Phase 3
N=77
A Single-arm, Open-label, Study to Assess the Pharmacokinetics of Darunavir and Ritonavir, Darunavir and Cobicistat, Etravirine, and Rilpivirine in HIV-1 Infected Pregnant Women
HIV · HIV Infections · Pregnancy
Bottom Line
View on ClinicalTrials.gov: NCT00855335 ↗Enrolled (actual)
77
Serious AEs
27.3%
Results posted
Sep 2017
Primary outcome: Primary: Predose (Trough) Plasma Concentration (C0h) — 3608; 491.4; 2481; 147 nanogram per milliliter (ng/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Darunavir (Drug); Ritonavir (Drug); Etravirine (Drug); Rilpivirine (Drug); Darunavir/Cobicistat (FDC) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Janssen Scientific Affairs, LLC
- Primary completion
- Aug 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Predose (Trough) Plasma Concentration (C0h) |
3608; 491.4; 2481; 147; 281; 127 | — |
| PRIMARY Minimum Plasma Concentration (Cmin) |
2851; 264.7; 1473; 40.5; 269; 84.0 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) |
6659; 1110; 7310; 742; 569; 167 | — |
| PRIMARY Time to Reach the Maximum Plasma Concentration (Tmax) |
3.00; 5.04; 4.00; 4.18; 4.00; 4.00 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 Hours Post-dose (AUC0-12h) |
56890; 7406; 5004; 39370; 3775; 6617 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC0-24h) |
92116; 6584; 2714; 99613; 8643; 62289 | — |
| SECONDARY Number of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Plasma Viral Load (<) 50 Copies/Milliliter (mL) |
6; 9; 12; 13; 6; 5 | — |
| SECONDARY Mean Change From Baseline in Log10 Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Viral Load Value |
2.12; 1.88; 2.06; 1.84; 1.77; -0.26 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count |
466.3; 497.9; 417.47; 495.79; 594.17; -14.8 | — |
| SECONDARY Number of Participants With Resistance at Virological Failure |
0; 0; 0; 0; 0 | — |
| SECONDARY Plasma Concentration of Drug in the Cord Plasma and Maternal Plasma Samples Collected at the Time of Delivery |
348.4; 17.07; 228; NA; 147; 32.8 | — |
| SECONDARY Number of Infants With Human Immunodeficiency Virus (HIV) Positive Test Result |
0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
14; 17; 12; 9; 5; 6 | — |
Summary
The purpose of this study is to study how changes in the body during pregnancy influence the blood levels of TMC114 (darunavir) and ritonavir taken together, darunavir and cobicistat taken as a fixed-dose combination, TMC125 (etravirine) taken alone or with darunavir and ritonavir or rilpivirine in patients with human immunodeficiency virus-1 (HIV-1). This study will examine how these drugs are absorbed in the body, how they are distributed within the body and how they are removed from the body over time. Any pregnant woman who is currently receiving darunavir with ritonavir, darunavir with cobicistat, etravirine or rilpivirine for HIV-1, and who meets the eligibility criteria for the study, will be allowed to enroll. Patients must be willing to remain on study medication during the course of their pregnancy, and 12 weeks postpartum. The information collected may help answer questions about how to best prescribe these three drugs for pregnant women.
Eligibility Criteria
Inclusion Criteria
- Pregnant females (18-26 weeks of gestation)
- documented HIV-1 infection
- Receiving darunavir/ritonavir, darunavir/cobicistat, etravirine, or rilpivirine at the time of study entry
- Willing to remain on darunavir/ritonavir, darunavir/cobicistat, etravirine, or rilpivirine as well as a background regimen, for the duration of the study, including 12 weeks postpartum
- Able to comply with the protocol requirements and to provide written informed consent.
Exclusion Criteria
- Patients with any currently active acquired immune deficiency syndrome (AIDS) defining illness and AIDS-related opportunistic infection
- Patients using cytokine inhibitors (e.g., thalidomide), anabolic hormones, cytokines (e.g., IL-2, INF), efavirenz, hydroxyurea, oral hypoglycemics, systemic chemotherapy or known teratogenic agent
- Use of an investigational agent within 90 days
- Any known fetal anomaly
- Any current obstetric complication, including multiple gestations and pre-term labor
- Hepatitis B and/or C virus infection
- Grade 2 or higher anemia
- Thyroid disease
- Uncontrolled Diabetes Mellitus Types I and II, or gestational diabetes, as determined by the investigator
Data sourced from ClinicalTrials.gov (NCT00855335). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.