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

NCT ID: NCT00855335

Last Updated: 2018-07-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-09
• Study Completion Date: 2016-08-11

Brief 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.

Detailed Description

There are many biological changes that occur during pregnancy, some of which may affect the way HIV medications are absorbed, distributed and removed within the body. Some medications have been used for HIV treatment during pregnancy, but little is known about how pregnancy affects the class of drugs being used in this study. To participate in this study, patients must be receiving 600mg of TMC114 (darunavir) taken with 100mg ritonavir twice daily or 800mg of TMC114 (darunavir) with 100mg of ritonavir once daily or 800 mg of darunavir taken with 150mg of cobicistat taken once daily or 200mg of TMC125 (etravirine) (with or without darunavir/ ritonavir) taken twice daily or 25mg of TMC278 (rilpivirine) taken once daily plus additional antiretroviral drugs needed to construct an active antiretroviral regimen. Darunavir and ritonavir, darunavir and cobicistat, etravirine, or rilpivirine will be supplied to study participants. Darunavir and ritonavir are human immunodeficiency virus (HIV) protease inhibitors (PIs); cobicistat is a pharmacoenhancer which boosts the levels of darunavir but has no anti-HIV activity; etravirine and rilpivirine are non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV. Twelve-hour or twenty four-hour blood sampling will be done for each patient at each of three study visits: Visit 4 (2nd trimester), Visit 5 (3rd trimester), and Visit 8 (6-12 weeks postpartum). Eight blood draws will be taken during each visit: One prior to intake of study medication, and one for each of seven post-dose sampling time-points (hours 1, 2, 3, 4, 6, 9 and 12). The study is designed primarily to examine the pharmacokinetics of darunavir/ritonavir (darunavir/r), darunavir/ cobicistat, etravirine or rilpivirine during the second and third trimesters of gestation, as well as postpartum. Pharmacokinetics measures how the body absorbs, distributes and excretes medication. The study will also examine any changes in anti-viral activity during pregnancy, and the postpartum period. It will note any safety and tolerability of the medications used by the mother, and will measure the level of darunavir/ritonavir, darunavir/ cobicistat, etravirine or rilpivirine in the newborn's cord blood at the time of delivery; outcomes for both mother and child will be assessed as well. During the treatment period, patients will be seen at regular visits in the clinic, where the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for efficacy and safety will be done at regular visits as well as blood pressure monitoring. Up to forty-eight (48) HIV positive pregnant women will participate in this study. Study enrollment will be closed once 12 evaluable patients taking darunavir/ritonavir once daily, 12 evaluable patients taking darunavir/cobicistat once daily, 12 evaluable patients taking darunavir/ritonavir twice daily, 12 evaluable patients taking etravirine taking twice daily and 12 evaluable patients taking rilpivirine once daily have been enrolled. The study will be conducted at approximately 14 research centers in the United States and 1 in Puerto Rico. In order to participate, patients must be pregnant for 13-24 weeks. The primary purpose (or outcome) of the study is to assess the influence of pregnancy on the pharmacokinetics of darunavir/ritonavir, darunavir/ cobicistat, etravirine or rilpivirine during the second and third trimesters of gestation, as well as postpartum. Darunavir: One 600 mg or two 300 mg tablets taken twice daily by mouth (two or four tablets a day total). Ritonavir: 100mg tablet taken twice daily by mouth (two tablets a day total), together with darunavir. Darunavir: Two 400 mg tablets taken once daily by mouth (two tablets a day total). Ritonavir: 100mg tablet taken once daily by mouth (one tablet a day total), together with darunavir. Darunavir/ cobicistat: a fixed dose combination containing 800mg of darunavir and 150mg of cobicistat. Etravirine: Two 100 mg tablets taken twice daily by mouth (four tablets a day total). Rilpivirine: One 25mg tablet taken once daily by mouth (one tablet a day total). Study medication will be given from the baseline visit (second pregnancy trimester) until Visit 8 (up to 12 weeks after delivery).

Conditions

HIV; HIV Infections; Pregnancy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1: Darunavir 600 /Ritonavir 100

TMC114 (darunavir) Two 300 milligram (mg) or one 600 mg tablet twice daily up to 12 weeks postpartum / ritonavir one 100 mg tablet twice daily with darunavir up to 12 weeks postpartum.

Group Type: EXPERIMENTAL

Darunavir

Intervention Type: DRUG

TMC114 (darunavir) two 300 mg or one 600 mg tablet twice daily up to 12 weeks postpartum in Group 1. TMC114 (darunavir) 800mg tablet once daily up to 12 weeks postpartum in Group 2.

Ritonavir

Intervention Type: DRUG

100 mg tablet twice daily up to 12 weeks postpartum.

Group 2: Darunavir 800/Ritonavir 100

TMC114 (darunavir) 800mg tablet once daily up to 12 weeks postpartum/ ritonavir one 100 mg tablet once daily with darunavir up to 12 weeks postpartum.

Group Type: EXPERIMENTAL

Darunavir

Intervention Type: DRUG

TMC114 (darunavir) two 300 mg or one 600 mg tablet twice daily up to 12 weeks postpartum in Group 1. TMC114 (darunavir) 800mg tablet once daily up to 12 weeks postpartum in Group 2.

Ritonavir

Intervention Type: DRUG

100 mg tablet twice daily up to 12 weeks postpartum.

Group 3: Etravirine

TMC125 (etravirine) 200 mg (1\*200 mg/2\*100 mg) tablets twice daily up to 12 weeks postpartum.

Group Type: EXPERIMENTAL

Etravirine

Intervention Type: DRUG

200 mg (1\*200 mg/2\*100 mg) tablets twice daily up to 12 weeks postpartum.

Group 4: Rilpivirine

TMC278 (rilpivirine) One 25 mg tablet once daily up to 12 weeks postpartum.

Group Type: EXPERIMENTAL

Rilpivirine

Intervention Type: DRUG

One 25 mg tablet once daily up to 12 weeks postpartum.

Group 5: Darunavir 800/Cobicistat 150

Fixed dose combination (FDC) tablet of TMC114 (darunavir) 800 mg and cobicistat 150 mg once daily up to 12 weeks postpartum.

Group Type: EXPERIMENTAL

Darunavir/Cobicistat (FDC)

Intervention Type: DRUG

Fixed dose combination (FDC) tablet of TMC114 (darunavir) 800 mg and cobicistat 150 mg once daily up to 12 weeks postpartum.

Interventions

Darunavir

TMC114 (darunavir) two 300 mg or one 600 mg tablet twice daily up to 12 weeks postpartum in Group 1. TMC114 (darunavir) 800mg tablet once daily up to 12 weeks postpartum in Group 2.

Intervention Type: DRUG

Ritonavir

100 mg tablet twice daily up to 12 weeks postpartum.

Intervention Type: DRUG

Etravirine

200 mg (1\*200 mg/2\*100 mg) tablets twice daily up to 12 weeks postpartum.

Intervention Type: DRUG

Rilpivirine

One 25 mg tablet once daily up to 12 weeks postpartum.

Intervention Type: DRUG

Darunavir/Cobicistat (FDC)

Fixed dose combination (FDC) tablet of TMC114 (darunavir) 800 mg and cobicistat 150 mg once daily up to 12 weeks postpartum.

Intervention Type: DRUG

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

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

Sponsors

Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Scientific Affairs, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Scientific Affairs, LLC

Locations

Daytona Beach, Florida, United States

Jacksonville, Florida, United States

Miami, Florida, United States

Pensacola, Florida, United States

Port Saint Lucie, Florida, United States

West Palm Beach, Florida, United States

Savannah, Georgia, United States

Chicago, Illinois, United States

Springfield, Massachusetts, United States

Dearborn, Michigan, United States

Syracuse, New York, United States

The Bronx, New York, United States

Chapel Hill, North Carolina, United States

Greensboro, North Carolina, United States

Philadelphia, Pennsylvania, United States

Bellaire, Texas, United States

San Juan Pr, , Puerto Rico

Countries

United States; Puerto Rico

References

Osiyemi O, Yasin S, Zorrilla C, Bicer C, Hillewaert V, Brown K, Crauwels HM. Pharmacokinetics, Antiviral Activity, and Safety of Rilpivirine in Pregnant Women with HIV-1 Infection: Results of a Phase 3b, Multicenter, Open-Label Study. Infect Dis Ther. 2018 Mar;7(1):147-159. doi: 10.1007/s40121-017-0184-8. Epub 2018 Jan 15.

Reference Type: DERIVED

PMID: 29335895 (View on PubMed)

Other Identifiers

TMC114HIV3015

Identifier Type: OTHER

Identifier Source: secondary_id

CR015442

Identifier Type: -

Identifier Source: org_study_id