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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01709318
First received: October 16, 2012
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

The study is designed to the evaluate ovulation inhibition, vaginal bleeding, and pharmacokinetics associated with three different doses of two next generation vaginal rings (NGRs), identifying at least one whose control of menstrual cycles is not inferior to that of NuvaRing®.


Condition Intervention Phase
Contraception
Drug: Nomegestrol acetate (NOMAC)
Drug: Etonogestrel (ENG)
Drug: Ethinyl estradiol (EE)
Drug: Estradiol (E2)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Partially-blinded, Phase IIb Dose-finding Study on Ovarian Function, Vaginal Bleeding Pattern, and Pharmacokinetics Associated With the Use of Combined Vaginal Rings Releasing 17β-estradiol Plus Three Different Doses of Either Nomegestrol Acetate or Etonogestrel in Healthy Women Aged 18-35 Years. Protocol MK-8175A/MK-8342B 012

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Incidence of Progesterone Concentrations >16 nmol/L [ Time Frame: Day 1 of Treatment Cycle 1 through Day 28 of Treatment Cycle 3 (Study Days 1-84) ] [ Designated as safety issue: No ]
  • Incidence of Break-through Bleeding and/Or Spotting (BTB-S) During Cycle 3 [ Time Frame: Day 1 of Cycle 3 through Day 28 of Cycle 3 (Study Days 57-84) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of Withdrawal Bleeding-spotting During Cycle 2 [ Time Frame: Day 1 of Cycle 2 through Day 28 of Cycle 2 (Study Days 29-56) ] [ Designated as safety issue: No ]
  • Intensity of Withdrawal Bleeding During Cycle 2 (Defined as the Ratio of Number of Withdrawal Bleeding Days/Number of Withdrawal Bleeding And/Or Spotting Days) [ Time Frame: Day 1 of Cycle 2 through Day 28 of Cycle 2 (Study Days 29-57) ] [ Designated as safety issue: No ]
  • Intensity of BTB-S during Cycle 3 (Defined as the Ratio of the Number of Breakthrough Bleeding Days/Number of BTB-S days) [ Time Frame: Day 1 of Cycle 3 through Day 28 of Cycle 3 (Study Days 57-84) ] [ Designated as safety issue: No ]
  • Number of Participants With Venous or Arterial Thrombotic/Thrombolic Events [ Time Frame: From Cycle 1, Day 1 up to 8 days after Day 28 of Cycle 3 (Study Days 1 through 91) ] [ Designated as safety issue: Yes ]

Enrollment: 666
Study Start Date: December 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NOMAC-E2 500/300
Participants will receive NOMAC-E2 500/300 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)
Daily release of 500, 700, or 900 μg.
Drug: Estradiol (E2)
Daily release of 300 μg
Experimental: NOMAC-E2 700/300
Participants will receive NOMAC-E2 700/300 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)
Daily release of 500, 700, or 900 μg.
Drug: Estradiol (E2)
Daily release of 300 μg
Experimental: NOMAC-E2 900/300
Participants will receive NOMAC-E2 900/300 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)
Daily release of 500, 700, or 900 μg.
Drug: Estradiol (E2)
Daily release of 300 μg
Experimental: ENG-E2 75/300
Participants will receive ENG-E2 75/300 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)
Daily release of 75, 100, or 125 μg
Drug: Estradiol (E2)
Daily release of 300 μg
Experimental: ENG-E2 100/300
Participants will receive ENG-E2 100/300 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)
Daily release of 75, 100, or 125 μg
Drug: Estradiol (E2)
Daily release of 300 μg
Experimental: ENG-E2 125/300
Participants will receive ENG-E2 125/300 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)
Daily release of 75, 100, or 125 μg
Drug: Estradiol (E2)
Daily release of 300 μg
Active Comparator: NuvaRing® (ENG-EE 120/15)
Participants will receive NuvaRing® 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)
Daily release of 75, 100, or 125 μg
Drug: Ethinyl estradiol (EE)
Daily release of 15 μg

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Body mass index (BMI) ≥18 and ≤35
  • Regular cycles from 24 to 35 days in length, with an intraindividual

variation of ±3 days permitted within this range

  • Good physical and mental health

Exclusion Criteria:

  • 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 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01709318     History of Changes
Other Study ID Numbers: P06109, 2012-002459-41
Study First Received: October 16, 2012
Last Updated: October 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
3-keto-desogestrel
Estradiol
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Estradiol valerate
Ethinyl Estradiol
Megestrol
Polyestradiol phosphate
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Synthetic
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014