Darunavir and Rilpivirine Interactions With Etonogestrel Contraceptive Implant

NCT03589040 | Unknown Phase 2 DMC

• 1 other identifier: PK21
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the pharmacokinetic properties of rilpivirine and darunavir when used in combination with etonogestrel

Conditions

HIV; Contraception

Outcome Measures

Primary Outcomes (1)

• Concentration of etonogestrel

  Comparison of the mean etonogestrel concentrations at month 6 between rilpivirine and darunavir treatment groups versus historical controls.

  Six months of combined use.

Secondary Outcomes (2)

• Concentration of rilpivirine and darunavir

  12 months

• Number and severity of adverse events

  12 months

Study Arms (2)

Ripivirine arm

OTHER

All subjects will be administered oral ripilvirine 25mg once daily together with the rest of their oral antiretroviral combination and an etonogestrel single-rod subdermal implant (68mg/rod). Study participants will have both interventions for a period of one year.

Drug: Etonogestrel 68Mg Implant; Drug: rilpivirine

Darunavir arm

OTHER

All subjects will be administered oral DRV/r 600/100mg twice daily together with the rest of their oral antiretroviral combination and an etonogestrel single-rod subdermal implant (68mg/rod). Study participants will have both interventions for a period of one year.

Drug: Etonogestrel 68Mg Implant; Drug: darunavir

Interventions

Etonogestrel 68Mg Implant DRUG

Etonogestrel single-rod subdermal implant (68mg/rod) will be administered to all study participants

Also known as: Implanon

Darunavir arm; Ripivirine arm

rilpivirine DRUG

Oral rilpvirine 25mg

Also known as: Edurant

Ripivirine arm

darunavir DRUG

Oral darunavir+ritonavir 600/100mg

Also known as: DRV

Darunavir arm

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
• Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Women age 18 years to 45 years
• Diagnosed with HIV infection
• Medically eligible for the ENG subdermal implant as a contraceptive method based on the WHO Medical Eligibility Criteria for Contraceptive Use
• Receiving EFV- or LPV/r-based ART for a minimum of 1 year
• 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.
• 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.

You may not qualify if:

• HIV RNA greater than 50 copies/mL at the screening visit
• CD4 count below 200 cells/mm3 at the screening visit
• History of virologic failure on the current regimen (two consecutive viral load results equal to or greater than 400 copies/mL)
• Serum hemoglobin less than 9.0 g/dl at screening
• Elevations in serum levels of alanine transaminase (ALT) above 5 times the upper limit of normal
• Elevations in serum creatinine above 2.5 times the upper limit of normal
• Use of drugs known to be contraindicated with ENG, 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 and the University of Liverpool HIV drug interaction tables (www.hiv-druginteractions.org)
• Currently pregnant or postpartum \<30 days at study entry.
• Breastfeeding women within 6 months of delivery.
• Patients with a history of hypersensitivity to ENG implant, undiagnosed vaginal bleeding, diagnosed or suspected sex hormone dependent neoplasia, benign or malignant liver tumor, or thromboembolic disease.
• 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.

Sponsors & Collaborators

• Makerere University: lead
• University of Nebraska: collaborator
• University of Pittsburgh: collaborator
• University of Liverpool: collaborator

Study Sites (1)

Infectious Diseases Institue

Kampala, 256, Uganda

RECRUITING

MeSH Terms

Interventions

etonogestrel; Drug Implants; Rilpivirine; Darunavir

Intervention Hierarchy (Ancestors)

Delayed-Action Preparations; Dosage Forms; Pharmaceutical Preparations; Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans

Study Officials

• Mohammed Lamorde, PhD

  Infectious Diseases Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Senior research administrator

CONTACT

0392878652; sokoboi@idi.co.ug

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department, Prevention Care and Treatment Infectious Diseases Institute, Makerere University College of Health Sciences

Model Details: A prospective, non-randomized, open-label, parallel, two-group, sparse-sampling pharmacokinetic study to describe etonogestrel (ENG) pharmacokinetic parameters in two treatment groups (rilpivirine or darunavir- based antiretroviral therapy) in 60 HIV-1 infected women. The primary endpoint is the comparison of the mean ENG concentrations at month 6 between the rilpivirine or darunavir treatment groups versus historical controls.

Study Record Dates

• First Submitted: May 28, 2018
• First Posted: July 17, 2018
• Study Start: September 25, 2018
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2020
• Last Updated: March 28, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)