Single Dose Pharmacokinetics of Doravirine in HIV-infected Pregnant Women

NCT04900974 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 20-0052
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to evaluate the effect of body changes in pregnancy on doravirine concentrations, to determine what dose of doravirine should be used. Study participants will remain on their normal antiretroviral medications (ARVs) while participating in this study as prescribed by their regular clinic provider. Study participants will come to the research clinic for three sampling visits throughout their time as a participant. Study participants will only take one dose of doravirine during each sampling visit, which will occur during the 2nd and 3rd trimesters, as well as after their baby is delivered. This study was designed intentionally to not give a dose of doravirine in the first trimester when there is the greatest chance for all drugs to potentially cause injury to the baby. Study participants that choose to participate in this study may be enrolled for up to 10 months depending on the length of their pregnancy and how the visits are scheduled.

Conditions

HIV Infections; Pregnancy Related

Outcome Measures

Primary Outcomes (5)

• Maximum Observed Plasma Concentration (Cmax) of Doraviraine During Pregnancy

  To describe single-dose total and protein-unbound Cmax of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum

  Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of Doravirine During Pregnancy

  To describe single-dose total and protein-unbound Tmax of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum

  Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.

• Concentration of Doravirine at 12 Hours (C12) Postdose Doravirine During Pregnancy

  To describe single-dose total and protein-unbound C12h of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum

  Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.

• Concentration of Doravirine at 24 Hours (C24) Postdose Doravirine During Pregnancy

  To describe single-dose total and protein-unbound C24 of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum

  Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.

• Area Under the Concentration-Time Curve From Zero to 24 Hours After Dosing (AUC0-24) of Doravirine During Pregnancy

  To describe single-dose total and protein-unbound AUC of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum

  Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.

Secondary Outcomes (1)

• Number of Adverse Events Reported After Single Doses of Doravirine in Pregnant Participants

  From enrollment visit to follow-up visit, an average of 10 months

Study Arms (1)

Doravirine

EXPERIMENTAL

100mg doravirine given by mouth once at each sampling visit.

Drug: Doravirine

Interventions

Doravirine DRUG

100mg

Doravirine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pregnant women living with Human Immunodeficiency Virus (HIV) ≥18 years of age
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
• Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the trial.
• On stable combination Antiretroviral Therapy (cART) for at least 30 days prior to enrollment
• Plasma HIV RNA \< 50 copies/mL within 90 days prior to enrollment
• Ability and willingness of participant to not change their cART regimen to avoid any confounding of pharmacokinetic (PK) parameters.
• o Note: Women who change cART regimens will be replaced.
• Aspartate aminotransferase and alanine aminotransferase \< 3x Upper Limit of Normal (ULN)
• Hemoglobin lower than Division of AIDs (Acquired Immunodeficiency Syndrome) (DAIDs) Grade 2 (9.0 g/dL)

You may not qualify if:

• Women with multiple gestation, active opportunistic infections, present obstetrical complications that would deem them unsuitable for study participation, or evidence of fetal anomalies in present pregnancy will be excluded.
• Women with severe renal impairment, end stage renal disease, undergoing dialysis, or severe hepatic impairment (Child-Pugh C)
• Women with a significant illness/condition at the time of enrollment that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence or assessment of safety.
• Women with pregnancies that have become complicated are excluded for safety reasons.
• Active hepatitis C (HCV) infection as defined by anti-hepatitis C virus serology (as determined by multi-antigen EIA) and detectable HCV RNA.
• Clinically significant labs greater than Grade 2 on the NIH Division of AIDs Table for Grading the Severity of Adult and Pediatric Adverse events
• Receiving CYP3A inducers including carbamazepine, phenobarbital, phenytoin, enzalutamide, rifampin, rifapentine, mitotane, or St. John's wort or other drugs, including antiretrovirals, that influence drug concentration or alter pharmacokinetic profiles (atazanavir, maraviroc, darunavir, norvir, efavirenz, tipranavir)
• Receiving moderate to strong cytochrome p450 3A (CYP3A) inhibitors including clarithromycin, boceprevir, cobicistat, danoprevir and ritonavir, elvitegravir and ritonavir, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, paritaprevir and ritonavir, posaconazole, ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, grapefruit juice, idelalisib, nefazodone, and nelfinavir.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

doravirine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Amanda Poliseno
• Organization: University of North Carolina at Chapel Hill

amanda_poliseno@unc.edu

919-962-5344

Study Officials

• Angela Kashuba, PharmD

  UNC Chapel Hill

  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

Study Record Dates

• First Submitted: May 13, 2021
• First Posted: May 25, 2021
• Study Start: June 9, 2022
• Primary Completion: March 27, 2025
• Study Completion: April 8, 2025
• Last Updated: April 16, 2026
• Results First Posted: April 16, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Beginning 9 to 36 months following publication.

Locations

US (1)