TuberculosisPhase 4NCT04551573
A Study of the Pharmacokinetic and Pharmacodynamic Interactions Between Bictegravir, Tenofovir Alafenamide and Rifapentine in Healthy Adult Subjects
A Phase 4 study testing Rifapentine daily and Rifapentine weekly in people with Tuberculosis and Hiv, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis, Hiv
- What is being tested?
- Rifapentine daily and Rifapentine weekly
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- May 2021to Nov 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 34Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale New Haven Hospital
New Haven, Connecticut, 06520
About this study
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
Read more
- 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
Read the detailed description
Subjects will receive once-daily Biktarvy for 4 weeks to ensure all moieties of interest reach steady-state prior to the baseline PK assessment. Thereafter, subjects will be enrolled in one of two groups for PK analysis as follows:
Group one will continue Biktarvy and have rifapentine dosed daily for 4 weeks (10 mg/kg; 600mg dose).
Group two will continue Biktarvy and have rifapentine dosed weekly for 4 weeks (15 mg/kg; 900mg dose).
After 4 weeks of Biktarvy dosing, subjects will have a baseline intensive PK of plasma bictegravir (BIC), tenofovir alafenamide (TAF), tenofovir (TFV) levels at all time points, and peripheral blood mononuclear cells (PBMCs) will be collected at 24 hours post-dose for IC TFV-DP. This will occur prior to receiving their first dose of directly observed oral rifapentine co-administered with Biktarvy, thus serving as their own control. Rifapentine will thereafter be administered by directly observed therapy (DOT) or ingestion monitored by smart phone application (e.g., Time Stamp App or other phone app platform). Intensive PK assessments will be repeated after 4 weeks of RPT dosing for both Group 1 and 2.
Intensive PK sampling will be performed at time 0 (pre-dose), 15 and 30 min; 1, 2, 3, 4, 8, 12 and 24 hours post-dose with BIC/TAF/FTC alone and when coadministered with rifapentine. Plasma will be isolated at all time points, and PBMCs will be isolated at 24 hours post-dose.
PK levels will be measured by colleagues at the Colorado Antiviral Pharmacology (CAVP) Laboratory at the University of Colorado Anschutz Medical Campus. Plasma concentrations of BIC, TAF, TFV, and IC TFV-DP in PBMCs will be measured by liquid chromatography-tandem mass spectrometry.
- Conditions
- Tuberculosis, Hiv
- Being tested
- Rifapentine daily, Rifapentine weekly
- Keywords
- Pharmacokinetic and Pharmacodynamic Interactions
- Medical subject headings
- Tuberculosis, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rifapentine dailyDrug
In addition to taking Biktarvy for four weeks, participants will also take Rifapentine dosed daily for four weeks (10mg/kg; 600 mg dose)
Rifapentine weeklyDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: Rifapentine weekly |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: 8 weeks
Secondary outcomes (4)
Plasma area under the curve (AUC) of tenofovir alafenamide (TAF) between groups
Determining plasma AUCtau of TAF when co-administered with rifapentine as once-daily or once-weekly
Measured: 8 weeks
Maximum plasma concentrations(Cmax) of TAF between groups
Determining Cmax of TAF when co-administered with rifapentine as once-daily or once-weekly
Measured: 8 weeks
Steady-state Intracellular (IC) concentration changes of tenofovir-diphosphate (TFV-DP)
Determining steady-state intracellular (IC) concentration changes of TFV-DP when co-administered with rifapentine at two different dosing intervals (daily and weekly)
Measured: 8 weeks
Adverse Events of medications
Adverse events of co-administration of rifapentine with BIC/TAF/ Emtrictabine (FTC)
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2020
- Study startMay 2021 (estimated)
- Primary completionOct 2021 (estimated)
- Study completionNov 2021 (estimated)
Why it stopped: COVID-19 Pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Sponsor
- Investigators
- Onyema Ogbuagu, MBBCh, FACP, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04551573
- Sponsor's protocol ID
- 2000027436
- Status last verified
- Sep 2021
- First submitted
- 9 Sep 2020
- Last updated
- 20 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of the Pharmacokinetic and Pharmacodynamic Interactions Between Bictegravir, Tenofovir Alafenamide and Rifapentine in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT04551573
- Acronym / sponsor ID
- 2000027436
- Conditions
- Tuberculosis, Hiv
- Keywords
- Pharmacokinetic and Pharmacodynamic Interactions
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: COVID-19 Pandemic
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- May 2021 (estimated)
- Primary completion
- Oct 2021 (estimated)
- Study completion
- Nov 2021 (estimated)
- First posted
- 16 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Subjects will receive once-daily Biktarvy for 4 weeks to ensure all moieties of interest reach steady-state prior to the baseline PK assessment. Thereafter, subjects will be enrolled in one of two groups for PK analysis as follows:
Group one will continue Biktarvy and have rifapentine dosed daily for 4 weeks (10 mg/kg; 600mg dose).
Group two will continue Biktarvy and have rifapentine dosed weekly for 4 weeks (15 mg/kg; 900mg dose).
After 4 weeks of Biktarvy dosing, subjects will have a baseline intensive PK of plasma bictegravir (BIC), tenofovir alafenamide (TAF), tenofovir (TFV) levels at all time points, and peripheral blood mononuclear cells (PBMCs) will be collected at 24 hours post-dose for IC TFV-DP. This will occur prior to receiving their first dose of directly observed oral rifapentine co-administered with Biktarvy, thus serving as their own control. Rifapentine will thereafter be administered by directly observed therapy (DOT) or ingestion monitored by smart phone application (e.g., Time Stamp App or other phone app platform). Intensive PK assessments will be repeated after 4 weeks of RPT dosing for both Group 1 and 2.
Intensive PK sampling will be performed at time 0 (pre-dose), 15 and 30 min; 1, 2, 3, 4, 8, 12 and 24 hours post-dose with BIC/TAF/FTC alone and when coadministered with rifapentine. Plasma will be isolated at all time points, and PBMCs will be isolated at 24 hours post-dose.
PK levels will be measured by colleagues at the Colorado Antiviral Pharmacology (CAVP) Laboratory at the University of Colorado Anschutz Medical Campus. Plasma concentrations of BIC, TAF, TFV, and IC TFV-DP in PBMCs will be measured by liquid chromatography-tandem mass spectrometry.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rifapentine daily | Experimental | Drug: Rifapentine dailyIn addition to taking Biktarvy for four weeks, participants will also take Rifapentine dosed daily for four weeks (10mg/kg; 600 mg dose) |
| Rifapentine weekly | Experimental | Drug: Rifapentine weeklyIn addition to taking Biktarvy for four weeks, participants will also take Rifapentine dosed weekly for another four more weeks (15 mg/kg; 900mg dose) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (34 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rifapentine dailyIn 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 weeklyIn 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 |
Primary outcome
Plasma area under the curve (AUC) of Bictegravir between groups
Time frame: 8 weeks
Determining plasma AUCtau of Bictegravir when co-administered with rifapentine as once-daily or once-weekly
Maximum plasma concentrations(Cmax) of Bictegravir between groups
Time frame: 8 weeks
Determining Cmax of Bictegravir when co-administered with rifapentine as once-daily or once-weekly
Concentrations at the end of dosing interval (Ctau) of Bictegravir between groups
Time frame: 8 weeks
Determining Ctau of Bictegravir when co-administered with rifapentine as once-daily or once-weekly
Time to total maximum plasma concentrations (Tmax) of Bictegravir between groups
Time frame: 8 weeks
Determining Tmax of Bictegravir when co-administered with rifapentine as once-daily or once-weekly
4 secondary outcomes
Plasma area under the curve (AUC) of tenofovir alafenamide (TAF) between groups
Time frame: 8 weeks
Maximum plasma concentrations(Cmax) of TAF between groups
Time frame: 8 weeks
Steady-state Intracellular (IC) concentration changes of tenofovir-diphosphate (TFV-DP)
Time frame: 8 weeks
Adverse Events of medications
Time frame: 8 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2021.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Onyema Ogbuagu, MBBCh, FACP principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rifapentine daily and Rifapentine weekly in people with Tuberculosis and Hiv, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 20 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma area under the curve (AUC) of Bictegravir between groups (time frame: 8 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2021.