Clinical trial NCT03154125: Sayana® Press Extension Study
Official title: A Study to Evaluate the Effectiveness, Pharmacokinetics, Safety, and Acceptability of Sayana® Press When Injected Every Four Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Contraception
Lead sponsor: FHI 360
Sponsor class: OTHER
First posted: 2017-05-16
Enrollment: 750
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All participants will receive the same study drug, Sayana® Press. However, women will be randomized to receive their injections in the abdomen, back of the upper arm, or upper thigh to control for potential confounding when assessing relationships between SC injection site, efficacy, and PK. One cohort of N=630 women will be randomized 1:1 to receive their injections in the abdomen or thigh, and a separate PK cohort of N=120 women agreeing to MPA testing will be randomized 1:1:1 to receive their injections in the abdomen, upper thigh, or back of the upper arm. Randomization will be stratified by cohort and site using appropriate randomly permuted block sizes.
Primary purpose: OTHER

Brief summary: This is a randomized clinical trial designed to evaluate the effectiveness, safety and acceptability of Sayana® Press when injected every 4 months (17-18 weeks) for 3 treatment cycles (12 months) of use.

Detailed description: This is a randomized, partially-blinded, multi-center, parallel-group study to evaluate the effectiveness, PK, safety, and acceptability of Sayana® Press when injected every 4 months (17-18 weeks) rather than the currently prescribed 3-month (12-14 weeks) regimen.

A total of 750 healthy, sexually active women aged 18 to 35 years with regular menstrual cycles and no DMPA use in the previous 12 months will be enrolled and followed for pregnancy. Among all enrolled, 710 will be randomized to receive injections in the abdomen or upper thigh in accordance with the PATH Sayana® injection instructions, which are consistent with prescribing information, for the primary effectiveness analysis. An additional 40 women will be randomized to receive injections subcutaneously in the back of the upper arm to assess whether differences in PK may exist which could impact the grace period for reinjections for that injection site.

A single MPA serum sample will be collected from all participants at baseline. All participants will receive re-injections at month 4 and month 8, and complete their scheduled follow-up at month 12. There will be a plus 7-day grace period for re-injections, but women who are up to 28 days late may continue treatment if they have a negative urine pregnancy test. Urine pregnancy testing will be performed at month 4, at study exit and at any other time during the study if clinically indicated. Participants will be evaluated for injection site reactions and asked to provide information on adverse events, prohibited concomitant medication and other contraceptive use, vaginal bleeding, and method acceptability at all regular follow-up visits (i.e., not including the PK visits at Months 2 and 3). Serious adverse events and adverse events leading to product withdrawal, will be recorded throughout the study.

Eligibility criteria: Inclusion Criteria:

* not pregnant and no desire to become pregnant in the next 18 months
* regular menstrual cycles (25 to 35 days in length when not using hormonal contraception, pregnant, or lactating)
* at risk of pregnancy (no diagnosis of infertility, no history of tubal ligation or hysterectomy, and an average of 1 or more unprotected acts of vaginal intercourse per month)
* in good general health as determined by a medical history
* 18 to 35 years of age, inclusive
* willing to provide informed consent, follow all study requirements, and rely on Sayana® Press injected every 4 months as the only means of contraception for 12 months
* has only one sexual partner and expects to have that same sexual partner for the next 12 months

Exclusion Criteria:

* has a primary partner who has received a vasectomy or is otherwise sterile
* medical contraindications to depot medroxyprogesterone acetate (DMPA) per World Health Organization medical eligibility criteria for contraceptive use
* known HIV-infection (for her or her partner)
* diagnosis or treatment for a sexually transmitted infection in the past month (for her or a partner), excluding recurrent herpes or condyloma
* received an injection of a progestin-only containing contraceptive (DMPA or norethisterone enanthate) in the past 12 months
* received an injection of a combined injectable contraceptive in the past 6 months
* known or suspected allergic reaction to DMPA
* used a levonorgestrel-releasing intrauterine system, NuvaRing, contraceptive patch, oral contraceptives or a contraceptive implant in the 7 days prior to enrollment (PK cohort only)
* previous (within 1 month prior to enrollment), current or planned (in the next 12 months) use of an investigational drug, prohibited drug per protocol or other drug which in the opinion of the site investigator could complicate study findings
* has been pregnant in the past month
* is lactating
* plans to move to another location in the next 12 months
* has a social or medical condition which in the opinion of the site investigator would make study participation unsafe, or interfere with adherence to protocol requirements.

Primary outcomes:
measure: Occurrence of Pregnancy
timeFrame: 12 months after treatment initiation
Secondary outcomes:
measure: Serum MPA Concentrations in a Subset of 120 Participants
timeFrame: 2, 3, 4, 8, and 12 months after treatment initiation
measure: Occurrence of Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Product Withdrawal
timeFrame: 12 months after treatment initiation
measure: Acceptability of Sayana® Press
timeFrame: 12 months after treatment initiation
Other outcomes:
measure: Return to Ovulation After 12 Months of Use of Sayana Press When Injected Every Four Months.
timeFrame: A maximum of 12 months from the last study injection.
Locations:
city: Campinas
country: Brazil
facility: Universidade Estadual de Campinas (UNICAMP)
city: Santiago
country: Chile
facility: Instituto Chileno De Medicina Reproductiva (ICMER)
city: Santo Domingo
country: Dominican Republic
facility: Asociación Dominicana Pro Bienestar de la Familia, Inc. (PROFAMILIA)
Study officials:
affiliation: FHI 360
name: Vera Halpern, MD
role: STUDY_DIRECTOR
References:
citation: Burke HM, Packer C, Fuchs R, Brache V, Bahamondes L, Salinas A, Veiga N, Miller A, Deese J. Acceptability of the contraceptive Sayana(R) Press when injected every four months: Results from a twelve-month trial in Brazil, Chile and the Dominican Republic. Contraception. 2022 Sep;113:95-100. doi: 10.1016/j.contraception.2022.04.007. Epub 2022 Apr 26.
citation: Deese J, Brache V, Bahamondes L, Salinas A, Jorge A, Veiga N Jr, Fuchs R, Miller A, Taylor D, Halpern V, Dorflinger L. Contraceptive effectiveness, pharmacokinetics, and safety of Sayana(R) Press when injected every four months: a multicenter phase 3 trial. EClinicalMedicine. 2022 Jan 29;44:101273. doi: 10.1016/j.eclinm.2022.101273. eCollection 2022 Feb.