Trial Outcomes & Findings for Bioequivalence of Nomegestrol Acetate (NOMAC) and Estradiol (E2) in Commercial Versus Phase 3 Pivotal Clinical Batches of NOMAC-E2 Tablets (P06328) (NCT NCT01345786)
NCT ID: NCT01345786
Last Updated: 2022-02-09
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
158 participants
Primary outcome timeframe
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)
Results posted on
2022-02-09
Participant Flow
Participant milestones
| Measure |
Part 1 - Sequence 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 A") on the first day of Period 2 and Period 4. Participants in Part 1 were from "Site 1".
|
Part 1 - Sequence 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 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".
|
Part 2 - Sequence 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".
|
Part 2 - Sequence 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".
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
41
|
41
|
38
|
38
|
|
Overall Study
Treated
|
41
|
41
|
37
|
37
|
|
Overall Study
COMPLETED
|
35
|
33
|
33
|
35
|
|
Overall Study
NOT COMPLETED
|
6
|
8
|
5
|
3
|
Reasons for withdrawal
| Measure |
Part 1 - Sequence 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 A") on the first day of Period 2 and Period 4. Participants in Part 1 were from "Site 1".
|
Part 1 - Sequence 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 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".
|
Part 2 - Sequence 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".
|
Part 2 - Sequence 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".
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
3
|
1
|
|
Overall Study
Subject withdrew consent
|
2
|
2
|
1
|
0
|
|
Overall Study
Noncompliance with protocol
|
1
|
0
|
1
|
0
|
|
Overall Study
Administrative
|
3
|
5
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
2
|
Baseline Characteristics
Bioequivalence of Nomegestrol Acetate (NOMAC) and Estradiol (E2) in Commercial Versus Phase 3 Pivotal Clinical Batches of NOMAC-E2 Tablets (P06328)
Baseline characteristics by cohort
| Measure |
Part 1 - Sequence 1
n=41 Participants
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".
|
Part 1 - Sequence 2
n=41 Participants
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".
|
Part 2 - Sequence 1
n=37 Participants
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".
|
Part 2 - Sequence 2
n=37 Participants
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
n=156 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
55.3 years
n=39 Participants
|
55.5 years
n=41 Participants
|
55.9 years
n=35 Participants
|
56.5 years
n=31 Participants
|
55.78 years
n=146 Participants
|
|
Sex: Female, Male
Female
|
41 Participants
n=39 Participants
|
41 Participants
n=41 Participants
|
37 Participants
n=35 Participants
|
37 Participants
n=31 Participants
|
156 Participants
n=146 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=146 Participants
|
PRIMARY outcome
Timeframe: 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)Population: 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.
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.
Outcome measures
| Measure |
Commercial NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Commercial NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC)
|
6.22 ng/mL
Interval 1.06 to 13.3
|
4.51 ng/mL
Interval 1.72 to 11.6
|
8.03 ng/mL
Interval 3.44 to 14.4
|
7.20 ng/mL
Interval 2.7 to 12.6
|
PRIMARY outcome
Timeframe: 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)Population: 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.
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.
Outcome measures
| Measure |
Commercial NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Commercial NOMAC-E2, Part 2
n=138 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 2
n=137 plasma profiles
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".
|
|---|---|---|---|---|
|
Baseline Corrected Maximum Observed Serum Concentration of E2 (Cmax of E2)
|
56.1 pg/mL
Interval 10.2 to 1255.0
|
45.1 pg/mL
Interval 9.76 to 324.0
|
44.4 pg/mL
Interval 14.1 to 347.0
|
41.5 pg/mL
Interval 19.8 to 133.0
|
PRIMARY outcome
Timeframe: 0 hours to time of the last measurable sample (blood samples were collected for NOMAC evaluation up to 144 hours postdose)Population: 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.
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.
Outcome measures
| Measure |
Commercial NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Commercial NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
|---|---|---|---|---|
|
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
AUC last
|
87.3 ng*h/mL
Interval 9.71 to 151.0
|
78.1 ng*h/mL
Interval 33.5 to 148.0
|
109 ng*h/mL
Interval 45.4 to 207.0
|
106 ng*h/mL
Interval 35.5 to 194.0
|
|
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
AUC infinity
|
102 ng*h/mL
Interval 13.6 to 182.0
|
93.3 ng*h/mL
Interval 42.4 to 200.0
|
134 ng*h/mL
Interval 49.2 to 299.0
|
131 ng*h/mL
Interval 39.4 to 262.0
|
PRIMARY outcome
Timeframe: 0 hours to 72 hoursPopulation: 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.
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.
Outcome measures
| Measure |
Commercial NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 1
n=137 plasma profiles
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".
|
Commercial NOMAC-E2, Part 2
n=138 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 2
n=137 plasma profiles
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".
|
|---|---|---|---|---|
|
Baseline Corrected Area Under the Concentration-time Curve From Time 0 to 72 Hours (AUC72) for E2
|
1315 pg*h/mL
Interval 184.0 to 3132.0
|
1278 pg*h/mL
Interval 140.0 to 3481.0
|
1359 pg*h/mL
Interval 335.0 to 2813.0
|
1342 pg*h/mL
Interval 297.0 to 3059.0
|
SECONDARY outcome
Timeframe: 0 hours to tmax of NOMAC (blood samples were collected for NOMAC evaluation up to 144 hours postdose)Population: 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.
Outcome measures
| Measure |
Commercial NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Commercial NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
|---|---|---|---|---|
|
Tmax of NOMAC
|
2 hours
Interval 0.5 to 6.0
|
2 hours
Interval 1.0 to 6.0
|
2 hours
Interval 1.0 to 6.0
|
2 hours
Interval 1.0 to 6.0
|
SECONDARY outcome
Timeframe: 0 hours to tmax of E2 (blood samples were collected for E2 evaluation up to 96 hours postdose)Population: 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.
Outcome measures
| Measure |
Commercial NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Commercial NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
|---|---|---|---|---|
|
Tmax of E2
|
6.02 hours
Interval 0.5 to 96.0
|
8 hours
Interval 0.5 to 96.0
|
8 hours
Interval 0.5 to 96.0
|
8 hours
Interval 0.5 to 24.0
|
SECONDARY outcome
Timeframe: 0 hours to t1/2 (blood samples were collected for NOMAC evaluation up to 144 hours postdose)Population: 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.
Outcome measures
| Measure |
Commercial NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Commercial NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
|---|---|---|---|---|
|
Terminal Phase Half Life (t1/2) of NOMAC
|
58.5 hours
Interval 17.3 to 137.0
|
61 hours
Interval 19.4 to 278.0
|
70.8 hours
Interval 23.5 to 201.0
|
69.9 hours
Interval 23.4 to 153.0
|
SECONDARY outcome
Timeframe: 0 hours to t1/2 (blood samples were collected for E2 evaluation up to 96 hours postdose)Population: 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.
Outcome measures
| Measure |
Commercial NOMAC-E2, Part 1
n=131 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 1
n=131 plasma profiles
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".
|
Commercial NOMAC-E2, Part 2
n=134 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 2
n=139 plasma profiles
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".
|
|---|---|---|---|---|
|
t1/2 of E2
|
39.9 hours
Interval 8.3 to 855.0
|
39.1 hours
Interval 11.2 to 853.0
|
33.1 hours
Interval 9.02 to 94.8
|
34.6 hours
Interval 7.13 to 128.0
|
SECONDARY outcome
Timeframe: blood samples were collected for NOMAC evaluation up to 144 hours postdosePopulation: 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.
Outcome measures
| Measure |
Commercial NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Commercial NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
|---|---|---|---|---|
|
Clearance (Calculated for NOMAC Only)
|
28.3 L/h
Standard Deviation 16.1
|
29.9 L/h
Standard Deviation 9.68
|
21.1 L/h
Standard Deviation 7.96
|
22.1 L/h
Standard Deviation 9.37
|
SECONDARY outcome
Timeframe: blood samples were collected for NOMAC evaluation up to 144 hours postdosePopulation: 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.
Outcome measures
| Measure |
Commercial NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 1
n=138 plasma profiles
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".
|
Commercial NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
Phase 3 NOMAC-E2, Part 2
n=140 plasma profiles
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".
|
|---|---|---|---|---|
|
Volume of Distribution (Calculated for NOMAC Only)
|
2208 L
Standard Deviation 886
|
2445 L
Standard Deviation 906
|
1988 L
Standard Deviation 631
|
2061 L
Standard Deviation 673
|
Adverse Events
Commercial NOMAC-E2, Part 1
Serious events: 0 serious events
Other events: 44 other events
Deaths: 0 deaths
Phase 3 NOMAC-E2, Part 1
Serious events: 0 serious events
Other events: 35 other events
Deaths: 0 deaths
Commercial NOMAC-E2, Part 2
Serious events: 0 serious events
Other events: 36 other events
Deaths: 0 deaths
Phase 3 NOMAC-E2, Part 2
Serious events: 0 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Commercial NOMAC-E2, Part 1
n=80 participants at risk
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".
|
Phase 3 NOMAC-E2, Part 1
n=77 participants at risk
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".
|
Commercial NOMAC-E2, Part 2
n=72 participants at risk
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".
|
Phase 3 NOMAC-E2, Part 2
n=72 participants at risk
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".
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
6.2%
5/80 • Number of events 10
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
1.3%
1/77 • Number of events 2
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
11.1%
8/72 • Number of events 22
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
11.1%
8/72 • Number of events 20
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Gastrointestinal disorders
Nausea
|
6.2%
5/80 • Number of events 10
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
9.1%
7/77 • Number of events 14
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
4.2%
3/72 • Number of events 6
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
1.4%
1/72 • Number of events 2
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.8%
3/80 • Number of events 6
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
2.6%
2/77 • Number of events 4
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
4.2%
3/72 • Number of events 6
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
8.3%
6/72 • Number of events 12
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Nervous system disorders
Dizziness
|
3.8%
3/80 • Number of events 8
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
6.5%
5/77 • Number of events 10
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
0.00%
0/72
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
1.4%
1/72 • Number of events 2
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Nervous system disorders
Headache
|
18.8%
15/80 • Number of events 40
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
18.2%
14/77 • Number of events 40
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
16.7%
12/72 • Number of events 26
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
18.1%
13/72 • Number of events 32
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Reproductive system and breast disorders
Breast tenderness
|
6.2%
5/80 • Number of events 10
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
3.9%
3/77 • Number of events 6
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
1.4%
1/72 • Number of events 2
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
2.8%
2/72 • Number of events 4
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/80
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
1.3%
1/77 • Number of events 2
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
4.2%
3/72 • Number of events 6
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
11.1%
8/72 • Number of events 18
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Reproductive system and breast disorders
Vaginal discharge
|
5.0%
4/80 • Number of events 12
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
5.2%
4/77 • Number of events 10
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
0.00%
0/72
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
0.00%
0/72
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.2%
1/80 • Number of events 2
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
1.3%
1/77 • Number of events 2
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
6.9%
5/72 • Number of events 10
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
1.4%
1/72 • Number of events 2
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.2%
1/80 • Number of events 2
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
6.5%
5/77 • Number of events 10
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
2.8%
2/72 • Number of events 4
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
5.6%
4/72 • Number of events 8
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Skin and subcutaneous tissue disorders
Acne
|
2.5%
2/80 • Number of events 4
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
0.00%
0/77
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
11.1%
8/72 • Number of events 18
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
16.7%
12/72 • Number of events 28
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/80
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
1.3%
1/77 • Number of events 1
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
2.8%
2/72 • Number of events 4
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
5.6%
4/72 • Number of events 8
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.00%
0/80
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
0.00%
0/77
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
5.6%
4/72 • Number of events 8
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
1.4%
1/72 • Number of events 2
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
|
Vascular disorders
Hot flush
|
17.5%
14/80 • Number of events 40
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
10.4%
8/77 • Number of events 20
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
12.5%
9/72 • Number of events 22
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
11.1%
8/72 • Number of events 16
Number of participants at risk for each group is the number of participants who received the treatment (batch).
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER