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/m².

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.

Keywords: Depot medroxyprogesterone acetate; contraception; pharmacokinetics; subcutaneous; suppression of ovulation.

Figure 1

Participant disposition.

Figure 2

Kaplan-Meier estimates of cumulative probabilities of return to ovulation, with 95% confidence intervals and numbers at risk below the x-axis. The estimated probabilities at month 12 were 65%, 25%, and 11% in the 150 mg, 300 mg, and Depo-SubQ 104 groups, respectively (P = .009 for test of difference in distributions across groups). The earliest ovulation occurred on day 226 in the 150 mg group (median = 320 days). All doses were administered subcutaneously. The Depo-SubQ 104 group received a second injection on day 91.

Figure 3

Geometric mean medroxyprogesterone acetate concentrations with 95% confidence intervals (shifted slightly for visibility). Reference line at 0.35 ng/mL is geometric mean at month 3 in the Depo-SubQ 104 group. All doses were administered subcutaneously. The Depo-SubQ 104 group received a second injection on day 91.