Contraceptive Efficacy and Safety of NOMAC-E2 Combined Oral Contraceptive

• ClinicalTrials.gov Identifier: NCT05264506
• Recruitment Status: Recruiting
• First Posted: March 3, 2022
• Last Update Posted: October 4, 2022
• Sponsor: Organon and Co
• Collaborators: IQVIA Inc.; OSTAtistics
• Information provided by (Responsible Party): Organon and Co

Tracking Information

• First Submitted Date: January 28, 2022
• First Posted Date: March 3, 2022
• Last Update Posted Date: October 4, 2022
• Actual Study Start Date: February 17, 2022
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 30, 2022)

Number of on-treatment pregnancies per 100 women-years of at risk exposure [ Time Frame: 1 year ]

The at-risk Pearl Index is defined as the number of on-treatment pregnancies (i.e., pregnancies from study drug start to 7 days after last intake of active study drug) divided by the number of 28-day cycles, either associated with a pregnancy or with both affirmed heterosexual vaginal intercourse and no use of additional contraception, with that number multiplied by 1300 to represent the number for 100 years of 13 cycles per year.

Original Primary Outcome Measures (submitted: March 2, 2022)

Number of on-treatment pregnancies per 100 women [ Time Frame: 1 year ]

The at-risk Pearl Index is defined as the number of on-treatment pregnancies (i.e., pregnancies from study drug start to 7 days after last intake of active study drug) divided by the number of 28-day cycles with affirmed heterosexual vaginal intercourse and no use of additional contraception, with that number multiplied by 1300 to represent the number for 100 years of 13 cycles per year.

Current Secondary Outcome Measures (submitted: September 30, 2022)

• Proportion of participants with an adverse event (regardless on potential relationship to study drug) [ Time Frame: 1 year ]
• Proportion of participants who prematurely discontinue study drug treatment [ Time Frame: 1 year ]
• Number of pregnancies during perfect use cycles per 100 women-years [ Time Frame: 1 year ]
  The perfect use Pearl Index is similar to the at-risk Pearl Index, but excludes subjects or select cycles per subject, from both the number of pregnancies and the number of cycles, where important deviations from the protocol have occurred. Important deviations for contraceptive cycles can include, but not be limited to, (a) non-compliance based on 4 missed active tablets during cycle, (b) non-compliance based on 2 consecutive missed active tablets during a cycle, (c) prohibited medications taken during the cycle. Important subject deviations for contraceptive analysis include, but not limited to, (a) >75% of cycles where participant is non-compliant with study drug or not at risk for pregnancy, (b) participant is pregnant or without documented negative pregnancy on day of first study drug intake, (c) participant did not meet eligibility requires for absence of abnormal bleeding or breastfeeding.
• Number of all on-treatment pregnancies per 100 years of exposure [ Time Frame: 1 year ]
  The typical-use Pearl Index is defined as the number of on-treatment pregnancies divided by the number of 28-day cycles, regardless of affirmed heterosexual vaginal intercourse or no use of additional contraception, with that number multiplied by 1300 to represent the number for 100 years of 13 cycles per year.
• Number of pregnancies with participants placed in subgroups based on baseline BMI categories (<30 kg/m2, ≥30 kg/m2) [ Time Frame: 1 year ]
  Each of the three Pearl Index measures previously described will be evaluated separately for participant with body mass index values of <30 kg/m2 and ≥ 30kg/m2, with the value as determined at the time of assignment to treatment.
• By-cycle summary of bleeding-spotting [ Time Frame: 28-day cycles across one year ]
  For each cycle, the number of participants will be summarized according to the bleeding-spotting patterns (unscheduled bleeding-spotting, absence of scheduled bleeding-spotting, experienced no scheduled or unscheduled bleeding-spotting at all) observed during the cycle.
• By-reference period summary of the bleeding and/or spotting days [ Time Frame: 91-day reference periods across one year ]
  For each 91-day reference period, the number of bleeding days, spotting days, and bleeding-spotting days will be summarized.
• By-reference period summary of frequency of bleeding/spotting episodes [ Time Frame: 91-day reference periods across one year ]
  Bleeding/spotting patterns during the 91-day reference periods will be classified as no episodes, 1-2 episodes, 3-5 episodes, and >5 episodes, where episodes are defined as one or more consecutive days during which bleeding or spotting occurred, bounded at each end by bleeding-spotting-free days.
• By-reference period summary of subjects with prolonged bleeding spotting [ Time Frame: 91-day reference periods across one year ]
  Bleeding/spotting patterns during the 91-day reference periods will be classified as based on at least one bleeding/spotting starting with the reference period, where a length of >7 days and of >14 days will be evaluated.
• NOMAC concentrations - relationship with body weight [ Time Frame: Treatment Week 5 and Treatment Week 17 ]
  NOMAC concentrations assessed through use of sparse sampling and population pharmacokinetic modeling to estimate the effect of body weight (kg).
• NOMAC concentrations - relationship with BMI [ Time Frame: Treatment Week 5 and Treatment Week 17 ]
  NOMAC concentrations assessed through use of sparse sampling and population pharmacokinetic modeling to estimate the effect of BMI (kg/m^2).

Original Secondary Outcome Measures (submitted: March 2, 2022)

• Proportion of participants with an adverse event (regardless on potential relationship to study drug) [ Time Frame: 1 year ]
• Proportion of participants who prematurely discontinue study drug treatment [ Time Frame: 1 year ]
• Number of pregnancies during perfect use cycles per 100 women-years [ Time Frame: 1 year ]
  The perfect use Pearl Index is similar to the at-risk Pearl Index, but excludes subjects or select cycles per subject, from both the number of pregnancies and the number of cycles, where important deviations from the protocol have occurred. Important deviations for contraceptive cycles can include, but not be limited to, (a) non-compliance based on 4 missed active tablets during cycle, (b) non-compliance based on 2 consecutive missed active tablets during a cycle, (c) prohibited medications taken during the cycle. Important subject deviations for contraceptive analysis include, but not limited to, (a) >75% of cycles where participant is non-compliant with study drug or not at risk for pregnancy, (b) participant is pregnant or without documented negative pregnancy on day of first study drug intake, (c) participant did not meet eligibility requires for absence of abnormal bleeding or breastfeeding.
• Number of all on-treatment pregnancies per 100 years of exposure [ Time Frame: 1 year ]
  The typical-use Pearl Index is defined as the number of on-treatment pregnancies divided by the number of 28-day cycles, regardless of affirmed heterosexual vaginal intercourse or no use of additional contraception, with that number multiplied by 1300 to represent the number for 100 years of 13 cycles per year.
• Number of pregnancies with participants placed in subgroups based on baseline BMI categories (<30 kg/m2, ≥30 kg/m2) [ Time Frame: 1 year ]
  Each of the three Pearl Index measures previously described will be evaluated separately for participant with body mass index values of <30 kg/m2 and ≥ 30kg/m2, with the value as determined at the time of assignment to treatment.
• By-cycle summary of bleeding-spotting [ Time Frame: 28-day cycles across one year ]
  For each cycle, the number of participants will be summarized according to the bleeding-spotting patterns (unscheduled bleeding-spotting, absence of scheduled bleeding-spotting, experienced no scheduled or unscheduled bleeding-spotting at all) observed during the cycle.
• By-reference period summary of the bleeding and/or spotting days [ Time Frame: 91-day reference periods across one year ]
  For each 91-day reference period, the number of bleeding days, spotting days, and bleeding-spotting days will be summarized.
• By-reference period summary of frequency of bleeding/spotting episodes [ Time Frame: 91-day reference periods across one year ]
  Bleeding/spotting patterns during the 91-day reference periods will be classified as no episodes, 1-2 episodes, 3-5 episodes, and >5 episodes, where episodes are defined as one or more consecutive days during which bleeding or spotting occurred, bounded at each end by bleeding-spotting-free days.
• By-reference period summary of subjects with prolonged bleeding spotting [ Time Frame: 91-day reference periods across one year ]
  Bleeding/spotting patterns during the 91-day reference periods will be classified as based on at least one bleeding/spotting starting with the reference period, where a length of >7 days and of >14 days will be evaluated.
• NOMAC concentrations - relationship with body weight [ Time Frame: Treatment Week 5 and Treatment Week 17 ]
  NOMAC concentrations assessed through use of sparse sampling and population pharmacokinetics to estimate the effect of body weight (kg).
• NOMAC concentrations - relationship with BMI [ Time Frame: Treatment Week 5 and Treatment Week 17 ]
  NOMAC concentrations assessed through use of sparse sampling and population pharmacokinetics to estimate the effect of BMI (kg/m^2).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Contraceptive Efficacy and Safety of NOMAC-E2 Combined Oral Contraceptive
• Official Title: 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Single Arm Study

Masking: None (Open Label)
Primary Purpose: Prevention

• Condition: Contraception

Intervention

Drug: 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.

Other Name: Nomegestrol acetate / estradiol

Study Arms

Experimental: 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.

Intervention: Drug: NOMAC-E2 COC

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 2, 2022): 1878
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2024
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 14 Years to 35 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sebastian Mirkin, MD; 561-862-7446; sebastian.mirkin@organon.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05264506
• Other Study ID Numbers: OG-8175A-023
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Organon and Co
• Original Responsible Party: Same as current
• Current Study Sponsor: Organon and Co
• Original Study Sponsor: Same as current

Collaborators

• IQVIA Inc.
• OSTAtistics

• Investigators: Not Provided
• PRS Account: Organon and Co
• Verification Date: September 2022