Clinical trial to evaluate pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after subcutaneous administration of Depo-Provera

Abstract

Objective To evaluate the pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after a single subcutaneous injection in the abdomen of 150 or 300 mg Depo-Provera and compare results to two injections of Depo-SubQ Provera 104 given 3 months apart. Design Partially randomized, multicenter, parallel-group study. Setting Research unit. Patient(s) Forty-two women of reproductive age with confirmed ovulatory cycle and body mass index of 18–35 kg/m 2 . Intervention(s) Women received a single subcutaneous injection of 150 mg (n = 24) or 300 mg (n = 9) of Depo-Provera or two injections of Depo-SubQ Provera 104 (n = 9). Main Outcome Measure(s) Suppression of ovulation as measured by progesterone, serum medroxyprogesterone acetate concentrations, and estimated pharmacokinetics parameters. Result(s) No ovulations were observed during 7 months after a single injection of 150 or 300 mg Depo-Provera. The 150 mg group had a similar C max as observed over two injection cycles of Depo-SubQ Provera 104 and a similar 6-month trough concentration as the 3-month trough of Depo-SubQ Provera 104. Conclusion(s) Our pharmacodynamics and pharmacokinetics data provide proof of concept that Depo-Provera (150 mg) may be an effective contraceptive method when injected subcutaneously every 6 months, with up to a 4-week grace period for reinjections. Clinical Trial Registration Number NCT02456584.

Suppression of ovulation and pharmacokinetics following subcutaneous administration of various doses of Depo-Provera®: a randomized trial

“…However, the subsequent increase of E2 levels could result in a fuller recovery of the ovarian function between re-injections and lower the risk of hypoestrogenism if re-injection interval is extended. These findings provide support for alternative strategies to lower overall MPA exposure and potentially improve the safety profile of MPA injectables, such as administering Sayana Press 3 times a year instead of 4 (clinicaltrials.gov no: NCT03154125) and administering 150 mg of Depo-Provera subcutaneously twice a year for a 6-month protection [18] .…”

Ovulation suppression following subcutaneous administration of depot medroxyprogesterone acetate

“…Detailed characteristics of the 101 participants contributing to our analyses are in the previous manuscripts [ 10 , 11 ]. Briefly, the median age was 34 years (range 22–40); 35.6% self-identified as white and 64.4% identified as black or biracial; and the median body mass index (BMI; kg/m 2 ) was 26.6 (range 18.1–33.9; Table 1 ).…”

“…We performed a secondary analysis of 2 contemporary pharmacokinetics and pharmacodynamics studies of subcutaneously administered MPA conducted between September 2015 and May 2018 [ 10 , 11 ]. Briefly, FHI 360 Study number 702179 (Clinical Trial Registration Number NCT02456584) randomized 36 women from sites in the Dominican Republic and the USA to receive a single 150 mg (1 mL) or 300 mg (2 mL) subcutaneous injection of Depo-Provera, or two 104 mg (0.65 mL) subcutaneous injections of Depo-subQ at 3-month intervals, in a 2:1:1 ratio.…”

“…We measured serum progesterone concentrations weekly starting 12 weeks after each injection. Participants who did not have an elevated progesterone concentration ≥4.7 ng/mL within 12 months of treatment initiation returned for weekly progesterone assessments in month 15 and (if still anovulatory) again in month 18 (the visit schedule within 12 weeks of injection and supportive pharmacodynamic measures are detailed elsewhere [10] ). FHI 360 Study number 834119 (NCT02732418) randomized 60 participants in the Dominican Republic, Chile, and Brazil to receive a single 45 mg (0.3 mL), 75 mg (0.5 mL), or 105 mg (0.7 mL) subcutaneous injection of Depo-Provera, or a single 104 mg subcutaneous injection of Depo-subQ, in a 1:1:1:1 ratio [11] .…”

“…The side effect profile coupled with a lack of appreciable ovulation risk for Depo-subQ has led various researchers to consider regimens that could further reduce MPA exposure [9] . Here we present a secondary analysis of 2 contemporary pharmacokinetics and pharmacodynamics studies designed to inform such strategies [ 10 , 11 ]. Our initial aim was to characterize the distribution of serum MPA concentrations when ovulation returns.…”