Low-dose Fostemsavir Extended Release Relative Bioavailability Study

NCT04757974 | Completed Phase 1 FDA Drug

• 1 other identifier: 213075
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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

Keywords

Temsavir; Fostemsavir; Bioavailability; Extended Release tablet; GSK3684934; Food effect

Outcome Measures

Primary Outcomes (3)

• Part 1: Area under the plasma concentration-time curve (AUC) from time zero to the last quantifiable time point (AUC[0-t]) of temsavir

  Predose (Day 1) until 72 hour post dose

• Part 1: AUC from time zero extrapolated to infinite time (AUC[0-infinity]) of temsavir

  Predose (Day 1) until 72 hour post dose

• Part 1: Maximum observed plasma concentration (Cmax)

  Predose (Day 1) until 72 hour post dose

Secondary Outcomes (8)

• Part 1: Time to Cmax (Tmax) of temsavir

  Predose (Day 1) until 72 hour post dose

• Part 1: Elimination half-life (T1/2) of temsavir

  Predose (Day 1) until 72 hour post dose

• Part 1: Concentration at 12 hours post-dose of temsavir

  12 hours post-dose

• Part 1 and Part 2: Number of participants with clinically significant change from Baseline in vital signs and clinical laboratory parameters

  Baseline (Day -1) until end of follow up at 4 weeks

• Part 1 and Part 2: Number of participants reporting adverse events (AEs) and serious adverse events (SAEs)

  Baseline (Day -1) until end of follow up at 4 weeks

Study Arms (8)

Part 1: Treatment sequence ABC

EXPERIMENTAL

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.

Drug: Fostemsavir 600 mg; Drug: Fostemsavir 200 mg

Part 1: Treatment sequence BCA

EXPERIMENTAL

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.

Drug: Fostemsavir 600 mg; Drug: Fostemsavir 200 mg

Part 1: Treatment sequence CAB

EXPERIMENTAL

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.

Drug: Fostemsavir 600 mg; Drug: Fostemsavir 200 mg

Part 1: Treatment sequence ACB

EXPERIMENTAL

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.

Drug: Fostemsavir 600 mg; Drug: Fostemsavir 200 mg

Part 1: Treatment sequence BAC

EXPERIMENTAL

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.

Drug: Fostemsavir 600 mg; Drug: Fostemsavir 200 mg

Part 1: Treatment sequence CBA

EXPERIMENTAL

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.

Drug: Fostemsavir 600 mg; Drug: Fostemsavir 200 mg

Part 2: Treatment sequence DE

EXPERIMENTAL

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.

Drug: Fostemsavir 200 mg

Part 2: Treatment sequence ED

EXPERIMENTAL

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.

Drug: Fostemsavir 200 mg

Interventions

Fostemsavir 600 mg DRUG

Fostemsavir tablets will be administered via oral route.

Part 1: Treatment sequence ABC; Part 1: Treatment sequence ACB; Part 1: Treatment sequence BAC; Part 1: Treatment sequence BCA; Part 1: Treatment sequence CAB; Part 1: Treatment sequence CBA

Fostemsavir 200 mg DRUG

Fostemsavir tablets will be administered via oral route.

Part 1: Treatment sequence ABC; Part 1: Treatment sequence ACB; Part 1: Treatment sequence BAC; Part 1: Treatment sequence BCA; Part 1: Treatment sequence CAB; Part 1: Treatment sequence CBA; Part 2: Treatment sequence DE; Part 2: Treatment sequence ED

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (1)

GSK Investigational Site

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

fostemsavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: This is a two-part study, where Part 1 will be conducted as a randomized three period, three treatment crossover study and Part 2 will have a randomized two period, two treatment crossover design.

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: February 17, 2021
• Study Start: March 5, 2021
• Primary Completion: July 31, 2021
• Study Completion: July 31, 2021
• Last Updated: September 22, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (1)