Clinical trial NCT01709318: A Dose-Finding Study to Evaluate Ovarian Function and Vaginal Bleeding in Next Generation Rings (P06109/MK-8175A/MK-8342B-012)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Contraception
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2012-10-18
Enrollment: 666
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

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 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

Primary outcomes:
measure: Percentage of Participants With Ovulation Incidence, by Cycle
timeFrame: Day 1 of Treatment Cycle 1 through Day 28 of Treatment Cycle 3 (Up to ~92 days)
measure: Percentage of Participants With Progesterone Concentrations >16 Nmol/L, by Cycle
timeFrame: Day 1 of Treatment Cycle 1 through Day 28 of Treatment Cycle 3 (Up to ~92 days)
measure: Percentage of Participants With Breakthrough Bleeding and/or Spotting During Cycle 3
timeFrame: Day 1 Cycle 3 through Day 28 Cycle 3 (Up to ~28 days)
Secondary outcomes:
measure: Percentage of Participants With Absence of Withdrawal Bleeding and/or Spotting During Cycle 2
timeFrame: Day 1 Cycle 2 through Day 28 Cycle 2 (Up to ~28 days)
measure: Intensity of Withdrawal Bleeding During Cycle 2
timeFrame: Day 1 Cycle 2 through Day 28 Cycle 2 (Up to ~28 days)
measure: Intensity of Breakthrough Bleeding and/or Spotting During Cycle 3
timeFrame: Day 1 Cycle 3 through Day 28 Cycle 3 (Up to ~ 28 days)
measure: Percentage of Participants Who Experienced At Least One Adverse Event
timeFrame: Up to ~92 days
measure: Percentage of Participants Who Experienced At Least One Serious Adverse Event
timeFrame: Up to ~92 days
measure: Percentage of Participants Who Experienced At Least One Drug-Related Adverse Event
timeFrame: Up to ~92 days
measure: Percentage of Participants With Any Drug-Related Serious Adverse Event
timeFrame: Up to ~92 days
measure: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event
timeFrame: Up to ~92 days
Other outcomes:
measure: Number of Participants With Venous or Arterial Thrombotic/Thromboembolic Events
timeFrame: From Cycle 1 Day 1 up to 8 days after Day 28 of Cycle 3 (Up to ~92 days)
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.