Latent TuberculosisPhase 1DORIISNCT03886701
Doravirine, Rifapentine and Isoniazid Interaction
A Phase 1 study testing Doravirine (DOR), Rifapentine (RPT) and Isoniazid (INH) in people with Latent Tuberculosis and Human Immunodeficiency Virus, run by Walter K. Kraft at 1 site in United States.
Trial summary
Drug therapy for persons living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) co-infected with latent tuberculosis infection (LTBI) is complex. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Latent Tuberculosis, Human Immunodeficiency Virus, Rifamycins Causing Adverse Effects in Therapeutic Use
- What is being tested?
- Doravirine (DOR), Rifapentine (RPT) and Isoniazid (INH)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Apr 2019to 20 May 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female between 18-60 years old at the time of screening.
- Have a Body Mass Index (BMI) > 19 and < 33.
- Weigh > 45 kg but < 120 kg.
- Non-smoker (tobacco or electronic cigarettes).
- Negative QuantiFERON-TB Gold at screening.
- Subjects who agree to abstain from alcohol consumption throughout the duration of the study.
- Female subjects of childbearing potential must demonstrate a urine beta-hCG consistent with non-pregnancy at the time of the screening visit and agree to the use (and/or have their partner use) of an acceptable method of birth-control at initial screening, during the time of the trial and until two weeks after the last dose of drug following the last treatment period.
- Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
Who cannot join
- History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, dermatologic, psychiatric abnormalities or neurological (including stroke and chronic seizure) diseases.
- >500 mL blood or plasma donation in the 6 weeks prior to study start
- Known anaphylactic or severe systemic reactions to any components of doravirine, rifapentine, isoniazid or pyridoxine.
- Positive HIV, Hepatitis B or Hepatitis C virus. Evidence of prior Hepatitis B infection and immunity is not exclusionary.
- Latent or active tuberculosis infection. Documented prior fully treated latent tuberculosis is not exclusionary.
- Females who are postpartum < 12 months.
Show all 10Show fewer
- Current drug or alcohol abuse.
- Received study drug in another study within 4 weeks or within 5 half-lives, which ever occurring first, before first anticipated dose of study drug in this study.
- Unable to refrain from use of over-the-counter, prescription (unless determined appropriate by the investigator), herbal or natural products, vitamins or supplements, or grapefruit juice/grapefruit products.
- Any clinical significant findings on lab, ECG or physical exam at screening.
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University Clinical Research Unit
Philadelphia, Pennsylvania, 19107
About this study
Official title: A Phase 1, Open-Label, Fixed-Sequence, Drug Interaction Study to Investigate the Effect of Once-Weekly Rifapentine and Isoniazid on the Pharmacokinetics of Steady-State Doravirine
Drug therapy for persons living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) co-infected with latent tuberculosis infection (LTBI) is complex. Anti-tuberculosis drugs used to treat LTBI often induce drug metabolizing enzymes that share the same metabolic pathway as antiretroviral drugs used for those living with HIV/AIDS. This study evaluates the drug-drug interaction (DDI) potential of an antiretroviral drug when co-administered with a common anti-tuberculosis regimen of drugs.
Read the detailed description
Rifapentine (RPT) and isoniazid (INH) given once weekly for 12 weeks is commonly used for treating LTBI in adults. For people living with HIV-1, the risks of LTBI is increased. Individuals living with HIV-1 are often on chronic antiretroviral drugs that prevent immunodeficiency and complications associated with infection. Unfortunately, antiretroviral drugs are subject to many DDIs especially with RPT which induces drug clearing enzymes.
Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection. Because RPT induces the metabolic pathway in which DOR is removed, there is concern that taking both concomitantly will result in an unwanted DDI leading to reduced DOR concentrations in the blood. Reduced levels will result in loss of efficacy for the drug and therefore not provide adequate viral suppression in those living with HIV. This study investigates the DDI potential of the once weekly regimen RPT and INH together with DOR in healthy volunteers.
- Conditions
- Latent Tuberculosis, Human Immunodeficiency Virus, Rifamycins Causing Adverse Effects in Therapeutic Use, Drug Interaction Potentiation
- Being tested
- Doravirine (DOR), Rifapentine (RPT), Isoniazid (INH)
- Keywords
- Drug-drug interaction, Pharmacokinetics, Non-nucleoside reverse transcriptase inhibitor, NNRTI, LTBI, Antimycobacterial
- Medical subject headings
- Latent Tuberculosis, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Doravirine (DOR)Drug
Also called Pifeltro
Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.
Rifapentine (RPT)Drug
Also called Priftin
Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
Isoniazid (INH)Drug
Also called Generic (various)
Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Period 1: DOR twice-daily alone (Study days 1-4) and Period 2: DOR twice-daily with RPT and INH once-weekly (Study days 7-21) Receives: Drug: Doravirine (DOR); Drug: Rifapentine (RPT); Drug: Isoniazid (INH) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Doravirine Maximum Concentration (Cmax)
Doravirine maximum observed concentration during the dosing interval
Measured: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12)
Doravirine area under the plasma-concentration time curve derived from plasma sampling during one dosing interval
Measured: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Doravirine Oral Clearance (CL/F)
Doravirine apparent oral clearance derived from plasma sampling
Measured: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Secondary outcomes (1)
Adverse Event
Safety and tolerability
Measured: Days 1-24 post-dose (period 1 and 2) and 31-34 post-dose (post-study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2019
- Study start22 Apr 2019
- Primary completion20 May 2019
- Study completion20 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Latent TuberculosisStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Walter K. Kraft
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Walter K. Kraft, Thomas Jefferson University
- Investigators
- Walter K Kraft, MD, Principal investigator, Sidney Kimmel Medical College at Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03886701
- Sponsor's protocol ID
- 12690
- Acronym
- DORIIS
- Status last verified
- Mar 2020
- First submitted
- 12 Mar 2019
- Last updated
- 27 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Fixed-Sequence, Drug Interaction Study to Investigate the Effect of Once-Weekly Rifapentine and Isoniazid on the Pharmacokinetics of Steady-State Doravirine
- ClinicalTrials.gov ID
- NCT03886701
- Acronym / sponsor ID
- DORIIS / 12690
- Conditions
- Latent Tuberculosis, Human Immunodeficiency Virus, Rifamycins Causing Adverse Effects in Therapeutic Use, Drug Interaction Potentiation
- Keywords
- Drug-drug interaction, Pharmacokinetics, Non-nucleoside reverse transcriptase inhibitor, NNRTI, LTBI, Antimycobacterial
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Walter K. KraftUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 22 Apr 2019 (actual)
- Primary completion
- 20 May 2019 (actual)
- Study completion
- 20 May 2019 (actual)
- First posted
- 22 Mar 2019 (actual)
- Results
- Posted 3 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Drug therapy for persons living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) co-infected with latent tuberculosis infection (LTBI) is complex. Anti-tuberculosis drugs used to treat LTBI often induce drug metabolizing enzymes that share the same metabolic pathway as antiretroviral drugs used for those living with HIV/AIDS. This study evaluates the drug-drug interaction (DDI) potential of an antiretroviral drug when co-administered with a common anti-tuberculosis regimen of drugs.
Detailed description
Rifapentine (RPT) and isoniazid (INH) given once weekly for 12 weeks is commonly used for treating LTBI in adults. For people living with HIV-1, the risks of LTBI is increased. Individuals living with HIV-1 are often on chronic antiretroviral drugs that prevent immunodeficiency and complications associated with infection. Unfortunately, antiretroviral drugs are subject to many DDIs especially with RPT which induces drug clearing enzymes.
Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection. Because RPT induces the metabolic pathway in which DOR is removed, there is concern that taking both concomitantly will result in an unwanted DDI leading to reduced DOR concentrations in the blood. Reduced levels will result in loss of efficacy for the drug and therefore not provide adequate viral suppression in those living with HIV. This study investigates the DDI potential of the once weekly regimen RPT and INH together with DOR in healthy volunteers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Doravirine (DOR), Drug: Rifapentine (RPT), Drug: Isoniazid (INH)Period 1: DOR twice-daily alone (Study days 1-4) and Period 2: DOR twice-daily with RPT and INH once-weekly (Study days 7-21) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Healthy male or female between 18-60 years old at the time of screening.
- Have a Body Mass Index (BMI) > 19 and < 33.
- Weigh > 45 kg but < 120 kg.
- Non-smoker (tobacco or electronic cigarettes).
- Negative QuantiFERON-TB Gold at screening.
Key exclusion criteria (10 listed)
- History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, dermatologic, psychiatric abnormalities or neurological (including stroke and chronic seizure) diseases.
- >500 mL blood or plasma donation in the 6 weeks prior to study start
- Known anaphylactic or severe systemic reactions to any components of doravirine, rifapentine, isoniazid or pyridoxine.
- Positive HIV, Hepatitis B or Hepatitis C virus. Evidence of prior Hepatitis B infection and immunity is not exclusionary.
- Latent or active tuberculosis infection. Documented prior fully treated latent tuberculosis is not exclusionary.
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 |
|---|---|---|
| Doravirine (DOR)Also: PifeltroNon-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents. | Drug | Experimental |
| Rifapentine (RPT)Also: PriftinRifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection. | Drug | Experimental |
| Isoniazid (INH)Also: Generic (various)Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection. | Drug | Experimental |
Primary outcome
Doravirine Maximum Concentration (Cmax)
Time frame: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Doravirine maximum observed concentration during the dosing interval
Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12)
Time frame: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Doravirine area under the plasma-concentration time curve derived from plasma sampling during one dosing interval
Doravirine Oral Clearance (CL/F)
Time frame: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Doravirine apparent oral clearance derived from plasma sampling
1 secondary outcome
Adverse Event
Time frame: Days 1-24 post-dose (period 1 and 2) and 31-34 post-dose (post-study)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Walter K Kraft, MD principal investigator
Sidney Kimmel Medical College at Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Doravirine (DOR), Rifapentine (RPT) and Isoniazid (INH) in people with Latent Tuberculosis and Human Immunodeficiency Virus, run by Walter K. Kraft 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 8 inclusion and 10 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: finished, as of the sponsor's last update on 27 Mar 2020. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Doravirine Maximum Concentration (Cmax) (time frame: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose). The study lists 3 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 27 Mar 2020.