Trial Outcomes & Findings for Effects on Hemostasis, Lipids, Carbohydrate Metabolism, Adrenal & Thyroid Function of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing LNG-EE (292004)(COMPLETED)(P05764) (NCT NCT00511355)

NCT ID: NCT00511355

Last Updated: 2022-02-09

Results Overview

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

121 participants

Primary outcome timeframe

Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Results posted on

2022-02-09

Participant Flow

Participant milestones

Participant milestones
Measure
NOMAC-E2
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Overall Study
STARTED
60
61
Overall Study
COMPLETED
53
52
Overall Study
NOT COMPLETED
7
9

Reasons for withdrawal

Reasons for withdrawal
Measure
NOMAC-E2
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Overall Study
Adverse Event
4
4
Overall Study
Pregnancy Wish
1
0
Overall Study
Lost to Follow-up
2
1
Overall Study
Other Reason
0
1
Overall Study
Pre-treatment (serious) adverse event
0
1
Overall Study
Withdrawal of informed consent
0
1
Overall Study
Other reason pre-treatment
0
1

Baseline Characteristics

Effects on Hemostasis, Lipids, Carbohydrate Metabolism, Adrenal & Thyroid Function of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing LNG-EE (292004)(COMPLETED)(P05764)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
NOMAC-E2
n=60 Participants
All-participants-treated group. Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles
LNG-EE
n=58 Participants
All-participants-treated group. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 6 consecutive 28-day cycles
Total
n=118 Participants
Total of all reporting groups
Age, Continuous
28.2 years
STANDARD_DEVIATION 8.2 • n=93 Participants
29.1 years
STANDARD_DEVIATION 7.8 • n=4 Participants
28.7 years
STANDARD_DEVIATION 8.0 • n=27 Participants
Sex: Female, Male
Female
60 Participants
n=93 Participants
58 Participants
n=4 Participants
118 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: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Prothrombin Fragments 1 + 2
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
0.18 nmol/L
Standard Deviation 0.20
0.19 nmol/L
Standard Deviation 0.08
Serum Concentration of Prothrombin Fragments 1 + 2
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
0.31 nmol/L
Standard Deviation 1.06
0.42 nmol/L
Standard Deviation 1.17

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of D-Dimer
Baseline (n=60; NOMAC-E2; n=58)
0.21 mg/L Fibrinogen Equivalent Units (FEU)
Standard Deviation 0.16
0.19 mg/L Fibrinogen Equivalent Units (FEU)
Standard Deviation 0.14
Serum Concentration of D-Dimer
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
0.18 mg/L Fibrinogen Equivalent Units (FEU)
Standard Deviation 0.14
0.26 mg/L Fibrinogen Equivalent Units (FEU)
Standard Deviation 0.21

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). APC resistance ratio (ETP-based) measures the anticoagulation response of plasma to APC after activation of the extrinsic coagulation pathway. An increase in the ratio indicates a reduced responsiveness to APC. Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Activated Protein C (APC) Resistance Ratio (Endogenous Thrombin Potential [ETP]-Based)
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
1.14 Ratio
Standard Deviation 0.45
1.99 Ratio
Standard Deviation 0.76
Activated Protein C (APC) Resistance Ratio (Endogenous Thrombin Potential [ETP]-Based)
Baseline (n=59 NOMAC-E2; n=58 LNG-EE)
0.80 Ratio
Standard Deviation 0.33
0.83 Ratio
Standard Deviation 0.40

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Clotting Factor VIIa
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
84 U/L
Standard Deviation 32
85 U/L
Standard Deviation 37
Serum Concentration of Clotting Factor VIIa
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
118 U/L
Standard Deviation 180
98 U/L
Standard Deviation 66

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Clotting Factor VIIc
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
105 Percent of normal
Standard Deviation 24
105 Percent of normal
Standard Deviation 22
Serum Concentration of Clotting Factor VIIc
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
109 Percent of normal
Standard Deviation 31
96 Percent of normal
Standard Deviation 25

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Clotting Factor VIII
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
93 Percent of normal
Standard Deviation 32
95 Percent of normal
Standard Deviation 32
Serum Concentration of Clotting Factor VIII
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
89 Percent of normal
Standard Deviation 34
98 Percent of normal
Standard Deviation 30

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Clotting Factor II
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
94 Percent of normal
Standard Deviation 11
94 Percent of normal
Standard Deviation 12
Serum Concentration of Clotting Factor II
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
95 Percent of normal
Standard Deviation 13
97 Percent of normal
Standard Deviation 11

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Antithrombin III
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
100 Percent of normal
Standard Deviation 10
99 Percent of normal
Standard Deviation 11
Serum Concentration of Antithrombin III
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
102 Percent of normal
Standard Deviation 9
96 Percent of normal
Standard Deviation 12

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Protein S (Free)
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
85 Percent of normal
Standard Deviation 16
86 Percent of normal
Standard Deviation 14
Serum Concentration of Protein S (Free)
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
99 Percent of normal
Standard Deviation 20
99 Percent of normal
Standard Deviation 17

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Protein S (Total)
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
78 Percent of normal
Standard Deviation 12
79 Percent of normal
Standard Deviation 10
Serum Concentration of Protein S (Total)
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
83 Percent of normal
Standard Deviation 12
76 Percent of normal
Standard Deviation 9

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Protein C
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
108 Percent of normal
Standard Deviation 21
113 Percent of normal
Standard Deviation 20
Serum Concentration of Protein C
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
107 Percent of normal
Standard Deviation 18
103 Percent of normal
Standard Deviation 19

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). APC resistance ratio (APTT-based) measures the anticoagulation response of plasma to APC after activation of the intrinsic coagulation pathway. An increase in the ratio indicates a increased responsiveness to APC. Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
APC Resistance Ratio (Activated Partial Thromboplastin Time [APTT]-Based)
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
1.01 Ratio
Standard Deviation 0.13
1.00 Ratio
Standard Deviation 0.13
APC Resistance Ratio (Activated Partial Thromboplastin Time [APTT]-Based)
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
1.05 Ratio
Standard Deviation 0.13
1.03 Ratio
Standard Deviation 0.12

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Sex Hormone Binding Globulin (SHBG)
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
74 nmol/L
Standard Deviation 34
77 nmol/L
Standard Deviation 26
Serum Concentration of Sex Hormone Binding Globulin (SHBG)
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
108 nmol/L
Standard Deviation 44
100 nmol/L
Standard Deviation 31

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of C-Reactive Protein (CRP)
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
0.82 mg/L
Standard Deviation 1.16
0.98 mg/L
Standard Deviation 1.35
Serum Concentration of C-Reactive Protein (CRP)
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
1.32 mg/L
Standard Deviation 2.36
4.43 mg/L
Standard Deviation 8.43

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Total Cholesterol
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
4.48 mmol/L
Standard Deviation 0.87
4.53 mmol/L
Standard Deviation 0.82
Serum Concentration of Total Cholesterol
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
4.51 mmol/L
Standard Deviation 0.83
4.48 mmol/L
Standard Deviation 0.75

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of High Density Lipoprotein (HDL)-Cholesterol
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
1.63 mmol/L
Standard Deviation 0.36
1.68 mmol/L
Standard Deviation 0.33
Serum Concentration of High Density Lipoprotein (HDL)-Cholesterol
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
1.65 mmol/L
Standard Deviation 0.34
1.41 mmol/L
Standard Deviation 0.26

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of HDL2-cholesterol
Baseline (n=58 NOMAC-E2; n=50 LNG-EE)
0.63 mmol/L
Standard Deviation 0.26
0.69 mmol/L
Standard Deviation 0.29
Serum Concentration of HDL2-cholesterol
Cycle 6 (n=52 NOMAC-E2; n=51 LNG-EE)
0.55 mmol/L
Standard Deviation 0.25
0.40 mmol/L
Standard Deviation 0.18

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of HDL3-cholesterol
Baseline (n=58 NOMAC-E2; n=50 LNG-EE)
1.10 mmol/L
Standard Deviation 0.16
1.14 mmol/L
Standard Deviation 0.19
Serum Concentration of HDL3-cholesterol
Cycle 6 (n=52 NOMAC-E2; n=51 LNG-EE)
1.16 mmol/L
Standard Deviation 0.16
1.10 mmol/L
Standard Deviation 0.14

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Low Density Lipoprotein (LDL)-Cholesterol
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
2.41 mmol/L
Standard Deviation 0.73
2.47 mmol/L
Standard Deviation 0.66
Serum Concentration of Low Density Lipoprotein (LDL)-Cholesterol
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
2.40 mmol/L
Standard Deviation 0.71
2.61 mmol/L
Standard Deviation 0.74

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Apolipoprotein A-1
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
1.78 g/L
Standard Deviation 0.27
1.67 g/L
Standard Deviation 0.20
Serum Concentration of Apolipoprotein A-1
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
1.58 g/L
Standard Deviation 0.27
1.60 g/L
Standard Deviation 0.25

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Apolipoprotein B
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
0.64 g/L
Standard Deviation 0.17
0.64 g/L
Standard Deviation 0.15
Serum Concentration of Apolipoprotein B
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
0.68 g/L
Standard Deviation 0.17
0.80 g/L
Standard Deviation 0.21

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Lipoprotein(a)
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
0.17 g/L
Standard Deviation 0.22
0.12 g/L
Standard Deviation 0.11
Serum Concentration of Lipoprotein(a)
Baseline (n=60 NOMAC-E2; n=57 LNG-EE)
0.15 g/L
Standard Deviation 0.18
0.15 g/L
Standard Deviation 0.14

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Total Triglycerides
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
0.94 mmol/L
Standard Deviation 0.30
0.82 mmol/L
Standard Deviation 0.23
Serum Concentration of Total Triglycerides
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
1.00 mmol/L
Standard Deviation 0.37
1.02 mmol/L
Standard Deviation 0.32

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Blood glucose levels were determined as fasting values just before oral glucose intake and each half hour thereafter for 2 hours and again after 3 hours. Oral glucose tolerance was analysed using the (unadjusted) area under the curve over the 3 hours (AUC3). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Area Under the Curve Over 3 Hours (AUC3) for Glucose (Oral Glucose Tolerance Test [OGTT])
Baseline (n=59 NOMAC-E2; n=55 LNG-EE)
15.82 hrs*mmol/L
Standard Deviation 3.27
14.44 hrs*mmol/L
Standard Deviation 2.47
Area Under the Curve Over 3 Hours (AUC3) for Glucose (Oral Glucose Tolerance Test [OGTT])
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
16.09 hrs*mmol/L
Standard Deviation 3.05
16.69 hrs*mmol/L
Standard Deviation 3.15

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Blood glucose levels were determined as fasting values just before oral glucose intake and each half hour thereafter for 2 hours and again after 3 hours. Oral glucose tolerance was analysed using the (unadjusted) area under the curve over the 3 hours (AUC3). Incremental area under the curve was defined as incremental AUC3 = AUC3 - 3\*fasting concentration. Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Incremental AUC3 for Glucose (OGTT)
Baseline (n=59 NOMAC-E2; n=55 LNG-EE)
1.58 hrs*mmol/L
Standard Deviation 3.05
1.06 hrs*mmol/L
Standard Deviation 2.55
Incremental AUC3 for Glucose (OGTT)
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
1.76 hrs*mmol/L
Standard Deviation 2.72
3.19 hrs*mmol/L
Standard Deviation 3.03

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Blood insulin levels were determined as fasting values just before oral glucose intake and each half hour thereafter for 2 hours and again after 3 hours. Oral glucose tolerance was analysed using the (unadjusted) area under the curve over the 3 hours (AUC3). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
AUC3 for Insulin (OGTT)
Cycle 6 (n=46 NOMAC-E2; n=47 LNG-EE)
658 hrs*pmol/L
Standard Deviation 281
721 hrs*pmol/L
Standard Deviation 264
AUC3 for Insulin (OGTT)
Baseline (n=51 NOMAC-E2; n=50 LNG-EE)
650 hrs*pmol/L
Standard Deviation 298
558 hrs*pmol/L
Standard Deviation 182

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Blood insulin levels were determined as fasting values just before oral glucose intake and each half hour thereafter for 2 hours and again after 3 hours. Oral glucose tolerance was analysed using the (unadjusted) area under the curve over the 3 hours (AUC3). Incremental area under the curve was defined as incremental AUC3 = AUC3 - 3\*fasting concentration. Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Incremental AUC3 for Insulin (OGTT)
Baseline (n=51 NOMAC-E2; n=50 LNG-EE)
517 hrs*pmol/L
Standard Deviation 268
451 hrs*pmol/L
Standard Deviation 160
Incremental AUC3 for Insulin (OGTT)
Cycle 6 (n=46 NOMAC-E2; n=47 LNG-EE)
534 hrs*pmol/L
Standard Deviation 239
603 hrs*pmol/L
Standard Deviation 237

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). HbA1c was determined before glucose loading. Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Hemoglobin Type A1c (HbA1c)
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
5.3 Percent of glycosylated hemoglobin
Standard Deviation 0.3
5.3 Percent of glycosylated hemoglobin
Standard Deviation 0.2
Serum Concentration of Hemoglobin Type A1c (HbA1c)
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
5.3 Percent of glycosylated hemoglobin
Standard Deviation 0.2
5.4 Percent of glycosylated hemoglobin
Standard Deviation 0.2

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Total Cortisol
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
482 nmol/L
Standard Deviation 128
502 nmol/L
Standard Deviation 153
Serum Concentration of Total Cortisol
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
608 nmol/L
Standard Deviation 167
944 nmol/L
Standard Deviation 183

PRIMARY outcome

Timeframe: Baseline to Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Corticosteroid Binding Globulin (CBG)
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
910 nmol/L
Standard Deviation 201
932 nmol/L
Standard Deviation 163
Serum Concentration of Corticosteroid Binding Globulin (CBG)
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
1116 nmol/L
Standard Deviation 252
1980 nmol/L
Standard Deviation 389

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Thyroid Stimulating Hormone (TSH)
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
2.96 mU/L
Standard Deviation 2.05
2.75 mU/L
Standard Deviation 3.36
Serum Concentration of Thyroid Stimulating Hormone (TSH)
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
2.69 mU/L
Standard Deviation 1.28
2.20 mU/L
Standard Deviation 1.08

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Free Thyroxine (T4)
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
14.0 pmol/L
Standard Deviation 1.5
14.1 pmol/L
Standard Deviation 1.5
Serum Concentration of Free Thyroxine (T4)
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
15.9 pmol/L
Standard Deviation 2.0
15.7 pmol/L
Standard Deviation 2.1

PRIMARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Thyroxin Binding Globulin (TBG)
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
20.3 mg/L
Standard Deviation 2.9
20.3 mg/L
Standard Deviation 3.3
Serum Concentration of Thyroxin Binding Globulin (TBG)
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
24.2 mg/L
Standard Deviation 3.6
28.4 mg/L
Standard Deviation 5.3

SECONDARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Total Testosterone
Baseline (n=60, NOMAC-E2; n=58 LNG-EE)
1.68 nmol/L
Standard Deviation 0.75
1.90 nmol/L
Standard Deviation 0.94
Serum Concentration of Total Testosterone
Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)
1.23 nmol/L
Standard Deviation 0.86
0.91 nmol/L
Standard Deviation 0.57

SECONDARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Free Testosterone
Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)
12.8 pmol/L
Standard Deviation 8.8
9.9 pmol/L
Standard Deviation 6.7
Serum Concentration of Free Testosterone
Baseline (n=60, NOMAC-E2; n=58 LNG-EE)
24.5 pmol/L
Standard Deviation 14.9
26.3 pmol/L
Standard Deviation 16.6

SECONDARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Dehydroepiandrosterone Sulphate (DHEAS)
Baseline (n=60, NOMAC-E2; n=58 LNG-EE)
4.94 umol/L
Standard Deviation 2.24
5.19 umol/L
Standard Deviation 2.26
Serum Concentration of Dehydroepiandrosterone Sulphate (DHEAS)
Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)
4.32 umol/L
Standard Deviation 1.82
4.00 umol/L
Standard Deviation 1.91

SECONDARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Androstenedione
Baseline (n=60, NOMAC-E2; n=58 LNG-EE)
9.60 nmol/L
Standard Deviation 3.45
10.27 nmol/L
Standard Deviation 3.91
Serum Concentration of Androstenedione
Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)
8.23 nmol/L
Standard Deviation 3.01
6.96 nmol/L
Standard Deviation 3.37

SECONDARY outcome

Timeframe: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Population: All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=60 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Serum Concentration of Dihydrotestosterone (DHT)
Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)
0.53 nmol/L
Standard Deviation 0.28
0.36 nmol/L
Standard Deviation 0.19
Serum Concentration of Dihydrotestosterone (DHT)
Baseline (n=60, NOMAC-E2; n=58 LNG-EE)
0.59 nmol/L
Standard Deviation 0.21
0.62 nmol/L
Standard Deviation 0.26

SECONDARY outcome

Timeframe: 6 cycles

Population: The "restricted ITT" set included all participants treated and excluded nonpregnant participants who didn't have \>=1 cycle expected to be at risk for pregnancy (with recorded use of condoms or w/o sexual intercourse per diary card data).

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 2 days. Each 13 cycles (28 days per cycle) constitutes a woman year. The Pearl Index was obtained by dividing the number of in-treatment pregnancies that occurred by the time (in 100 women years) that the women were under risk of becoming pregnant.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=23 Woman years (rounded to nearest integer)
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=22 Woman years (rounded to nearest integer)
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
0 Pregnancies per 100 woman years
Interval 0.0 to 16.1
0 Pregnancies per 100 woman years
Interval 0.0 to 17.1

SECONDARY outcome

Timeframe: Every 28-day cycle for 6 cycles

Population: The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles.

Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary 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: NOMAC-E2: 21-day period starting on Day 4 of the cycle; LNG-EE: 21-day period starting on Day 1 of the cycle.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=56 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=53 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)
8 Participants
2 Participants
Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)
6 Participants
4 Participants
Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
6 Participants
3 Participants
Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)
18 Participants
16 Participants
Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)
11 Participants
9 Participants
Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)
5 Participants
5 Participants

SECONDARY outcome

Timeframe: Every 28-day cycle for 6 cycles

Population: The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles.

Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary 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: NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle; LNG-EE: 7-day period starting on Day 22 of the cycle.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=56 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=53 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)
6 Participants
0 Participants
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)
8 Participants
1 Participants
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)
5 Participants
0 Participants
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)
8 Participants
0 Participants
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)
5 Participants
0 Participants
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
10 Participants
1 Participants

SECONDARY outcome

Timeframe: Every 28-day cycle for 6 cycles

Population: The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles.

Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary 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: NOMAC-E2: 21-day period starting on Day 4 of the cycle; LNG-EE: 21-day period starting on Day 1 of the cycle.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=56 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=53 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)
3 Participants
1 Participants
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)
1 Participants
0 Participants
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)
1 Participants
0 Participants
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)
1 Participants
0 Participants
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)
2 Participants
0 Participants
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
3 Participants
0 Participants

SECONDARY outcome

Timeframe: Every 28-day cycle for 6 cycles

Population: The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles.

Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary 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: NOMAC-E2: 21-day period starting on Day 4 of the cycle; LNG-EE: 21-day period starting on Day 1 of the cycle.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=56 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=53 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)
17 Participants
16 Participants
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)
10 Participants
9 Participants
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)
4 Participants
5 Participants
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)
7 Participants
2 Participants
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)
4 Participants
4 Participants
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
4 Participants
3 Participants

SECONDARY outcome

Timeframe: Every 28-day cycle for 6 cycles

Population: The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles.

Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary 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: NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle; LNG-EE: 7-day period starting on Day 22 of the cycle.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=56 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=53 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)
5 Participants
4 Participants
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)
4 Participants
1 Participants
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
2 Participants
2 Participants
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)
3 Participants
1 Participants
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)
2 Participants
0 Participants
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)
1 Participants
0 Participants

SECONDARY outcome

Timeframe: Every 28-day cycle for 5 cycles

Population: The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length.

Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary 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: NOMAC-E2: 21-day period starting on Day 4 of the cycle; LNG-EE: 21-day period starting on Day 1 of the cycle.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=56 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=53 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)
15 Participants
25 Participants
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 2 (n=54 NOMAC-E2; n=50 LNG-EE)
11 Participants
28 Participants
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 4 (n=53 NOMAC-E2; n=52 LNG-EE)
11 Participants
27 Participants
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)
13 Participants
29 Participants
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)
13 Participants
26 Participants

SECONDARY outcome

Timeframe: Every 28-day cycle for 6 cycles

Population: ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants who had breakthrough bleeding/spotting for the respective cycle.

Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary 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: NOMAC-E2: 21-day period starting on Day 4 of the cycle; LNG-EE: 21-day period starting on Day 1 of the cycle.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=56 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=53 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Average Number of Breakthrough Bleeding/Spotting Days
Cycle 1 (n=18 NOMAC-E2; n=16 LNG-EE)
3.5 Days
Standard Error 2.7
4.6 Days
Standard Error 3.6
Average Number of Breakthrough Bleeding/Spotting Days
Cycle 5 (n=6 NOMAC-E2; n=4 LNG-EE)
3.3 Days
Standard Error 2.5
2.0 Days
Standard Error 2.0
Average Number of Breakthrough Bleeding/Spotting Days
Cycle 2 (n=11 NOMAC-E2; n=9 LNG-EE)
4.3 Days
Standard Error 1.4
3.3 Days
Standard Error 2.2
Average Number of Breakthrough Bleeding/Spotting Days
Cycle 3 (n=5 NOMAC-E2; n=5 LNG-EE)
4.6 Days
Standard Error 2.5
3.2 Days
Standard Error 2.2
Average Number of Breakthrough Bleeding/Spotting Days
Cycle 4 (n=8 NOMAC-E2; n=2 LNG-EE)
3.8 Days
Standard Error 2.3
4.0 Days
Standard Error 0.0
Average Number of Breakthrough Bleeding/Spotting Days
Cycle 6 (n=6 NOMAC-E2; n=3 LNG-EE)
4.7 Days
Standard Error 3.7
3.0 Days
Standard Error 2.0

SECONDARY outcome

Timeframe: Every 28-day cycle for 6 cycles

Population: ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants who had withdrawal bleeding/spotting for the respective cycle.

Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Withdrawal bleeding/spotting was defined as any episode that occurred during the "expected bleeding period". Expected bleeding period: NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle; LNG-EE: 7-day period starting on Day 22 of the cycle.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=56 Participants
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=53 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Average Number of Withdrawal Bleeding/Spotting Days
Cycle 2 (n=47 NOMAC-E2; n=50 LNG-EE)
4.7 Days
Standard Deviation 3.6
4.9 Days
Standard Deviation 1.2
Average Number of Withdrawal Bleeding/Spotting Days
Cycle 1 (n=50 NOMAC-E2; n=53 LNG-EE)
4.8 Days
Standard Deviation 2.3
5.8 Days
Standard Deviation 3.6
Average Number of Withdrawal Bleeding/Spotting Days
Cycle 4 (n=46 NOMAC-E2; n=52 LNG-EE)
4.0 Days
Standard Deviation 2.5
5.0 Days
Standard Deviation 1.5
Average Number of Withdrawal Bleeding/Spotting Days
Cycle 5 (n=47 NOMAC-E2; n=51 LNG-EE)
3.8 Days
Standard Deviation 1.7
4.9 Days
Standard Deviation 1.5
Average Number of Withdrawal Bleeding/Spotting Days
Cycle 6 (n=42 NOMAC-E2; n=49 LNG-EE)
3.5 Days
Standard Deviation 1.2
4.2 Days
Standard Deviation 1.7
Average Number of Withdrawal Bleeding/Spotting Days
Cycle 3 (n=49 NOMAC-E2); n=52 LNG-EE)
3.9 Days
Standard Deviation 2.0
4.9 Days
Standard Deviation 1.4

Adverse Events

NOMAC-E2

Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths

LNG-EE

Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
NOMAC-E2
n=60 participants at risk
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 participants at risk
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Congenital, familial and genetic disorders
Congenital mitral valve incompetence
1.7%
1/60 • Number of events 1
0.00%
0/58

Other adverse events

Other adverse events
Measure
NOMAC-E2
n=60 participants at risk
Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE
n=58 participants at risk
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
Infections and infestations
Influenza
1.7%
1/60 • Number of events 1
6.9%
4/58 • Number of events 4
Infections and infestations
Upper respiratory tract infection
10.0%
6/60 • Number of events 14
8.6%
5/58 • Number of events 6
Nervous system disorders
Headache
5.0%
3/60 • Number of events 5
12.1%
7/58 • Number of events 14
Skin and subcutaneous tissue disorders
Acne
3.3%
2/60 • Number of events 2
6.9%
4/58 • Number of events 4

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Results disclosure agreements

  • Principal investigator is a sponsor employee The SPONSOR recognizes the right of the investigator(s) to publish, but all publications must be based on data validated and released by the SPONSOR. Any such scientific paper, presentation, or other communication concerning the clinical trial will first be submitted to the SPONSOR, at least six weeks ahead of estimated publication or presentation, for consent, which shall not be withheld unreasonably.
  • Publication restrictions are in place

Restriction type: OTHER