Bioequivalence of Nomegestrol Acetate (NOMAC) and Estradiol (E2) in Commercial Versus Phase 3 Pivotal Clinical Batches of NOMAC-E2 Tablets (P06328)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01345786
• Collaborator: (none)
• Enrollment: 158
• Arms: 4
• Duration (Months): 7

Study Details

Study Description

Brief Summary

For the contraceptive application a film-coated tablet has been developed which combines nomegestrol acetate (NOMAC) with estradiol (E2). This was an open-label, randomized, single-dose, four-way, replicate, cross-over study design conducted in 2 parallel parts at two sites, one site per study part. The primary objective of Part 1 was to assess the bioequivalence of NOMAC and E2 of the drug product manufactured using the commercial process ("commercial batch") versus the Phase 3 drug product ("Batch A"). The primary objective of Part 2 was to assess bioequivalence of NOMAC and E2 of the drug product manufactured using the commercial process ("commercial batch") versus the Phase 3 drug product ("Batch B").

Condition or Disease	Intervention/Treatment	Phase
Healthy Postmenopausal Females	Drug: Commercial NOMAC-E2; Drug: Phase 3 NOMAC-E2 "Batch A"; Drug: Phase 3 NOMAC-E2 "Batch B"	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 158 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A 2-part, Cross-over Trial of NOMAC-E2 to Assess Bioequivalence Between the Phase 3 Pivotal Clinical Batches and a Batch Prepared Using the Commercial Drug Manufacturing Process
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Commercial NOMAC-E2, Part 1 Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Drug: Commercial NOMAC-E2; 1 x 2.5 mg NOMAC/1.5 mg E2 fixed dose combination commercial tablet orally in the morning on Day 1 for all periods; Other Names: SCH 900121
Active Comparator: Phase 3 NOMAC-E2, Part 1 Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Drug: Phase 3 NOMAC-E2 "Batch A"; 1 x 2.5 mg NOMAC/1.5 mg E2 fixed dose combination tablet from the Phase 3 clinical trial program ("Batch A") orally in the morning on Day 1 for all periods; Other Names: SCH900121
Experimental: Commercial NOMAC-E2, Part 2 Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".	Drug: Commercial NOMAC-E2; 1 x 2.5 mg NOMAC/1.5 mg E2 fixed dose combination commercial tablet orally in the morning on Day 1 for all periods; Other Names: SCH 900121
Active Comparator: Phase 3 NOMAC-E2, Part 2 Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".	Drug: Phase 3 NOMAC-E2 "Batch B"; 1 x 2.5 mg NOMAC/1.5 mg E2 fixed dose combination tablet from the Phase 3 clinical trial program ("Batch B") orally in the morning on Day 1 for all periods; Other Names: SCH 900121

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC) [0 hours to time of maximum observed plasma concentration of NOMAC (tmax of NOMAC) (blood samples were collected for NOMAC evaluation up to 144 hours postdose)]

   Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. Blood samples for pharmacokinetic (PK) evaluation of NOMAC were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 144 hours postdose Day 1.

2. Baseline Corrected Maximum Observed Serum Concentration of E2 (Cmax of E2) [0 hours to time of maximum observed serum concentration of E2 (tmax of E2) (blood samples were collected for E2 evaluation up to 96 hours postdose)]

   Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. Blood samples for PK evaluation of E2 were collected predose (-1, -0.5, and 0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose Day 1; multiple predose samples were needed to correct for endogenous levels.

3. Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC [0 hours to time of the last measurable sample (blood samples were collected for NOMAC evaluation up to 144 hours postdose)]

   Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. AUClast is the AUC from time 0 to the time of the final quantifiable sample. AUC infinity is the AUC from time 0 to infinity. Blood samples for PK evaluation of NOMAC were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 144 hours postdose Day 1.

4. Baseline Corrected Area Under the Concentration-time Curve From Time 0 to 72 Hours (AUC72) for E2 [0 hours to 72 hours]

   Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. AUC72 is the AUC from time 0 to 72 hours. Blood samples for PK evaluation of E2 were collected predose (-1, -0.5, and 0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose Day 1; multiple predose samples were needed to correct for endogenous levels.

Secondary Outcome Measures

1. Tmax of NOMAC [0 hours to tmax of NOMAC (blood samples were collected for NOMAC evaluation up to 144 hours postdose)]

2. Tmax of E2 [0 hours to tmax of E2 (blood samples were collected for E2 evaluation up to 96 hours postdose)]

3. Terminal Phase Half Life (t1/2) of NOMAC [0 hours to t1/2 (blood samples were collected for NOMAC evaluation up to 144 hours postdose)]

4. t1/2 of E2 [0 hours to t1/2 (blood samples were collected for E2 evaluation up to 96 hours postdose)]

5. Clearance (Calculated for NOMAC Only) [blood samples were collected for NOMAC evaluation up to 144 hours postdose]

6. Volume of Distribution (Calculated for NOMAC Only) [blood samples were collected for NOMAC evaluation up to 144 hours postdose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Key Inclusion Criteria:

• Healthy postmenopausal females between the ages of 45 and 70 years, inclusive, having a Body Mass Index (BMI) between 18 and 32, inclusive;

• Free of any clinically significant disease that would interfere with the study evaluations.

Key Exclusion Criteria:

• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug;

• History of any infectious disease that affected the subject's ability to participate in the trial;

• History of alcohol or drug abuse in the past 2 years;

• Previously received NOMAC-E2;

• Current participation in another clinical study or had participated in a clinical study (eg, laboratory or clinical evaluation) within 30 days of baseline;

• Smoked more than 10 cigarettes or equivalent tobacco use per day;

• History of malignancy;

• Contraindications for the use of contraceptive steroids;

• Recent history of medication use of certain medications specified in the protocol.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT01345786
• Other Study ID Numbers: P06328
• First Posted: May 2, 2011
• Last Update Posted: Feb 9, 2022
• Last Verified: Feb 1, 2022

Study Results

Participant Flow

Arm/Group Title	Part 1 - Sequence 1	Part 1 - Sequence 2	Part 2 - Sequence 1	Part 2 - Sequence 2
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2) on the first day of Period 1 and Period 3; Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A") on the first day of Period 2 and Period 4. Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A") on the first day of Period 1 and Period 3; Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2) on the first day of Period 2 and Period 4. Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2) on the first day of Period 1 and Period 3; Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B") on the first day of Period 2 and Period 4. Participants in Part 2 were from "Site 2".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B") on the first day of Period 1 and Period 3; Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2) on the first day of Period 2 and Period 4. Participants in Part 2 were from "Site 2".
Period Title: Overall Study
STARTED	41	41	38	38
Treated	41	41	37	37
COMPLETED	35	33	33	35
NOT COMPLETED	6	8	5	3

Baseline Characteristics

Arm/Group Title	Part 1 - Sequence 1	Part 1 - Sequence 2	Part 2 - Sequence 1	Part 2 - Sequence 2	Total
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2) on the first day of Period 1 and Period 3; Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A") on the first day of Period 2 and Period 4. Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A") on the first day of Period 1 and Period 3; Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2) on the first day of Period 2 and Period 4. Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2) on the first day of Period 1 and Period 3; Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B") on the first day of Period 2 and Period 4. Participants in Part 2 were from "Site 2".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B") on the first day of Period 1 and Period 3; Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2) on the first day of Period 2 and Period 4. Participants in Part 2 were from "Site 2".	Total of all reporting groups
Overall Participants	41	41	37	37	156
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	55.3	55.5	55.9	56.5	55.78
Sex: Female, Male (Count of Participants)
Female	41 100%	41 100%	37 100%	37 100%	156 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC)
Description	Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. Blood samples for pharmacokinetic (PK) evaluation of NOMAC were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 144 hours postdose Day 1.
Time Frame	0 hours to time of maximum observed plasma concentration of NOMAC (tmax of NOMAC) (blood samples were collected for NOMAC evaluation up to 144 hours postdose)

Outcome Measure Data

Analysis Population Description

The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods). Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.

Arm/Group Title	Commercial NOMAC-E2, Part 1	Phase 3 NOMAC-E2, Part 1	Commercial NOMAC-E2, Part 2	Phase 3 NOMAC-E2, Part 2
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
Measure Participants	70	71	72	72
Measure plasma profiles	138	138	140	140
Mean (Full Range) [ng/mL]	6.22	4.51	8.03	7.20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Commercial NOMAC-E2, Part 1, Phase 3 NOMAC-E2, Part 1
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Acceptance criteria of 80 - 125% were used for bioequivalence evaluations (bioequivalence concluded when 90% confidence interval fully contained within acceptance criteria).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (Test/Ref %)
	Estimated Value	137.5
	Confidence Interval	() 90%; 131 to 144.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Commercial Batch Test / Phase 3 Batch Reference.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Commercial NOMAC-E2, Part 2, Phase 3 NOMAC-E2, Part 2
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Acceptance criteria of 80 - 125% were used for bioequivalence evaluations (bioequivalence concluded when 90% confidence interval fully contained within acceptance criteria).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (Test/Ref %)
	Estimated Value	111.8
	Confidence Interval	() 90%; 107.5 to 116.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Commercial Batch Test / Phase 3 Batch Reference.

2. Primary Outcome

Title	Baseline Corrected Maximum Observed Serum Concentration of E2 (Cmax of E2)
Description	Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. Blood samples for PK evaluation of E2 were collected predose (-1, -0.5, and 0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose Day 1; multiple predose samples were needed to correct for endogenous levels.
Time Frame	0 hours to time of maximum observed serum concentration of E2 (tmax of E2) (blood samples were collected for E2 evaluation up to 96 hours postdose)

Outcome Measure Data

Analysis Population Description

The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods). Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.

Arm/Group Title	Commercial NOMAC-E2, Part 1	Phase 3 NOMAC-E2, Part 1	Commercial NOMAC-E2, Part 2	Phase 3 NOMAC-E2, Part 2
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
Measure Participants	70	71	72	72
Measure plasma profiles	138	138	138	137
Mean (Full Range) [pg/mL]	56.1	45.1	44.4	41.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Commercial NOMAC-E2, Part 1, Phase 3 NOMAC-E2, Part 1
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Acceptance criteria of 80 - 125% were used for bioequivalence evaluations (bioequivalence concluded when 90% confidence interval fully contained within acceptance criteria).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (Test/Ref %)
	Estimated Value	107.3
	Confidence Interval	() 90%; 99 to 116.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Commercial Batch Test / Phase 3 Batch Reference.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Commercial NOMAC-E2, Part 2, Phase 3 NOMAC-E2, Part 2
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Acceptance criteria of 80 - 125% were used for bioequivalence evaluations (bioequivalence concluded when 90% confidence interval fully contained within acceptance criteria).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (Test/Ref %)
	Estimated Value	103.6
	Confidence Interval	() 90%; 99.2 to 108.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Commercial Batch Test / Phase 3 Batch Reference. In addition to the participants/profiles excluded, 1 participant from the Phase 3 Batch Reference group did not contribute to this comparison.

3. Primary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC
Description	Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. AUClast is the AUC from time 0 to the time of the final quantifiable sample. AUC infinity is the AUC from time 0 to infinity. Blood samples for PK evaluation of NOMAC were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 144 hours postdose Day 1.
Time Frame	0 hours to time of the last measurable sample (blood samples were collected for NOMAC evaluation up to 144 hours postdose)

Outcome Measure Data

Analysis Population Description

The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods). Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.

Arm/Group Title	Commercial NOMAC-E2, Part 1	Phase 3 NOMAC-E2, Part 1	Commercial NOMAC-E2, Part 2	Phase 3 NOMAC-E2, Part 2
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
Measure Participants	70	71	72	72
Measure plasma profiles	138	138	140	140
AUC last	87.3	78.1	109	106
AUC infinity	102	93.3	134	131

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Commercial NOMAC-E2, Part 1, Phase 3 NOMAC-E2, Part 1
	Comments	Analysis for AUClast
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Acceptance criteria of 80 - 125% were used for bioequivalence evaluations (bioequivalence concluded when 90% confidence interval fully contained within acceptance criteria).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (Test/Ref %)
	Estimated Value	110.0
	Confidence Interval	() 90%; 106.4 to 113.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Commercial Batch Test / Phase 3 Batch Reference.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Commercial NOMAC-E2, Part 2, Phase 3 NOMAC-E2, Part 2
	Comments	Analysis for AUC last
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Acceptance criteria of 80 - 125% were used for bioequivalence evaluations (bioequivalence concluded when 90% confidence interval fully contained within acceptance criteria).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (Test/Ref %)
	Estimated Value	103.3
	Confidence Interval	() 90%; 100.9 to 105.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Commercial Batch Test / Phase 3 Batch Reference

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Commercial NOMAC-E2, Part 1, Phase 3 NOMAC-E2, Part 1
	Comments	Analysis for AUC infinity
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Acceptance criteria of 80 - 125% were used for bioequivalence evaluations (bioequivalence concluded when 90% confidence interval fully contained within acceptance criteria).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (Test/Ref %)
	Estimated Value	108.1
	Confidence Interval	() 90%; 104.7 to 111.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Commercial Batch Test / Phase 3 Batch Reference.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Commercial NOMAC-E2, Part 2, Phase 3 NOMAC-E2, Part 2
	Comments	Analysis for AUC infinity
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Acceptance criteria of 80 - 125% were used for bioequivalence evaluations (bioequivalence concluded when 90% confidence interval fully contained within acceptance criteria).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (Test/Ref %)
	Estimated Value	103.1
	Confidence Interval	() 90%; 100.5 to 105.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Commercial Batch Test / Phase 3 Batch Reference

4. Primary Outcome

Title	Baseline Corrected Area Under the Concentration-time Curve From Time 0 to 72 Hours (AUC72) for E2
Description	Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2. AUC72 is the AUC from time 0 to 72 hours. Blood samples for PK evaluation of E2 were collected predose (-1, -0.5, and 0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose Day 1; multiple predose samples were needed to correct for endogenous levels.
Time Frame	0 hours to 72 hours

Outcome Measure Data

Analysis Population Description

The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods). Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.

Arm/Group Title	Commercial NOMAC-E2, Part 1	Phase 3 NOMAC-E2, Part 1	Commercial NOMAC-E2, Part 2	Phase 3 NOMAC-E2, Part 2
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
Measure Participants	70	71	72	72
Measure plasma profiles	138	137	138	137
Mean (Full Range) [pg*h/mL]	1315	1278	1359	1342

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Commercial NOMAC-E2, Part 1, Phase 3 NOMAC-E2, Part 1
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Acceptance criteria of 80 - 125% were used for bioequivalence evaluations (bioequivalence concluded when 90% confidence interval fully contained within acceptance criteria).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (Test/Ref %)
	Estimated Value	101.5
	Confidence Interval	() 90%; 96.7 to 106.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Commercial Batch Test / Phase 3 Batch Reference.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Commercial NOMAC-E2, Part 2, Phase 3 NOMAC-E2, Part 2
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Acceptance criteria of 80 - 125% were used for bioequivalence evaluations (bioequivalence concluded when 90% confidence interval fully contained within acceptance criteria).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio (Test/Ref %)
	Estimated Value	101.3
	Confidence Interval	() 90%; 98.1 to 104.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Commercial Batch Test / Phase 3 Batch Reference. In addition to the participants/profiles excluded, 1 participant from the Phase 3 Batch Reference group did not contribute to this comparison.

5. Secondary Outcome

Title	Tmax of NOMAC
Time Frame	0 hours to tmax of NOMAC (blood samples were collected for NOMAC evaluation up to 144 hours postdose)

Outcome Measure Data

Analysis Population Description

The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods). Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.

Arm/Group Title	Commercial NOMAC-E2, Part 1	Phase 3 NOMAC-E2, Part 1	Commercial NOMAC-E2, Part 2	Phase 3 NOMAC-E2, Part 2
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
Measure Participants	70	71	72	72
Measure plasma profiles	138	138	140	140
Median (Full Range) [hours]	2	2	2	2

6. Secondary Outcome

Title	Tmax of E2
Time Frame	0 hours to tmax of E2 (blood samples were collected for E2 evaluation up to 96 hours postdose)

Outcome Measure Data

Analysis Population Description

The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods). Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.

Arm/Group Title	Commercial NOMAC-E2, Part 1	Phase 3 NOMAC-E2, Part 1	Commercial NOMAC-E2, Part 2	Phase 3 NOMAC-E2, Part 2
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
Measure Participants	70	71	72	72
Measure plasma profiles	138	138	140	140
Median (Full Range) [hours]	6.02	8	8	8

7. Secondary Outcome

Title	Terminal Phase Half Life (t1/2) of NOMAC
Time Frame	0 hours to t1/2 (blood samples were collected for NOMAC evaluation up to 144 hours postdose)

Outcome Measure Data

Analysis Population Description

The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods). Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.

Arm/Group Title	Commercial NOMAC-E2, Part 1	Phase 3 NOMAC-E2, Part 1	Commercial NOMAC-E2, Part 2	Phase 3 NOMAC-E2, Part 2
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
Measure Participants	70	71	72	72
Measure plasma profiles	138	138	140	140
Mean (Full Range) [hours]	58.5	61	70.8	69.9

8. Secondary Outcome

Title	t1/2 of E2
Time Frame	0 hours to t1/2 (blood samples were collected for E2 evaluation up to 96 hours postdose)

Outcome Measure Data

Analysis Population Description

The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods). Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.

Arm/Group Title	Commercial NOMAC-E2, Part 1	Phase 3 NOMAC-E2, Part 1	Commercial NOMAC-E2, Part 2	Phase 3 NOMAC-E2, Part 2
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
Measure Participants	70	71	72	72
Measure plasma profiles	131	131	134	139
Mean (Full Range) [hours]	39.9	39.1	33.1	34.6

9. Secondary Outcome

Title	Clearance (Calculated for NOMAC Only)
Time Frame	blood samples were collected for NOMAC evaluation up to 144 hours postdose

Outcome Measure Data

Analysis Population Description

The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods). Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.

Arm/Group Title	Commercial NOMAC-E2, Part 1	Phase 3 NOMAC-E2, Part 1	Commercial NOMAC-E2, Part 2	Phase 3 NOMAC-E2, Part 2
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
Measure Participants	70	71	72	72
Measure plasma profiles	138	138	140	140
Mean (Standard Deviation) [L/h]	28.3 (16.1)	29.9 (9.68)	21.1 (7.96)	22.1 (9.37)

10. Secondary Outcome

Title	Volume of Distribution (Calculated for NOMAC Only)
Time Frame	blood samples were collected for NOMAC evaluation up to 144 hours postdose

Outcome Measure Data

Analysis Population Description

The # of plasma profiles analyzed is based on the # of single-dose administration periods actually completed (some participants discontinued without completing all 4 dosing periods). Part 1 analyses also excluded certain data from participants who were misdosed, and Part 2 analyses excluded participants who did not receive drug.

Arm/Group Title	Commercial NOMAC-E2, Part 1	Phase 3 NOMAC-E2, Part 1	Commercial NOMAC-E2, Part 2	Phase 3 NOMAC-E2, Part 2
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
Measure Participants	70	71	72	72
Measure plasma profiles	138	138	140	140
Mean (Standard Deviation) [L]	2208 (886)	2445 (906)	1988 (631)	2061 (673)

Adverse Events

Adverse Event Reporting Description	Number of participants at risk for each group is the number of participants who received the treatment (batch).
Arm/Group Title	Commercial NOMAC-E2, Part 1		Phase 3 NOMAC-E2, Part 1		Commercial NOMAC-E2, Part 2		Phase 3 NOMAC-E2, Part 2
Arm/Group Description	Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".		Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".		Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".		Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
All Cause Mortality
	Commercial NOMAC-E2, Part 1		Phase 3 NOMAC-E2, Part 1		Commercial NOMAC-E2, Part 2		Phase 3 NOMAC-E2, Part 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Commercial NOMAC-E2, Part 1		Phase 3 NOMAC-E2, Part 1		Commercial NOMAC-E2, Part 2		Phase 3 NOMAC-E2, Part 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/80 (0%)		0/77 (0%)		0/72 (0%)		0/72 (0%)
Other (Not Including Serious) Adverse Events
	Commercial NOMAC-E2, Part 1		Phase 3 NOMAC-E2, Part 1		Commercial NOMAC-E2, Part 2		Phase 3 NOMAC-E2, Part 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/80 (55%)		35/77 (45.5%)		36/72 (50%)		35/72 (48.6%)
Gastrointestinal disorders
Constipation	5/80 (6.3%)	10	1/77 (1.3%)	2	8/72 (11.1%)	22	8/72 (11.1%)	20
Nausea	5/80 (6.3%)	10	7/77 (9.1%)	14	3/72 (4.2%)	6	1/72 (1.4%)	2
Musculoskeletal and connective tissue disorders
Back pain	3/80 (3.8%)	6	2/77 (2.6%)	4	3/72 (4.2%)	6	6/72 (8.3%)	12
Nervous system disorders
Dizziness	3/80 (3.8%)	8	5/77 (6.5%)	10	0/72 (0%)	0	1/72 (1.4%)	2
Headache	15/80 (18.8%)	40	14/77 (18.2%)	40	12/72 (16.7%)	26	13/72 (18.1%)	32
Reproductive system and breast disorders
Breast tenderness	5/80 (6.3%)	10	3/77 (3.9%)	6	1/72 (1.4%)	2	2/72 (2.8%)	4
Pelvic pain	0/80 (0%)	0	1/77 (1.3%)	2	3/72 (4.2%)	6	8/72 (11.1%)	18
Vaginal discharge	4/80 (5%)	12	4/77 (5.2%)	10	0/72 (0%)	0	0/72 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/80 (1.3%)	2	1/77 (1.3%)	2	5/72 (6.9%)	10	1/72 (1.4%)	2
Oropharyngeal pain	1/80 (1.3%)	2	5/77 (6.5%)	10	2/72 (2.8%)	4	4/72 (5.6%)	8
Skin and subcutaneous tissue disorders
Acne	2/80 (2.5%)	4	0/77 (0%)	0	8/72 (11.1%)	18	12/72 (16.7%)	28
Pruritus	0/80 (0%)	0	1/77 (1.3%)	1	2/72 (2.8%)	4	4/72 (5.6%)	8
Pruritus generalised	0/80 (0%)	0	0/77 (0%)	0	4/72 (5.6%)	8	1/72 (1.4%)	2
Vascular disorders
Hot flush	14/80 (17.5%)	40	8/77 (10.4%)	20	9/72 (12.5%)	22	8/72 (11.1%)	16

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI must provide sponsor w/ review copies of abstracts or manuscripts for publication that report any results of the study, 45 days before submission for publication or presentation. The sponsor shall have the right to review/comment on the material. If the parties disagree about the appropriateness of the material, PI must meet with sponsor's representatives before submission for publication, for the purpose of making good faith efforts to discuss and resolve any issues of disagreement.