Single Dose Pharmacokinetics of Doravirine in HIV-infected Pregnant Women

• Status: Recruiting
• Trial end date: 2023-05-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: Merck Sharp & Dohme Corp.

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.