The Effect of Biktarvy (B/F/TAF) on Whole-body Insulin Sensitivity, Lipid and Endocrine Profile in Healthy Volunteers

NCT04950530 | Completed Phase 1

• 1 other identifier: CRF007
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate changes in insulin sensitivity, lipid metabolism and endocrine profile in HIV-negative subjects exposed to Biktarvy (B/F/TAF) compared to subject not exposed to B/F/TAF for 28 days.

Conditions

HIV-1-infection

Keywords

HIV; Insulin; Biktarvy

Outcome Measures

Primary Outcomes (1)

• Change in insulin sensitivity in participants from baseline to end of study between two crossover groups

  Change in insulin sensitivity will be determined by peripheral glucose uptake using a euglycaemic clamp.

  Baseline, day 28, 44, and 72 for both groups

Secondary Outcomes (7)

• Effect of Biktarvy on adipocytokines

  Baseline, day 28, 44, and 72 for both groups

• Effect of Biktarvy on fasting ghrelin

  Baseline, day 28, 44, and 72 for both groups

• Effect of Biktarvy on pituitary hormones

  Baseline, day 28, 44, and 72 for both groups

• Effect of Biktarvy on lipid profile including lipid fractions

  Baseline, day 28, 44, and 72 for both groups

• Effect of Biktarvy on changes in indirect calorimetry

  Baseline, day 28, 44, and 72 for both groups

Study Arms (2)

Arm 1

EXPERIMENTAL

Biktarvy - one tablet once daily, orally administered for the first 28 days of the study. No treatment for the last 44 days of the study.

Drug: BIKTARVY 50Mg-200Mg-25Mg Tablet

Arm 2

EXPERIMENTAL

No treatment for the first 28 days of the study. Biktarvy - one tablet once daily, orally administered for the last 28 days of the study (day 44-72).

Drug: BIKTARVY 50Mg-200Mg-25Mg Tablet

Interventions

BIKTARVY 50Mg-200Mg-25Mg Tablet DRUG

A three-drug fixed dose combination tablet containing 50mg of bictegravir, 200mg of emtricitabine, and 25mg of tenofovir alafenamide taken once daily, orally

Also known as: BIC/FTC/TAF, Bictegravir

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to provide informed consent
• Cis-Male and Cis-Female healthy subjects without underlying conditions
• Cis-Male and Cis-Female subjects with recruitment stratified to include at least 6 female subjects and at least 6 subjects of black Africa origin
• Subjects must have documented negative HIV serology by ELISA and P24 antigen and not receiving anti-HIV pre-exposure prophylaxis (PreP)
• Subjects must be clinically well volunteers aged between 18 to 60 years with BMI \<30 kg/m2 but \>18 kg/m2
• Healthy, as determined by the investigator or medically qualified designee based on a medical evaluation, including medical history, physical examination, laboratory tests, and cardiac evaluation (including ECG)
• Non-fasting blood glucose, total cholesterol and triglycerides within normal limits
• Subjects should have complete blood count (FBC) with normal differential and platelet count
• A female, may be eligible to enter and participate in the study if she:
• is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
• is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:
• Complete abstinence from penile-vaginal intercourse. Abstinence is acceptable only as true abstinence when this is in line with the preferred and usual lifestyle of the participant;
• Any intrauterine device with published data showing that the expected failure rate is \<1% per year (not all intrauterine devices meet this criterion, see Appendix 6\] for an example listing of approved intrauterine devices);
• Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject;
• Approved hormonal contraception (see Appendix 6\] for a listing of examples of approved hormonal contraception)\*;

You may not qualify if:

• Subjects with a waist hip ratio \> 0.97 or BMI \> 30kg/m2 and BMI \<18 kg/m2 will be excluded
• Acute or chronic hepatitis B infection (determined by positive hepatitis B surface antigen result at the screening visit)
• Acute or chronic hepatitis C infection (determined by positive hepatitis C antibody result at the screening visit)
• Diabetes mellitus, other metabolic syndrome or disease process in the opinion of the investigator likely to cause marked disturbance in glucose and lipid homeostasis including hypertension. Subject with HbA1c \>42 mmol/mol will be excluded.
• History or presence of allergy to the B/F/TAF
• ALT greater than or equal to 1.5 x ULN and total bilirubin greater than or equal to 1.5 x ULN excluded;
• Pregnancy and breastfeeding women
• Alcohol consumption \>10 units/week
• Clinically relevant drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study.
• 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 prior to the baseline visit and throughout the study until the follow-up period, unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise participant safety.
• This includes on-going therapy with any of the following
• Metabolically active medications
• Any lipid-lowering medication
• Hormonal agents (oestrogens or androgens)
• Glucocorticoids including inhaled steroids except for 'as necessary' use

Sponsors & Collaborators

• Chelsea and Westminster NHS Foundation Trust: lead

Study Sites (1)

Chelsea & Westminster Hospital NHS Foundation Trust

London, SW10 9NH, United Kingdom

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

bictegravir, emtricitabine, tenofovir alafenamide, drug combination; bictegravir

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Ana Milinkovic

  Chelsea and Westminster Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects will be randomised to start on Biktarvy tablet once daily OR no treatment for the first 28 day dosing phase of the study then will cross over to the alternative for the second dosing phase, following a 2 week washout period (equivalent to 5+ B/F/TAF elimination half-lives).

Study Record Dates

• First Submitted: June 24, 2021
• First Posted: July 6, 2021
• Study Start: December 22, 2022
• Primary Completion: February 29, 2024
• Study Completion: February 29, 2024
• Last Updated: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)