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HIVPhase 3NCT00855335

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

A Phase 3 study testing Darunavir, Ritonavir and Etravirine in people with HIV and HIV Infections, run by Janssen Scientific Affairs, LLC at 17 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
HIV, HIV Infections, Pregnancy
What is being tested?
Darunavir, Ritonavir and Etravirine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
17 sitesin 2 countries
Study dates
9 Apr 2009to 11 Aug 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 9Show fewer
  • Grade 2 or higher anemia
  • Thyroid disease
  • Uncontrolled Diabetes Mellitus Types I and II, or gestational diabetes, as determined by the investigator

Trial locations and contacts

17 sites in 2 countries.

17 sites in 2 countries

United States16 sites

  • Study site

    Bellaire, Texas

  • Study site

    Chapel Hill, North Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Daytona Beach, Florida

  • Study site

    Dearborn, Michigan

  • Study site

    Greensboro, North Carolina

  • Study site

    Jacksonville, Florida

  • Study site

    Miami, Florida

  • Study site

    Pensacola, Florida

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Port Saint Lucie, Florida

  • Study site

    Savannah, Georgia

  • Study site

    Springfield, Massachusetts

  • Study site

    Syracuse, New York

  • Study site

    The Bronx, New York

  • Study site

    West Palm Beach, Florida

Other trials in United States

Puerto Rico1 site

  • Study site

    San Juan Pr

Other trials in Puerto Rico

About this study

Official title: 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

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.

Read the 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).

Being tested
Darunavir, Ritonavir, Etravirine, Rilpivirine, Darunavir/Cobicistat (FDC)
Keywords
HIV-1, HIV, Pregnancy, Postpartum, Human immunodeficiency virus, PREZISTA, INTELENCE, NORVIR, TMC114, TMC125, darunavir, ritonavir, etravirine, rilpivirine, TMC278, Cobicistat, treatment experienced
Medical subject headings
HIV Infections, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DarunavirDrug

    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.

  • RitonavirDrug

    100 mg tablet twice daily up to 12 weeks postpartum.

  • EtravirineDrug

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

  • RilpivirineDrug

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

  • 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.

Study groups in NCT00855335
Study groupRoleWhat they receive
Group 1: Darunavir 600 /Ritonavir 100ExperimentalTMC114 (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.
Receives: Drug: Darunavir; Drug: Ritonavir
Group 2: Darunavir 800/Ritonavir 100ExperimentalTMC114 (darunavir) 800mg tablet once daily up to 12 weeks postpartum/ ritonavir one 100 mg tablet once daily with darunavir up to 12 weeks postpartum.
Receives: Drug: Darunavir; Drug: Ritonavir
Group 3: EtravirineExperimentalTMC125 (etravirine) 200 mg (1*200 mg/2*100 mg) tablets twice daily up to 12 weeks postpartum.
Receives: Drug: Etravirine
Group 4: RilpivirineExperimentalTMC278 (rilpivirine) One 25 mg tablet once daily up to 12 weeks postpartum.
Receives: Drug: Rilpivirine
Group 5: Darunavir 800/Cobicistat 150ExperimentalFixed dose combination (FDC) tablet of TMC114 (darunavir) 800 mg and cobicistat 150 mg once daily up to 12 weeks postpartum.
Receives: Drug: Darunavir/Cobicistat (FDC)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Predose (Trough) Plasma Concentration (C0h)

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

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

  2. Minimum Plasma Concentration (Cmin)

    The Cmin is the minimum observed plasma concentration.

    Measured: 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)

  3. Maximum Plasma Concentration (Cmax)

    The Cmax is the maximum observed plasma concentration.

    Measured: 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)

  4. Time to Reach the Maximum Plasma Concentration (Tmax)

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

    Measured: 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)

  5. 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).

    Measured: 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)

  6. 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).

    Measured: 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)

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

    Number of participants were assessed with a viral load (VL) lesser than (<) 50 HIV-1 RNA copies/ mL over time.

    Measured: Up to postpartum (6-12 weeks)

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

    Mean change from baseline in log 10 HIV-1 RNA VL was assessed up to postpartum (6-12 weeks).

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

  3. Mean Change From Baseline in CD4+ Cell Count

    Mean Change From Baseline in CD4+ Cell Count were assessed for immunology testing.

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

  4. Number of Participants With Resistance at Virological Failure

    Resistance analysis was determined using genotypic and phenotypic analysis at the time of virological failure. For participants with a baseline viral load greater than (>) 200 copies/mL, virologic failure was defined as follows: HIV ribonucleic acid (RNA) levels that did not fall by at least 0.5 log 4 weeks after Baseline; viral load >1000 copies/mL (at 2 successive visits) by gestational weeks 34-38; or viral load >200 copies/mL (at 2 successive visits) after reaching a viral load less than or equal to (<=) 200 copies/mL. For participants with a baseline viral load <=200 copies/mL, virologic failure was defined as viral load of >200 copies/mL (at 2 successive visits) at any point during the study.

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

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

    The drug concentrations were evaluated in the cord plasma and maternal plasma samples collected at the time of delivery.

    Measured: On day of delivery - Intrapartum (Visit 6)

  6. Number of Infants With Human Immunodeficiency Virus (HIV) Positive Test Result

    The infants were evaluated for HIV positive tests using HIV polymerase chain reaction test (PCR).

    Measured: Birth to age 16 weeks

  7. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

    Measured: Up to follow up period (16 weeks after postpartum)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Mar 2009 (estimated)
  2. Study start9 Apr 2009
  3. Primary completion11 Aug 2016
  4. Study completion11 Aug 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00855335
Sponsor's protocol ID
CR015442
Other IDs
TMC114HIV3015
Status last verified
May 2018
First submitted
2 Mar 2009
Last updated
6 Jul 2018
Data monitoring committee
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 29335895

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Darunavir, Ritonavir and Etravirine in people with HIV and HIV Infections, run by Janssen Scientific Affairs, LLC at 17 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Predose (Trough) Plasma Concentration (C0h) (time frame: Predose on Weeks 24-28 (Visit 4, 2nd trimester), 34-38 (visit 5, 3rd trimester) and 6-12 weeks postpartum (visit 8)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00855335, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2018.

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Clinical Trial NCT00855335 | AzTrials