Trial Outcomes & Findings for Estradiol/Norethindrone Acetate Tablets, 1/0.5 mg Under Fasting Conditions (NCT NCT01157182)
NCT ID: NCT01157182
Last Updated: 2010-12-17
Results Overview
Bioequivalence based on Norethindrone Cmax.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
36 participants
Primary outcome timeframe
Blood samples collected over a 36 hour period.
Results posted on
2010-12-17
Participant Flow
Participant milestones
| Measure |
Estradiol/Norethindrone Acetate (Test) First
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in first period followed by 1/0.5 mg Activella® Tablets reference product dosed in the second period.
|
Activella® (Reference) First
1/0.5 mg Activella® Tablets reference product dosed in first period followed by 1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in the second period.
|
|---|---|---|
|
First Intervention
STARTED
|
18
|
18
|
|
First Intervention
COMPLETED
|
18
|
18
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
|
Washout of 28 Days
STARTED
|
18
|
18
|
|
Washout of 28 Days
COMPLETED
|
16
|
18
|
|
Washout of 28 Days
NOT COMPLETED
|
2
|
0
|
|
Second Intervention
STARTED
|
16
|
18
|
|
Second Intervention
COMPLETED
|
16
|
18
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Estradiol/Norethindrone Acetate (Test) First
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in first period followed by 1/0.5 mg Activella® Tablets reference product dosed in the second period.
|
Activella® (Reference) First
1/0.5 mg Activella® Tablets reference product dosed in first period followed by 1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in the second period.
|
|---|---|---|
|
Washout of 28 Days
Adverse Event
|
2
|
0
|
Baseline Characteristics
Estradiol/Norethindrone Acetate Tablets, 1/0.5 mg Under Fasting Conditions
Baseline characteristics by cohort
| Measure |
Estradiol/Norethindrone Acetate (Test) First
n=18 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in first period followed by 1/0.5 mg Activella® Tablets reference product dosed in the second period.
|
Activella® (Reference) First
n=18 Participants
1/0.5 mg Activella® Tablets reference product dosed in first period followed by 1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in the second period.
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
12 participants
n=5 Participants
|
14 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
0 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
18 participants
n=5 Participants
|
18 participants
n=7 Participants
|
36 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Blood samples collected over a 36 hour period.Population: All participants that completed the study had their samples analyzed.
Bioequivalence based on Norethindrone Cmax.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax for Norethindrone(Maximum Observed Concentration of Drug Substance in Plasma)
|
10.08 ng/mL
Standard Deviation 3.32
|
9.90 ng/mL
Standard Deviation 3.68
|
PRIMARY outcome
Timeframe: Blood samples collected over a 36 hour period.Population: All participants that completed the study had their samples analyzed.
Bioequivalence based on Norethindrone AUC0-t.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t for Norethindrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
36.59 ng*h/mL
Standard Deviation 19.54
|
37.05 ng*h/mL
Standard Deviation 18.07
|
PRIMARY outcome
Timeframe: Blood samples collected over a 36 hour period.Population: All participants that completed the study had their samples analyzed.
Bioequivalence based on Norethindrone AUC0-inf.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf for Norethindrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
39.94 ng*h/mL
Standard Deviation 20.14
|
40.40 ng*h/mL
Standard Deviation 18.90
|
PRIMARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Bioequivalence based on Corrected Total Estrone Cmax.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax for Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
|
43997.17 pg/mL
Standard Deviation 10387.84
|
47015.47 pg/mL
Standard Deviation 9894.22
|
PRIMARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Bioequivalence based on Corrected Total Estrone AUC0-t.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t for Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
365242.88 pg*h/mL
Standard Deviation 155344.76
|
374730.12 pg*h/mL
Standard Deviation 145770.97
|
PRIMARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Bioequivalence based on Corrected Total Estrone AUC0-inf.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf for Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
375439.71 pg*h/mL
Standard Deviation 164404.58
|
384535.16 pg*h/mL
Standard Deviation 153333.46
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of Cmax values for Uncorrected Total Estrone.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax for Uncorrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
|
43723.53 pg/mL
Standard Deviation 10562.40
|
47170.59 pg/mL
Standard Deviation 9913.52
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of AUC0-t values for Uncorrected Total Estrone.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t for Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
372088.37 pg*h/mL
Standard Deviation 159941.67
|
385829.05 pg*h/mL
Standard Deviation 150207.71
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of AUC0-inf values for Uncorrected Total Estrone.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf for Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
387085.29 pg*h/mL
Standard Deviation 172021.74
|
400726.94 pg*h/mL
Standard Deviation 160336.60
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of Cmax values for Uncorrected Unconjugated Estradiol.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax for Uncorrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)
|
52.09 pg/mL
Standard Deviation 19.78
|
56.26 pg/mL
Standard Deviation 18.96
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of AUC0-t values for Uncorrected Unconjugated Estradiol.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t for Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
1575.01 pg*h/mL
Standard Deviation 670.36
|
1656.16 pg*h/mL
Standard Deviation 680.55
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of AUC0-inf values for Uncorrected Unconjugated Estradiol.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf for Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
1739.31 pg*h/mL
Standard Deviation 671.74
|
1905.28 pg*h/mL
Standard Deviation 865.43
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of Cmax values for Uncorrected Unconjugated Estrone.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax for Uncorrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
|
475.44 pg/mL
Standard Deviation 155.40
|
502.24 pg/mL
Standard Deviation 163.45
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of AUC0-t values for Uncorrected Unconjugated Estrone.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t for Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
10870.03 pg*h/mL
Standard Deviation 4207.05
|
11252.64 pg*h/mL
Standard Deviation 4220.20
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of AUC0-inf values for Uncorrected Unconjugated Estrone.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf for Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
12387.14 pg*h/mL
Standard Deviation 4715.23
|
12646.49 pg*h/mL
Standard Deviation 4673.97
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of Cmax values for Corrected Unconjugated Estradiol.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax for Corrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)
|
47.80 pg/mL
Standard Deviation 19.05
|
51.59 pg/mL
Standard Deviation 18.77
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of AUC0-t values for Corrected Unconjugated Estradiol.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t for Corrected Unconjugated Estradiol.(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
1267.50 pg*h/mL
Standard Deviation 574.02
|
1323.70 pg*h/mL
Standard Deviation 615.33
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of AUC0-inf values for Corrected Unconjugated Estradiol.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf for Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
1359.50 pg*h/mL
Standard Deviation 664.41
|
1410.51 pg*h/mL
Standard Deviation 695.23
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of Cmax values for Corrected Unconjugated Estrone.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax for Corrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
|
455.16 pg/mL
Standard Deviation 153.38
|
481.46 pg/mL
Standard Deviation 163.19
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of AUC0-t values for Corrected Unconjugated Estrone.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t for Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
9409.59 pg*h/mL
Standard Deviation 4029.75
|
9762.49 pg*h/mL
Standard Deviation 4170.35
|
SECONDARY outcome
Timeframe: Blood samples collected over a 72 hour period.Population: All participants that completed the study had their samples analyzed.
Informational comparison of AUC0-inf values for Corrected Unconjugated Estrone.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=34 Participants
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=34 Participants
1/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf for Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
10267.03 pg*h/mL
Standard Deviation 4156.10
|
10214.23 pg*h/mL
Standard Deviation 4497.68
|
Adverse Events
Estradiol/Norethindrone Acetate (Test) First
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Activella® (Reference) First
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Estradiol/Norethindrone Acetate (Test) First
n=36 participants at risk
1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in first period followed by 1/0.5 mg Activella® Tablets reference product dosed in the second period.
|
Activella® (Reference) First
n=36 participants at risk
1/0.5 mg Activella® Tablets reference product dosed in first period followed by 1/0.5 mg Estradiol/Norethindrone acetate Tablets test product dosed in the second period.
|
|---|---|---|
|
General disorders
Headache
|
8.3%
3/36 • Number of events 4 • Adverse event data was collected over the course of the study, which was approximately 6 weeks in duration.
Volunteers were monitored throughout the study for any adverse experiences. AEs were collected through both solicited and unsolicited methods. The volunteers were encouraged to report signs, symptoms, and any changes in health to the clinic staff.
|
0.00%
0/36 • Adverse event data was collected over the course of the study, which was approximately 6 weeks in duration.
Volunteers were monitored throughout the study for any adverse experiences. AEs were collected through both solicited and unsolicited methods. The volunteers were encouraged to report signs, symptoms, and any changes in health to the clinic staff.
|
Additional Information
Associate Director, Biopharmaceutics
TEVA Pharmaceuticals, USA
Phone: 1-866-384-5525
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Principal Investigator is not permitted to discuss or publish trial results.
- Publication restrictions are in place
Restriction type: OTHER