Effects on Ovarian Function of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing DRSP/EE (292003)(COMPLETED)(P05723) - Full Text View

Sponsor:	Schering-Plough
Information provided by:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00511433

Purpose

The primary purpose of this study is to evaluate the effects of the nomegestrol acetate-estradiol (NOMAC-E2) combined oral contraceptive (COC) on ovarian function.

Condition	Intervention	Phase
Contraception	Drug: NOMAC-E2 Drug: DRSP-EE	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	A Randomized, Open-Label, Comparative Trial to Evaluate the Effects on Ovarian Function of a Monophasic Combined Oral Contraceptive (COC) Containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2), Compared to a Monophasic COC Containing 3 mg Drospirenone (DRSP) and 30 ug Ethinyl Estradiol (EE)

Resource links provided by NLM:

MedlinePlus related topics: Birth Control

Drug Information available for: Estradiol Estradiol 3-benzoate Ethinyl estradiol Polyestradiol phosphate TX 066 Nomegestrol Depogen 1,2-Dihydrospirorenone Estradiol dipropionate Estradiol cypionate Estradiol valerate Estradiol acetate

U.S. FDA Resources

Further study details as provided by Schering-Plough:

Primary Outcome Measures:

Effect on Ovarian Function as Determined by the Number of Participants With an Occurrence of Ovulation [ Time Frame: Cycle 1, Cycle 2, and Cycle 6 ] [ Designated as safety issue: No ]
During treatment, ovulation was assessed for each participant by the investigator on the basis of ultrasound scanning (USS). The final analysis was based on assessor-blind adjudication.
Effect on Ovarian Function as Determined by the Maximum Follicle Diameter [ Time Frame: Screening cycle, Cycle 1, Cycle 2, Cycle 3, and Cycle 6 ] [ Designated as safety issue: No ]
The maximum follicular diameter was defined as the largest follicular diameter during a treatment cycle.
Effect on Ovarian Function as Determined by the Maximum Progesterone Value [ Time Frame: Screening cycle, Cycle 1, Cycle 2, Cycle 3, and Cycle 6 ] [ Designated as safety issue: No ]
The maximum progesterone value was defined as the largest value during a cycle.
Effect on Ovarian Function as Determined by 17 Beta-estradiol (E2) [ Time Frame: Cycle 1, Cycle 2, Cycle 3, and Cycle 6 ] [ Designated as safety issue: No ]
The parameter was measured at pre-defined study days.
Effect on Ovarian Function as Determined by Follicle Stimulating Hormone (FSH) [ Time Frame: Cycle 1, Cycle 2, Cycle 3, and Cycle 6 ] [ Designated as safety issue: No ]
The parameter was measured at pre-defined study days.
Effect on Ovarian Function as Determined by Luteinizing Hormone (LH) [ Time Frame: Cycle 1, Cycle 2, Cycle 3, and Cycle 6 ] [ Designated as safety issue: No ]
The parameter was measured at pre-defined study days.

Secondary Outcome Measures:

Effect on Cervical Mucus as Determined by Insler Score [ Time Frame: Screening Cycle, Cycle 1, Cycle 2, and Cycle 7 (post-treatment cycle) ] [ Designated as safety issue: No ]
The Insler Score was assessed on Day 6 after ovulation during the Screening Cycle, on Day 21 of Cycle 1, and when the maximum follicle diameter was greater than or equal to 15 mm. The Insler Score consisted of four categories each scaled from 0 (none) to 3 (complete). The higher the score, the greater the cervical reaction.
Effect on Maximum Endometrial Thickness [ Time Frame: Screening Cycle, Cycle 1, Cycle 2, and Cycle 6 ] [ Designated as safety issue: No ]
Maximum endometrial thickness was defined as the largest endometrial thickness during a cycle.
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) [ Time Frame: 6 cycles ] [ Designated as safety issue: No ]
In-treatment pregnancies were pregnancies with an estimated date of conception from the day of first intake of trial medication up to and including the day of last (active or placebo) intake of trial medication extended with a maximum of two days. Each 13 cycles (28 days per cycle) of exposure constitutes a woman year. The Pearl Index was obtained by dividing the number of in-treatment pregnancies that occurred by the time (in 100 woman years) that the women were under risk of becoming pregnant.
Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting [ Time Frame: Every 28-day cycle for 6 cycles ] [ Designated as safety issue: No ]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 6 cycles ] [ Designated as safety issue: No ]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Absence of withdrawal bleeding was defined as no bleeding/spotting episode that began during or continued into the "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
Number of Participants With an Occurrence of Breakthrough Bleeding [ Time Frame: Every 28-day cycle for 6 cycles ] [ Designated as safety issue: No ]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding was defined as any bleeding episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2:21-day period starting on Day 4 of the cycle.
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) [ Time Frame: Every 28-day cycle for 6 cycles ] [ Designated as safety issue: No ]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough spotting was defined as any spotting episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2:21-day period starting on Day 4 of the cycle.
Number of Participants With an Occurrence of Early Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 6 cycles ] [ Designated as safety issue: No ]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Early withdrawal bleeding was defined as any withdrawal bleeding that started before the current "expected bleeding period". Expected bleeding period: DRSP-EE: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
Number of Participants With an Occurrence of Continued Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 5 cycles ] [ Designated as safety issue: No ]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Continued withdrawal bleeding was defined as any withdrawal bleeding that continued into the "expected non-bleeding period" of the next cycle. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
Average Number of Breakthrough Bleeding/Spotting Days [ Time Frame: Every 28-day cycle for 6 cycles ] [ Designated as safety issue: No ]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
Average Number of Withdrawal Bleeding Days [ Time Frame: Every 28-day cycle for 6 cycles ] [ Designated as safety issue: No ]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Withdrawal bleeding was defined as bleeding/spotting episode that started during or continued into the "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.

Enrollment:	48
Study Start Date:	October 2006
Study Completion Date:	January 2008
Primary Completion Date:	January 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: NOMAC-E2 Nomegestrol Acetate (NOMAC) and Estradiol (E2), 2.5 mg NOMAC and 1.5 mg E2 monophasic combined oral contraceptive	Drug: NOMAC-E2 Nomegestrol Acetate and Estradiol Tablets, 2.5 mg NOMAC and 1.5 mg E2 taken once daily from Day 1 of menstrual period up to and including Day 28 for 6 consecutive 28-day menstrual cycles.
Active Comparator: DRSP-EE Drospirenone (DRSP) and Ethinyl Estradiol (EE), 3 mg DRSP and 30 mcg EE monophasic combined oral contraceptive	Drug: DRSP-EE Drospirenone and Ethinyl Estradiol Tablets, 3 mg DRSP and 30 mcg EE taken once daily from Day 1 of menstrual period up to and including Day 28 for 6 consecutive 28-day menstrual cycles.

Eligibility

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

Criteria

Inclusion Criteria:

Willing to use COC for at least 6 cycles.
18 - 35 years of age at screening.
Body Mass Index (BMI) of >/= 17 and </= 35.
Good physical and mental health.
Willing to use condoms as the sole contraceptive method during screening cycle and 1 post-treatment cycle.
Willing to give informed consent.

Exclusion Criteria:

Contraindications for contraceptive steroids (general).
Additional contraindications (renal, hepatic or adrenal insufficiency).
Breastfeeding.
Present use (or use within 2 months prior to start of the trial medication) of the following drugs: phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, ketoconazole, sex steroids (other than pre- and post treatment contraceptive method) and herbal remedies containing Hypericum perforatum (St. John's Wort).
Administration of any other investigational drugs and/or participation in another clinical trial within 2 months prior to the start of the trial medication or during the trial period.
Abnormal cervical smear at screening, or documentation of an abnormal smear performed within 6 months before screening.
Clinically relevant abnormal laboratory result at screening as judged by the investigator.

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00511433 History of Changes
Other Study ID Numbers:	Organon protocol 292003, P05723
Study First Received:	August 2, 2007
Results First Received:	July 28, 2011
Last Updated:	July 28, 2011
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:

Contraceptive Agents
Estradiol valerate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Megestrol
Contraceptives, Oral
Contraceptives, Oral, Combined
Estradiol
Polyestradiol phosphate
Ethinyl Estradiol
Drospirenone
Reproductive Control Agents

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

ClinicalTrials.gov processed this record on February 09, 2012