Clinical trial NCT04626596: A Study to Assess Contraceptive Efficacy and Safety of Etonogestrel (ENG) Implant Beyond 3 Years of Use (MK-8415-060)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Contraception
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2020-11-12
Enrollment: 498
Sex: FEMALE
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pregnancy Rate (Pearl Index) for At Risk Cycles During Extended-Duration Use
timeFrame: Up to 24 months
measure: Pregnancy Rate (Pearl Index) for Alternative At Risk Cycles During Extended-Duration Use
timeFrame: Up to 24 months
measure: Number of Participants Who Experience One or More Adverse Events During Extended-Duration Use
timeFrame: Up to approximately 27 months
measure: Number of Participants Who Discontinue Treatment (Implant Removed) Due to an Adverse Event During Extended-Duration Use
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Pregnancy Rate (Pearl Index) for At Risk Cycles During Year 4 of Implant Use
timeFrame: Up to 12 months
measure: Pregnancy Rate (Pearl Index) for At Risk Cycles During Year 5 of Implant Use
timeFrame: Up to 12 months
measure: Cumulative Pregnancy Rate During 5 Years of Implant Use
timeFrame: Up to 60 months (From 3 years prior to study entry to 2 years after study entry)
measure: Cumulative Pregnancy Rate During 4 Years of Implant Use
timeFrame: Up to 48 months (From 3 years prior to study entry to 1 year after study entry)
measure: Pregnancy Rate (Pearl Index) for At Risk Cycles During 5 Years of Implant Use
timeFrame: Up to 60 months (From 3 years prior to study entry to 2 years after study entry)
measure: Pregnancy Rate (Pearl Index) for Alternative At Risk Cycles During 5 Years of Implant Use
timeFrame: Up to 60 months (From 3 years prior to study entry to 2 years after study entry)
measure: Number of Bleeding Days During Extended-Duration Use as Assessed in 90-day Reference Periods
timeFrame: Up to 24 months
measure: Number of Spotting Days During Extended-Duration Use as Assessed in 90-day Reference Periods
timeFrame: Up to 24 months
measure: Number of Bleeding and/or Spotting Days During Extended-Duration Use as Assessed in 90-day Reference Periods
timeFrame: Up to 24 months
measure: Mean Length of Bleeding and/or Spotting Episodes During Extended-Duration Use as Assessed in 90-day Reference Periods
timeFrame: Up to 24 months
measure: Percentage of Participants per 90-day Reference Period with Amenorrhea During Extended-Duration Use
timeFrame: Up to 24 months
measure: Percentage of Participants per 90-Day Reference Period with Infrequent Bleeding and/or Spotting During Extended-Duration Use
timeFrame: Up to 24 months
measure: Percentage of Participants per 90-Day Reference Period with Frequent Bleeding and/or Spotting During Extended-Duration Use
timeFrame: Up to 24 months
measure: Percentage of Participants per 90-Day Reference Period with Normal Frequency Bleeding and/or Spotting During Extended-Duration Use
timeFrame: Up to 24 months
measure: Percentage of Participants per 90-Day Reference Period with Prolonged Bleeding and/or Spotting During Extended-Duration Use
timeFrame: Up to 24 months
measure: Number of Complications Associated with Implant Removal
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics (Site 0222)
state: Alabama
city: Phoenix
country: United States
facility: Desert Star Family Planning (Site 0193)
state: Arizona
city: Phoenix
country: United States
facility: Precision Trials (Site 0187)
state: Arizona
city: Tucson
country: United States
facility: Visions Clinical Research Tucson (Site 0134)
state: Arizona
city: Los Angeles
country: United States
facility: Essential Access Health (Site 0163)
state: California
city: Los Angeles
country: United States
facility: Matrix Clinical Research Inc (Site 0105)
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles (Site 0119)
state: California
city: Sacramento
country: United States
facility: University of California, Davis (Site 0124)
state: California
city: Stanford
country: United States
facility: Stanford University (Site 0112)
state: California
city: Denver
country: United States
facility: Planned Parenthood of the Rocky Mountains (Site 0196)
state: Colorado
city: Denver
country: United States
facility: Comprehensive Womens Health Center (Site 0194)
state: Colorado
city: Lakewood
country: United States
facility: Physicians' Research Options, LLC (Site 0166)
state: Colorado
city: Jacksonville
country: United States
facility: University Of Florida (Site 0144)
state: Florida
city: Panama City
country: United States
facility: Emerald Coast Obstetrics and Gynecology (Site 0203)
state: Florida
city: Sweetwater
country: United States
facility: Lenus Research & Medical Group Llc (Site 0102)
state: Florida
city: West Palm Beach
country: United States
facility: Comprehensive Clinical Trials LLC (Site 0101)
state: Florida
city: Sandy Springs
country: United States
facility: Mount Vernon Clinical Research (Site 0111)
state: Georgia
city: Idaho Falls
country: United States
facility: Rosemark (Site 0177)
state: Idaho
city: Chicago
country: United States
facility: Planned Parenthood of Illinois (PPIL) (Site 0200)
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University (Site 0220)
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, PC (Site 0217)
state: Iowa
city: Wichita
country: United States
facility: Cypress Medical Research Center (Site 0226)
state: Kansas
city: Metairie
country: United States
facility: Southern Clinical Research Associates (Site 0219)
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center (Site 0225)
state: Maryland
city: Boston
country: United States
facility: Boston University Medical Center (Site 0167)
state: Massachusetts
city: Boston
country: United States
facility: Planned Parenthood League of Massachusetts (Site 0135)
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine (Site 0108)
state: Michigan
city: Saginaw
country: United States
facility: Saginaw Valley Medical Research Group, LLC (Site 0198)
state: Michigan
city: Minneapolis
country: United States
facility: Planned Parenthood of North Central States (PPNCS) (Site 0113)
state: Minnesota
city: Jackson
country: United States
facility: Metro Jackson OBGYN/SKYCRNG (Site 0233)
state: Mississippi
city: Saint Louis
country: United States
facility: Planned Parenthood of the Saint Louis Region & Southwest Missouri (Site 0158)
state: Missouri
city: Saint Louis
country: United States
facility: Washington University (Site 0129)
state: Missouri
city: Las Vegas
country: United States
facility: Office of Edmond Pack, MD (Site 0168)
state: Nevada
city: Lawrenceville
country: United States
facility: Capital Health OB/GYN- Lawrenceville (Site 0190)
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials (Site 0210)
state: New Mexico
city: Albuquerque
country: United States
facility: Bosque Women's Care (Site 0211)
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center (Site 0103)
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai (Site 0155)
state: New York
city: New York
country: United States
facility: Columbia Univ. Medical Center (Site 0118)
state: New York
city: Durham
country: United States
facility: Carolina Women's Research and Wellness Center (Site 0154)
state: North Carolina
city: New Bern
country: United States
facility: Eastern Carolina Women's Center (Site 0159)
state: North Carolina
city: Cincinnati
country: United States
facility: Velocity Clinical Research, Cincinnati (Site 0230)
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University (Site 0176)
state: Ohio
city: Englewood
country: United States
facility: HWC Women's Research Center (Site 0199)
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University Hospital (Site 0128)
state: Oregon
city: Erie
country: United States
facility: OB/GYN Associates of Erie (Site 0183)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh - Magee Womens Hospital (Site 0100)
state: Pennsylvania
city: Summerville
country: United States
facility: Palmetto Clinical Research (Site 0133)
state: South Carolina
city: Knoxville
country: United States
facility: University of Tennessee Medical Center Knoxville (Site 0218)
state: Tennessee
city: Beaumont
country: United States
facility: Gadolin Research (Site 0232)
state: Texas
city: Fort Worth
country: United States
facility: Signature Gyn Services (Site 0201)
state: Texas
city: Houston
country: United States
facility: Planned Parenthood of the Gulf Coast (Site 0106)
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center (Site 0178)
state: Texas
city: Houston
country: United States
facility: Centex Studies, Inc. (Site 0171)
state: Texas
city: Pearland
country: United States
facility: Advances in Health, Inc. (Site 0209)
state: Texas
city: San Antonio
country: United States
facility: Tekton Research - Floyd Curl Drive (Site 0228)
state: Texas
city: Pleasant Grove
country: United States
facility: Physicians' Research Options, LLC (Site 0204)
state: Utah
city: Salt Lake City
country: United States
facility: JBR Clinical Research (Site 0174)
state: Utah
city: Norfolk
country: United States
facility: Tidewater Clinical Research Inc (Site 0162)
state: Virginia
city: Norfolk
country: United States
facility: Eastern Virginia Medical School (Site 0146)
state: Virginia
city: Cheney
country: United States
facility: Multicare Health System Institute for Research and Innovation (Site 0188)
state: Washington
city: Seattle
country: United States
facility: Seattle Women's: Health, Research, Gynecology (Site 0149)
state: Washington
city: Seattle
country: United States
facility: Planned Parenthood Great Northwest, Hawai'i, Alaska, Indiana, Kentucky (Site 0110)
state: Washington
city: Spokane
country: United States
facility: North Spokane Women's Clinic (Site 0137)
state: Washington
city: Cidra
country: Puerto Rico
facility: Advance Medical Concept PSC (Site 0313)
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico Inc (Site 0302)
city: San Juan
country: Puerto Rico
facility: FDI Clinical Research (Site 0305)
Study officials:
affiliation: Organon and Co
name: Clinical Lead
role: STUDY_DIRECTOR
References: