Sayana® Press Extension Study

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Contraception

Intervention / Treatment
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* Drug: Sayana® Press


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abdomen<br>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<br>* 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.<br>* Other names: medroxyprogesterone acetate (MPA) injectable suspension;|
| Experimental: Upper thigh<br>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<br>* 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.<br>* Other names: medroxyprogesterone acetate (MPA) injectable suspension;|
| Experimental: Back of the upper arm<br>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<br>* 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.<br>* Other names: medroxyprogesterone acetate (MPA) injectable suspension;|

What is the study measuring?
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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 |