Darunavir and Rilpivirine Interactions With Levonorgestrel Implant

NCT03589027 | Unknown Phase 2 DMC

• 1 other identifier: PK22
• 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 Levonorgestrel

Conditions

HIV-1-infection; Contraception

Outcome Measures

Primary Outcomes (1)

• Levonorgestrel concentrations: Change in mean levonorgestrel (LNG) concentrations

  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 Outcomes (3)

• Change in mean rilpivirine concentration

  12 months

• Change in mean darunavir concentration

  12 months

• Adverse events

  12 months

Study Arms (2)

Rilpivirine arm

EXPERIMENTAL

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; Drug: Rilpivirine

Darunavir arm

EXPERIMENTAL

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; Drug: Darunavir+Ritonavir

Interventions

Levonorgestrel two rod sub-dermal implant DRUG

Levonorgestrel (75 mg/rod), 2 rods (150 mg) inserted subdermally

Also known as: Levonorgestrel, Jadelle

Darunavir arm; Rilpivirine arm

Rilpivirine DRUG

Oral ripilvirine 25mg once daily

Also known as: Edurant

Rilpivirine arm

Darunavir+Ritonavir DRUG

Oral DRV/r 600/100mg twice daily

Also known as: DRV/r

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 LNG subdermal implant as a contraceptive method based on the WHO Medical Eligibility Criteria for Contraceptive Use11
• 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 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)
• Currently pregnant or postpartum \<30 days at study entry.
• Breastfeeding women within 6 months of delivery.
• 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.
• 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

Levonorgestrel; Rilpivirine

Intervention Hierarchy (Ancestors)

Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mohammed Lamorde, PhD

  Infectious Diseases Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Senior Research Manager

CONTACT

0704817590; 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 (PK) study to describe levonorgestrel (LNG) PK parameters in two treatment groups (Rilpivirine or Darunavir- based ART) in 60 HIV-1 infected women.

Study Record Dates

• First Submitted: May 29, 2018
• First Posted: July 17, 2018
• Study Start: August 7, 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)