Dataset Information

A randomized crossover study to evaluate local tolerability following subcutaneous administration of a new depot medroxyprogesterone acetate contraceptive formulation.

ABSTRACT:

Objectives

This study aimed to evaluate and compare local tolerability of investigational drug TV-46046 and reference drug Depo-subQ Provera 104, both containing medroxyprogesterone acetate (MPA) as an active ingredient.

Study design

We conducted a randomized, crossover, single-center study. Twenty-seven healthy women aged 25 to 47 years at low risk of pregnancy received a subcutaneous injection of each of the four study drugs (120 mg/0.3 mL of TV-46046, 60 mg/0.3 mL of diluted TV-46046, 0.3 mL of TV-46046 placebo, and 104 mg/0.65 mL of Depo-subQ 104) in different quadrants of the abdomen. We assessed local tolerability by occurrence of injection site reactions (ISRs), as well as injection site pain and overall safety for at least 9 months postinjections.

Results

Of a total of 108 study injections, three injections were partial due to needle blockage. We observed a total of 30 ISRs following 105 full-dose injections, including hypopigmentation (n = 24), bruising (n = 4), and atrophy/dimple (n = 2). Eleven cases of hypopigmentation occurred following 25 full-dose injections of undiluted TV-46046 (44.0%), six following 27 full-dose injections of diluted TV-46046 (22.2%), and seven following 26 full-dose injections of Depo-subQ 104 (26.9%). Hypopigmentations occurred on average 8 months postinjection. Injection pain was minimal and dissipated quickly after all four injections.

Conclusions

Subcutaneous administration of MPA in a suspension formulation is associated with the delayed onset of hypopigmentation at the site of injection. Although not statistically significant, the rate of ISRs was over 60% higher for undiluted TV-46046 compared to Depo-subQ 104. This difference bears careful monitoring in future studies of TV-46046.

Implications

From a safety standpoint, investigational drug TV-46046 is appropriate for further clinical testing as a 6-month contraceptive injectable. The previously underreported hypopigmentation associated with subcutaneous administration of MPA warrants further investigation and acceptability assessment among users of existing Depo-subQ 104 as well as careful monitoring of local tolerability of TV-46046 in future clinical trials.

Trial registration

Registered at clinicaltrials.gov no: NCT02817464.

SUBMITTER: Halpern V

PROVIDER: S-EPMC10562734 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

A randomized crossover study to evaluate local tolerability following subcutaneous administration of a new depot medroxyprogesterone acetate contraceptive formulation.

Halpern Vera V Wheeless Angie A Brache Vivian V Lendvay Anja A Cochón Leila L Taylor Douglas D Dorflinger Laneta J LJ

Contraception: X 20230912

<h4>Objectives</h4>This study aimed to evaluate and compare local tolerability of investigational drug TV-46046 and reference drug Depo-subQ Provera 104, both containing medroxyprogesterone acetate (MPA) as an active ingredient.<h4>Study design</h4>We conducted a randomized, crossover, single-center study. Twenty-seven healthy women aged 25 to 47 years at low risk of pregnancy received a subcutaneous injection of each of the four study drugs (120 mg/0.3 mL of TV-46046, 60 mg/0.3 mL of diluted TV ...[more]

PMID: 37823034

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Project description:ObjectivesTo characterize the relationship between serum medroxyprogesterone acetate (MPA) concentrations and ovulation suppression, and to estimate the risk of ovulation for investigational subcutaneous regimens of Depo-Provera CI (Depo-Provera) and Depo-subQ Provera 104 (Depo-subQ).Study designWe performed a secondary analysis of 2 studies that assessed the pharmacokinetics and pharmacodynamics of MPA when Depo-Provera is administered subcutaneously rather than by the labeled intramuscular route. Each woman received a single 45 mg to 300 mg subcutaneous injection of Depo-Provera, a single 104 mg subcutaneous injection of Depo-subQ, or 2 injections of Depo-subQ at 3-month intervals. We used an elevation of serum progesterone ≥4.7 ng/mL as a surrogate for ovulation and non-parametric statistical methods to assess pharmacokinetic and pharmacodynamic relationships.ResultsThis analysis included 101 women with body mass index (BMI) 18 to 34 kg/m2. Return of ovulation occurred at a median MPA concentration of 0.07 ng/mL (95% CI: 0.06-0.08) and the 90th percentile was 0.10 ng/mL (95% CI: 0.09-0.14). Neither age, race, nor BMI significantly influenced this relationship. The estimated probabilities of ovulation within 4 months of a 104 mg subcutaneous injection and within 7 months of a 150 mg subcutaneous injection (6 plus a 1-month grace) were each below 2.2%.ConclusionsThe typical MPA concentration associated with loss of ovulation suppression is substantially less than the commonly cited threshold of 0.2 ng/mL. Based on our results, MPA levels would rarely be low enough to permit ovulation if the Depo-subQ reinjection interval were extended to four months or if 150 mg Depo-Provera were injected subcutaneously every 6 months.ImplicationsExtending the three-month Depo-subQ reinjection interval by one month would result in a 25% reduction in yearly MPA exposure, with little risk of pregnancy. Off-label subcutaneous administration of 150 mg Depo-Provera every 6 months would be a highly effective repurposing of an excellent product, with a similar reduction in cumulative exposure.

Project description:ObjectivesTo evaluate feasibility, acceptability, continuation, and trough serum levels following self-administration of subcutaneous (sc) depot medroxyprogesterone acetate (DMPA).Study designWomen presenting to a family planning clinic to initiate, restart or continue DMPA were offered study entry. Participants were randomized in a 2:1 ratio to self- or clinician administered sc DMPA 104 mg. Those randomized to self-administration were taught to self-inject and were supervised in performing the initial injection; they received printed instructions and a supply of contraceptive injections for home use. Participants randomized to clinician administration received usual care. Continued DMPA use was assessed by self-report and trough medroxyprogesterone acetate levels at 6 and 12 months.ResultsTwo hundred fifty women were invited to participate, and 137 (55%) enrolled. Of these, 91 were allocated to self-administration, and 90/91 were able to correctly self-administer sc DMPA. Eighty-seven percent completed follow-up. DMPA use at 1 year was 71% for the self-administration group and 63% for the clinic group (p=0.47). Uninterrupted DMPA use was 47% and 48% for the self and clinic administration groups at 1 year (p=0.70), respectively. Serum analyses confirmed similar mean DMPA levels in both groups and therapeutic trough levels in all participants.ConclusionsSixty-three percent of women approached were interested in trying self-administration of DMPA, even in the context of a randomized trial, and nearly all eligible for enrollment were successful at doing so. Self-administration and clinic administration resulted in similar continuation rates and similar DMPA serum levels. Self-administration of sc DMPA is feasible and may be an attractive alternative for many women.ImplicationsSelf-administration of sc DMPA is a feasible and attractive option for many women. Benefits include increased control over contraceptive measures and less time spent on contracepting behaviors. Globally, self-administration has the potential to revolutionize contraceptive uptake by increasing the number of women with access to DMPA.

Project description:OBJECTIVES:The subcutaneous depot medroxyprogesterone acetate (DMPA-SC) injectable contraceptive was introduced in South West Nigeria in 2015 through private sector channels. The introduction included community-based distribution and was supported by a social marketing approach. From program monitoring and evaluation, aimed at understanding performance, market reach and other process measures, we identify lessons learned to inform future scale-up efforts. METHODS:We synthesized the findings from a core set of key performance indicators collected through different methods: (1) implementer performance indicators, (2) phone survey of DMPA-SC users (n=541) with a follow-up after 3 months (n=342) and (3) in-depth interviews with 57 providers and 42 users of DMPA-SC. RESULTS:Distribution of DMPA-SC to private providers was concentrated in states with large urban populations. A shift toward focusing on high-volume family planning facilities coincided with a rapid increase in distribution in late 2016. Users reached in the phone survey were generally older and married with children; few were under age 25. Users and providers reported favorable opinions of DMPA-SC. Many users reported choosing DMPA-SC due to recommendations from providers and friends, and the hope of experiencing reduced side effects compared to other methods. While users reported positive experiences interacting with community-based distributors, the delivery model encountered a number of challenges - high turnover, low motivation, lack of an appropriate compensation package and logistical costs - and was ultimately disbanded. CONCLUSIONS:In the DMPA-SC introductory program in Nigeria, distribution was amplified when focused on high-volume contraceptive providers. Although community-based distribution can be one effective service delivery model for reaching underserved populations, more consideration for balancing cost recovery and public health goals through private sector approaches are needed in the context of South West Nigeria. Additional communications and outreach efforts are needed to reach younger, unmarried users with contraceptive services.

Project description:ObjectiveTo examine the rate of ovulatory disruption when intramuscular depot medroxyprogesterone acetate (DMPA) is administered across graded stages of dominant follicle development.Study designWe assigned enrolled participants to one of three preassigned dominant follicle size groups: 12-14 mm, 15-17 mm and ≥ 18 mm. We followed dominant follicles via serial transvaginal ultrasound (TVUS) until the follicles reached their assigned size, at which time we administered DMPA. For 5 consecutive days thereafter, we followed the follicles via TVUS to observe follicle rupture and obtained serum luteinizing hormone (LH), estradiol, and progesterone concentrations. In the following 2 weeks, we collected serum progesterone concentrations twice weekly to detect possible ovulatory delay or dysfunction. We also collected serum medroxyprogesterone acetate (MPA) concentrations at 1 and 24 h after DMPA administration to examine against ovulatory outcomes.ResultsTwenty-six of 29 enrolled women completed the study. DMPA suppressed ovulation in 17/26 (65%) and caused ovulatory dysfunction in 1/26 (4%) participants. Larger follicles were more likely to rupture despite DMPA (12-14 mm: 0/10 (0%); 15-17 mm: 3/10 (30%); ≥ 18 mm: 6/6 (100%); p < .01). Pre-DMPA LH concentrations ranged from 13.8 to 93.7 IU/L (mean 49.0 IU/L) in cases of follicle rupture. We observed no cases of follicle rupture when DMPA was administered through cycle day 12. All 24-h MPA concentrations exceeded those needed for ovulation suppression.ConclusionDMPA suppressed and additionally disrupted ovulation in 65% and 4% of observed cycles, respectively. DMPA may provide effective emergency contraception as well as ongoing contraception if administered prior to an expected ovulation and specifically before the LH surge.ImplicationsDMPA may be an alternative form of emergency contraception that can also self-bridge to ongoing contraception. As ovulation was not observed among any follicles when DMPA was given through cycle day 12, women who initiate DMPA up through cycle day 12 may not require backup contraception.

Project description:BackgroundSelf-administered depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) is registered in many countries. It shows great potential for improving contraceptive access, continuation, and autonomy. However, there are challenges in rolling out this new efficacious intervention, and major implementation problems have been encountered during scale-up.ObjectiveTo describe the implementation strategies to scale up self-administered DMPA-SC and the barriers, facilitators, and outcomes of these programs.MethodRecent guidelines, including the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews, were used to design and report this review. An article or report was eligible for inclusion if it reported interventions that could scale up self-administered DMPA-SC implementation or its facilitators, barriers, or outcomes. We searched six electronic databases and the grey literature for eligible articles and reports. Two reviewers independently screened the document titles, abstracts, and full texts to identify eligible documents. Data were extracted using structured forms. Using the Effective Practice and Organization of Care (EPOC) taxonomy of health systems framework for thematic analysis, data were presented in a narrative approach.ResultsOf the 755 retrieved documents, 34 were included in this review. Most of the documents included were multi-country reports (n = 14), and all documents were published within the last 5 years (2018-2021). This review identified documents that reported interventions in all EPOC domains. The most-reported interventions were: task-sharing amongst health workforce cadres, engaged leadership, encouraging policies, training and education, DMPA-SC demand generation, integration into existing programs, improved funding mechanisms, collaboration with development partners, and supply chain strengthening. The main barriers were suboptimal funding, inadequate human resources, and poor logistics supply of DMPA-SC. There was minimal evidence of scale-up outcomes.ConclusionThis scoping review reported a wide range of interventions employed by countries and programs to scale up DMPA-SC self-administration but minimal evidence of the scale-up outcomes. Evidence from this review can help design better programs that improves access to quality family planning services to achieve the Sustainable Development Goals (SDG) targets 3.7. However, efforts should focus on rigorous implementation research that assess scaled up self-administered DMPA-SC interventions and report their outcomes.RegistrationThe protocol for this review was registered in the protocols.io repository ( https://www.protocols.io/view/a-protocol-for-a-scoping-review-of-implementation-x54v9yemmg3e/v1 ).

Dataset Information

A randomized crossover study to evaluate local tolerability following subcutaneous administration of a new depot medroxyprogesterone acetate contraceptive formulation.

Objectives

Study design

Results

Conclusions

Implications

Trial registration

Publications

A randomized crossover study to evaluate local tolerability following subcutaneous administration of a new depot medroxyprogesterone acetate contraceptive formulation.

Similar Datasets

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