A Study to Assess Contraceptive Efficacy and Safety of Etonogestrel (ENG) Implant Beyond 3 Years of Use (MK-8415-060)

Contraception Clinical Trial

Official title:

A Phase 3, Open-label, Multi-center, Single Arm Study to Assess Contraceptive Efficacy and Safety of the Etonogestrel (MK-8415) Implant During Extended Use From 3 Years After Insertion in Females 35 Years of Age or Younger

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04626596
• Other study ID #: 8415-060
• Secondary ID: 2020-001232-95MK
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 19, 2020
• Est. completion date: December 28, 2024

Study information

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

Clinical Trial Summary

The primary purpose of this study is to assess the efficacy and safety of the etonogestrel (ENG) contraceptive implant during participants' fourth and fifth years of use when used as the only method of contraception. The ENG implant is currently approved for a 3-year duration, and this study aims to confirm available evidence suggesting that the ENG implant remains highly effective when used up to 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 498
• Est. completion date: December 28, 2024
• Est. primary completion date: December 28, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A to 35 Years

Eligibility

Inclusion Criteria:

• Not diagnosed with perimenopause or menopause.

• Heterosexually active with a partner who is not known to be subfertile, sterilized, or infertile, and is seeking contraception for pregnancy.

• Palpable intact ENG implant in the upper inner-arm for 36 months from the date of insertion at the time of enrollment, and has documentation of the insertion date (for example, Nexplanon user card or medical record completed on the date of insertion).

• Does not desire a pregnancy within the 24 months after enrollment, is willing to continue use of the implant for an additional 24 months, and is not intending to use any other form of contraception (eg, condoms) from enrollment until after implant removal at 24 months post enrollment.

• Good physical and mental health in the medical judgment of the investigator.

• History of regular menstrual cycles of 21 to 35 days before the insertion of the ENG implant or before hormonal contraceptive use (which may have preceded the current implant use).

• Able and willing to adhere to all required study procedures, including study visits and eDiary entries, and not planning to relocate during the study.

Exclusion Criteria:

• Conceived a pregnancy during use of the current implant or a past contraceptive implant.

• Known or suspected pregnancy at the time of screening or enrollment visit.

• History of subfertility or infertility.

• Breastfeeding.

• Untreated gonorrhea, chlamydia, or trichomonas or symptomatic vaginitis/cervicitis.

• Significantly abnormal cervical cytology (Pap) or pathology results either at screening or documented in the 36-month period prior to enrollment.

• Current use of an intrauterine device/intrauterine system (IUD/IUS).

• Presence of more than one ENG implant.

• Use of daily/monthly hormonal contraceptives, sex steroids, or GnRH agonist/antagonist within 3 months prior to enrollment.

• Use of injectable hormonal contraceptive with 3-month duration within 9 months prior to enrollment.

• Use of injectable GnRH agonist with 3-month duration within 10 months prior to enrollment .

• Use of medications that induce liver enzymes within 2 months prior to enrollment.

• Untreated or unresolved vaginal bleeding or spotting attributable to underlying pathology in the 12 months before screening.

• Frequent, prolonged, or excessive vaginal bleeding/spotting in the 12 months prior to screening which has not been evaluated to detect underlying pathology.

• History of venous thromboembolism or arterial thromboembolism, transient ischemic attack, angina pectoris, or claudication.

• Any condition associated with an increased risk of venous thromboembolism.

• Uncontrolled or severe hypertension at screening visit.

• Clinically significant liver disease, including active viral hepatitis or cirrhosis.

• History of malignancy within 5 years before screening, except treated skin cancer.

• History of sex steroid-influenced malignancies (eg, genital organs, breasts).

• History or presence of liver tumors (benign or malignant).

• Known allergy/sensitivity or contraindication to the ENG implant or lidocaine with epinephrine.

• History of drug or alcohol abuse or dependence within 24 months prior to enrollment. Routine use of alcohol or marijuana that is not considered abuse or dependence is not exclusionary.

• Use of an investigational drug within 2 months prior to enrollment. Long-term follow up of an investigational compound for COVID-19 is allowed 2 months after the last administered dose.

• Staff or immediate family members of the investigational site or Sponsor directly involved with this study.

Related Conditions & MeSH terms

• Contraception

Intervention

Combination Product:
• Radiopaque Etonogestrel (ENG) Implant
68 mg subdermal implant

Locations

Country	Name	City	State
Puerto Rico	Cooperativa de Facultad Medica SANACOOP (Site 0310)	Bayamon
Puerto Rico	Advance Medical Concept PSC (Site 0313)	Cidra
Puerto Rico	Clinical Research Puerto Rico Inc (Site 0302)	San Juan
Puerto Rico	FDI Clinical Research (Site 0305)	San Juan
Puerto Rico	La Alianza Hispana para Investigacion Clinica y Traslacional - LA ALIANZA (Site 0300)	San Juan
United States	Alabama Clinical Therapeutics (Site 0224)	Alabaster	Alabama
United States	Albuquerque Clinical Trials (Site 0210)	Albuquerque	New Mexico
United States	Bosque Women's Care (Site 0211)	Albuquerque	New Mexico
United States	McFarland Clinic, PC (Site 0217)	Ames	Iowa
United States	Michigan Medicine (Site 0108)	Ann Arbor	Michigan
United States	Johns Hopkins Bayview Medical Center (Site 0225)	Baltimore	Maryland
United States	Gadolin Research (Site 0232)	Beaumont	Texas
United States	Alabama Clinical Therapeutics (Site 0222)	Birmingham	Alabama
United States	Boston University Medical Center (Site 0167)	Boston	Massachusetts
United States	Planned Parenthood League of Massachusetts (Site 0135)	Boston	Massachusetts
United States	Montefiore Medical Center (Site 0103)	Bronx	New York
United States	Multicare Health System Institute for Research and Innovation (Site 0188)	Cheney	Washington
United States	Planned Parenthood of Illinois (PPIL) (Site 0200)	Chicago	Illinois
United States	Velocity Clinical Research, Cincinnati (Site 0230)	Cincinnati	Ohio
United States	The Ohio State University (Site 0176)	Columbus	Ohio
United States	Comprehensive Womens Health Center (Site 0194)	Denver	Colorado
United States	Planned Parenthood of the Rocky Mountains (Site 0196)	Denver	Colorado
United States	Physicians' Research Options, LLC (Site 0197)	Draper	Utah
United States	Carolina Women's Research and Wellness Center (Site 0154)	Durham	North Carolina
United States	HWC Women's Research Center (Site 0199)	Englewood	Ohio
United States	OB/GYN Associates of Erie (Site 0183)	Erie	Pennsylvania
United States	Carolina Institute for Clinical Research, LLC (Site 0215)	Fayetteville	North Carolina
United States	Signature Gyn Services (Site 0201)	Fort Worth	Texas
United States	Centex Studies, Inc. (Site 0171)	Houston	Texas
United States	Planned Parenthood of the Gulf Coast (Site 0106)	Houston	Texas
United States	University of Texas Health Science Center (Site 0178)	Houston	Texas
United States	Rosemark (Site 0177)	Idaho Falls	Idaho
United States	Indiana University (Site 0220)	Indianapolis	Indiana
United States	Metro Jackson OBGYN/SKYCRNG (Site 0233)	Jackson	Mississippi
United States	University Of Florida (Site 0144)	Jacksonville	Florida
United States	University of Tennessee Medical Center Knoxville (Site 0218)	Knoxville	Tennessee
United States	Physicians' Research Options, LLC (Site 0166)	Lakewood	Colorado
United States	Clinical Research Center of Nevada, LLC (Site 0179)	Las Vegas	Nevada
United States	Office of Edmond Pack, MD (Site 0168)	Las Vegas	Nevada
United States	Capital Health OB/GYN- Lawrenceville (Site 0190)	Lawrenceville	New Jersey
United States	Women's Clinic of Lincoln PC (Site 0156)	Lincoln	Nebraska
United States	Essential Access Health (Site 0163)	Los Angeles	California
United States	Matrix Clinical Research Inc (Site 0105)	Los Angeles	California
United States	University of California Los Angeles (Site 0119)	Los Angeles	California
United States	WR-Medical Research Center of Memphis, LLC (Site 0229)	Memphis	Tennessee
United States	Southern Clinical Research Associates (Site 0219)	Metairie	Louisiana
United States	Planned Parenthood of North Central States (PPNCS) (Site 0113)	Minneapolis	Minnesota
United States	Eastern Carolina Women's Center (Site 0159)	New Bern	North Carolina
United States	Planned Parenthood of Southern New England (Site 0143)	New Haven	Connecticut
United States	Columbia Univ. Medical Center (Site 0118)	New York	New York
United States	Icahn School of Medicine at Mount Sinai (Site 0155)	New York	New York
United States	Eastern Virginia Medical School (Site 0146)	Norfolk	Virginia
United States	Tidewater Clinical Research Inc (Site 0162)	Norfolk	Virginia
United States	Emerald Coast Obstetrics and Gynecology (Site 0203)	Panama City	Florida
United States	Advances in Health, Inc. (Site 0209)	Pearland	Texas
United States	Desert Star Family Planning (Site 0193)	Phoenix	Arizona
United States	Precision Trials (Site 0187)	Phoenix	Arizona
United States	University of Pittsburgh - Magee Womens Hospital (Site 0100)	Pittsburgh	Pennsylvania
United States	Physicians' Research Options, LLC (Site 0204)	Pleasant Grove	Utah
United States	Oregon Health Sciences University Hospital (Site 0128)	Portland	Oregon
United States	University of California, Davis (Site 0124)	Sacramento	California
United States	Saginaw Valley Medical Research Group, LLC (Site 0198)	Saginaw	Michigan
United States	Planned Parenthood of the Saint Louis Region & Southwest Missouri (Site 0158)	Saint Louis	Missouri
United States	Washington University (Site 0129)	Saint Louis	Missouri
United States	JBR Clinical Research (Site 0174)	Salt Lake City	Utah
United States	Tekton Research - Floyd Curl Drive (Site 0228)	San Antonio	Texas
United States	Mount Vernon Clinical Research (Site 0111)	Sandy Springs	Georgia
United States	Planned Parenthood Great Northwest, Hawai'i, Alaska, Indiana, Kentucky (Site 0110)	Seattle	Washington
United States	Seattle Women's: Health, Research, Gynecology (Site 0149)	Seattle	Washington
United States	University of Washington Medical Center (Site 0160)	Seattle	Washington
United States	North Spokane Women's Clinic (Site 0137)	Spokane	Washington
United States	Stanford University (Site 0112)	Stanford	California
United States	Palmetto Clinical Research (Site 0133)	Summerville	South Carolina
United States	Lenus Research & Medical Group Llc (Site 0102)	Sweetwater	Florida
United States	Visions Clinical Research Tucson (Site 0134)	Tucson	Arizona
United States	Comprehensive Clinical Trials LLC (Site 0101)	West Palm Beach	Florida
United States	Cypress Medical Research Center (Site 0226)	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Organon and Co

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pregnancy Rate (Pearl Index) for At Risk Cycles During Extended-Duration Use	The Pearl Index is expressed as the number of on-treatment pregnancies per 100 woman-years of exposure. An on-treatment pregnancy is defined as a confirmed pregnancy with an estimated date of conception 36 months to 60 months since the date of implant insertion. Exposure in 100 woman-years is equal to the number of cycles of use/1300, and one woman-year is defined as a period of 13 treatment cycles, each 28 days long. Only "at risk" cycles for conception will be included in this Pearl Index calculation. An at risk cycle is defined as a cycle during which participants with ENG implant had affirmed heterosexual intercourse without the use of additional contraception.	Up to 24 months
Primary	Pregnancy Rate (Pearl Index) for Alternative At Risk Cycles During Extended-Duration Use	The Pearl Index is expressed as the number of on-treatment pregnancies per 100 woman-years of exposure. An on-treatment pregnancy is defined as a confirmed pregnancy conceived with an estimated date of conception 36 months to 60 months since the date of implant insertion. Exposure in 100 woman-years is equal to the number of cycles of use/1300, and one woman-year is defined as a period of 13 treatment cycles, each 28 days long. Only "alternative at risk" cycles will be included in this Pearl Index calculation. An alternative at risk cycle is defined as a cycle in which participants with ENG implant did not use additional contraception, but without the requirement for affirmed heterosexual intercourse.	Up to 24 months
Primary	Number of Participants Who Experience One or More Adverse Events During Extended-Duration Use	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 27 months
Primary	Number of Participants Who Discontinue Treatment (Implant Removed) Due to an Adverse Event During Extended-Duration Use	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 24 months
Secondary	Pregnancy Rate (Pearl Index) for At Risk Cycles During Year 4 of Implant Use	Pearl Index will be calculated as the number of on-treatment pregnancies per 100 woman-years of exposure. Exposure in 100 woman-years is equal to the number of cycles of use/1300, and one woman-year is defined as a period of 13 treatment cycles, each 28 days long. Only "at risk" cycles for conception will be included in this Pearl Index calculation. An at risk cycle is defined as a cycle during which participants with ENG implant had affirmed heterosexual intercourse without the use of additional contraception.	Up to 12 months
Secondary	Pregnancy Rate (Pearl Index) for At Risk Cycles During Year 5 of Implant Use	Pearl Index will be calculated as the number of on-treatment pregnancies per 100 woman-years of exposure. Exposure in 100 woman-years is equal to the number of cycles of use/1300, and one woman-year is defined as a period of 13 treatment cycles, each 28 days long. Only "at risk" cycles for conception will be included in this Pearl Index calculation. An at risk cycle is defined as a cycle during which participants with ENG implant had affirmed heterosexual intercourse without the use of additional contraception.	Up to 12 months
Secondary	Cumulative Pregnancy Rate During 5 Years of Implant Use	Cumulative on-treatment pregnancy rate will be calculated based on life table analysis over 5 years of implant use.	Up to 60 months (From 3 years prior to study entry to 2 years after study entry)
Secondary	Cumulative Pregnancy Rate During 4 Years of Implant Use	Cumulative on-treatment pregnancy rate will be calculated based on life table analysis over 4 years of implant use.	Up to 48 months (From 3 years prior to study entry to 1 year after study entry)
Secondary	Pregnancy Rate (Pearl Index) for At Risk Cycles During 5 Years of Implant Use	Pearl Index will be calculated as the number of on-treatment pregnancies per 100 woman-years of exposure. Exposure in 100 woman-years is equal to the number of cycles of use/1300, and one woman-year is defined as a period of 13 treatment cycles, each 28 days long. Only "at risk" cycles for conception will be included in this Pearl Index calculation. An at risk cycle is defined as a cycle during which participants with ENG implant had affirmed heterosexual intercourse without the use of additional contraception. The number of at-risk cycles of use for each of the 3 years prior to study entry will be estimated.	Up to 60 months (From 3 years prior to study entry to 2 years after study entry)
Secondary	Pregnancy Rate (Pearl Index) for Alternative At Risk Cycles During 5 Years of Implant Use	Pearl Index will be calculated as the number of on-treatment pregnancies per 100 woman-years of exposure. Exposure in 100 woman-years is equal to the number of cycles of use/1300, and one woman-year is defined as a period of 13 treatment cycles, each 28 days long. Only "alternative at risk" cycles will be included in this Pearl Index calculation. An alternative at risk cycle is defined as a cycle in which participants with ENG implant did not use additional contraception, but without the requirement for affirmed heterosexual intercourse. The number of alternative at risk cycles of use for each of the 3 years prior to study entry will be estimated.	Up to 60 months (From 3 years prior to study entry to 2 years after study entry)
Secondary	Number of Bleeding Days During Extended-Duration Use as Assessed in 90-day Reference Periods	Participants will record daily vaginal bleeding in an electronic diary. A bleeding day is defined as any day (24 hours) with bloody vaginal discharge requiring more than one sanitary product (i.e., pad, panty liner, tampon, or menstrual cup) or, if only a menstrual cup is used, more than 5 mL of blood accumulates. Number of bleeding days will be assessed per 90-day reference period (RP).	Up to 24 months
Secondary	Number of Spotting Days During Extended-Duration Use as Assessed in 90-day Reference Periods	Participants will record daily vaginal spotting in an electronic diary. A spotting day is defined as any day (24 hours) with bloody vaginal discharge requiring at most one sanitary product (i.e. pad, panty liner, tampon, or menstrual cup containing 5 ml [inclusive] or less of blood). Number of spotting days will be assessed per 90-day reference period (RP).	Up to 24 months
Secondary	Number of Bleeding and/or Spotting Days During Extended-Duration Use as Assessed in 90-day Reference Periods	Participants will record daily vaginal bleeding and/or spotting in an electronic diary. A bleeding day is defined as any day (24 hours) with bloody vaginal discharge requiring more than one sanitary product (i.e., pad, panty liner, tampon, or menstrual cup) or, if only a menstrual cup is used, more than 5 mL of blood accumulates. A spotting day is defined as any day (24 hours) with bloody vaginal discharge requiring at most one sanitary product (i.e. pad, panty liner, tampon, or menstrual cup containing 5 ml [inclusive] or less of blood). Number of bleeding and/or spotting days will be assessed per 90-day reference period (RP).	Up to 24 months
Secondary	Mean Length of Bleeding and/or Spotting Episodes During Extended-Duration Use as Assessed in 90-day Reference Periods	Participants will record daily vaginal bleeding and/or spotting in an electronic diary (eDiary). A bleeding day is defined as any day (24 hours) with bloody vaginal discharge requiring more than one sanitary product (i.e., pad, panty liner, tampon, or menstrual cup) or, if only a menstrual cup is used, more than 5 mL of blood accumulates. A spotting day is defined as any day (24 hours) with bloody vaginal discharge requiring at most one sanitary product (i.e. pad, panty liner, tampon, or menstrual cup containing 5 ml [inclusive] or less of blood). A bleeding and/or spotting episode is defined as one or more consecutive days during which bleeding and/or spotting is recorded in the eDiary, bounded bleeding/spotting-free days.	Up to 24 months
Secondary	Percentage of Participants per 90-day Reference Period with Amenorrhea During Extended-Duration Use	Participants will record daily vaginal bleeding and/or spotting in an electronic diary (eDiary). Amenorrhea is defined as no bleeding or spotting recorded in the eDiary per 90-day reference period (RP).	Up to 24 months
Secondary	Percentage of Participants per 90-Day Reference Period with Infrequent Bleeding and/or Spotting During Extended-Duration Use	Participants will record daily vaginal bleeding and/or spotting in an electronic diary (eDiary). A bleeding day is defined as any day (24 hours) with bloody vaginal discharge requiring more than one sanitary product (i.e., pad, panty liner, tampon, or menstrual cup) or, if only a menstrual cup is used, more than 5 mL of blood accumulates. A spotting day is defined as any day (24 hours) with bloody vaginal discharge requiring at most one sanitary product (i.e. pad, panty liner, tampon, or menstrual cup containing 5 ml [inclusive] or less of blood). Infrequent bleeding and/or spotting is defined as less than 3 episodes of bleeding and/or spotting per 90-day reference period (RP).	Up to 24 months
Secondary	Percentage of Participants per 90-Day Reference Period with Frequent Bleeding and/or Spotting During Extended-Duration Use	Participants will record daily vaginal bleeding and/or spotting in an electronic diary (eDiary). A bleeding day is defined as any day (24 hours) with bloody vaginal discharge requiring more than one sanitary product (i.e., pad, panty liner, tampon, or menstrual cup) or, if only a menstrual cup is used, more than 5 mL of blood accumulates. A spotting day is defined as any day (24 hours) with bloody vaginal discharge requiring at most one sanitary product (i.e. pad, panty liner, tampon, or menstrual cup containing 5 ml [inclusive] or less of blood). Frequent bleeding and/or spotting is defined as more than 5 episodes of bleeding and/or spotting per 90-day reference period (RP).	Up to 24 months
Secondary	Percentage of Participants per 90-Day Reference Period with Normal Frequency Bleeding and/or Spotting During Extended-Duration Use	Participants will record daily vaginal bleeding and/or spotting in an electronic diary (eDiary). A bleeding day is defined as any day (24 hours) with bloody vaginal discharge requiring more than one sanitary product (i.e., pad, panty liner, tampon, or menstrual cup) or, if only a menstrual cup is used, more than 5 mL of blood accumulates. A spotting day is defined as any day (24 hours) with bloody vaginal discharge requiring at most one sanitary product (i.e. pad, panty liner, tampon, or menstrual cup containing 5 ml [inclusive] or less of blood). Normal frequency of bleeding and/or spotting is defined as 3 to 5 episodes of bleeding and/or spotting per 90-day reference period (RP).	Up to 24 months
Secondary	Percentage of Participants per 90-Day Reference Period with Prolonged Bleeding and/or Spotting During Extended-Duration Use	Participants will record daily vaginal bleeding and/or spotting in an electronic diary (eDiary). A bleeding day is defined as any day (24 hours) with bloody vaginal discharge requiring more than one sanitary product (i.e., pad, panty liner, tampon, or menstrual cup) or, if only a menstrual cup is used, more than 5 mL of blood accumulates. A spotting day is defined as any day (24 hours) with bloody vaginal discharge requiring at most one sanitary product (i.e. pad, panty liner, tampon, or menstrual cup containing 5 ml [inclusive] or less of blood). Prolonged bleeding and/or spotting is defined more than 14 continuous days of bleeding and/or spotting, per 90-day reference period (RP).	Up to 24 months
Secondary	Number of Complications Associated with Implant Removal	Complications associated with implant removal will include failed implant removal; implant site fibrosis; extension of incision of >1 cm; removal of a nonpalpable implant; removal of a deeply placed implant; implant removal in an operating room; implant removal requiring general anesthesia; implant removal requiring regional anesthesia; implant removal requiring imaging guidance; nerve injury during implant removal; vascular injury during implant removal; other complications of device removal not previously mentioned.	Up to 24 months