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A Pharmacokinetic Evaluation of Levonorgestrel Implant and Antiretroviral Therapy
This study has been completed.
Sponsor:
University of Nebraska
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Makerere University
University of Liverpool
Information provided by (Responsible Party):
Kimberly Scarsi, PharmD, MS, BCPS-ID, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01789879
First received: February 7, 2013
Last updated: March 31, 2016
Last verified: March 2016
| Tracking Information | ||||
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| First Received Date ICMJE | February 7, 2013 | |||
| Last Updated Date | March 31, 2016 | |||
| Start Date ICMJE | June 2013 | |||
| Primary Completion Date | April 2014 (Final data collection date for primary outcome measure) | |||
| Current Primary Outcome Measures ICMJE |
Levonorgestrel plasma concentrations [ Time Frame: 6 months after implant is placed ] | |||
| Original Primary Outcome Measures ICMJE | Same as current | |||
| Change History | Complete list of historical versions of study NCT01789879 on ClinicalTrials.gov Archive Site | |||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE | Same as current | |||
| Current Other Outcome Measures ICMJE | Not Provided | |||
| Original Other Outcome Measures ICMJE | Not Provided | |||
| Descriptive Information | ||||
| Brief Title ICMJE | A Pharmacokinetic Evaluation of Levonorgestrel Implant and Antiretroviral Therapy | |||
| Official Title ICMJE | A Pharmacokinetic Evaluation of Levonorgestrel Implant and Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Based Antiretroviral Therapy in HIV-infected Ugandan Women | |||
| Brief Summary | The use of hormone contraception poses a significant challenge for the estimated 16 million HIV-infected women of childbearing age. This is due to known drug interactions with antiretroviral therapy (medicines used to treat HIV) that may jeopardize contraception effectiveness. By evaluating the impact of antiretroviral therapy on a levonorgestrel subdermal implant, the most widely available hormone implant in low and middle-income countries, this study will translate its findings into an evidence-based approach to co-manage these important medications. The investigators hypothesize that women receiving nevirapine or efavirenz-based antiretroviral therapy will have a significant decrease in the mean levonorgestrel plasma concentration measured six months after the implant's insertion as compared to those women who are not taking antiretroviral therapy. Although the implant's efficacy may be retained initially, the investigators propose that a decrease in levonorgestrel concentrations in women receiving antiretroviral therapy may jeopardize the implant's effectiveness near the end of its intended duration of use (5 years). | |||
| Detailed Description | Family planning services, including hormone contraceptives, are critical for HIV-infected women, in whom prevention of unintended pregnancy not only decreases maternal and child mortality, but also reduces the risk of mother-to-child HIV transmission. Similarly, antiretroviral therapy (ART) is a lifesaving intervention that improves the health and economic status of HIV-infected women throughout the world. Therefore, it is of significant public health importance to guide the appropriate use these essential medications. To this end, millions of HIV-infected women in low and middle income countries (LMIC) currently use or are gaining access to subdermal progestin-containing implants as a preferred method of long-acting reversible contraception. These implants are often combined with ART despite the lack of critically needed pharmacokinetic (PK) drug-interaction data to inform their safe and effective concomitant use. Highlighting this concern are several case reports of unintended pregnancy that occurred in patients with subdermal progestin-containing implants concurrently receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART, the most commonly used ART in LMICs. While NNRTIs are known to significantly decrease oral pill progestin concentrations, no data are available to inform healthcare providers of the impact of NNRTIs on progestin concentrations following release from subdermal implants. To fill this critical gap in knowledge, the overall aim of this proposal is to conduct a PK study to evaluate the combination of a levonorgestrel (LNG) implant and NNRTI (nevirapine or efavirenz)-based ART in HIV-infected Ugandan women. The investigators propose that lower LNG concentrations will be observed in patients on NNRTI-based ART and although the implant's efficacy may be retained initially, this negative interaction will jeopardize implant effectiveness near the end of its intended duration of use (5 years). The specific aims of this project are (1) to characterize the PK of LNG released from a subdermal implant over one year in HIV-infected women with and without NNRTI-based ART and (2) to evaluate the potential for a bidirectional drug-interaction resulting from the long-term impact of chronic progestin exposure on antiretroviral concentrations. To achieve these aims, this study will enroll 20 HIV-infected women into each of three study groups: a control group not receiving ART and two treatment arms consisting of patients receiving nevirapine- or efavirenz- based ART. Using sparse PK sampling strategies, LNG, nevirapine or efavirenz concentrations will be measured over one-year and compared between and within groups, as appropriate. The LNG data will also be used to develop a PK model that will predict LNG disposition over the following three years of intended use, allowing for identification of the safe duration of LNG implant use in women on NNRTI-based ART. At the conclusion of this project, the first evidence-based medical knowledge will be available to guide the safe and effective concomitant use of subdermal LNG implants and NNRTIs, thereby improving management of reproductive health in millions of HIV-infected women worldwide. | |||
| Study Type ICMJE | Interventional | |||
| Study Phase | Phase 2 | |||
| Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | ||||
| Recruitment Status ICMJE | Completed | |||
| Enrollment ICMJE | 60 | |||
| Completion Date | October 2014 | |||
| Primary Completion Date | April 2014 (Final data collection date for primary outcome measure) | |||
| Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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| Ages | 18 Years and older (Adult, Senior) | |||
| Accepts Healthy Volunteers | No | |||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
| Listed Location Countries ICMJE | Uganda | |||
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| Administrative Information | ||||
| NCT Number ICMJE | NCT01789879 | |||
| Other Study ID Numbers ICMJE | LNG-NNRTI PK study 1R21HD074462-01 ( U.S. NIH Grant/Contract ) |
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| Has Data Monitoring Committee | No | |||
| U.S. FDA-regulated Product | Not Provided | |||
| IPD Sharing Statement |
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| Responsible Party | Kimberly Scarsi, PharmD, MS, BCPS-ID, University of Nebraska | |||
| Study Sponsor ICMJE | University of Nebraska | |||
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| PRS Account | University of Nebraska | |||
| Verification Date | March 2016 | |||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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