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

Organon

Status and phase: Completed; Phase 2

Conditions: Contraception

Treatments: Drug: Ethinyl estradiol (EE); Drug: Etonogestrel (ENG); Drug: Nomegestrol acetate (NOMAC); Drug: Estradiol (E2)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01709318

2012-002459-41 (Other Identifier)

P06109 (Other Identifier)

MK-8175A/MK-8342B-012 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 666 patients

Sex: Female

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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666 participants in 7 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Estradiol (E2)

Drug: Nomegestrol acetate (NOMAC)

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

Experimental group

Description:

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.

Treatment:

Drug: Estradiol (E2)

Drug: Nomegestrol acetate (NOMAC)

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

Experimental group

Description:

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.

Treatment:

Drug: Estradiol (E2)

Drug: Nomegestrol acetate (NOMAC)

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

Experimental group

Description:

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.

Treatment:

Drug: Estradiol (E2)

Drug: Etonogestrel (ENG)

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

Experimental group

Description:

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.

Treatment:

Drug: Estradiol (E2)

Drug: Etonogestrel (ENG)

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

Experimental group

Description:

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.

Treatment:

Drug: Estradiol (E2)

Drug: Etonogestrel (ENG)

NuvaRing®

Active Comparator group

Description:

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.

Treatment:

Drug: Etonogestrel (ENG)

Drug: Ethinyl estradiol (EE)