Trial Outcomes & Findings for Study of the Contraceptive Efficacy and Safety of a NOMAC-E2 Combined Oral Contraceptive (COC)(P06448) (NCT NCT01656434)

Last Updated: 2024-06-20

Results Overview

Primary Efficacy Outcome measure for this study was contraceptive efficacy, or the prevention of in-treatment pregnancy. The total incidence of in-treatment pregnancies was expressed as the Pearl Index, which is defined as the number of in-treatment pregnancies per 100 woman-years of exposure.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

3173 participants

Primary outcome timeframe

Up to 1 year (13 cycles)

Results posted on

2024-06-20

Participant Flow

Participant milestones

Participant milestones
Measure	NOMAC-E2 Participants received a NOMAC-E2 tablet (2.5 mg nomegestrol acetate and 1.5 mg 17ß-estradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NOMAC-E2 tablets on Days 1 to 24 and placebo tablets on Days 25 to 28.	NETA-EE Participants received a NETA-EE tablet (1 mg norethisterone acetate and 10 μg ethinylestradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NETA-EE tablets on Days 1 to 24; EE 10 μg tablets on Days 25 and 26; and ferrous fumarate 75 mg tablets on Days 27 and 28.
Overall Study STARTED	2553	620
Overall Study Treated	2466	604
Overall Study COMPLETED	152	40
Overall Study NOT COMPLETED	2401	580

Reasons for withdrawal

Reasons for withdrawal
Measure	NOMAC-E2 Participants received a NOMAC-E2 tablet (2.5 mg nomegestrol acetate and 1.5 mg 17ß-estradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NOMAC-E2 tablets on Days 1 to 24 and placebo tablets on Days 25 to 28.	NETA-EE Participants received a NETA-EE tablet (1 mg norethisterone acetate and 10 μg ethinylestradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NETA-EE tablets on Days 1 to 24; EE 10 μg tablets on Days 25 and 26; and ferrous fumarate 75 mg tablets on Days 27 and 28.
Overall Study Adverse Event	199	63
Overall Study Enrollment terminated at trial site	2	0
Overall Study Lost to Follow-up	309	76
Overall Study Site discontinued study participation	24	9
Overall Study Screen failure	2	0
Overall Study Protocol Violation	7	0
Overall Study Pregnancy wish	18	6
Overall Study Pregnancy	45	10
Overall Study Physician Decision	7	2
Overall Study Non-compliance with study drug	48	9
Overall Study Study terminated by sponsor	1501	348
Overall Study Participant discontinued; drug related	13	4
Overall Study Part. discontinued; unrelated to drug	55	10
Overall Study Non-compliance with protocol	39	15
Overall Study Participant moved	40	12
Overall Study Participant withdrew consent	28	9
Overall Study Withdrawal by Subject	64	7

Baseline Characteristics

Study of the Contraceptive Efficacy and Safety of a NOMAC-E2 Combined Oral Contraceptive (COC)(P06448)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NOMAC-E2 n=2466 Participants Participants received a NOMAC-E2 tablet (2.5 mg nomegestrol acetate and 1.5 mg 17ß-estradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NOMAC-E2 tablets on Days 1 to 24 and placebo tablets on Days 25 to 28.	NETA-EE n=604 Participants Participants received a NETA-EE tablet (1 mg norethisterone acetate and 10 μg ethinylestradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NETA-EE tablets on Days 1 to 24; EE 10 μg tablets on Days 25 and 26; and ferrous fumarate 75 mg tablets on Days 27 and 28.	Total n=3070 Participants Total of all reporting groups
Age, Continuous	29.2 Years STANDARD_DEVIATION 7.6 • n=93 Participants	29.5 Years STANDARD_DEVIATION 7.7 • n=4 Participants	29.3 Years STANDARD_DEVIATION 7.6 • n=27 Participants
Sex: Female, Male Female	2466 Participants n=93 Participants	604 Participants n=4 Participants	3070 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Up to 1 year (13 cycles)

Population: Planned analysis for this primary endpoint was not performed due to early study termination.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 1 year (13 cycles)

Population: Planned analysis for this secondary endpoint was not performed due to early study termination.

Participants kept e-diaries to record their vaginal bleeding events. They were asked to record, on a daily basis, whether they experienced vaginal bleeding, which included BLEEDING or SPOTTING, at any time during a cycle other than normal menstruation while in the study. (This is also known as "breakthough" bleeding.) Vaginal bleeding that required \>=1 pad/tampon per day was classified as BLEEDING. Vaginal bleeding that did not require a pad/tampon per day was classified as SPOTTING.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 1 year (13 cycles)

Population: Planned analysis for this secondary endpoint was not performed due to early study termination.

Participants kept e-diaries to record vaginal bleeding events. They were asked to record, on a daily basis, whether vaginal bleeding was present. Absence of withdrawal bleeding was defined as no bleeding/spotting during the expected bleeding period.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 54 weeks

Population: All Subjects as Treated Population, which consisted of all randomized participants who took at least one dose of trial medication. One treated participant in the NOMAC-E2 treatment group had incomplete data and was not included in the Safety Analyses.

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.

Outcome measures

Outcome measures
Measure	NOMAC-E2 n=2465 Participants Participants received a NOMAC-E2 tablet (2.5 mg nomegestrol acetate and 1.5 mg 17ß-estradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NOMAC-E2 tablets on Days 1 to 24 and placebo tablets on Days 25 to 28.	NETA-EE n=604 Participants Participants received a NETA-EE tablet (1 mg norethisterone acetate and 10 μg ethinylestradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NETA-EE tablets on Days 1 to 24; EE 10 μg tablets on Days 25 and 26; and ferrous fumarate 75 mg tablets on Days 27 and 28.
Percentage of Participants Who Experienced At Least One Adverse Event	41.2 Percentage of Participants	45.2 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 54 weeks

Outcome measures

Outcome measures
Measure	NOMAC-E2 n=2465 Participants Participants received a NOMAC-E2 tablet (2.5 mg nomegestrol acetate and 1.5 mg 17ß-estradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NOMAC-E2 tablets on Days 1 to 24 and placebo tablets on Days 25 to 28.	NETA-EE n=604 Participants Participants received a NETA-EE tablet (1 mg norethisterone acetate and 10 μg ethinylestradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NETA-EE tablets on Days 1 to 24; EE 10 μg tablets on Days 25 and 26; and ferrous fumarate 75 mg tablets on Days 27 and 28.
Number of Participants Who Experience at Least One Venous or Arterial Thrombotic/Thromboembolic Event	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Participants from All Subjects as Treated Population (all randomized participants who took at least one dose of trial medication) who had data available for Change from Baseline in Body Weight endpoint.

Participants' body weights were measured in a consistent manner throughout the trial, using standardized equirpment. Last In-Treatment Measurement refers to a participant's end of trial visit, the timing of which differed among participants.

Outcome measures

Outcome measures
Measure	NOMAC-E2 n=2231 Participants Participants received a NOMAC-E2 tablet (2.5 mg nomegestrol acetate and 1.5 mg 17ß-estradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NOMAC-E2 tablets on Days 1 to 24 and placebo tablets on Days 25 to 28.	NETA-EE n=549 Participants Participants received a NETA-EE tablet (1 mg norethisterone acetate and 10 μg ethinylestradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NETA-EE tablets on Days 1 to 24; EE 10 μg tablets on Days 25 and 26; and ferrous fumarate 75 mg tablets on Days 27 and 28.
Change From Baseline in Body Weight After Cycle 3 (n=2135; n=527)	0.14 kilograms Standard Error 0.14	0.41 kilograms Standard Error 0.24
Change From Baseline in Body Weight After Cycle 6 (n=1809; n=459)	0.64 kilograms Standard Error 0.18	0.29 kilograms Standard Error 0.28
Change From Baseline in Body Weight After Cycle 9 (n=1468; n=391)	1.21 kilograms Standard Error 0.23	0.32 kilograms Standard Error 0.35
Change From Baseline in Body Weight After Cycle 13 (n=462; n=145)	1.57 kilograms Standard Error 0.29	0.90 kilograms Standard Error 0.46
Change From Baseline in Body Weight Last In-Treatment Measurement (n=2231; n=549)	1.39 kilograms Standard Error 0.17	0.75 kilograms Standard Error 0.29

Adverse Events

NOMAC-E2

Serious events: 20 serious events

Other events: 0 other events

Deaths: 0 deaths

NETA-EE

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees to provide to the Sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including slides and texts of oral or other public presentations that report any results of the trial). The Sponsor has the right to review and comment on publications, abstracts, slides, and manuscripts, as well as the data analysis and presentation.
Publication restrictions are in place

Restriction type: OTHER