To Assess the Relative Bioavailability (BA) of TRIUMEQ® and Dolutegravir and Lamivudine (DTG/3TC) Pediatric Dispersible Tablet Formulations in Healthy Volunteers

NCT ID: NCT03441984

Last Updated: 2019-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-26
• Study Completion Date: 2018-04-28

Brief Summary

This is a 2-part, single-dose, open label, randomized 3-way cross-over study to compare BA of pediatric study drugs TRIUMEQ and (DTG/3TC) in healthy volunteers under fasted conditions. Study will be conducted in 2-parts. Each part 1 and part 2 will comprise of 3-treatment periods (TP) where Part 1, will assess BA, of pediatric TRIUMEQ dispersible tablets with an adult TRIUMEQ conventional tablet formulation and Part 2, will assess BA, of pediatric DTG/3TC dispersible tablets with adult DTG and 3TC conventional tablets formulation. Total duration of study is 9-weeks and will be conducted in approximately 36 subjects. The 2-parts, may be run in parallel as they are independent of each other. TRIUMEQ is a registered trademark of GlaxoSmithKline group of companies.

Conditions

HIV Infections

Keywords

Pediatric dispersible tablets; Bioavailability

Study Design

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

Study Groups

Subjects with treatment sequence ABC

The subjects in Part 1 of the study, will receive a single dose of treatment A= adult TRIUMEQ (DTG 50 mg/ABC 600 mg/3TC 300 mg, 1 conventional tablet) administered as direct-to-mouth, in TP1; treatment B=Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 10 dispersible tablets) administered as a dispersion and taken immediately in TP2; and treatment C=Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 10 dispersible tablets) administered as direct-to-mouth in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.

Treatment B

Intervention Type: DRUG

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets

Treatment C

Intervention Type: DRUG

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.

Subjects with treatment sequence BCA

The subjects in Part 1 of the study, will receive treatment B in TP1, treatment C in TP2 and treatment A in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.

Treatment B

Intervention Type: DRUG

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets

Treatment C

Intervention Type: DRUG

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.

Subjects with treatment sequence CAB

The subjects in Part 1 of the study will receive a single dose each of, treatment C in TP1, treatment A in TP2 and treatment B in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.

Treatment B

Intervention Type: DRUG

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets

Treatment C

Intervention Type: DRUG

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.

Subjects with treatment sequence ACB

The subjects in Part 1 of the study will receive, treatment A in TP1, treatment C in TP2 and treatment B in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.

Treatment B

Intervention Type: DRUG

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets

Treatment C

Intervention Type: DRUG

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.

Subjects with treatment sequence BAC

The subjects in Part 1 of the study will receive a single dose each of, treatment B in TP1, treatment A in TP2 and treatment C in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.

Treatment B

Intervention Type: DRUG

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets

Treatment C

Intervention Type: DRUG

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.

Subjects with treatment sequence CBA

The subjects in Part 1 of the study will receive a single dose each of, treatment C in TP1, treatment B in TP2 and treatment A in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.

Treatment B

Intervention Type: DRUG

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets

Treatment C

Intervention Type: DRUG

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.

Subjects with treatment sequence DEF

The subjects in Part 2 of the study, will receive a single dose of treatment D= Adult DTG (50 mg, 1 conventional tablet) and adult 3TC (300 mg, 1 conventional tablet) administered as direct-to-mouth, in TP1; treatment E= Pediatric DTG/3TC (DTG 5 mg/3TC 30 mg, 10 dispersible tablets) administered as a dispersion and taken immediately in TP2; and treatment F= Pediatric DTG/3TC (DTG 5 mg/3TC 30 mg, 10 dispersible tablets) administered as direct-to-mouth in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.

Group Type: EXPERIMENTAL

Treatment D

Intervention Type: DRUG

DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and

1 tablet 3TC (300 mg), orally as direct-to-mouth.

Treatment E

Intervention Type: DRUG

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as 10 dispersible tablets.

Treatment F

Intervention Type: DRUG

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.

Subjects with treatment sequence EFD

The subjects in Part 2 of the study, will receive a single dose respectively of treatment E in TP1, treatment F in TP2 and treatment D in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.

Group Type: EXPERIMENTAL

Treatment D

Intervention Type: DRUG

DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and

1 tablet 3TC (300 mg), orally as direct-to-mouth.

Treatment E

Intervention Type: DRUG

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as 10 dispersible tablets.

Treatment F

Intervention Type: DRUG

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.

Subjects with treatment sequence FDE

The subjects in Part 2 of the study, will receive a single dose of treatment F in TP1, treatment D in TP2 and treatment E in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.

Group Type: EXPERIMENTAL

Treatment D

Intervention Type: DRUG

DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and

1 tablet 3TC (300 mg), orally as direct-to-mouth.

Treatment E

Intervention Type: DRUG

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as 10 dispersible tablets.

Treatment F

Intervention Type: DRUG

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.

Subjects with treatment sequence DFE

The subjects in Part 2 of the study, will receive a single dose of treatment D in TP1, treatment F in TP2 and treatment E in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.

Group Type: EXPERIMENTAL

Treatment D

Intervention Type: DRUG

DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and

1 tablet 3TC (300 mg), orally as direct-to-mouth.

Treatment E

Intervention Type: DRUG

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as 10 dispersible tablets.

Treatment F

Intervention Type: DRUG

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.

Subjects with treatment sequence EDF

The subjects in Part 2 of the study, will receive a single dose of treatment E in TP1, treatment D in TP2 and treatment F in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.

Group Type: EXPERIMENTAL

Treatment D

Intervention Type: DRUG

DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and

1 tablet 3TC (300 mg), orally as direct-to-mouth.

Treatment E

Intervention Type: DRUG

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as 10 dispersible tablets.

Treatment F

Intervention Type: DRUG

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.

Subjects with treatment sequence FED

The subjects in Part 2 of the study, will receive a single dose of treatment F in TP1, treatment E in TP2 and treatment D in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.

Group Type: EXPERIMENTAL

Treatment D

Intervention Type: DRUG

DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and

1 tablet 3TC (300 mg), orally as direct-to-mouth.

Treatment F

Intervention Type: DRUG

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.

Interventions

Treatment A

TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.

Intervention Type: DRUG

Treatment B

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets

Intervention Type: DRUG

Treatment C

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.

Intervention Type: DRUG

Treatment D

DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and

1 tablet 3TC (300 mg), orally as direct-to-mouth.

Intervention Type: DRUG

Treatment E

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as 10 dispersible tablets.

Intervention Type: DRUG

Treatment F

DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Between 18 and 65 years of age, inclusive, at the time of signing the informed consent.
• Healthy subjects 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 ECG).
• Body weight >=50 kilogram (kg) for males and >=45 kg for females and body mass index (BMI) within the range 18.5 - 31.0 kilogram per square meter (kg/m^2) (inclusive).
• Male and female subjects where the male subjects must agree to use contraception during the TP and for at least 2 weeks plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period. For the female subjects, female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and at least 1 of the following conditions applies: Female with non-reproductive potential, defined as Premenopausal females with one of the following like documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, documented hysterectomy, documented bilateral oophorectomy, the Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone 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; Females with reproductive potential and agrees to follow one of the options for avoiding pregnancy in females of reproductive potential, 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; the investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception; All female subjects participating in the study should be counselled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of human immune virus (HIV) transmission to an uninfected partner.
• Subjects capable of giving signed informed consent.
• For participation in Part 1, documentation that the subject is negative for the human leukocyte antigen (HLA)-B*5701 allele.

Exclusion Criteria

• The medical conditions included where ALT and bilirubin >1.5 × upper limit of normal (ULN) (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < =35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Subjects with use of prior or concomitant therapy who are unable to refrain from the use of prescription (e.g., dofetilide) 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 Healthcare 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 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.
• Contraindications like 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. The subject has participated in a clinical trial and has received an investigational product (IP) 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 IP (whichever is longer).
• The subject has participated in a clinical trial and has received an IP 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 IP (whichever is longer).
• Creatinine clearance (CrCL) < 90 mL per minute.
• Presence of hepatitis B surface antigen (HBsAg), 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/cotinine 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 60 days.
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Pharmaceutical Product Development (PPD), Inc

UNKNOWN

Sponsor Role: collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Austin, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34817414 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

205894

Identifier Type: -

Identifier Source: org_study_id