Sayana® Press Extension Study

A Study to Evaluate the Effectiveness, Pharmacokinetics, Safety, and Acceptability of Sayana® Press When Injected Every Four Months

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.

Study Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: Sayana® Press

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.

• Study Type: Interventional
• Enrollment (Actual): 750
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Campinas, Brazil, 13084-971
    • Universidade Estadual de Campinas (UNICAMP)
• Chile
  • Santiago, Chile
    • Instituto Chileno de Medicina Reproductiva (ICMER)
• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Asociación Dominicana Pro Bienestar de la Familia, Inc. (PROFAMILIA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abdomen; Sayana® Press (MPA injectable suspension, 104 mg/0.65 mL, pre-filled in the UnijectTM delivery injection system) injected subcutaneously every 4 months (17-18 weeks) for 3 treatment cycles (12 months).	Drug: Sayana® Press; The active ingredient in Sayana® Press is Medroxyprogesterone acetate (MPA). Sayana® Press (MPA injectable suspension, 104 mg/0.65 mL, pre-filled in the UnijectTM delivery injection system) for subcutaneous injection.; Other Names: medroxyprogesterone acetate (MPA) injectable suspension
Experimental: Upper thigh; Sayana® Press (MPA injectable suspension, 104 mg/0.65 mL, pre-filled in the UnijectTM delivery injection system) injected subcutaneously every 4 months (17-18 weeks) for 3 treatment cycles (12 months).	Drug: Sayana® Press; The active ingredient in Sayana® Press is Medroxyprogesterone acetate (MPA). Sayana® Press (MPA injectable suspension, 104 mg/0.65 mL, pre-filled in the UnijectTM delivery injection system) for subcutaneous injection.; Other Names: medroxyprogesterone acetate (MPA) injectable suspension
Experimental: Back of the upper arm; Sayana® Press (MPA injectable suspension, 104 mg/0.65 mL, pre-filled in the UnijectTM delivery injection system) injected subcutaneously every 4 months (17-18 weeks) for 3 treatment cycles (12 months).	Drug: Sayana® Press; The active ingredient in Sayana® Press is Medroxyprogesterone acetate (MPA). Sayana® Press (MPA injectable suspension, 104 mg/0.65 mL, pre-filled in the UnijectTM delivery injection system) for subcutaneous injection.; Other Names: medroxyprogesterone acetate (MPA) injectable suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of pregnancy	Pregnancy is defined as having a positive urine pregnancy test. Positive urine tests will be confirmed by ultrasound and/or serum hCG testing whenever possible. The primary efficacy analysis will be based on the pregnancy Pearl Index, computed as the number of pregnancies that occur during the treatment period multiplied by 100 and divided by the number of WY of treatment contributed to the Treated Analysis Set among women receiving injections in the abdomen or thigh.	12 months after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum MPA concentrations (trough concentrations, accumulation and apparent terminal half-life of MPA) in a subset of 120 participants	Pharmacokinetic endpoints include serum MPA concentrations at month 2, 3, 4, 8, and 12.	12 months after treatment initiation
Occurrence of serious adverse events (SAEs) and adverse events (AEs) leading to product withdrawal	The overall safety of study drug will be assessed throughout the study by evaluating the occurrence of SAEs and AEs leading to product discontinuation, blood pressure and weight at regularly scheduled visits, and changes in bleeding pattern.	12 months after treatment initiation
Acceptability of Sayana® Press	Perception of bleeding patterns and other responses to acceptability questions will be summarized using descriptive statistics based on routine questions asked at regularly scheduled visits (enrollment, months 4 and 8, and final).	12 months after treatment initiation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Return to ovulation among a subset of study participants who received month 4 and month 8 injections and plan to use non-hormonal methods of contraception, or no contraception for up to a maximum of 12 months from the last study injection.	Ovulation is defined as a single elevated serum progesterone (P ≥4.7 ng/mL) or a confirmed pregnancy test.	A maximum of 12 months from the last study injection.

Collaborators and Investigators

• Sponsor: FHI 360
• Investigators: Study Director: Jennifer Deese, PhD, MPH, FHI 360

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2017
• Primary Completion (Actual): May 30, 2020
• Study Completion (Actual): May 30, 2020

Study Registration Dates

• First Submitted: May 12, 2017
• First Submitted That Met QC Criteria: May 12, 2017
• First Posted (Actual): May 16, 2017

Study Record Updates

• Last Update Posted (Actual): December 10, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Medroxyprogesterone Acetate; Medroxyprogesterone
• Other Study ID Numbers: 926400

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Study sites will collect baseline and longitudinal data among 750 women in Brazil, Chile and the Dominican Republic relevant to the protocol objectives including demographics; sexual, reproductive and medical history; acceptability; serious adverse events; concomitant medication use and laboratory data (including serum blood medroxyprogesterone acetate concentrations in a subset of women).

• FHI 360 will submit the study dataset using the platform-independent and non-proprietary comma separated values (also known as [CSV]) format. The study dataset will be posted to a third-party data repository, then the link will be submitted to USAID's Data Development Library within 30 calendar days after the dataset is first used to produce an Intellectual Work.

A code book defining all variables, a data dictionary describing the relationships among the files within the dataset, and a document describing the methodology used to collect the data will be shared with the study dataset.

• IPD Sharing Time Frame: Within 30 calendar days after the dataset is first used to produce an Intellectual Work

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No