Contraception
Conditions
Brief summary
The purpose of this study is to assess the contraceptive efficacy of the Etonogestrel (ENG) + 17β-Estradiol (E2) vaginal ring in women between 18 and 35 years of age based on the number of in-treatment pregnancies as expressed by the Pearl Index (PI). The study will also assess the safety and tolerability of the ENG-E2 vaginal ring.
Interventions
Up to 13 cycles of ENG-E2 125 μg/300 μg administered intravaginally, each cycle consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
Sponsors
Organon and Co
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Premenopausal female at risk for pregnancy and seeking contraception. * Willing to use a hormonal contraceptive vaginal ring for up to 13 treatment cycles, and not intending to use any other form of contraception. * Body mass index (BMI) of ≥18 and \<38 kg/m2. * Willing to adhere to use of vaginal ring and all required trial procedures.
Exclusion criteria
* Cardiovascular risks and disorders, including history of venous thromboembolic \[VTE\] events, arterial thrombotic or thromboembolic \[ATE\] events, transient ischemic attack, angina pectoris, or claudication; at higher risk of VTE events due to recent prolonged immobilization, plans for surgery requiring prolonged immobilization, or a hereditary or acquired predisposition or elevated risk for venous or arterial thrombosis; currently smoking or uses tobacco/nicotine containing products and is ≥35 years of age; uncontrolled or severe hypertension; history of severe dyslipoproteinemia; \<35 years of age with a history of migraine with aura or focal neurological symptoms or ≥35 years of age with a history of migraines with or without aura or focal neurologic symptoms; diabetes mellitus with end-organ involvement or \>20 years duration; multiple cardiovascular risk factors such as older age, obesity, inadequately controlled hypertension, use of tobacco/ nicotine products, or inadequately controlled diabetes. * Gastrointestinal disorders, including history of pancreatitis associated with severe hypertriglyceridemia; clinically significant liver disease, including active viral hepatitis or cirrhosis. * Other medical disorders, including history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer; any disease that may worsen under hormonal treatment such as disturbances in bile flow, systemic lupus erythematosus, pemphigoid gestationis or idiopathic icterus during previous pregnancy, middle-ear deafness, Sydenham chorea, or porphyria; known allergy/sensitivity or contraindication to investigational product or its excipients; history of drug or alcohol abuse or dependence. * Recent, current, or suspected pregnancy; or has not had at least 2 menstrual cycles or has not completed two 28-day cycles of a hormonal contraceptive (pill, patch or ring) following a recent pregnancy; or is breastfeeding. * Gynecologic conditions: has gonorrhea, chlamydia, or trichomonas or symptomatic vaginitis/cervicitis; has abnormal cervical Pap test or positive high-risk human papillomavirus (HPV) test at screening or documented within 3 years of screening; currently using an intrauterine device/ intrauterine system (IUD/ IUS) or contraceptive implant; within past 6 months has had undiagnosed (unexplained) abnormal vaginal bleeding or any abnormal bleeding expected to recur during trial; has stage 4 pelvic organ prolapse (1 cm beyond introitus) or lesser degrees of prolapse with history of difficulty retaining tampons, vaginal rings, or other products within vagina. * Has used investigational drug and/or participated in other clinical trial within past 8 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of In-Treatment Pregnancies Per 100 Woman-Years of Exposure in Participants 18-35 Years of Age (Pearl Index) | Up to 1 year (13 28-day cycles) | The Pearl Index is the number of in-treatment pregnancies with a conception date in any of the in-treatment cycles, divided by all treatment cycles in each participant from the first treatment cycle to the last treatment cycle (due either to discontinuation or completion), regardless of whether a treatment cycle was at risk or not. One woman-year is defined as 13 treatment cycles x 28 days. These efficacy results should be interpreted with caution. Due to the discontinuation of product development and early trial termination, the number of at risk treatment cycles in the denominator is based on uncleaned diary data. |
| Number of Participants With One or More Adverse Events (AEs) | From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. |
| Number of Participants Who Discontinued Treatment Due to an AE | From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. |
| Number of Participants With One or More Drug-related AEs | From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. An investigator who is a qualified physician determined whether an AE is drug-related. |
| Number of Participants Who Discontinued Treatment Due to a Drug-related AE | From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. An investigator who is a qualified physician determined whether an AE is drug-related. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ENG-E2 125 μg/300 μg Participants were to receive up to 13 cycles of Etonogestrel (ENG) 125 μg and 17β-Estradiol (E2) 300 μg. Each cycle would consist of 21 days of vaginal ring use followed by 7 vaginal ring-free days. | 1,941 |
| Total | 1,941 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 115 |
| Overall Study | Lost to Follow-up | 216 |
| Overall Study | Non-Compliance With Protocol | 32 |
| Overall Study | Non-Compliance With Study Drug | 14 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Pregnancy | 22 |
| Overall Study | Pregnancy Wish | 6 |
| Overall Study | Protocol Violation | 6 |
| Overall Study | Screen Failure | 2 |
| Overall Study | Site Discontinued Study Participation | 1 |
| Overall Study | Study Terminated By Sponsor | 1,417 |
| Overall Study | Subject Moved | 32 |
| Overall Study | Withdrawal by Subject | 76 |
Baseline characteristics
| Characteristic | ENG-E2 125 μg/300 μg |
|---|---|
| Age, Continuous | 27.6 Years STANDARD_DEVIATION 6.2 |
| Sex: Female, Male Female | 1941 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 1,936 |
| serious Total, serious adverse events | 12 / 1,936 |
Outcome results
Primary
Number of In-Treatment Pregnancies Per 100 Woman-Years of Exposure in Participants 18-35 Years of Age (Pearl Index)
The Pearl Index is the number of in-treatment pregnancies with a conception date in any of the in-treatment cycles, divided by all treatment cycles in each participant from the first treatment cycle to the last treatment cycle (due either to discontinuation or completion), regardless of whether a treatment cycle was at risk or not. One woman-year is defined as 13 treatment cycles x 28 days. These efficacy results should be interpreted with caution. Due to the discontinuation of product development and early trial termination, the number of at risk treatment cycles in the denominator is based on uncleaned diary data.
Time frame: Up to 1 year (13 28-day cycles)
Population: All participants assigned to treatment who inserted at least 1 ENG-E2 ring, and who had at least 1 at risk treatment cycle, or participants with a treatment cycle (at risk or not) in which a pregnancy had occurred (i.e., treatment cycle containing an estimated conception date for a pregnancy).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ENG-E2 125 μg/300 μg | Number of In-Treatment Pregnancies Per 100 Woman-Years of Exposure in Participants 18-35 Years of Age (Pearl Index) | 4.32 Pregnancies per 100 woman years |
Primary
Number of Participants Who Discontinued Treatment Due to a Drug-related AE
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. An investigator who is a qualified physician determined whether an AE is drug-related.
Time frame: From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year)
Population: All randomized participants in whom at least 1 vaginal ring was inserted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ENG-E2 125 μg/300 μg | Number of Participants Who Discontinued Treatment Due to a Drug-related AE | 91 Participants |
Primary
Number of Participants Who Discontinued Treatment Due to an AE
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year)
Population: All randomized participants in whom at least 1 vaginal ring was inserted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ENG-E2 125 μg/300 μg | Number of Participants Who Discontinued Treatment Due to an AE | 112 Participants |
Primary
Number of Participants With One or More Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year)
Population: All randomized participants in whom at least 1 vaginal ring was inserted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ENG-E2 125 μg/300 μg | Number of Participants With One or More Adverse Events (AEs) | 830 Participants |
Primary
Number of Participants With One or More Drug-related AEs
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. An investigator who is a qualified physician determined whether an AE is drug-related.
Time frame: From insertion of the first vaginal ring up to and including 14 days after removal of the last vaginal ring (up to approximately 1 year)
Population: All randomized participants in whom at least 1 vaginal ring was inserted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ENG-E2 125 μg/300 μg | Number of Participants With One or More Drug-related AEs | 439 Participants |