Contraceptive Efficacy and Safety of NOMAC-E2 Combined Oral Contraceptive

Contraception Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05264506
• Other study ID #: OG-8175A-023
• Status: Terminated
• Phase: Phase 3
• Start date: February 17, 2022
• Est. completion date: January 26, 2024

Study information

• Verified date: February 2024
• Source: Organon and Co
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2007
• Est. completion date: January 26, 2024
• Est. primary completion date: January 12, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 14 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• 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.

Locations

Country	Name	City	State
United States	Albuquerque Clinical Trials, Inc	Albuquerque	New Mexico
United States	Bosque Women's Care	Albuquerque	New Mexico
United States	The Iowa Clinic	Ankeny	Iowa
United States	Agile Clinical Research Trials, LLC	Atlanta	Georgia
United States	Tekton Research, Inc	Austin	Texas
United States	Gardens Medical Center / Alliance Research Institute	Bell Gardens	California
United States	Alabama Clinical Therapeutics, LLC	Birmingham	Alabama
United States	Helios Clinical Research	Burleson	Texas
United States	Alliance Research Institute, LLC	Canoga Park	California
United States	Chattanooga Medical Research, LLC	Chattanooga	Tennessee
United States	University of Cincinnati Physicians	Cincinnati	Ohio
United States	Alliance for Multispecialty Research, LLC	Coral Gables	Florida
United States	Velocity Clinical Research - Covington	Covington	Louisiana
United States	Cedar Health Research	Dallas	Texas
United States	Velocity Clinical Research	Denver	Colorado
United States	Universal Axon Clinical Research, LLC	Doral	Florida
United States	SEC Clinical Research	Dothan	Alabama
United States	Carolina Women's Research and Wellness Center	Durham	North Carolina
United States	Alliance for Multispecialty Research, LLC	El Dorado	Kansas
United States	OB/GYN Associates of Erie	Erie	Pennsylvania
United States	Exordia Medical Research, Inc	Fall River	Massachusetts
United States	NECCR PrimaCare Research, LLC	Fall River	Massachusetts
United States	Carolina Institute For Clinical Research	Fayetteville	North Carolina
United States	Javara Research	Forest	Virginia
United States	Alliance for Multispecialty Research, LLC	Fort Myers	Florida
United States	Helios Clinical Research	Fort Worth	Texas
United States	Velocity Clinical Research	Grand Island	Nebraska
United States	Velocity Clinical Research	Gulfport	Mississippi
United States	CMR of Greater New Haven, LLC	Hamden	Connecticut
United States	Velocity Clinical Research	Hastings	Nebraska
United States	Advanced Investigative Medicine, Inc	Hawthorne	California
United States	Accurate Clinical Research, Inc	Houston	Texas
United States	Clinical Trial Network	Houston	Texas
United States	Javara Inc	Houston	Texas
United States	Marvel Clinical Research	Huntington Beach	California
United States	Leavitt Clinical Research	Idaho Falls	Idaho
United States	Women's Healthcare Associates P.A.	Idaho Falls	Idaho
United States	Alliance for Multispecialty Research, LLC	Kansas City	Missouri
United States	Alliance for Multispecialty Research, LLC	Knoxville	Tennessee
United States	New Phase Research & Development	Knoxville	Tennessee
United States	Velocity Clinical Research	Lafayette	Louisiana
United States	Altus Research, Inc.	Lake Worth	Florida
United States	Physicians' Research Options / Red Rocks OB/GYN	Lakewood	Colorado
United States	Om Research LLC	Lancaster	California
United States	Accel Research Sites - St. Petersburg Clinical Research Unit	Largo	Florida
United States	Alliance for Multispecialty Research, LLC	Las Vegas	Nevada
United States	Essential Women's Health Associates	Las Vegas	Nevada
United States	Jubilee Clinical Research, Inc	Las Vegas	Nevada
United States	OB-GYN Associates of Mid-Florida, PA	Leesburg	Florida
United States	Alliance for Multispecialty Research, LLC - Lexington	Lexington	Kentucky
United States	WR-Medical Research Center of Memphis	Memphis	Tennessee
United States	Desert Clinical Research, LLC/CCT Research	Mesa	Arizona
United States	Mesa Obstetricians and Gynecologists	Mesa	Arizona
United States	Southern Clinical Research Associates	Metairie	Louisiana
United States	Velocity Clinical Research	Metairie	Louisiana
United States	Admed Research, LLC	Miami	Florida
United States	Avantis Clinical Research, LLC	Miami	Florida
United States	Genoma Research Group, Inc.	Miami	Florida
United States	Miami Clinical Research	Miami	Florida
United States	New Age Medical Research Corporation	Miami	Florida
United States	Spotlight Research Center, LLC	Miami	Florida
United States	Quantum Clinical Trials	Miami Beach	Florida
United States	Quality Research of South Florida	Miami Lakes	Florida
United States	Alliance for Multispecialty Research, LLC	Mobile	Alabama
United States	Velocity Clinical Research	Mobile	Alabama
United States	Infinite Clinical Trials	Morrow	Georgia
United States	Venus Gynecology, LLC	Myrtle Beach	South Carolina
United States	Alliance for Multispecialty Research, LLC	New Orleans	Louisiana
United States	Alliance for Multispecialty Research, LLC	Newton	Kansas
United States	Alliance for Multispecialty Research, LLC	Norfolk	Virginia
United States	Tidewater Clinical Research	Norfolk	Virginia
United States	Healthcare Clinical Data, Inc.	North Miami	Florida
United States	Sensible Healthcare LLC	Ocoee	Florida
United States	Velocity Clinical Research	Omaha	Nebraska
United States	Innovation Medical Research Center	Palmetto Bay	Florida
United States	Planned Parenthood of Northern, Central, and Southern New Jersey	Perth Amboy	New Jersey
United States	Clinical Research of Philadelphia, LLC	Philadelphia	Pennsylvania
United States	Precision Trials AZ, LLC	Phoenix	Arizona
United States	Velocity Clinical Research - Phoenix	Phoenix	Arizona
United States	Empire Clinical Research	Pomona	California
United States	Clinical Research Center of Florida	Pompano Beach	Florida
United States	Javara Inc / Privia Medical Group Georgia, LLC	Pooler	Georgia
United States	M3 Wake Research, Inc	Raleigh	North Carolina
United States	Texas Health Care, PLLC d/b/d Privia Medical Group - North Texas	Rowlett	Texas
United States	Wasatch Clinical Research	Salt Lake City	Utah
United States	Tekton Research, Inc	San Antonio	Texas
United States	WR-Medical Center For Clinical Research - San Diego	San Diego	California
United States	WR-Women's Health Care Research, LLC	San Diego	California
United States	WR-Mount Vernon Clinical Research, LLC	Sandy Springs	Georgia
United States	Seattle Clinical Research Center	Seattle	Washington
United States	Velocity Clinical Research	Slidell	Louisiana
United States	Javara Research	Stephenville	Texas
United States	Javara Inc	Sugar Land	Texas
United States	R & B Medical Center LLC	Tampa	Florida
United States	Alliance for Multispecialty Research	Tempe	Arizona
United States	Continental Clinical Solutions	Towson	Maryland
United States	Eclipse Clinical Research	Tucson	Arizona
United States	Noble Clinical Research	Tucson	Arizona
United States	Meridian Clinical Research, LLC	Vestal	New York
United States	Helios Clinical Research - Weatherford	Weatherford	Texas
United States	Comprehensive Clinical Research, LLC	West Palm Beach	Florida
United States	Alliance for Multispecialty Research, LLC	Wichita	Kansas
United States	Alliance for Multispecialty Research, LLC	Wichita	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Organon and Co	IQVIA Inc., OSTAtistics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of on-treatment pregnancies per 100 women-years of at risk exposure	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.	1 year
Secondary	Proportion of participants with an adverse event (regardless on potential relationship to study drug)		1 year
Secondary	Proportion of participants who prematurely discontinue study drug treatment		1 year
Secondary	Number of pregnancies during perfect use cycles per 100 women-years	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.	1 year
Secondary	Number of all on-treatment pregnancies per 100 years of exposure	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.	1 year
Secondary	Number of pregnancies with participants placed in subgroups based on baseline BMI categories (<30 kg/m2, =30 kg/m2)	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.	1 year
Secondary	By-cycle summary of bleeding-spotting	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.	28-day cycles across one year
Secondary	By-reference period summary of the bleeding and/or spotting days	For each 91-day reference period, the number of bleeding days, spotting days, and bleeding-spotting days will be summarized.	91-day reference periods across one year
Secondary	By-reference period summary of frequency of bleeding/spotting episodes	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.	91-day reference periods across one year
Secondary	By-reference period summary of subjects with prolonged bleeding spotting	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.	91-day reference periods across one year
Secondary	NOMAC concentrations - relationship with body weight	NOMAC concentrations assessed through use of sparse sampling and population pharmacokinetic modeling to estimate the effect of body weight (kg).	Treatment Week 5 and Treatment Week 17
Secondary	NOMAC concentrations - relationship with BMI	NOMAC concentrations assessed through use of sparse sampling and population pharmacokinetic modeling to estimate the effect of BMI (kg/m^2).	Treatment Week 5 and Treatment Week 17