Single Dose Pharmacokinetics of Doravirine in HIV-infected Pregnant Women

NCT ID: NCT04900974

Last Updated: 2025-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-09
• Study Completion Date: 2025-04-08

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.

Detailed Description

Antiretroviral (ARV) medications are used to treat infection with human immunodeficiency virus (HIV). During pregnancy, ARV therapy keeps women healthy and decreases the spread of HIV to their babies (<1-2%).

Many changes occur in the body during pregnancy, which can alter the concentrations of drug in the body. Doravirine (DOR) is a Food and Drug Administration (FDA) approved ARV, but the extent to which the drug concentrations of doravirine change during pregnancy is unknown. Because these changes are unknown, DOR has not been approved by the FDA for use among pregnant women; however, the FDA has given the researchers permission to use it in this study Pregnant women are often excluded from clinical trials, so it can take several years after a drug gets approved before contemporary ARV is available to them.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Doravirine

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

Group Type: EXPERIMENTAL

Doravirine

Intervention Type: DRUG

100mg

Interventions

Doravirine

100mg

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angela Kashuba, PharmD

Role: PRINCIPAL_INVESTIGATOR

UNC Chapel Hill

Locations

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

Other Identifiers

20-0052

Identifier Type: -

Identifier Source: org_study_id