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

NCT00855335 | Completed Phase 3 Results

• 2 other identifiers: CR015442TMC114HIV3015
• Study Type: interventional
• Target: 77
• Locations: 2 countries
• Sites: 17

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.

Conditions

HIV; HIV Infections; Pregnancy

Keywords

HIV-1; HIV; Pregnancy; Postpartum; Human immunodeficiency virus; PREZISTA; INTELENCE; NORVIR; TMC114; TMC125; darunavir; ritonavir; etravirine; rilpivirine; TMC278; Cobicistat; treatment experienced

Outcome Measures

Primary Outcomes (6)

• Predose (Trough) Plasma Concentration (C0h)

  C0h is defined as the predose (trough) plasma concentration or concentration just prior to study drug administration.

  Predose on Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)

• Minimum Plasma Concentration (Cmin)

  The Cmin is the minimum observed plasma concentration.

  Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)

• Maximum Plasma Concentration (Cmax)

  The Cmax is the maximum observed plasma concentration.

  Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)

• Time to Reach the Maximum Plasma Concentration (Tmax)

  The Tmax is defined as actual sampling time to reach maximum observed plasma concentration.

  Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)

• Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 Hours Post-dose (AUC0-12h)

  The AUC (0-12) is the area under the plasma concentration-time curve from time zero to 12 hours post dose. The selected arms were based on the dosing frequency (twice daily).

  Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)

• Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC0-24h)

  The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours post dose. The selected arms were based on the dosing frequency (once daily).

  Between Predose and 24 hours postdose at Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)

Secondary Outcomes (7)

• Number of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Plasma Viral Load (<) 50 Copies/Milliliter (mL)

  Up to postpartum (6-12 weeks)

• Mean Change From Baseline in Log10 Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Viral Load Value

  Baseline, 4 weeks after baseline, 2nd and 3rd trimesters of pregnancy and postpartum (2-5 weeks and 6-12 weeks)

• Mean Change From Baseline in CD4+ Cell Count

  Baseline, 4 weeks after baseline, 2nd and 3rd trimesters of pregnancy and postpartum (2-5 weeks and 6-12 weeks)

• Number of Participants With Resistance at Virological Failure

  Up to follow-up phase (16 weeks after postpartum)

• Plasma Concentration of Drug in the Cord Plasma and Maternal Plasma Samples Collected at the Time of Delivery

  On day of delivery - Intrapartum (Visit 6)

Study Arms (5)

Group 1: Darunavir 600 /Ritonavir 100

EXPERIMENTAL

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.

Drug: Darunavir; Drug: Ritonavir

Group 2: Darunavir 800/Ritonavir 100

EXPERIMENTAL

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.

Drug: Darunavir; Drug: Ritonavir

Group 3: Etravirine

EXPERIMENTAL

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

Drug: Etravirine

Group 4: Rilpivirine

EXPERIMENTAL

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

Drug: Rilpivirine

Group 5: Darunavir 800/Cobicistat 150

EXPERIMENTAL

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

Drug: Darunavir/Cobicistat (FDC)

Interventions

Darunavir 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.

Group 1: Darunavir 600 /Ritonavir 100; Group 2: Darunavir 800/Ritonavir 100

Ritonavir DRUG

100 mg tablet twice daily up to 12 weeks postpartum.

Group 1: Darunavir 600 /Ritonavir 100; Group 2: Darunavir 800/Ritonavir 100

Etravirine DRUG

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

Group 3: Etravirine

Rilpivirine DRUG

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

Group 4: Rilpivirine

Darunavir/Cobicistat (FDC) DRUG

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

Group 5: Darunavir 800/Cobicistat 150

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Scientific Affairs, LLC: lead

Study Sites (17)

Unknown Facility

Daytona Beach, Florida, United States

Location

Unknown Facility

Jacksonville, Florida, United States

Location

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Pensacola, Florida, United States

Location

Unknown Facility

Port Saint Lucie, Florida, United States

Location

Unknown Facility

West Palm Beach, Florida, United States

Location

Unknown Facility

Savannah, Georgia, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Springfield, Massachusetts, United States

Location

Unknown Facility

Dearborn, Michigan, United States

Location

Unknown Facility

Syracuse, New York, United States

Location

Unknown Facility

The Bronx, New York, United States

Location

Unknown Facility

Chapel Hill, North Carolina, United States

Location

Unknown Facility

Greensboro, North Carolina, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Bellaire, Texas, United States

Location

Unknown Facility

San Juan Pr, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 29335895 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Darunavir; Ritonavir; etravirine; Rilpivirine; Cobicistat

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; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Nitriles; Pyrimidines

Results Point of Contact

• Title: Medical Leader, Medical Department
• Organization: Janssen Scientific Affairs, LLC

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Janssen Scientific Affairs, LLC Clinical Trial

  Janssen Scientific Affairs, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2009
• First Posted: March 4, 2009
• Study Start: April 9, 2009
• Primary Completion: August 11, 2016
• Study Completion: August 11, 2016
• Last Updated: July 6, 2018
• Results First Posted: September 15, 2017

Record last verified: 2018-05

Locations

US (16); PR (1)