Doravirine, Rifapentine and Isoniazid Interaction

NCT03886701 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 12690
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

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

Outcome Measures

Primary Outcomes (3)

• Doravirine Maximum Concentration (Cmax)

  Doravirine maximum observed concentration during the dosing interval

  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

  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

  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

  Days 1-24 post-dose (period 1 and 2) and 31-34 post-dose (post-study)

Study Arms (1)

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)

Drug: Doravirine (DOR); Drug: Rifapentine (RPT); Drug: Isoniazid (INH)

Interventions

Doravirine (DOR) DRUG

Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.

Also known as: Pifeltro

Experimental

Rifapentine (RPT) DRUG

Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

Also known as: Priftin

Experimental

Isoniazid (INH) DRUG

Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

Also known as: Generic (various)

Experimental

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Females who are postpartum \< 12 months.
• 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.

Sponsors & Collaborators

• Walter K. Kraft: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Thomas Jefferson University Clinical Research Unit

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Latent Tuberculosis; Acquired Immunodeficiency Syndrome

Interventions

doravirine; rifapentine; Isoniazid; Drugs, Generic

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection; 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

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Walter K. Kraft
• Organization: Thomas Jefferson University

walter.kraft@jefferson.edu

215 955-9077

Study Officials

• Walter K Kraft, MD

  Sidney Kimmel Medical College at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: March 22, 2019
• Study Start: April 22, 2019
• Primary Completion: May 20, 2019
• Study Completion: May 20, 2019
• Last Updated: March 27, 2020
• Results First Posted: March 3, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)