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.
Brief Title
A Study to Assess Contraceptive Efficacy and Safety of Etonogestrel (ENG) Implant Beyond 3 Years of Use (MK-8415-060)
Completion Date
Completion Date Type
Actual
Conditions
Contraception
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.
* 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.
Inclusion 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.
* 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.
Gender
Female
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
35 Years
NCT Id
NCT04626596
Org Class
Industry
Org Full Name
Organon and Co
Org Study Id
8415-060
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Pregnancy Rate (Pearl Index) for At Risk Cycles During Extended-Duration Use
Outcome Time Frame
Up to 24 months
Outcome Description
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.
Outcome Measure
Pregnancy Rate (Pearl Index) for Alternative At Risk Cycles During Extended-Duration Use
Outcome Time Frame
Up to 24 months
Outcome Description
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.
Outcome Measure
Number of Participants Who Experience One or More Adverse Events During Extended-Duration Use
Outcome Time Frame
Up to approximately 27 months
Outcome Description
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.
Outcome Measure
Number of Participants Who Discontinue Treatment (Implant Removed) Due to an Adverse Event During Extended-Duration Use
Outcome Time Frame
Up to approximately 24 months
Secondary Ids
Secondary Id
2020-001232-95
Secondary Id
MK-8415-060
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Up to 12 months
Outcome Measure
Pregnancy Rate (Pearl Index) for At Risk Cycles During Year 4 of Implant Use
Outcome Description
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.
Outcome Time Frame
Up to 12 months
Outcome Measure
Pregnancy Rate (Pearl Index) for At Risk Cycles During Year 5 of Implant Use
Outcome Description
Cumulative on-treatment pregnancy rate will be calculated based on life table analysis over 5 years of implant use.
Outcome Time Frame
Up to 60 months (From 3 years prior to study entry to 2 years after study entry)
Outcome Measure
Cumulative Pregnancy Rate During 5 Years of Implant Use
Outcome Description
Cumulative on-treatment pregnancy rate will be calculated based on life table analysis over 4 years of implant use.
Outcome Time Frame
Up to 48 months (From 3 years prior to study entry to 1 year after study entry)
Outcome Measure
Cumulative Pregnancy Rate During 4 Years of Implant Use
Outcome Description
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.
Outcome Time Frame
Up to 60 months (From 3 years prior to study entry to 2 years after study entry)
Outcome Measure
Pregnancy Rate (Pearl Index) for At Risk Cycles During 5 Years of Implant Use
Outcome Description
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.
Outcome Time Frame
Up to 60 months (From 3 years prior to study entry to 2 years after study entry)
Outcome Measure
Pregnancy Rate (Pearl Index) for Alternative At Risk Cycles During 5 Years of Implant Use
Outcome Description
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).
Outcome Time Frame
Up to 24 months
Outcome Measure
Number of Bleeding Days During Extended-Duration Use as Assessed in 90-day Reference Periods
Outcome Description
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).
Outcome Time Frame
Up to 24 months
Outcome Measure
Number of Spotting Days During Extended-Duration Use as Assessed in 90-day Reference Periods
Outcome Description
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).
Outcome Time Frame
Up to 24 months
Outcome Measure
Number of Bleeding and/or Spotting Days During Extended-Duration Use as Assessed in 90-day Reference Periods
Outcome Description
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.
Outcome Time Frame
Up to 24 months
Outcome Measure
Mean Length of Bleeding and/or Spotting Episodes During Extended-Duration Use as Assessed in 90-day Reference Periods
Outcome Description
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).
Outcome Time Frame
Up to 24 months
Outcome Measure
Percentage of Participants per 90-day Reference Period with Amenorrhea During Extended-Duration Use
Outcome Description
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).
Outcome Time Frame
Up to 24 months
Outcome Measure
Percentage of Participants per 90-Day Reference Period with Infrequent Bleeding and/or Spotting During Extended-Duration Use
Outcome Description
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).
Outcome Time Frame
Up to 24 months
Outcome Measure
Percentage of Participants per 90-Day Reference Period with Frequent Bleeding and/or Spotting During Extended-Duration Use
Outcome Description
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).
Outcome Time Frame
Up to 24 months
Outcome Measure
Percentage of Participants per 90-Day Reference Period with Normal Frequency Bleeding and/or Spotting During Extended-Duration Use
Outcome Description
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).
Outcome Time Frame
Up to 24 months
Outcome Measure
Percentage of Participants per 90-Day Reference Period with Prolonged Bleeding and/or Spotting During Extended-Duration Use
Outcome Description
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.
Outcome Time Frame
Up to 24 months
Outcome Measure
Number of Complications Associated with Implant Removal
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
35
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jessica Atrio
Investigator Email
jatrio@montefiore.org