Contraception
Conditions
Keywords
Birth control methods, Contraceptive, Postmenarcheal Premenopausal Women, Hormonal, Sexually Active
Brief summary
The purpose of this study is evaluating Contraceptive Efficacy and Safety of NOMAC-E2 Combined Oral Contraceptive in Premenopausal Females Aged 14 to 35 Years (Inclusive).
Detailed description
This is a Phase 3, Open-label, Multi-center, Single-arm Study to Assess Contraceptive Efficacy and Safety of the Nomegestrol Acetate + 17β-estradiol Combined Oral Contraceptive (OG-8175A) in Premenopausal Females Aged 14 to 35 Years (Inclusive). Potential participants must be sexually active and engage in heterosexual vaginal intercourse at least once per month with a partner who is not known to be subfertile, sterilized, or infertile, and should not routinely use any other form of contraception. A total of 2,680 fertile premenopausal women aged 14 to 35 years (inclusive) will be screened to achieve about 1,878 (with at least 657 participants with BMI ≥30 kg/m2) being allocated to study treatment. Over 1,000 total participants are expected to complete 1 year of treatment (13 cycles). The total duration of study participation will be up to 60 weeks, which includes a Pre-treatment Period of approximately 6 weeks, a Treatment Period of 52 weeks, and a Follow-up Period of 2 weeks after the last intake of study drug.
Interventions
DRUGNOMAC-E2 COC
Dosage Formulation: Film-coated Tablet Unit Dose Strength: Nomegestrol acetate (NOMAC) 2.5 mg and estradiol (E2) 1.5 mg; Each blister strip contains 28 tablets: 24 tablets with the active drug (number 1 to 24) and 4 tablets with placebo (number 25 to 28). Dosing Instructions: oral. Take 1 tablet daily at about the same time as directed.
Sponsors
Iqvia Pty Ltd
Organon and Co
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Single Arm Study
Eligibility
Sex/Gender
FEMALE
Age
14 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Postmenarcheal, premenopausal female aged 14 to 35 years (inclusive) * At risk for pregnancy (including heterosexual vaginal intercourse at least once a month and not sterilized). * No desire for pregnancy within 1 year following screening and is not intending to use any other form of contraception * Good physical and mental health * History of regular menstrual cycles prior to the use of any hormonal contraceptive. * Able and willing to adhere study procedures
Exclusion criteria
* Current known or expected pregnancy * History of subfertility or infertility * Less than 2 normal menstrual cycles following recent pregnancy of gestational age * Breastfeeding within 2 months of study drug start * Known HIV infection * Untreated gonorrhea, chlamydia, or trichomonas * abnormal PAP within timeline of standard of care guidelines * Unexplained/unresolved abnormal vaginal bleeding * Presence/history of VTE, ATE, transient ischemic attack, angina pectoris, or claudication * Higher risk for VTE * Uncontrolled or severe hypertension * Severe dyslipoproteinemia * History of migraine with aura or focal neurological symptoms * Diabetes mellitus (with either end-organ involvement or \>20 years duration) * Multiple cardiovascular risk factors * History of pancreatitis associated with severe hypertriglyceridemia * Presence/history of clinically significant liver disease * History of malabsorptive surgical procedures * History of malignancy in last 5 years * Presence/history of meningioma * Disease that may worsen under hormonal treatment * Presence/history of severe depression (unless currently stable and asymptomatic) * Known allergy/sensitivity to NOMAC-E2 * Drug or alcohol abuse/dependence in last 2 years * Clinically relevant abnormal lab result at screening * Expected use of other contraceptive medications or medications that induce liver enzymes during study * Used another investigational drug within 2 months of study drug start
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With On-treatment Pregnancies | 1 year | Raw count of the number of pregnancies that occurred while participants were taking study drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Prematurely Discontinue Study Drug Treatment | 1 year | — |
| Percentage of Participants With On-treatment Pregnancies With at Least One Completed Cycle | 1 year | Number of participants with on-treatment pregnancies as a percentage of the number of participants with at least one completed cycle |
| Number of Cycles of Exposure Prior to Pregnancy | 1 year | In participants who experienced on-treatment pregnancy, the mean number of completed treatment cycles prior to occurrence of the pregnancy (for participants with known date of conception) |
| Number of Participants With a Pregnancy, Based on Baseline BMI Categories (<30 kg/m2, ≥30 kg/m2) | 1 year | Raw count of the number of pregnancies that occurred while participants were taking study drug in each BMI category |
| Proportion of Participants With Bleeding-spotting Days | 28-day cycles across one year | Number of participants with bleeding-spotting days as a proportion of the number of participants who had at least one completed cycle |
| Mean Number of Bleeding and/or Spotting Days Per Cycle | 28-day cycles across one year | For participants who had at least one completed cycle, the mean number of bleeding-spotting days per cycle |
| Proportion of Participants With an Adverse Event (Regardless on Potential Relationship to Study Drug) | 1 year | — |
| Proportion of Participants With 8 or More Bleeding-spotting Days | 28-day cycles across one year | Proportion of participants who had at least one completed cycle with 8 or more bleeding-spotting days in a cycle |
| Mean NOMAC Concentration, Visit 3 Pre-Dose | Treatment Week 5 | NOMAC concentrations assessed through use of sparse sampling |
| Mean NOMAC Concentration, Visit 3 Post-Dose | Treatment Week 5 | NOMAC concentrations assessed through use of sparse sampling |
| Mean NOMAC Concentration, Visit 4 Pre-Dose | Treatment Week 17 | NOMAC concentrations assessed through use of sparse sampling |
| Mean NOMAC Concentration, Visit 4 Post-Dose | Treatment Week 17 | NOMAC concentrations assessed through use of sparse sampling |
| Average Number of Bleeding-spotting Days Per Reference Period | 91-day reference periods across one year | For participants with at least one completed reference period, the average number of bleeding-spotting days per reference period |
Countries
United States
Participant flow
Pre-assignment details
A total of 3,055 participants were screened for the study. Out of these 1,135 participants failed the screening process. One participant was found pregnant before starting treatment, however not identified as a screen failure
Participants by arm
| Arm | Count |
|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) The NOMAC-E2 COC active tablets contain 2.5 mg NOMAC and 1.5 mg E2 and will be used in a 24/4 regimen, i.e., 28-day cycles with 24 days of active tablet intake followed by 4 days of placebo tablet intake.
NOMAC-E2 COC: Dosage Formulation: Film-coated Tablet Unit Dose Strength: Nomegestrol acetate (NOMAC) 2.5 mg and estradiol (E2) 1.5 mg; Each blister strip contains 28 tablets: 24 tablets with the active drug (number 1 to 24) and 4 tablets with placebo (number 25 to 28).
Dosing Instructions: oral. Take 1 tablet daily at about the same time as directed. | 1,830 |
| Total | 1,830 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 59 |
| Overall Study | Discontinued prior treatment | 89 |
| Overall Study | Lost to Follow-up | 204 |
| Overall Study | Non-compliance with Study Drug | 29 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Pregnancy | 60 |
| Overall Study | Protocol Violation | 185 |
| Overall Study | Study termination | 677 |
| Overall Study | Withdrawal by Subject | 208 |
Baseline characteristics
| Characteristic | Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) |
|---|---|
| Age, Continuous | 27.2 years STANDARD_DEVIATION 4.99 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1004 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 817 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 15 Participants |
| Race (NIH/OMB) Asian | 29 Participants |
| Race (NIH/OMB) Black or African American | 356 Participants |
| Race (NIH/OMB) More than one race | 34 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 32 Participants |
| Race (NIH/OMB) White | 1358 Participants |
| Region of Enrollment United States | 1830 Participants |
| Sex: Female, Male Female | 1830 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1,830 |
| other Total, other adverse events | 0 / 1,830 |
| serious Total, serious adverse events | 10 / 1,830 |
Outcome results
Primary
Number of Participants With On-treatment Pregnancies
Raw count of the number of pregnancies that occurred while participants were taking study drug
Time frame: 1 year
Population: All Participants as Treated Population, which consisted of all participants who took at least one dose of trial medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Number of Participants With On-treatment Pregnancies | 57 Participants |
Secondary
Average Number of Bleeding-spotting Days Per Reference Period
For participants with at least one completed reference period, the average number of bleeding-spotting days per reference period
Time frame: 91-day reference periods across one year
Population: Participants with at least one completed reference period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Average Number of Bleeding-spotting Days Per Reference Period | 13.1 bleeding-spotting days | Standard Deviation 8.54 |
Secondary
Mean NOMAC Concentration, Visit 3 Post-Dose
NOMAC concentrations assessed through use of sparse sampling
Time frame: Treatment Week 5
Population: PK participants who completed Visit 3 post-dose sampling
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Mean NOMAC Concentration, Visit 3 Post-Dose | 73.61 ng/mL | Standard Deviation 742.41 |
Secondary
Mean NOMAC Concentration, Visit 3 Pre-Dose
NOMAC concentrations assessed through use of sparse sampling
Time frame: Treatment Week 5
Population: PK participants who completed Visit 3 pre-dose sampling
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Mean NOMAC Concentration, Visit 3 Pre-Dose | 32.26 ng/mL | Standard Deviation 310.457 |
Secondary
Mean NOMAC Concentration, Visit 4 Post-Dose
NOMAC concentrations assessed through use of sparse sampling
Time frame: Treatment Week 17
Population: PK participants who completed Visit 4 post-dose sampling
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Mean NOMAC Concentration, Visit 4 Post-Dose | 58.01 ng/mL | Standard Deviation 363.4 |
Secondary
Mean NOMAC Concentration, Visit 4 Pre-Dose
NOMAC concentrations assessed through use of sparse sampling
Time frame: Treatment Week 17
Population: PK participants who completed Visit 4 pre-dose sampling
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Mean NOMAC Concentration, Visit 4 Pre-Dose | 36.01 ng/mL | Standard Deviation 229.607 |
Secondary
Mean Number of Bleeding and/or Spotting Days Per Cycle
For participants who had at least one completed cycle, the mean number of bleeding-spotting days per cycle
Time frame: 28-day cycles across one year
Population: Participants with at least one completed cycle
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Mean Number of Bleeding and/or Spotting Days Per Cycle | 4.0 bleeding-spotting days | Standard Deviation 3.44 |
Secondary
Number of Cycles of Exposure Prior to Pregnancy
In participants who experienced on-treatment pregnancy, the mean number of completed treatment cycles prior to occurrence of the pregnancy (for participants with known date of conception)
Time frame: 1 year
Population: Participants with a known date of conception
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Number of Cycles of Exposure Prior to Pregnancy | 4.2 completed cycles | Standard Deviation 3.47 |
Secondary
Number of Participants With a Pregnancy, Based on Baseline BMI Categories (<30 kg/m2, ≥30 kg/m2)
Raw count of the number of pregnancies that occurred while participants were taking study drug in each BMI category
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Number of Participants With a Pregnancy, Based on Baseline BMI Categories (<30 kg/m2, ≥30 kg/m2) | BMI >=30 kg/m2 | 18 Participants |
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Number of Participants With a Pregnancy, Based on Baseline BMI Categories (<30 kg/m2, ≥30 kg/m2) | BMI <30 kg/m2 | 39 Participants |
Secondary
Percentage of Participants With On-treatment Pregnancies With at Least One Completed Cycle
Number of participants with on-treatment pregnancies as a percentage of the number of participants with at least one completed cycle
Time frame: 1 year
Population: Participants with at least one completed cycle
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Percentage of Participants With On-treatment Pregnancies With at Least One Completed Cycle | 3.1 percentage of participants |
Secondary
Proportion of Participants Who Prematurely Discontinue Study Drug Treatment
Time frame: 1 year
Population: All Participants as Treated Population, which consisted of all randomized participants who took at least one dose of trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Proportion of Participants Who Prematurely Discontinue Study Drug Treatment | 62 participants |
Secondary
Proportion of Participants With 8 or More Bleeding-spotting Days
Proportion of participants who had at least one completed cycle with 8 or more bleeding-spotting days in a cycle
Time frame: 28-day cycles across one year
Population: Participants with at least one completed cycle
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Proportion of Participants With 8 or More Bleeding-spotting Days | 709 participants |
Secondary
Proportion of Participants With an Adverse Event (Regardless on Potential Relationship to Study Drug)
Time frame: 1 year
Population: All Participants as Treated Population, which consisted of all participants who took at least one dose of trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Proportion of Participants With an Adverse Event (Regardless on Potential Relationship to Study Drug) | 485 participants |
Secondary
Proportion of Participants With Bleeding-spotting Days
Number of participants with bleeding-spotting days as a proportion of the number of participants who had at least one completed cycle
Time frame: 28-day cycles across one year
Population: Participants with at least one completed cycle
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nomegestrol Acetate + 17β-estradiol (NOMAC-E2; OG-8175A) | Proportion of Participants With Bleeding-spotting Days | 1721 participants |