Darunavir and Rilpivirine Interactions With Levonorgestrel Implant (DRIVE-2)

March 26, 2019 updated by: Infectious Diseases Institute, Makerere University

A Pharmacokinetic Evaluation of Levonorgestrel Implant in HIV-Infected Women on Darunavir Versus Rilpivirine-based Antiretroviral Therapy

This study will evaluate the pharmacokinetic properties of Rilpivirine and Darunavir when used in combination with Levonorgestrel

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Despite the benefits of hormonal contraceptives, significant drug-drug interactions (DDIs) with some antiretroviral therapies (ART) represent a barrier to effective family planning methods for HIV-infected women. It is therefore critical to generate data on the combined use of hormonal contraceptives and ART. This study is a prospective, non-randomized, open-label, parallel, two-group, sparse-sampling pharmacokinetic (PK) study to describe levonorgestrel (LNG) PK parameters in two treatment groups (rilpivirine or darunavir- based ART) in 60 HIV-1 infected women. The primary endpoint is the comparison of the mean LNG concentrations at month 6 between the rilpivirine or darunavir treatment groups versus historical controls. This study will provide information on effective ART options for HIV positive women who opt for the contraceptive implant as a family planning method of choice.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Uganda
      • Kampala, Uganda, 256
        • Recruiting
        • Infectious Diseases Institue

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
  2. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  3. Women age 18 years to 45 years
  4. Diagnosed with HIV infection
  5. Medically eligible for the LNG subdermal implant as a contraceptive method based on the WHO Medical Eligibility Criteria for Contraceptive Use11
  6. Receiving EFV- or LPV/r-based ART for a minimum of 1 year
  7. If not abstinent, must agree to use an effective non-hormonal method of contraception for the duration of the study including male and female condoms or the copper-T intrauterine device.

  8. Participants must have a negative urine pregnancy test at entry and report no unprotected sex since the last menstrual period or in the last two weeks.

    -

Exclusion Criteria:

  1. HIV RNA greater than 50 copies/mL at the screening visit
  2. CD4 count below 200 cells/mm3 at the screening visit
  3. History of virologic failure on the current regimen (two consecutive viral load results equal to or greater than 400 copies/mL)
  4. Serum hemoglobin less than 9.0 g/dl at screening
  5. Elevations in serum levels of alanine transaminase (ALT) above 5 times the upper limit of normal
  6. Elevations in serum creatinine above 2.5 times the upper limit of normal
  7. Use of drugs known to be contraindicated with LNG, RPV (for women taking EFV-based ART), or DRV (for women taking LPV-based ART) within 30 days of study entry. Due to the dynamic nature of drug interactions related to antiretroviral therapy, the study team will review all concomitant medications at screening based on the US Department of Health and Human Services drug interaction table 14 and the University of Liverpool HIV drug interaction tables (www.hiv-druginteractions.org)
  8. Currently pregnant or postpartum <30 days at study entry.
  9. Breastfeeding women within 6 months of delivery.
  10. Patients with a history of hypersensitivity to LNG implant, undiagnosed vaginal bleeding, diagnosed or suspected sex hormone dependent neoplasia, benign or malignant liver tumor, or thromboembolic disease.

  11. Presence of any active clinically significant disease or life-threatening disease that, in the investigator's opinion, would compromise the subject's safety or outcome of the study.

    -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Rilpivirine arm
All subjects will be administered oral rilpivirine 25mg once daily together with the rest of their oral antiretroviral combination plus a levonorgestrel two-rod subdermal implant (75mg/rod) through out the study period
Drug: Levonorgestrel two rod sub-dermal implant
Levonorgestrel (75 mg/rod), 2 rods (150 mg) inserted subdermally
Other Names:
  • Jadelle
  • Levonorgestrel
Drug: Rilpivirine
Oral ripilvirine 25mg once daily
Other Names:
  • Edurant
Experimental: Darunavir arm
All subjects will be administered oral darunavir/ritonavir 600/100mg twice daily together with the rest of their oral antiretroviral combination plus a levonorgestrel two-rod subdermal implant (75mg/rod) through out the study period
Drug: Levonorgestrel two rod sub-dermal implant
Levonorgestrel (75 mg/rod), 2 rods (150 mg) inserted subdermally
Other Names:
  • Jadelle
  • Levonorgestrel
Drug: Darunavir+Ritonavir
Oral DRV/r 600/100mg twice daily
Other Names:
  • DRV/r

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Levonorgestrel concentrations: Change in mean levonorgestrel (LNG) concentrations
Time Frame: 6 months
Comparison of the mean levonorgestrel (LNG) concentrations at month 6 between the rilpivirine (RPV) or darunavir (DRV) treatment groups versus historical controls
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in mean rilpivirine concentration
Time Frame: 12 months
Rilpivirine mean concentration change prior to implant placement and then over the duration of the study time period.
12 months
Change in mean darunavir concentration
Time Frame: 12 months
Darunavir mean concentration change prior to implant placement and then over the duration of the study time period.
12 months
Adverse events
Time Frame: 12 months
Any signs and symptoms related to hormone exposure, including abnormal vaginal bleeding and local or systemic adverse events observed during the study period in both study groups.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Makerere University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Pittsburgh
University of Nebraska
University of Liverpool

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 7, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2019

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 29, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 17, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 28, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 26, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PK22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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