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

• Status: Withdrawn
• Trial end date: 2021-11-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Yale University
• Collaborator: Gilead Sciences
• Treatments: Emtricitabine; Rifampin; Rifapentine

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

• Exposure to any investigational drug within 4 weeks of enrollment and throughout the study.

• Use of any agent, within 2 weeks of dosing, that is known to induce or inhibit drug metabolizing enzymes (e.g., cimetidine and compounds in the barbiturate and phenothiazine classes), affect renal tubular secretion (e.g., probenecid, beta-lactam antibiotics), gastrointestinal motility (e.g., metoclopramide, propantheline, loperamide, or narcotic analgesics or opioids other than methadone), or uric acid metabolism (e.g., allopurinol) or gastrointestinal pH (including antacids, H2-receptor antagonists, proton pump inhibitors etc.).

• Use of any prescription drugs (other than methadone) or over-the-counter acid controllers within 2 weeks prior to enrollment and throughout the study.

• Positive breathalyzer alcohol test, or positive urine screen for barbiturates, benzodiazepines, amphetamines, THC, cocaine or opioids other than methadone at screening.

• Use of any other drugs, including over-the-counter medications (e.g., acetaminophen) and herbal preparations, within 1 week prior to enrollment and throughout the study. Use of any other concurrent medication, must be discussed with the medical monitor prior to use.

• Use of an oral, injectable or implantable hormonal contraceptive agent within 3 months of enrollment and throughout the study.

• History of any significant drug allergy, drug rash or sensitivity to any class of drugs relevant to the study drugs.

• Use of St. John's Wort (Hypericum) within four weeks prior to study enrollment and throughout the study.

• Consumption of grapefruit or grapefruit juice within 1 week of study entry and throughout the study.

• Women who are pregnant or breastfeeding

• Women of child bearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks before and after the study.

• WOCBP using a prohibited contraceptive method (oral, injectable or implantable hormonal agents)

• Women who are pregnant or breastfeeding

• Women with a positive pregnancy test on screening, enrollment or prior to study drug administration.

• Donation of blood or plasma to a blood bank or as part of a clinical study (except at screening visit) within 4 weeks of enrollment.

• Blood transfusion within 4 weeks of enrollment.

• Inability to tolerate oral medications.

• Inability to tolerate venipuncture and/or absence of secure venous access.

• Inability to refrain from smoking during in-residence period.