Dolutegravir Pediatric Liquid Formulation Study

NCT ID: NCT03921723

Last Updated: 2020-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-07
• Study Completion Date: 2019-07-25

Brief Summary

This is an open-label, single-center, single dose, non-randomized, sequential, fixed-sequence study, which will evaluate pharmacokinetics (PK) of dolutegravir (DTG) in healthy adult subjects. The study will contain 6 periods with five prototype liquid formulations for evaluation in fasted state. In period 1, 2 and 3 single reference dose of 2 dispersible tablets of 5 milligram DTG will be administered and at least 2 liquid prototype DTG formulations (containing a target total dose of 10mg DTG). There will be a wash-out period of 7 days between each period. In period 4 through 6, there would be options to evaluate additional prototype liquid formulations. The total duration of study will be up to 17 weeks. DTG has been found to be safe and effective in adults infected with human immunodeficiency virus (HIV). DTG dispersible tablets have been developed primarily for use in children from 4 weeks to 6 years of age, and a DTG liquid formulation are is being developed to study the appropriate dose needed for the HIV-exposed and infected neonatal population in the first four weeks of life. Approximately 18 subjects will be enrolled in this study.

Conditions

HIV Infections

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Subject receiving Dolutegravir 10 mg

Subject will receive a prototype equivalent to DTG 10 mg liquid formulation in period 1, a prototype equivalent to DTG 10 mg liquid formulation in period 2, a DTG 10 mg dispersible tablet in Period 3, each period will be separated by washout period of \>= 7 days, if required a prototype equivalent to DTG 10 mg liquid formulation in period 4, a prototype equivalent to DTG 10 mg liquid formulation in period 5, and a prototype equivalent to DTG 10 mg liquid formulation in period 6 will be evaluated.

Group Type: EXPERIMENTAL

Dolutegravir dispersible tablet

Intervention Type: DRUG

DTG will be available as an oral tablet with dosing strength of 5 mg 2 tablet will be dispersed in water will be administered orally for prescribed regimen.

Dolutegravir oral suspension

Intervention Type: DRUG

DTG will be available as an oral suspension with dosing strength of 5 mg per milliliter (ml) or 2 mg per ml with miglyol 812N or ethyl cellulose in miglyol 812N as vehicle for suspension administered orally for prescribed regimen.

Dolutegravir oral solution

Intervention Type: DRUG

DTG will be available as an oral solution with dosing strength of 2 mg per ml will be administered orally for prescribed regimen.

Interventions

Dolutegravir dispersible tablet

DTG will be available as an oral tablet with dosing strength of 5 mg 2 tablet will be dispersed in water will be administered orally for prescribed regimen.

Intervention Type: DRUG

Dolutegravir oral suspension

DTG will be available as an oral suspension with dosing strength of 5 mg per milliliter (ml) or 2 mg per ml with miglyol 812N or ethyl cellulose in miglyol 812N as vehicle for suspension administered orally for prescribed regimen.

Intervention Type: DRUG

Dolutegravir oral solution

DTG will be available as an oral solution with dosing strength of 2 mg per ml will be administered orally for prescribed regimen.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
• Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac evaluation.
• Body weight >= 50 kg (110 pounds [lbs]) for men and >=45 kg (99 lbs) for women and body mass index (BMI) within the range 18.5-31.0 kilogram per meter square (kg/m^2) (inclusive).
• Male and female subjects will be part of study. A female subject is eligible to participate if she is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP).
• Additional requirements for pregnancy testing, if needed, during and after study intervention; The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Subject should be capable of giving signed informed consent as which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).

Exclusion Criteria

• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
• Abnormal blood pressure as determined by the investigator.
• Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).
• Bilirubin >1.5times ULN (isolated bilirubin >1.5 times 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).
• QT correction using Fridericia Formula (QTcF) >450 millisecond (msec)
• Past or intended use of over-the-counter or prescription medication (including herbal medications) within 7 days prior to dosing. Paracetamol.
• History of allergy or sensitivity to DTG.
• Participation in the study would result in loss of blood or blood products in excess of 500 mL within 56 days.
• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• Current enrollment or past participation within the last 30 days before signing of consent in this or any other clinical study involving an investigational study intervention or any other type of medical research.
• Presence of Hepatitis B surface antigen (HBsAg), or a positive hepatitis B core antibody with a negative hepatitis B surface antibody at screening.
• Positive Hepatitis C antibody test result at screening: Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) test is obtained.
• Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention.
• Positive pre-study drug/alcohol screen.
• Positive HIV antibody test.
• Regular use of known drugs of abuse.
• Regular alcohol consumption within one month prior to the study defined as: For the United Kingdom an average weekly intake of >14 units for males or females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening.

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

Sponsors

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

Nottingham, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

209354

Identifier Type: -

Identifier Source: org_study_id