Trial Outcomes & Findings for Estradiol/Norethindrone Acetate Tablets, 1/0.5 mg Under Fed Conditions (NCT NCT01181726)
NCT ID: NCT01181726
Last Updated: 2010-12-08
Results Overview
Bioequivalence based on Norethindrone Cmax.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
40 participants
Primary outcome timeframe
Blood samples collected over a 36 hour period.
Results posted on
2010-12-08
Participant Flow
Participant milestones
| Measure |
Estradiol/Norethindrone Acetate (Test) First
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in first period followed by 1 mg/0.5 mg Activella® Tablets reference product dosed in the second period.
|
Activella® (Reference) First
1 mg/0.5 mg Activella® Tablets reference product dosed in first period followed by 1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in the second period.
|
|---|---|---|
|
First Intervention
STARTED
|
20
|
20
|
|
First Intervention
COMPLETED
|
19
|
20
|
|
First Intervention
NOT COMPLETED
|
1
|
0
|
|
Washout of 28 Days
STARTED
|
19
|
20
|
|
Washout of 28 Days
COMPLETED
|
19
|
20
|
|
Washout of 28 Days
NOT COMPLETED
|
0
|
0
|
|
Second Intervention
STARTED
|
19
|
20
|
|
Second Intervention
COMPLETED
|
19
|
20
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Estradiol/Norethindrone Acetate (Test) First
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in first period followed by 1 mg/0.5 mg Activella® Tablets reference product dosed in the second period.
|
Activella® (Reference) First
1 mg/0.5 mg Activella® Tablets reference product dosed in first period followed by 1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in the second period.
|
|---|---|---|
|
First Intervention
Adverse Event
|
1
|
0
|
Baseline Characteristics
Estradiol/Norethindrone Acetate Tablets, 1/0.5 mg Under Fed Conditions
Baseline characteristics by cohort
| Measure |
Estradiol/Norethindrone Acetate (Test) First
n=20 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in first period followed by 1 mg/0.5 mg Activella® Tablets reference product dosed in the second period.
|
Activella® (Reference) First
n=20 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in first period followed by 1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in the second period.
|
Total
n=40 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
|
20 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
40 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
|
13 participants
n=5 Participants
|
15 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 participants
n=5 Participants
|
1 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
|
20 participants
n=5 Participants
|
20 participants
n=7 Participants
|
40 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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax of Norethindrone (Maximum Observed Concentration of Drug Substance in Plasma)
|
6.54 ng/mL
Standard Deviation 3.62
|
6.06 ng/mL
Standard Deviation 2.95
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t of Norethindrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
45.03 ng*h/mL
Standard Deviation 21.76
|
46.13 ng*h/mL
Standard Deviation 21.62
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf of Norethindrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
49.55 ng*h/mL
Standard Deviation 23.08
|
50.68 ng*h/mL
Standard Deviation 22.78
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax of Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
|
27076.08 pg/mL
Standard Deviation 11600.13
|
27240.03 pg/mL
Standard Deviation 11610.70
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t of Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
384547.68 pg*h/mL
Standard Deviation 185543.06
|
407028.98 pg*h/mL
Standard Deviation 191192.18
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf of Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
380131.12 pg*h/mL
Standard Deviation 163543.17
|
424801.99 pg*h/mL
Standard Deviation 216597.41
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax of Uncorrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
|
27256.41 pg/mL
Standard Deviation 11652.78
|
27430.77 pg/mL
Standard Deviation 11674.97
|
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 AUC0-t values for Uncorrected Total Estrone.
Outcome measures
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t of Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
397537.88 pg*h/mL
Standard Deviation 193337.67
|
420763.02 pg*h/mL
Standard Deviation 198975.61
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf of Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
398139.63 pg*h/mL
Standard Deviation 173723.79
|
425739.45 pg*h/mL
Standard Deviation 198546.75
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax of Uncorrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)
|
59.24 pg/mL
Standard Deviation 19.10
|
60.33 pg/mL
Standard Deviation 19.04
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t of Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
2016.26 pg*h/mL
Standard Deviation 596.40
|
2086.39 pg*h/mL
Standard Deviation 746.24
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf of Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
2301.59 pg*h/mL
Standard Deviation 642.09
|
2274.04 pg*h/mL
Standard Deviation 784.48
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax of Uncorrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
|
513.56 pg/mL
Standard Deviation 165.85
|
529.23 pg/mL
Standard Deviation 217.12
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t of Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
12444.22 pg*h/mL
Standard Deviation 4018.39
|
12977.00 pg*h/mL
Standard Deviation 5291.36
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf of Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
13592.44 pg*h/mL
Standard Deviation 3686.14
|
14155.46 pg*h/mL
Standard Deviation 5300.06
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax of Corrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)
|
55.18 pg/mL
Standard Deviation 19.31
|
56.24 pg/mL
Standard Deviation 19.26
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t of Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
1723.44 pg*h/mL
Standard Deviation 540.76
|
1793.04 pg*h/mL
Standard Deviation 689.12
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf of Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
1823.43 pg*h/mL
Standard Deviation 551.11
|
1871.56 pg*h/mL
Standard Deviation 730.51
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
Cmax of Corrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma)
|
492.81 pg/mL
Standard Deviation 166.57
|
509.81 pg/mL
Standard Deviation 217.80
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-t of Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
|
10952.25 pg*h/mL
Standard Deviation 3887.84
|
11369.60 pg*h/mL
Standard Deviation 5058.92
|
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=39 Participants
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=39 Participants
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
AUC0-inf of Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)
|
11293.21 pg*h/mL
Standard Deviation 3899.12
|
11747.97 pg*h/mL
Standard Deviation 5289.05
|
Adverse Events
Estradiol/Norethindrone Acetate (Test)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Activella® (Reference)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Estradiol/Norethindrone Acetate (Test)
n=40 participants at risk
1 mg/0.5 mg Estradiol/Norethindrone Acetate Tablets test product dosed in either period.
|
Activella® (Reference)
n=40 participants at risk
1 mg/0.5 mg Activella® Tablets reference product dosed in either period.
|
|---|---|---|
|
General disorders
Headache
|
2.5%
1/40 • Number of events 1 • 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.
|
5.0%
2/40 • Number of events 2 • 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