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

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ClinicalTrials.gov Identifier: NCT04626596
Recruitment Status : Recruiting
First Posted : November 12, 2020
Last Update Posted : November 29, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Contraception Drug: Radiopaque Etonogestrel (ENG) Implant Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : November 19, 2020
Estimated Primary Completion Date : June 19, 2024
Estimated Study Completion Date : June 19, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Birth Control

Arm Intervention/treatment
Experimental: ENG implant
Participants will have the ENG 68 mg implant inserted and in place for 36 months before enrollment. The ENG implant will remain in place for an additional 24 months.
Drug: Radiopaque Etonogestrel (ENG) Implant
68 mg subdermal implant
Other Names:
  • Org 32222
  • Nexplanon
  • Implanon-NXT
  • SCH900415
  • MK-8415




Primary Outcome Measures :
  1. Pregnancy Rate (Pearl Index) for At Risk Cycles During Extended-Duration Use [ Time Frame: Up to 24 months ]
    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.

  2. Pregnancy Rate (Pearl Index) for Alternative At Risk Cycles During Extended-Duration Use [ Time Frame: Up to 24 months ]
    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.

  3. Number of Participants Who Experience One or More Adverse Events During Extended-Duration Use [ Time Frame: Up to approximately 27 months ]
    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.

  4. Number of Participants Who Discontinue Treatment (Implant Removed) Due to an Adverse Event During Extended-Duration Use [ Time Frame: Up to approximately 24 months ]
    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.


Secondary Outcome Measures :
  1. Pregnancy Rate (Pearl Index) for At Risk Cycles During Year 4 of Implant Use [ Time Frame: Up to 12 months ]
    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.

  2. Pregnancy Rate (Pearl Index) for At Risk Cycles During Year 5 of Implant Use [ Time Frame: Up to 12 months ]
    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.

  3. Cumulative Pregnancy Rate During 5 Years of Implant Use [ Time Frame: Up to 60 months (From 3 years prior to study entry to 2 years after study entry) ]
    Cumulative on-treatment pregnancy rate will be calculated based on life table analysis over 5 years of implant use.

  4. Cumulative Pregnancy Rate During 4 Years of Implant Use [ Time Frame: Up to 48 months (From 3 years prior to study entry to 1 year after study entry) ]
    Cumulative on-treatment pregnancy rate will be calculated based on life table analysis over 4 years of implant use.

  5. Pregnancy Rate (Pearl Index) for At Risk Cycles During 5 Years of Implant Use [ Time Frame: Up to 60 months (From 3 years prior to study entry to 2 years after study entry) ]
    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.

  6. Pregnancy Rate (Pearl Index) for Alternative At Risk Cycles During 5 Years of Implant Use [ Time Frame: Up to 60 months (From 3 years prior to study entry to 2 years after study entry) ]
    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.

  7. Number of Bleeding Days During Extended-Duration Use as Assessed in 90-day Reference Periods [ Time Frame: Up to 24 months ]
    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).

  8. Number of Spotting Days During Extended-Duration Use as Assessed in 90-day Reference Periods [ Time Frame: Up to 24 months ]
    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).

  9. Number of Bleeding and/or Spotting Days During Extended-Duration Use as Assessed in 90-day Reference Periods [ Time Frame: Up to 24 months ]
    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).

  10. Mean Length of Bleeding and/or Spotting Episodes During Extended-Duration Use as Assessed in 90-day Reference Periods [ Time Frame: Up to 24 months ]
    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.

  11. Percentage of Participants per 90-day Reference Period with Amenorrhea During Extended-Duration Use [ Time Frame: Up to 24 months ]
    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).

  12. Percentage of Participants per 90-Day Reference Period with Infrequent Bleeding and/or Spotting During Extended-Duration Use [ Time Frame: Up to 24 months ]
    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).

  13. Percentage of Participants per 90-Day Reference Period with Frequent Bleeding and/or Spotting During Extended-Duration Use [ Time Frame: Up to 24 months ]
    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).

  14. Percentage of Participants per 90-Day Reference Period with Normal Frequency Bleeding and/or Spotting During Extended-Duration Use [ Time Frame: Up to 24 months ]
    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).

  15. Percentage of Participants per 90-Day Reference Period with Prolonged Bleeding and/or Spotting During Extended-Duration Use [ Time Frame: Up to 24 months ]
    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).

  16. Number of Complications Associated with Implant Removal [ Time Frame: Up to 24 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 35 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04626596


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04626596    
Other Study ID Numbers: 8415-060
2020-001232-95 ( EudraCT Number )
MK-8415-060 ( Other Identifier: Merck )
First Posted: November 12, 2020    Key Record Dates
Last Update Posted: November 29, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Etonogestrel
Contraceptive Agents, Hormonal
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptive Agents, Female