Low-dose Fostemsavir Extended Release Relative Bioavailability Study

HIV Infections Clinical Trial

Official title:

A Two-Part Randomized Study to Evaluate the Relative Bioavailability of Temsavir Following Single Dose Administration of Fostemsavir 600 mg Tablets Compared to Two Fostemsavir 200 mg Tablet Formulations and to Evaluate the Effect of Food on Bioavailability of Selected Fostemsavir 200 mg Tablet Formulation in Healthy Adult Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04757974
• Other study ID #: 213075
• Status: Completed
• Phase: Phase 1
• Start date: March 5, 2021
• Est. completion date: July 31, 2021

Study information

• Verified date: September 2021
• Source: ViiV Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: July 31, 2021
• Est. primary completion date: July 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 18 to 50 years of age inclusive.

• Healthy as determined by the investigator or medically qualified designee.

• A participant 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 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Fostemsavir 600 mg
Fostemsavir tablets will be administered via oral route.
• Fostemsavir 200 mg
Fostemsavir tablets will be administered via oral route.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
ViiV Healthcare

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Part 1: AUC from time zero extrapolated to infinite time (AUC[0-infinity]) of temsavir		Predose (Day 1) until 72 hour post dose
Primary	Part 1: Maximum observed plasma concentration (Cmax)		Predose (Day 1) until 72 hour post dose
Secondary	Part 1: Time to Cmax (Tmax) of temsavir		Predose (Day 1) until 72 hour post dose
Secondary	Part 1: Elimination half-life (T1/2) of temsavir		Predose (Day 1) until 72 hour post dose
Secondary	Part 1: Concentration at 12 hours post-dose of temsavir		12 hours post-dose
Secondary	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
Secondary	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
Secondary	Part 2: AUC [0-t] of temsavir		Predose (Day 1) until 72 hour post dose
Secondary	Part 2: AUC [0-infinity] of temsavir		Predose (Day 1) until 72 hour post dose
Secondary	Part 2: Cmax of temsavir		Predose (Day 1) until 72 hour post dose