A Dose-Finding Study to Evaluate Ovarian Function and Vaginal Bleeding in Next Generation Rings (P06109/MK-8175A/MK-8342B-012 AM2) - Full Text View

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:

MedlinePlus related topics: Birth Control

Drug Information available for: Estradiol Ethinyl Estradiol Estradiol cypionate Estradiol valerate Estradiol acetate Estradiol hemihydrate Etonogestrel

U.S. FDA Resources

Further study details as provided by Merck:

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 ]

Estimated Enrollment:	680
Study Start Date:	December 2012
Estimated Study Completion Date:	November 2013
Estimated Primary Completion Date:	November 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01709318

Contacts

Contact: Toll Free Number

1-888-577-8839

Locations

Denmark
Merck Sharp & Dohme	Recruiting
Glostrup, Denmark
Contact: Gert Andersen 45 43287726
Germany
Merck Sharp & Dohme GmbH	Recruiting
Haar, Germany
Contact: Kristian Lobner 49 89 4561 1102
Hungary
MSD Pharma Hungary Kft.	Recruiting
Budapest, Hungary
Contact: Simona Martinkova 36 1 457 8522
Netherlands
Merck Sharp & Dohme BV	Recruiting
Haarlem, Netherlands
Contact: Trea van der Galien 31-(0)23-5153153
Norway
MSD Norge A/S	Recruiting
Drammen, Norway
Contact: Jon Sigurd Riis 47 32207465
Poland
MSD Polska Sp. Z o.o.	Recruiting
Warsaw, Poland
Contact: Adam Czernik 48 22 4784324
Spain
Merck Sharp and Dohme de Espana S.A.	Recruiting
Madrid, Spain
Contact: Cesar Sanz Rodriguez 34 913210600

Sponsors and Collaborators

Merck

More Information

No publications provided

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT01709318 History of Changes
Other Study ID Numbers:	P06109, 2012-002459-41
Study First Received:	October 16, 2012
Last Updated:	April 24, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Hemorrhage
Uterine Hemorrhage
Pathologic Processes
Uterine Diseases
Genital Diseases, Female
Estradiol
Polyestradiol phosphate
Ethinyl Estradiol
Estradiol valerate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
3-keto-desogestrel
Megestrol

Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Female
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Contraceptives, Oral, Synthetic
Contraceptives, Oral

ClinicalTrials.gov processed this record on May 19, 2013