A Study of the Pharmacokinetic and Pharmacodynamic Interactions Between Bictegravir, Tenofovir Alafenamide and Rifapentine in Healthy Adult Subjects

NCT04551573 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: 2000027436
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label, fixed sequence, pharmacokinetic interaction study between bictegravir and tenofovir alafenamide with rifapentine dosed either daily or weekly. Primary Aims

• To assess the effect of once-weekly rifapentine on the steady-state PK of BIC
• To assess the effect of once-daily rifapentine on the steady-state PK of BIC Secondary Aims
• To assess the effect of daily dosed rifapentine on steady-state PK of TAF (measured as plasma and IC concentrations of TFV-DP)
• To assess the effect and timing of interactions of weekly dosed rifapentine on steady-state PK of TAF (measured as plasma and IC concentrations of TFV-DP)
• To assess the safety of BIC/TAF/FTC when coadministered with once-weekly or once-daily rifapentine

Conditions

Tuberculosis; Hiv

Keywords

Pharmacokinetic and Pharmacodynamic Interactions

Outcome Measures

Primary Outcomes (4)

• Plasma area under the curve (AUC) of Bictegravir between groups

  Determining plasma AUCtau of Bictegravir when co-administered with rifapentine as once-daily or once-weekly

  8 weeks

• Maximum plasma concentrations(Cmax) of Bictegravir between groups

  Determining Cmax of Bictegravir when co-administered with rifapentine as once-daily or once-weekly

  8 weeks

• Concentrations at the end of dosing interval (Ctau) of Bictegravir between groups

  Determining Ctau of Bictegravir when co-administered with rifapentine as once-daily or once-weekly

  8 weeks

• Time to total maximum plasma concentrations (Tmax) of Bictegravir between groups

  Determining Tmax of Bictegravir when co-administered with rifapentine as once-daily or once-weekly

  8 weeks

Secondary Outcomes (4)

• Plasma area under the curve (AUC) of tenofovir alafenamide (TAF) between groups

  8 weeks

• Maximum plasma concentrations(Cmax) of TAF between groups

  8 weeks

• Steady-state Intracellular (IC) concentration changes of tenofovir-diphosphate (TFV-DP)

  8 weeks

• Adverse Events of medications

  8 weeks

Study Arms (2)

Rifapentine daily

EXPERIMENTAL

In addition to taking Biktarvy for four weeks, participants will also take Rifapentine dosed daily for four weeks (10mg/kg; 600 mg dose)

Drug: Rifapentine daily

Rifapentine weekly

EXPERIMENTAL

In addition to taking Biktarvy for four weeks, participants will also take Rifapentine dosed weekly for another four more weeks (15 mg/kg; 900mg dose)

Drug: Rifapentine weekly

Interventions

Rifapentine daily DRUG

In addition to taking Biktarvy for four weeks, participants will also take Rifapentine dosed daily for four weeks (10mg/kg; 600 mg dose)

Rifapentine daily

Rifapentine weekly DRUG

In addition to taking Biktarvy for four weeks, participants will also take Rifapentine dosed weekly for another four more weeks (15 mg/kg; 900mg dose)

Rifapentine weekly

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adults deemed by the investigator to have acceptable medical history, physical examination, 12 lead electrocardiogram, and clinical laboratory evaluations
• Body weight \> or equal to 50 kg for males and females
• Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive. BMI = weight (kg)/ height (m2)
• Male or females, ages \> or equal to 18 years

You may not qualify if:

• Positive screening HIV+ as determined by standard serologic and molecular assays or suspected acute HIV infection in the opinion of the clinician
• Subjects with AST, ALT or bilirubin \> 2.5X the upper limit of normal.
• Hemoglobin \< 9 g/dL, and platelet count \< 75, 000/mm3.
• Positive serum or urine for HCG.
• Positive or indeterminate interferon gamma release assay
• History or current evidence of any significant acute or chronic medical illness that, within the investigator's discretion, would interfere with the conduct or interpretation of the study.
• Proven or suspected acute hepatitis at the time of study entry
• Untreated and /or active Hepatitis B or C infection or chronic liver disease with liver cirrhosis (as determined by biopsy or non-invasive testing)
• Current or recent (within 3 months) gastrointestinal disease that would interfere with the conduct or interpretation of the study.
• Any gastrointestinal surgery that could impact upon the absorption of study drug.
• Evidence of organ dysfunction or any clinically relevant deviations (as determined by the investigator) from the norms observed in the general population regarding physical examination, vital signs, ECG or clinical laboratory determinations.
• Any major surgery within 4 weeks of enrollment. Minor surgical procedures requiring local anesthesia are exceptions.
• Signs and symptoms of or known pulmonary or extra-pulmonary tuberculosis
• A history of porphyria
• History of or known allergy to rifamycins.

Sponsors & Collaborators

• Yale University: lead
• Gilead Sciences: collaborator

Study Sites (1)

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Conditions

Tuberculosis; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Onyema Ogbuagu, MBBCh, FACP

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: September 16, 2020
• Study Start: May 1, 2021
• Primary Completion: October 1, 2021
• Study Completion: November 1, 2021
• Last Updated: September 20, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)