Low-dose Fostemsavir Extended Release Relative Bioavailability Study

NCT ID: NCT04757974

Last Updated: 2021-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-05
• Study Completion Date: 2021-07-31

Brief Summary

This is a two-part study. Part 1 will evaluate relative bioavailability of temsavir (TMR) following single dose administration of the reference fostemsavir (FTR) compared to two low-dose ER tablet formulations of FTR. In Part 2, the effect of food on the bioavailability of TMR will be assessed on the selected low-dose ER tablet formulation from Part 1.

Conditions

HIV Infections

Study Design

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

Study Groups

Part 1: Treatment sequence ABC

Participants will receive FTR 3×200 mg ER tablets (Treatment A) in Period 1 followed by FTR 3×200 mg ER tablets (Treatment B) in Period 2 followed by FTR 600 mg ER tablet (Treatment C, reference) in Period 3.

Group Type: EXPERIMENTAL

Fostemsavir 600 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Fostemsavir 200 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Part 1: Treatment sequence BCA

Participants will receive FTR 3×200 mg ER tablets (Treatment B) in Period 1 followed by FTR 600 mg ER tablet (Treatment C, reference) in Period 2 followed by FTR 3×200 mg ER tablets (Treatment A) in Period 3.

Group Type: EXPERIMENTAL

Fostemsavir 600 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Fostemsavir 200 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Part 1: Treatment sequence CAB

Participants will receive FTR 600 mg ER tablet in Period 1 (Treatment C, reference) followed by FTR 3×200 mg ER tablets (Treatment A) in Period 2 followed by FTR 3×200 mg ER tablets (Treatment B) in Period 3.

Group Type: EXPERIMENTAL

Fostemsavir 600 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Fostemsavir 200 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Part 1: Treatment sequence ACB

Participants will receive FTR 3×200 mg ER tablets (Treatment A) in Period 1 followed by FTR 600 mg ER tablet (Treatment C, reference) in Period 2 followed by FTR 3×200 mg ER tablets (Treatment B) in Period 3.

Group Type: EXPERIMENTAL

Fostemsavir 600 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Fostemsavir 200 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Part 1: Treatment sequence BAC

Participants will receive FTR 3×200 mg ER tablets (Treatment B) in Period 1 followed by FTR 3×200 mg ER tablets (Treatment A) in Period 2 followed by FTR 600 mg ER tablet (Treatment C, reference) in Period 3.

Group Type: EXPERIMENTAL

Fostemsavir 600 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Fostemsavir 200 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Part 1: Treatment sequence CBA

Participants will receive FTR 600 mg ER tablet (Treatment C, reference) in Period 1 followed by FTR 3×200 mg ER tablets (Treatment B) in Period 2 followed by FTR 3×200 mg ER tablets (Treatment A) in Period 3.

Group Type: EXPERIMENTAL

Fostemsavir 600 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Fostemsavir 200 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Part 2: Treatment sequence DE

Participants will receive the selected low-dose formulation of FTR 3 × 200 mg ER tablets in a fasted state (Treatment D) in Period 1 and following a high fat high calorie meal (Treatment E) in Period 2.

Group Type: EXPERIMENTAL

Fostemsavir 200 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Part 2: Treatment sequence ED

Participants will receive the selected low-dose formulation of FTR 3 × 200 mg ER tablets following a high fat high calorie meal (Treatment E) in Period 1 and in a fasted state (Treatment D) in Period 2.

Group Type: EXPERIMENTAL

Fostemsavir 200 mg

Intervention Type: DRUG

Fostemsavir tablets will be administered via oral route.

Interventions

Fostemsavir 600 mg

Fostemsavir tablets will be administered via oral route.

Intervention Type: DRUG

Fostemsavir 200 mg

Fostemsavir tablets will be administered via oral route.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18 to 50 years of age inclusive.
• Healthy as determined by the investigator or medically qualified designee.

Exclusion Criteria

• Body weight >= 50 kilograms (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 participants are eligible to participate if they agree to use contraceptive methods.
• A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP). OR Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective.
• Capable of giving signed informed consent.

• History or presence of/significant history of or current 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.
• Alanine transaminase (ALT) >1.5x upper limit of normal (ULN).
• Total bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if total 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 interval corrected for heart rate according to Fridericia's formula (QTcF) >450 millisecond (msec) for males and QTcF>470 msec for females.
• 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/GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise participant safety.
• Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (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 or five half-lives whichever is longer, before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research.
• Presence of hepatitis B surface antigen (HBsAg) [or hepatitis B core antibody (HBcAb)] at screening or within 3 months prior to first dose of study intervention.
• Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
• Positive hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
• Positive Human immunodeficiency virus (HIV)-1 and -2 antigen/antibody immunoassay.
• Cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• 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.
• Regular use of known drugs of abuse.
• Sensitivity to heparin or heparin-induced thrombocytopenia.
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
• A participant with a history of beta-lactam allergy, regardless of severity/seriousness.
• A participant with known or suspected active Coronavirus disease-2019 (COVID-19) infection OR contact with an individual with known COVID-19, within 14 days of study enrollment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 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

Austin, Texas, United States

Countries

United States

Other Identifiers

213075

Identifier Type: -

Identifier Source: org_study_id