A phase 1, randomized, open-label, single-dose relative bioavailability study of upper arm injection of depot medroxyprogesterone acetate comparing pharmacokinetics and hormone indicators of ovulation with anterior thigh and abdomen injection.

内容摘要

Subcutaneous depot medroxyprogesterone acetate (Sayana® Press; DMPA-SC 104 mg) is approved for contraception, administered by subcutaneous injection into the anterior thigh or abdomen every three months. This study aimed to compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles for a new injection site (the upper arm) to the profiles for the currently approved reference injection sites. We randomized 67 healthy, pre-menopausal women 18 years of age or older to one of the three injection sites (upper arm: test; abdomen or anterior thigh: reference) in this single-center, open-label relative bioavailability trial. Participants received one dose of DMPA-SC (104 mg) on Day 1. We collected serum samples for MPA concentration and hormone analyses at regular intervals starting on Day 1 (pre-dosing), determined serum PK and PD parameters and reported them using summary statistics. Serum MPA AUCtau (area-under-the-curve, Day 1 to Day 92) and Cmax (maximum MPA serum concentration) were 42% and 24% greater, respectively, following upper arm administration, while trough concentrations (Ctrough, Day 92) for the upper arm and combined reference injection sites were similar (Ctrough test/reference = 95.17%; 90% CI: 73.80, 122.73). No participants who were successfully injected with DMPA-SC showed serum hormone indications of ovulation starting after drug administration. We noted no new adverse safety findings in either the test or reference groups. The results demonstrate that upper arm injection of DMPA-SC is safe and effective and could offer another option for administration of this contraceptive injection. This study shows upper arm injection of DMPA-SC (104 mg) should have safety and effectiveness comparable to injection at the currently approved sites (anterior thigh, abdomen), based on MPA PK parameters and hormonal markers of ovulation and could be an acceptable option for women using this form of injectable contraception.