Chemistry Toxicities of Grade 2 as Defined by Division of Acquired Immunodeficiency Syndrome (DAIDS) for Part 1

The DAIDS toxicity table provides descriptive terminology for grading the severity of adult adverse events. Laboratory grades also provide ranges for each parameter. Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: potentially life threatening. low LDL (low-density lipid); HDL (high-density lipid). Data has been presented for clinical chemistry laboratory result parameter (serum sodium) with toxicity of Grade 2 for Part 1.

Number of Participants With Urinalysis Toxicities of Grade 2 as Defined by DAIDS for Part 1

The DAIDS toxicity table provides descriptive terminology for grading the severity of adult adverse events. Laboratory grades also provide ranges for each parameter. Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: potentially life threatening, low LDL and HDL Data has been presented for urinalysis laboratory result parameter (urine protein by dipstick analysis) with toxicity of Grade 2 for Part 1.

Full Information

NCT ID

NCT03095638

First Posted

March 23, 2017

Last Updated

July 11, 2019

Sponsor

ViiV Healthcare

Collaborators

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT03095638

Brief Title

Bioavailability Study of 10 Milligram (mg) and 5 mg Tablets Versus Conventional Tablets of Dolutegravir

Official Title

A 2-Part, Phase I, Single Dose, Crossover Relative Bioavailability Study of Both TIVICAY 10 mg Conventional Tablets and 5 mg Dispersible Tablets Compared to Conventional TIVICAY Tablets in Fasted Healthy Adult Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Completed

Study Start Date

May 3, 2017 (Actual)

Primary Completion Date

June 23, 2017 (Actual)

Study Completion Date

June 23, 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

The aim of this cross-over study is to compare the relative bioavailability and pharmacokinetic parameters of both 10 mg conventional tablets and 5 mg dispersible tablets of dolutegravir (DTG) with that of 25 mg or 50 mg conventional DTG tablets. The study will be carried out in 2 parts. Part 1 of the study will be open-label, 2 period designs with a wash out period of at least 7 days between the dosing periods. Subjects will be randomized to receive either single dose of five 10 mg DTG tablets or one 50 mg DTG tablet in a crossover manner in the fasting state. Part 2 of the study will be a 3 period crossover design with a wash out period of at least 7 days between the dosing periods. Subjects will be randomized to receive either single dose of five 5 mg DTG tablets (administered as dispersed with water or directly to mouth) or one 25 mg DTG tablet in a crossover manner in the fasting state. Subjects will have a follow-up visit 7-10 days post last dose of study treatment. Approximately 14 healthy subjects will participate in Part 1 and approximately 24 healthy subjects will participate in Part 2 of the study. The total duration of Part 1 will be approximately 7 to 8 weeks and that of part 2 will be approximately 8 to 9 weeks. TIVICAY® is a trademark of the GlaxoSmithKline group of companies.

6. Conditions and Keywords

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

HIV Infections

Keywords

Dispersible tablets, Bioavailability, Dolutegravir, Healthy, Conventional tablets

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment sequence A/B: Part 1

Arm Type

Experimental

Arm Description

Arm Title

Treatment sequence B/A: Part 1

Arm Type

Experimental

Arm Description

Arm Title

Treatment sequence C/D/E: Part 2

Arm Type

Experimental

Arm Description

Arm Title

Treatment sequence D/E/C: Part 2

Arm Type

Experimental

Arm Description

Arm Title

Treatment sequence E/C/D: Part 2

Arm Type

Experimental

Arm Description

Arm Title

Treatment sequence C/E/D: Part 2

Arm Type

Experimental

Arm Description

Arm Title

Treatment sequence D/C/E: Part 2

Arm Type

Experimental

Arm Description

Arm Title

Treatment sequence E/D/C: Part 2

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Conventional dolutegravir 10 mg tablet

Intervention Description

Single dose of five 10 mg DTG tablets will be administered directly to mouth with 240 mL of water in the morning to randomized subjects in fasting state present in Part 1. DTG will be a white, round shaped, biconvex tablet.

Intervention Type

Drug

Intervention Name(s)

Conventional dolutegravir 50 mg tablet

Intervention Description

Single dose of one 50 mg tablet will be administered directly to mouth with 240 mL of water in the morning to randomized subjects in fasting state present in Part 1. DTG will be a white, round shaped, biconvex tablet.

Intervention Type

Drug

Intervention Name(s)

Dispersible dolutegravir 5 mg tablet

Intervention Description

Single dose of five 5 mg DTG tablets will be administered as dispersed in water or direct to mouth with 240 mL of water in the morning to randomized subjects in fasting state present in Part 2. DTG will be a white, round shaped, biconvex tablet.

Intervention Type

Drug

Intervention Name(s)

Conventional dolutegravir 25 mg tablet

Intervention Description

Single dose of one 25 mg DTG tablet will be administered directly to mouth with 240 mL of water in the morning to randomized subjects in fasting state present in Part 2. DTG will be a white, round shaped, biconvex tablet.

Primary Outcome Measure Information:

Title

Area Under the Plasma Concentration-time Curve From Time of Dose Extrapolated to Infinite Time (AUC[0-infinity]) of DTG for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

Area Under the Plasma Concentration-time Curve From Time of Dose to Last Measurable Concentration AUC [0-t] of DTG for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

Maximum Observed Concentration (Cmax) of DTG for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

AUC (0-infinity) of DTG for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Secondary Outcome Measure Information:

Title

AUC (0-t) of DTG for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Title

Cmax of DTG for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Title

Plasma DTG Lag Time Before Observation of Drug Concentrations (Tlag) for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

Time to First Occurrence of Cmax (Tmax) of DTG for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

Terminal Phase Half-life (t1/2) of DTG for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

Terminal-phase Rate Constant (Lambda z) of DTG for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

Percentage of AUC (0-infinity) Obtained by Extrapolation (%AUCex) of DTG for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

Area Under the Concentration-time Curve Over Time Zero (Pre-dose) to 24 Hours After Dose Administration (AUC[0-24]) of DTG for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

Apparent Oral Clearance (CL/F) of DTG for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

Apparent Volume of Distribution During the Terminal Phase (Vz/F) of DTG for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

Last Observed Quantifiable Concentration (Ct) of DTG for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

Observed Concentration at 24 Hours After Dose Administration (C24) of DTG for Part 1

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 1

Title

Plasma DTG Tlag for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Title

Tmax of DTG for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Title

t1/2 of DTG for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Title

Lambda Z of DTG for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Title

%AUCex of DTG for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Title

AUC (0-24) of DTG for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Title

DTG CL/F for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Title

Vz/F of DTG for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Title

Ct of DTG for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Title

C24 of DTG for Part 2

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours post-dose in Part 2

Title

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

Description

Time Frame

Up to 25 days in Part 1

Title

Number of Participants With Adverse Events AEs and Serious Adverse Events SAEs for Part 2

Description

Time Frame

Up to 36 days in Part 2

Title

Change From Baseline in Clinical Laboratory Parameters Serum Glucose, Serum Calcium, Serum Potassium, Serum Sodium, Serum Urea for Part 1

Description

Time Frame

Baseline and up to 25 days in Part 1

Title

Change From Baseline in Clinical Chemistry Parameters Serum Alanine Amino Transferase (ALT), Serum Alkaline Phosphatase, Serum Aspartate Amino Transferase (AST), Serum Creatine Kinase for Part 1

Description

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum ALT, serum alkaline phosphatase, serum AST, serum creatine kinase results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Time Frame

Baseline and up to 25 days in Part 1

Title

Change From Baseline in Clinical Chemistry Parameters Serum Albumin and Serum Protein for Part 1

Description

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum albumin and serum protein results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Time Frame

Baseline and up to 25 days in Part 1

Title

Change From Baseline in Clinical Chemistry Parameters Serum Bilirubin, Serum Creatinine and Serum Direct Bilirubin for Part 1

Description

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum bilirubin, serum creatinine and serum direct bilirubin results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Time Frame

Baseline and up to 25 days in Part 1

Title

Change From Baseline in Clinical Chemistry Parameters Serum Glucose, Serum Calcium, Serum Potassium, Serum Sodium, Serum Urea for Part 2

Description

Time Frame

Baseline and up to 36 days in Part 2

Title

Change From Baseline in Clinical Chemistry Parameters Serum ALT, Serum Alkaline Phosphate, Serum AST, Serum Creatine Kinase for Part 2

Description

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum ALT, serum alkaline phosphatase, serum AST, serum creatine kinase results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Time Frame

Baseline and up to 36 days in Part 2

Title

Change From Baseline in Clinical Chemistry Parameters Serum Albumin and Serum Protein for Part 2

Description

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum albumin and serum protein results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Time Frame

Baseline and up to 36 days in Part 2

Title

Change From Baseline in Clinical Chemistry Parameters Serum Bilirubin, Serum Creatine and Serum Direct Bilirubin for Part 2

Description

Blood samples for the assessment of chemistry parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for serum bilirubin, serum creatine and serum direct bilirubin results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Time Frame

Baseline and up to 36 days in Part 2

Title

Change From Baseline in Hematology Parameter Blood Erythrocyte Mean Corpuscular Hemoglobin (MCH) for Part 1

Description

Time Frame

Baseline and up to 25 days in Part 1

Title

Change From Baseline in Hematology Parameter Blood Erythrocyte Mean Corpuscular Volume (MCV) for Part 1

Description

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood erythrocyte MCV results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x,x in the category titles).

Time Frame

Baseline and up to 25 days in Part 1

Title

Change From Baseline in Hematology Parameters Blood Basophils, Blood Eosinophils, Blood Leukocytes, Blood Lymphocytes, Blood Monocytes, Blood Neutrophils, Blood Platelets for Part 1

Description

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood basophils, blood eosinophils, blood leukocytes, blood lymphocytes, blood monocytes, blood neutrophils, blood platelets results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x,x in the category titles)

Time Frame

Baseline and up to 25 days in Part 1

Title

Change From Baseline in Hematology Parameter Blood Hemoglobin for Part 1

Description

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood hemoglobin results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x,x in the category titles)

Time Frame

Baseline and up to 25 days in Part 1

Title

Change From Baseline in Hematology Parameter Blood Hematocrit for Part 1

Description

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood hematocrit results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x,x in the category titles).

Time Frame

Baseline and up to 25 days in Part 1

Title

Change From Baseline in Hematology Parameter Blood Erythrocytes for Part 1

Description

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 25) in Part 1. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood erythrocyte results for Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x,x in the category titles).

Time Frame

Baseline and up to 25 days in Part 1

Title

Change From Baseline in Hematology Parameter Blood Erythrocyte MCH for Part 2

Description

Time Frame

Baseline and up to 36 days in Part 2

Title

Change From Baseline in Hematology Parameter Blood Erythrocyte MCV for Part 2

Description

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood erythrocyte MCV results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles).

Time Frame

Baseline and up to 36 days in Part 2

Title

Change From Baseline in Hematology Parameters Blood Basophils, Blood Eosinophils,, Blood Leukocytes, Blood Lymphocytes, Blood Monocytes, Blood Neutrophils, Blood Platelets for Part 2

Description

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood basophils, blood eosinophils, blood leukocytes, blood lymphocytes, blood monocytes, blood neutrophils, blood platelets results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles)

Time Frame

Baseline and up to 36 days in Part 2

Title

Change From Baseline in Hematology Parameter Blood Hemoglobin for Part 2

Description

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood hemoglobin results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles)

Time Frame

Baseline and up to 36 days in Part 2

Title

Change From Baseline in Hematology Parameter Blood Hematocrit for Part 2

Description

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood hematocrit results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles)

Time Frame

Baseline and up to 36 days in Part 2

Title

Change From Baseline in Hematology Parameter Blood Erythrocytes for Part 2

Description

Blood samples for the assessment of hematology parameters were collected at Baseline and up-to follow-up (Day 36) in Part 2. Baseline was defined as pre-dose assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Data has been presented for blood erythrocytes results for Part 2. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles).

Time Frame

Baseline and up to 36 days in Part 2

Title

Number of Participants With Abnormal Values on Urinalysis by Dipstick Method for Part 1

Description

Time Frame

Up to 25 days in Part 1

Title

Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part 1

Description

Time Frame

Up to 25 days in Part 1

Title

Urine Specific Gravity Analysis by Dipstick Method for Part 1

Description

Time Frame

Up to 25 days in Part 1

Title

Number of Participants With Abnormal Values on Urinalysis by Dipstick Method for Part 2

Description

Urinalysis parameters assessed were urine ketones, urine glucose, urine occult blood and urine protein. In this dipstick test, the level of ketones, glucose, occult blood and protein in urine samples was recorded as negative trace, 1+, 2+, and 3+ (the plus sign increases with a higher level of glucose, ketones, or proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive). Urine samples were collected for the measurement of urinalysis parameters by dipstick method up-to follow-up (Day 36) in Part 2. Only categories with significant values have been presented.

Time Frame

Up to 36 days in Part 2

Title

Urine pH Analysis by Dipstick Method for Part 2

Description

Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by dipstick method up-to follow-up (Day 36) in Part 2. Only categories with significant values have been presented. Only those participants with data available at the specified time were analyzed (represented by n=x,x,x in the category titles).

Time Frame

Up to 36 days in Part 2

Title

Urine Specific Gravity Analysis by Dipstick Method for Part 2

Description

Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected for the measurement of urine specific gravity by dipstick method up-to follow-up (Day 36) in Part 2. Only categories with significant values have been presented. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

Time Frame

Up to 36 days in Part 2

Title

Number of Participants With Chemistry Toxicities of Grade 2 as Defined by Division of Acquired Immunodeficiency Syndrome (DAIDS) for Part 1

Description

Time Frame

Up to 25 days in Part 1

Title

Number of Participants With Urinalysis Toxicities of Grade 2 as Defined by DAIDS for Part 1

Description

The DAIDS toxicity table provides descriptive terminology for grading the severity of adult adverse events. Laboratory grades also provide ranges for each parameter. Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: potentially life threatening, low LDL and HDL Data has been presented for urinalysis laboratory result parameter (urine protein by dipstick analysis) with toxicity of Grade 2 for Part 1.

Time Frame

Up to 25 days in Part 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Between 18 and 65 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 and 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 agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Body weight >= 50 kilogram (kg) for males and >= 45 kg for females and body mass index (BMI) within the range 18.5 - 31.0 kg per meter square (kg/m^2) (inclusive). Male or female. 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. 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 2 weeks after dosing with 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 amino transferase (ALT) and bilirubin >1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent). Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). QT correction using Fridericia Formula (QTcF) >450 Milliseconds (msec). Unable to refrain from the use of prescription [that is (i.e. 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 milliliters [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 Human Immuno-deficiency Virus (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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

ViiV Healthcare

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Austin

State/Province

Texas

ZIP/Postal Code

78744

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34817414

Citation

Singh RP, Adkison KK, Baker M, Parasrampuria R, Wolstenholme A, Davies M, Sewell N, Brothers C, Buchanan AM. Development of Dolutegravir Single-entity and Fixed-dose Combination Formulations for Children. Pediatr Infect Dis J. 2022 Mar 1;41(3):230-237. doi: 10.1097/INF.0000000000003366.

Results Reference

derived

Learn more about this trial

Bioavailability Study of 10 Milligram (mg) and 5 mg Tablets Versus Conventional Tablets of Dolutegravir

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