A Dose-Finding Study to Evaluate Ovarian Function and Vaginal Bleeding in Next Generation Rings (P06109/MK-8175A/MK-8342B-012)

NCT01709318 | Completed Phase 2 Results

• 3 other identifiers: P061092012-002459-41MK-8175A/MK-8342B-012
• Study Type: interventional
• Target: 666
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this trial was to identify at least one next generation ring (NGR) that demonstrates inhibition of ovulation (which was considered confirmed if in the subset of participants ovulation was observed in less than 15% of the participants at any time during the 3 treatment cycles of the study) and cycle control that was non-inferior to NuvaRing®, as judged by the incidence of breakthrough bleeding and/or spotting (BTB-S) during Cycle 3. The primary hypothesis was that at least 1 of the 6 NGRs would show inhibition of ovulation and cycle control during Treatment Cycle 3 that is non-inferior to NuvaRing®, as judged by the incidence of BTB-S.

Conditions

Contraception

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Ovulation Incidence, by Cycle

  Ovulation was defined as having 2 or more consecutive progesterone concentrations \>16 nmol/L within 5 days, confirmed by ultrasound evidence of ovulation (follicular rupture or preceding presence of a follicle-like structure \>15 mm in size).

  Day 1 of Treatment Cycle 1 through Day 28 of Treatment Cycle 3 (Up to ~92 days)

• Percentage of Participants With Progesterone Concentrations >16 Nmol/L, by Cycle

  Maximum progesterone (Max P) was defined as the maximum progesterone value. Ovulation was defined as 2 or more consecutive progesterone concentrations \>16 nmol/L within 5 days during the 3 treatment cycles, supported by ultrasound evidence of ovulation. The Max P values greater than 16 nmol/L are presented by vaginal ring group and cycle.

  Day 1 of Treatment Cycle 1 through Day 28 of Treatment Cycle 3 (Up to ~92 days)

• Percentage of Participants With Breakthrough Bleeding and/or Spotting During Cycle 3

  Breakthrough bleeding and/or spotting (BTB-S) is defined as any bleeding or spotting episode that occurred during the expected non-bleeding period that was neither an early nor a continued withdrawal bleeding. Bleeding = any bloody vaginal discharge that required one or more sanitary pads or tampons per day; Spotting = any bloody vaginal discharge that required no sanitary pads or tampons per day.

  Day 1 Cycle 3 through Day 28 Cycle 3 (Up to ~28 days)

Secondary Outcomes (8)

• Percentage of Participants With Absence of Withdrawal Bleeding and/or Spotting During Cycle 2

  Day 1 Cycle 2 through Day 28 Cycle 2 (Up to ~28 days)

• Intensity of Withdrawal Bleeding During Cycle 2

  Day 1 Cycle 2 through Day 28 Cycle 2 (Up to ~28 days)

• Intensity of Breakthrough Bleeding and/or Spotting During Cycle 3

  Day 1 Cycle 3 through Day 28 Cycle 3 (Up to ~ 28 days)

• Percentage of Participants Who Experienced At Least One Adverse Event

  Up to ~92 days

• Percentage of Participants Who Experienced At Least One Serious Adverse Event

  Up to ~92 days

Other Outcomes (1)

• Number of Participants With Venous or Arterial Thrombotic/Thromboembolic Events

  From Cycle 1 Day 1 up to 8 days after Day 28 of Cycle 3 (Up to ~92 days)

Study Arms (7)

Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 500/300 μg/day

EXPERIMENTAL

Participants will receive nomegestrol acetate 17β-estradiol (NOMAC-E2) 500/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.

Drug: Nomegestrol acetate (NOMAC); Drug: Estradiol (E2)

Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 700/300 μg/day

EXPERIMENTAL

Participants will receive nomegestrol acetate 17β-estradiol (NOMAC-E2) 700/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.

Drug: Nomegestrol acetate (NOMAC); Drug: Estradiol (E2)

Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 900/300 μg/day

EXPERIMENTAL

Participants will receive nomegestrol acetate 17β-estradiol (NOMAC-E2) 900/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.

Drug: Nomegestrol acetate (NOMAC); Drug: Estradiol (E2)

Etonogestrel-17β-Estradiol (ENG-E2) 75/300 μg/day

EXPERIMENTAL

Participants will receive etonogestrel 17β-estradiol (ENG-E2) 75/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.

Drug: Etonogestrel (ENG); Drug: Estradiol (E2)

Etonogestrel-17β-Estradiol (ENG-E2) 100/300 μg/day

EXPERIMENTAL

Participants will receive etonogestrel 17β-estradiol (ENG-E2) 100/300 μg for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.

Drug: Etonogestrel (ENG); Drug: Estradiol (E2)

Etonogestrel-17β-Estradiol (ENG-E2) 125/300 μg/day

EXPERIMENTAL

Participants will receive etonogestrel 17β-estradiol (ENG-E2)125/300 μg for three 28-day treatment periods, each treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.

Drug: Etonogestrel (ENG); Drug: Estradiol (E2)

NuvaRing®

ACTIVE COMPARATOR

Participants will receive NuvaRing® (etonogestrel-ethinyl estradiol \[ENG-EE\] 120/15 μg) for three treatment periods, each 28-day treatment period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.

Drug: Etonogestrel (ENG); Drug: Ethinyl estradiol (EE)

Interventions

Nomegestrol acetate (NOMAC) DRUG

Daily release of 500, 700, or 900 μg.

Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 500/300 μg/day; Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 700/300 μg/day; Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 900/300 μg/day

Etonogestrel (ENG) DRUG

Daily release of 75, 100, 120 or 125 μg

Etonogestrel-17β-Estradiol (ENG-E2) 100/300 μg/day; Etonogestrel-17β-Estradiol (ENG-E2) 125/300 μg/day; Etonogestrel-17β-Estradiol (ENG-E2) 75/300 μg/day; NuvaRing®

Ethinyl estradiol (EE) DRUG

Daily release of 15 μg

NuvaRing®

Estradiol (E2) DRUG

Daily release of 300 μg

Etonogestrel-17β-Estradiol (ENG-E2) 100/300 μg/day; Etonogestrel-17β-Estradiol (ENG-E2) 125/300 μg/day; Etonogestrel-17β-Estradiol (ENG-E2) 75/300 μg/day; Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 500/300 μg/day; Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 700/300 μg/day; Nomegestrol Acetate-17β-Estradiol (NOMAC-E2) 900/300 μg/day

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body mass index (BMI) ≥18 and ≤35
• Regular cycles from 24 to 35 days in length, with an intra-individual variation of ±3 days permitted within this range
• Good physical and mental health

You may not qualify if:

• Diabetes mellitus with vascular involvement
• Presence of a severe or multiple risk factor(s) for venous or arterial thrombosis
• Severe dyslipoproteinemia
• Severe hypertension
• Presence or history of pancreatitis associated with severe hypertriglyceridaemia
• Presence or history of severe hepatic disease
• Undiagnosed vaginal bleeding
• Known or suspected pregnancy
• Participation in another investigational drug study within 30 days prior to screening visit
• History of malignancy ≤5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
• Documented abnormal cervical smear result in 6 months prior to screening visit
• Sterilization using a fallopian tube occlusion device (e.g., Essure method)
• Sex hormone therapy within 2 months prior to screening visit for purpose other than contraception, or injectable hormonal contraception within 6 months prior to screening

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (1)

• Duijkers I, Klipping C, Heger-Mahn D, Fayad GN, Frenkl TL, Cruz SM, Korver T. Phase II dose-finding study on ovulation inhibition and cycle control associated with the use of contraceptive vaginal rings containing 17beta-estradiol and the progestagens etonogestrel or nomegestrol acetate compared to NuvaRing. Eur J Contracept Reprod Health Care. 2018 Aug;23(4):245-254. doi: 10.1080/13625187.2018.1506101. Epub 2018 Sep 11.

  PMID: 30203681 RESULT

MeSH Terms

Interventions

nomegestrol acetate; etonogestrel; Ethinyl Estradiol; Estradiol

Intervention Hierarchy (Ancestors)

Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrenes; Estranes

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2012
• First Posted: October 18, 2012
• Study Start: December 12, 2012
• Primary Completion: October 22, 2013
• Study Completion: October 22, 2013
• Last Updated: May 28, 2024
• Results First Posted: December 5, 2019

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share