Doravirine, Rifapentine and Isoniazid Interaction
Condition: Latent Tuberculosis; Human Immunodeficiency Virus; Rifamycins Causing Adverse Effects in Therapeutic Use; Drug Interaction Potentiation
MeSH terms: Tuberculosis; Acquired Immunodeficiency Syndrome; HIV Infections; Latent Tuberculosis
Intervention: Doravirine (DOR); Rifapentine (RPT); Isoniazid (INH)
Intervention description: Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.; Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.; Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
Intervention MeSH terms: Isoniazid; Rifapentine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug-drug interaction; Pharmacokinetics; Non-nucleoside reverse transcriptase inhibitor; NNRTI; LTBI; Antimycobacterial

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. 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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy male or female between 18-60 years old at the time of screening.

          2. Have a Body Mass Index (BMI) > 19 and < 33.

          3. Weigh > 45 kg but < 120 kg.

          4. Non-smoker (tobacco or electronic cigarettes).

          5. Negative QuantiFERON-TB Gold at screening.

          6. Subjects who agree to abstain from alcohol consumption throughout the duration of the
             study.

          7. 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.

          8. Evidence of a personally signed and dated informed consent document indicating that
             the subject has been informed of all pertinent aspects of the study.

        Exclusion Criteria:

          1. History of clinically significant endocrine, gastrointestinal, cardiovascular,
             hematological, hepatic, immunological, renal, respiratory, genitourinary,
             dermatologic, psychiatric abnormalities or neurological (including stroke and chronic
             seizure) diseases.

          2. >500 mL blood or plasma donation in the 6 weeks prior to study start

          3. Known anaphylactic or severe systemic reactions to any components of doravirine,
             rifapentine, isoniazid or pyridoxine.

          4. Positive HIV, Hepatitis B or Hepatitis C virus. Evidence of prior Hepatitis B
             infection and immunity is not exclusionary.

          5. Latent or active tuberculosis infection. Documented prior fully treated latent
             tuberculosis is not exclusionary.

          6. Females who are postpartum < 12 months.

          7. Current drug or alcohol abuse.

          8. 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.

          9. 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.

         10. Any clinical significant findings on lab, ECG or physical exam at screening.