Trial Outcomes & Findings for A Dose-finding Study to Evaluate the Effect of a Contraceptive Vaginal Ring, Releasing Nestorone® and Estradiol, on Cycle Control, Ovulation Inhibition, and Pharmacokinetics in Normal Cycling Women (NCT NCT01586000)
NCT ID: NCT01586000
Last Updated: 2025-12-08
Results Overview
The primary outcome will be the number of days that bleeding or spotting is reported in the first 3 cycles (90 days) of treatment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
197 participants
Primary outcome timeframe
Three months
Results posted on
2025-12-08
Participant Flow
Participant milestones
| Measure |
10 µg/day E2
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Overall Study
STARTED
|
67
|
66
|
64
|
|
Overall Study
COMPLETED
|
45
|
47
|
47
|
|
Overall Study
NOT COMPLETED
|
22
|
19
|
17
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Dose-finding Study to Evaluate the Effect of a Contraceptive Vaginal Ring, Releasing Nestorone® and Estradiol, on Cycle Control, Ovulation Inhibition, and Pharmacokinetics in Normal Cycling Women
Baseline characteristics by cohort
| Measure |
10 µg/Day E2
n=67 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/Day E2
n=66 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/Day E2
n=64 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
Total
n=197 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=37 Participants
|
0 Participants
n=37 Participants
|
0 Participants
n=74 Participants
|
0 Participants
n=175 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
67 Participants
n=37 Participants
|
66 Participants
n=37 Participants
|
64 Participants
n=74 Participants
|
197 Participants
n=175 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=37 Participants
|
0 Participants
n=37 Participants
|
0 Participants
n=74 Participants
|
0 Participants
n=175 Participants
|
|
Age, Continuous
|
28.8 Years
n=37 Participants
|
28.2 Years
n=37 Participants
|
29.6 Years
n=74 Participants
|
28.8 Years
n=175 Participants
|
|
Sex: Female, Male
Female
|
67 Participants
n=37 Participants
|
66 Participants
n=37 Participants
|
64 Participants
n=74 Participants
|
197 Participants
n=175 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=37 Participants
|
0 Participants
n=37 Participants
|
0 Participants
n=74 Participants
|
0 Participants
n=175 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=37 Participants
|
9 Participants
n=37 Participants
|
10 Participants
n=74 Participants
|
29 Participants
n=175 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
57 Participants
n=37 Participants
|
57 Participants
n=37 Participants
|
54 Participants
n=74 Participants
|
168 Participants
n=175 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=37 Participants
|
0 Participants
n=37 Participants
|
0 Participants
n=74 Participants
|
0 Participants
n=175 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=37 Participants
|
0 Participants
n=37 Participants
|
0 Participants
n=74 Participants
|
0 Participants
n=175 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=37 Participants
|
2 Participants
n=37 Participants
|
3 Participants
n=74 Participants
|
10 Participants
n=175 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=37 Participants
|
0 Participants
n=37 Participants
|
0 Participants
n=74 Participants
|
0 Participants
n=175 Participants
|
|
Race (NIH/OMB)
Black or African American
|
28 Participants
n=37 Participants
|
31 Participants
n=37 Participants
|
20 Participants
n=74 Participants
|
79 Participants
n=175 Participants
|
|
Race (NIH/OMB)
White
|
33 Participants
n=37 Participants
|
27 Participants
n=37 Participants
|
34 Participants
n=74 Participants
|
94 Participants
n=175 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=37 Participants
|
0 Participants
n=37 Participants
|
0 Participants
n=74 Participants
|
0 Participants
n=175 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=37 Participants
|
6 Participants
n=37 Participants
|
7 Participants
n=74 Participants
|
14 Participants
n=175 Participants
|
|
Marital Status
Never Married
|
50 Participants
n=37 Participants
|
41 Participants
n=37 Participants
|
43 Participants
n=74 Participants
|
134 Participants
n=175 Participants
|
|
Marital Status
Married
|
10 Participants
n=37 Participants
|
17 Participants
n=37 Participants
|
11 Participants
n=74 Participants
|
38 Participants
n=175 Participants
|
|
Marital Status
Divorced
|
5 Participants
n=37 Participants
|
4 Participants
n=37 Participants
|
8 Participants
n=74 Participants
|
17 Participants
n=175 Participants
|
|
Marital Status
Separated
|
2 Participants
n=37 Participants
|
2 Participants
n=37 Participants
|
2 Participants
n=74 Participants
|
6 Participants
n=175 Participants
|
|
Marital Status
Widowed
|
0 Participants
n=37 Participants
|
2 Participants
n=37 Participants
|
0 Participants
n=74 Participants
|
2 Participants
n=175 Participants
|
|
Highest Level of Education Completed
Has not completed high school
|
0 Participants
n=37 Participants
|
1 Participants
n=37 Participants
|
2 Participants
n=74 Participants
|
3 Participants
n=175 Participants
|
|
Highest Level of Education Completed
High school diploma or equivalent
|
10 Participants
n=37 Participants
|
8 Participants
n=37 Participants
|
6 Participants
n=74 Participants
|
24 Participants
n=175 Participants
|
|
Highest Level of Education Completed
Some college
|
24 Participants
n=37 Participants
|
28 Participants
n=37 Participants
|
29 Participants
n=74 Participants
|
81 Participants
n=175 Participants
|
|
Highest Level of Education Completed
College degree or higher
|
33 Participants
n=37 Participants
|
29 Participants
n=37 Participants
|
27 Participants
n=74 Participants
|
89 Participants
n=175 Participants
|
|
Alcohol Use
Never
|
8 Participants
n=37 Participants
|
7 Participants
n=37 Participants
|
13 Participants
n=74 Participants
|
28 Participants
n=175 Participants
|
|
Alcohol Use
Former
|
3 Participants
n=37 Participants
|
5 Participants
n=37 Participants
|
1 Participants
n=74 Participants
|
9 Participants
n=175 Participants
|
|
Alcohol Use
Current
|
56 Participants
n=37 Participants
|
54 Participants
n=37 Participants
|
50 Participants
n=74 Participants
|
160 Participants
n=175 Participants
|
|
Body Mass Index (BMI)
|
26.4 kg/m^2
STANDARD_DEVIATION 4.210 • n=37 Participants
|
25.35 kg/m^2
STANDARD_DEVIATION 4.412 • n=37 Participants
|
25.70 kg/m^2
STANDARD_DEVIATION 4.232 • n=74 Participants
|
25.82 kg/m^2
STANDARD_DEVIATION 4.287 • n=175 Participants
|
PRIMARY outcome
Timeframe: Three monthsPopulation: All Safety population subjects with at least one non-missing bleeding record (from their diaries). All subjects enrolled in the study were included in the Safety population. In total, 2 subjects (both in the 200 µg/day NES and 40 µg/day E2 group) were not included in the Bleeding and Ovulation populations
The primary outcome will be the number of days that bleeding or spotting is reported in the first 3 cycles (90 days) of treatment.
Outcome measures
| Measure |
10 µg/day E2
n=67 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=66 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Number of Days Bleeding is Reported.
Bleeding Only
|
14.7 Days
Standard Deviation 15.36
|
16.3 Days
Standard Deviation 16.3
|
15.0 Days
Standard Deviation 14.80
|
|
Number of Days Bleeding is Reported.
Bleeding or Spotting
|
34.0 Days
Standard Deviation 23.17
|
42.1 Days
Standard Deviation 24.51
|
39.8 Days
Standard Deviation 22.83
|
|
Number of Days Bleeding is Reported.
Spotting Only
|
19.3 Days
Standard Deviation 18.61
|
25.8 Days
Standard Deviation 22.2
|
24.8 Days
Standard Deviation 19.06
|
SECONDARY outcome
Timeframe: Control Cycle 1, Treatment Cycles 2, 3, and 7, Recovery Cycle 8, up to 8 monthsPopulation: All Safety population subjects that had any cycle with a progesterone value and a TVUS assessment. All subjects enrolled in the study were included in the Safety population. In total, 2 subjects (both in the 200 µg/day NES and 40 µg/day E2 group) were not included in the Bleeding and Ovulation populations
A subject will be considered to have ovulated if she has two consecutive progesterone values of ≥10 nmol/L (≥3 ng/mL) preceded by a follicular measurement of \>10 mm in the previous 10 days. Number of subjects considered to have ovulated during each cycle is reported.
Outcome measures
| Measure |
10 µg/day E2
n=67 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=66 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Number of Subjects With Ovulation at During Each Cycle
Control Cycle 1
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Number of Subjects With Ovulation at During Each Cycle
Treatment Cycle 2
|
27 Participants
|
25 Participants
|
25 Participants
|
|
Number of Subjects With Ovulation at During Each Cycle
Treatment Cycle 3
|
21 Participants
|
19 Participants
|
20 Participants
|
|
Number of Subjects With Ovulation at During Each Cycle
Treatment Cycle 7
|
18 Participants
|
15 Participants
|
14 Participants
|
|
Number of Subjects With Ovulation at During Each Cycle
Recovery Cycle 8
|
7 Participants
|
2 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Visits 12, 32, and 41 (Treatment Period)Population: The number analyzed at each time point is dependent on the number of subjects that completed each time point.
Pharmacokinetic assessments will be performed to measure absorption in a substudy of 22 women (7-8 in each dose group) at a single center (Oregon Health and Science University) at initiation of each ring use and at final ring removal. Blood will be collected for measurements before insertion of the first ring (at Visit 12), before removal of the second ring (at Visit 41), and at 2, 4, 6, 8, 10, 12, 24, 48 and approximately 72 hours after the first ring is inserted (at Visit 12) and after the second ring is removed (at Visit 41). PK samples will also be collected at the time of removal of the first ring (0 hours) at Visit 32, 2 hours after removal of the first ring and insertion of the second ring, and at 24 hours after removal of the first ring and insertion of the second ring.
Outcome measures
| Measure |
10 µg/day E2
n=7 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=7 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=8 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Area Under the Curve of NES and E2 at Specified Time Points
Visit 12 NES 0-72 hrs post Ring 1 Insertion
|
38685.7 hour*pg/mL
Standard Deviation 9770.06
|
31201.4 hour*pg/mL
Standard Deviation 4912.98
|
32845.0 hour*pg/mL
Standard Deviation 5370.53
|
|
Area Under the Curve of NES and E2 at Specified Time Points
Visit 32 NES 0-24 hrs after Removal of Ring 1 and Insertion of Ring 2
|
12906.4 hour*pg/mL
Standard Deviation 2574.38
|
16495.3 hour*pg/mL
Standard Deviation 3512.32
|
14073.3 hour*pg/mL
Standard Deviation 1729.37
|
|
Area Under the Curve of NES and E2 at Specified Time Points
Visit 41 NES 0-72 hrs post Ring 2 Removal
|
742.7 hour*pg/mL
Standard Deviation 352.83
|
902.0 hour*pg/mL
Standard Deviation 460.43
|
863.5 hour*pg/mL
Standard Deviation 361.81
|
|
Area Under the Curve of NES and E2 at Specified Time Points
Visit 12 E2 0-72 hrs post Ring 1 Insertion
|
3690.77 hour*pg/mL
Standard Deviation 1414.324
|
4910.31 hour*pg/mL
Standard Deviation 1067.716
|
3648.83 hour*pg/mL
Standard Deviation 1341.309
|
|
Area Under the Curve of NES and E2 at Specified Time Points
Visit 32 E2 0-24 hrs after Removal of Ring 1 and Insertion of Ring 2
|
1237.10 hour*pg/mL
Standard Deviation 605.026
|
2470.0 hour*pg/mL
Standard Deviation 801.086
|
1198.83 hour*pg/mL
Standard Deviation 453.937
|
|
Area Under the Curve of NES and E2 at Specified Time Points
Visit 41 E2 0-72 hrs post Ring 2 Removal
|
2098.36 hour*pg/mL
Standard Deviation 628.917
|
3208.62 hour*pg/mL
Standard Deviation 2470.399
|
2317.45 hour*pg/mL
Standard Deviation 963.316
|
SECONDARY outcome
Timeframe: Through Recovery Cycle 8, up to 8 monthsClinical safety will be evaluated by collection of adverse events (AEs).
Outcome measures
| Measure |
10 µg/day E2
n=67 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=66 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=64 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
The Safety of Administering 200 µg/Day of NES and One of Three Doses (10, 20, or 40 µg/Day) of E2 Delivered by CVR Continuously for 6 Months (180 Days).
Total Number of Subjects with at Least One Severe AE
|
2 Participants
|
4 Participants
|
3 Participants
|
|
The Safety of Administering 200 µg/Day of NES and One of Three Doses (10, 20, or 40 µg/Day) of E2 Delivered by CVR Continuously for 6 Months (180 Days).
Total Number of Subjects with at Least One AE Probably Related
|
11 Participants
|
9 Participants
|
5 Participants
|
|
The Safety of Administering 200 µg/Day of NES and One of Three Doses (10, 20, or 40 µg/Day) of E2 Delivered by CVR Continuously for 6 Months (180 Days).
Total Number of Subjects with at Least One AE Highly Probably Related
|
1 Participants
|
3 Participants
|
1 Participants
|
|
The Safety of Administering 200 µg/Day of NES and One of Three Doses (10, 20, or 40 µg/Day) of E2 Delivered by CVR Continuously for 6 Months (180 Days).
Total Number of Subjects with at Least One SAE
|
0 Participants
|
0 Participants
|
1 Participants
|
|
The Safety of Administering 200 µg/Day of NES and One of Three Doses (10, 20, or 40 µg/Day) of E2 Delivered by CVR Continuously for 6 Months (180 Days).
Total Number of Subjects with at Least One Moderate AE
|
34 Participants
|
32 Participants
|
26 Participants
|
|
The Safety of Administering 200 µg/Day of NES and One of Three Doses (10, 20, or 40 µg/Day) of E2 Delivered by CVR Continuously for 6 Months (180 Days).
Total Number of Subjects with at Least One AE
|
58 Participants
|
57 Participants
|
55 Participants
|
|
The Safety of Administering 200 µg/Day of NES and One of Three Doses (10, 20, or 40 µg/Day) of E2 Delivered by CVR Continuously for 6 Months (180 Days).
Total Number of Subjects with at Least One AE Leading to Discontinuation
|
7 Participants
|
7 Participants
|
4 Participants
|
|
The Safety of Administering 200 µg/Day of NES and One of Three Doses (10, 20, or 40 µg/Day) of E2 Delivered by CVR Continuously for 6 Months (180 Days).
Total Number of Subjects with at Least One Mild AE
|
22 Participants
|
21 Participants
|
26 Participants
|
SECONDARY outcome
Timeframe: Three monthsPopulation: All subjects enrolled in the study were included in the Safety population. In total, 2 subjects (both in the 200 µg/day NES and 40 µg/day E2 group) were not included in the Bleeding and Ovulation populations
The primary outcome will be the number of days that bleeding or spotting is reported in the last 3 cycles (90 days) of treatment.
Outcome measures
| Measure |
10 µg/day E2
n=67 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=66 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Number of Days Bleeding is Reported.
Bleeding or Spotting
|
31.3 Days
Standard Deviation 27.07
|
38.1 Days
Standard Deviation 31.12
|
30.8 Days
Standard Deviation 28.54
|
|
Number of Days Bleeding is Reported.
Bleeding Only
|
8.2 Days
Standard Deviation 11.81
|
13.7 Days
Standard Deviation 22.89
|
8 Days
Standard Deviation 12.36
|
|
Number of Days Bleeding is Reported.
Spotting Only
|
23.1 Days
Standard Deviation 23.19
|
24.4 Days
Standard Deviation 24.42
|
22.8 Days
Standard Deviation 25.1
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Albumin (g/dL)
|
0.01 g/dL
Standard Deviation 0.294
|
-0.09 g/dL
Standard Deviation 0.281
|
-0.02 g/dL
Standard Deviation 0.330
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in ALT/SGPT (U/L)
|
2.6 U/L
Standard Deviation 23.18
|
-0.2 U/L
Standard Deviation 7.72
|
-1.4 U/L
Standard Deviation 10.64
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in AST/SGOT (U/L)
|
4.0 U/L
Standard Deviation 43.51
|
-2.7 U/L
Standard Deviation 7.53
|
-1.8 U/L
Standard Deviation 16.57
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in BUN (mg/dL)
|
0.5 mg/dL
Standard Deviation 3.04
|
0.8 mg/dL
Standard Deviation 3.45
|
1.0 mg/dL
Standard Deviation 2.99
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Calcium (mg/dL)
|
-0.02 mg/dL
Standard Deviation 0.434
|
-0.16 mg/dL
Standard Deviation 0.434
|
0.00 mg/dL
Standard Deviation 0.447
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Creatinine (mg/dL)
|
0.035 mg/dL
Standard Deviation 0.1116
|
0.041 mg/dL
Standard Deviation 0.0969
|
0.046 mg/dL
Standard Deviation 0.0827
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Glucose (mg/dL)
|
2.2 mg/dL
Standard Deviation 13.61
|
2.7 mg/dL
Standard Deviation 11.97
|
1.5 mg/dL
Standard Deviation 14.20
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=55 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=58 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=53 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in GGT (U/L)
|
1.0 U/L
Standard Deviation 5.67
|
2.5 U/L
Standard Deviation 5.56
|
2.1 U/L
Standard Deviation 7.67
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Total Bilirubin (mg/dL)
|
-0.03 mg/dL
Standard Deviation 0.212
|
-0.07 mg/dL
Standard Deviation 0.227
|
-0.03 mg/dL
Standard Deviation 0.227
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Total Protein (g/dL)
|
0.00 g/dL
Standard Deviation 0.488
|
-0.11 g/dL
Standard Deviation 0.455
|
-0.03 g/dL
Standard Deviation 0.468
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=60 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=56 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Total Cholesterol (mg/dL)
|
-6.6 mg/dL
Standard Deviation 23.26
|
-9.5 mg/dL
Standard Deviation 23.79
|
-37.9 mg/dL
Standard Deviation 24.83
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=60 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=56 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in HDL Cholesterol (mg/dL)
|
-3.9 mg/dL
Standard Deviation 11.70
|
-7.0 mg/dL
Standard Deviation 10.84
|
-3.5 mg/dL
Standard Deviation 11.86
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=60 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=56 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in LDL Cholesterol (mg/dL)
|
-5.3 mg/dL
Standard Deviation 24.05
|
-4.8 mg/dL
Standard Deviation 25.01
|
-7.8 mg/dL
Standard Deviation 21.54
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=60 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=56 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Triglycerides (mg/dL)
|
0.2 mg/dL
Standard Deviation 34.05
|
0.4 mg/dL
Standard Deviation 31.81
|
4.6 mg/dL
Standard Deviation 40.70
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Chloride (mmol/L)
|
1.5 mmol/L
Standard Deviation 2.75
|
2.3 mmol/L
Standard Deviation 2.09
|
1.2 mmol/L
Standard Deviation 3.00
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Potassium (mmol/L)
|
-0.11 mmol/L
Standard Deviation 0.446
|
-0.12 mmol/L
Standard Deviation 0.414
|
-0.14 mmol/L
Standard Deviation 0.456
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Sodium (mmol/L)
|
0.6 mmol/L
Standard Deviation 2.72
|
1.3 mmol/L
Standard Deviation 2.83
|
0.3 mmol/L
Standard Deviation 2.70
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=56 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=58 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in RBC (MIL/uL)
|
-0.004 MIL/uL
Standard Deviation 0.2342
|
-0.062 MIL/uL
Standard Deviation 0.2260
|
0.032 MIL/uL
Standard Deviation 0.2855
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=56 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=58 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in WBC (THOU/uL)
|
0.028 THOU/uL
Standard Deviation 1.4519
|
67.522 THOU/uL
Standard Deviation 532.9508
|
0.089 THOU/uL
Standard Deviation 1.8263
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=58 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Hemoglobin (g/dL)
|
-0.21 g/dL
Standard Deviation 0.772
|
-0.38 g/dL
Standard Deviation 0.798
|
-0.25 g/dL
Standard Deviation 0.950
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=56 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=58 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Hematocrit (%)
|
-0.41 percentage
Standard Deviation 2.337
|
-0.99 percentage
Standard Deviation 2.269
|
-0.45 percentage
Standard Deviation 2.770
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=56 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=62 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=58 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Platelet Count (THOU/uL)
|
-3.0 THOU/uL
Standard Deviation 45.50
|
4.6 THOU/uL
Standard Deviation 29.92
|
20.8 THOU/uL
Standard Deviation 32.88
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=54 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=55 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Basophils (%)
|
3.19 percentage
Standard Deviation 16.656
|
0.20 percentage
Standard Deviation 0.524
|
-0.52 percentage
Standard Deviation 4.283
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=54 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=56 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Eosinophils (%)
|
-0.180 percentage
Standard Deviation 5.1571
|
0.198 percentage
Standard Deviation 1.8886
|
-1.054 percentage
Standard Deviation 8.2595
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=54 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=56 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Lymphocytes (%)
|
-0.141 percentage
Standard Deviation 13.1510
|
2.919 percentage
Standard Deviation 10.7313
|
2.518 percentage
Standard Deviation 12.7415
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=54 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=57 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=56 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Monocytes (%)
|
-0.310 percentage
Standard Deviation 3.2383
|
-0.260 percentage
Standard Deviation 4.9032
|
0.030 percentage
Standard Deviation 3.4508
|
SECONDARY outcome
Timeframe: Visit 41 (end of Treatment Cycle 7) compared to Visit 1 (Screening)Population: Change from Baseline to Final Evaluation. Subjects that had lab values at Visit 1 and Visit 41 were analyzed.
Clinical safety will also be evaluated by changes from baseline through end of treatment of blood chemistry and hematologic profile to assess safety of the three treatment groups.
Outcome measures
| Measure |
10 µg/day E2
n=54 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=55 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=55 Participants
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Changes From Baseline in Neutrophils (%)
|
0.080 percentage
Standard Deviation 18.6460
|
0.357 percentage
Standard Deviation 19.6337
|
-2.740 percentage
Standard Deviation 22.3667
|
Adverse Events
10 µg/day E2
Serious events: 0 serious events
Other events: 58 other events
Deaths: 0 deaths
20 µg/day E2
Serious events: 0 serious events
Other events: 57 other events
Deaths: 0 deaths
40 µg/day E2
Serious events: 1 serious events
Other events: 55 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
10 µg/day E2
n=67 participants at risk
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=66 participants at risk
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=64 participants at risk
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/67 • from enrollment through Recovery Cycle 8, up to 8 months
|
0.00%
0/66 • from enrollment through Recovery Cycle 8, up to 8 months
|
1.6%
1/64 • Number of events 1 • from enrollment through Recovery Cycle 8, up to 8 months
|
Other adverse events
| Measure |
10 µg/day E2
n=67 participants at risk
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
10 µg/day E2 with NES 200® µg/day: 10 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
20 µg/day E2
n=66 participants at risk
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
20 µg/day E2 with NES 200® µg/day: 20 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
40 µg/day E2
n=64 participants at risk
Two consecutive 3-month (90-day) rings will be used continuously for six months (180 days).
40 µg/day E2 with NES 200® µg/day: 40 µg/day E2 with NES 200® µg/day delivered by CVR continuously for 6 months (180 days)
|
|---|---|---|---|
|
Infections and infestations
NASOPHARYNGITIS
|
13.4%
9/67 • Number of events 37 • from enrollment through Recovery Cycle 8, up to 8 months
|
24.2%
16/66 • Number of events 37 • from enrollment through Recovery Cycle 8, up to 8 months
|
18.8%
12/64 • Number of events 37 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Gastrointestinal disorders
Nausea
|
7.5%
5/67 • Number of events 25 • from enrollment through Recovery Cycle 8, up to 8 months
|
15.2%
10/66 • Number of events 25 • from enrollment through Recovery Cycle 8, up to 8 months
|
15.6%
10/64 • Number of events 25 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
14.9%
10/67 • Number of events 23 • from enrollment through Recovery Cycle 8, up to 8 months
|
10.6%
7/66 • Number of events 23 • from enrollment through Recovery Cycle 8, up to 8 months
|
9.4%
6/64 • Number of events 23 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Infections and infestations
VULVOVAGINAL MYCOTIC INFECTION
|
10.4%
7/67 • Number of events 22 • from enrollment through Recovery Cycle 8, up to 8 months
|
15.2%
10/66 • Number of events 22 • from enrollment through Recovery Cycle 8, up to 8 months
|
7.8%
5/64 • Number of events 22 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
7.5%
5/67 • Number of events 19 • from enrollment through Recovery Cycle 8, up to 8 months
|
7.6%
5/66 • Number of events 19 • from enrollment through Recovery Cycle 8, up to 8 months
|
14.1%
9/64 • Number of events 19 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Infections and infestations
VAGINITIS BACTERIAL
|
11.9%
8/67 • Number of events 17 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.1%
4/66 • Number of events 17 • from enrollment through Recovery Cycle 8, up to 8 months
|
7.8%
5/64 • Number of events 17 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Gastrointestinal disorders
DIARRHOEA
|
9.0%
6/67 • Number of events 16 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.1%
4/66 • Number of events 16 • from enrollment through Recovery Cycle 8, up to 8 months
|
9.4%
6/64 • Number of events 16 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Infections and infestations
INFLUENZA
|
13.4%
9/67 • Number of events 16 • from enrollment through Recovery Cycle 8, up to 8 months
|
7.6%
5/66 • Number of events 16 • from enrollment through Recovery Cycle 8, up to 8 months
|
3.1%
2/64 • Number of events 16 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Skin and subcutaneous tissue disorders
ACNE
|
11.9%
8/67 • Number of events 15 • from enrollment through Recovery Cycle 8, up to 8 months
|
9.1%
6/66 • Number of events 15 • from enrollment through Recovery Cycle 8, up to 8 months
|
1.6%
1/64 • Number of events 15 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Psychiatric disorders
MOOD SWINGS
|
6.0%
4/67 • Number of events 14 • from enrollment through Recovery Cycle 8, up to 8 months
|
10.6%
7/66 • Number of events 14 • from enrollment through Recovery Cycle 8, up to 8 months
|
4.7%
3/64 • Number of events 14 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
6.0%
4/67 • Number of events 12 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.1%
4/66 • Number of events 12 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.2%
4/64 • Number of events 12 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Nervous system disorders
DIZZINESS
|
4.5%
3/67 • Number of events 12 • from enrollment through Recovery Cycle 8, up to 8 months
|
7.6%
5/66 • Number of events 12 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.2%
4/64 • Number of events 12 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Infections and infestations
FUNGAL INFECTION
|
4.5%
3/67 • Number of events 12 • from enrollment through Recovery Cycle 8, up to 8 months
|
9.1%
6/66 • Number of events 12 • from enrollment through Recovery Cycle 8, up to 8 months
|
4.7%
3/64 • Number of events 12 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Psychiatric disorders
ANXIETY
|
6.0%
4/67 • Number of events 11 • from enrollment through Recovery Cycle 8, up to 8 months
|
4.5%
3/66 • Number of events 11 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.2%
4/64 • Number of events 11 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Psychiatric disorders
DYSPAREUNIA
|
6.0%
4/67 • Number of events 11 • from enrollment through Recovery Cycle 8, up to 8 months
|
7.6%
5/66 • Number of events 11 • from enrollment through Recovery Cycle 8, up to 8 months
|
3.1%
2/64 • Number of events 11 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
4.5%
3/67 • Number of events 11 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.1%
4/66 • Number of events 11 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.2%
4/64 • Number of events 11 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Reproductive system and breast disorders
VAGINAL DISCHARGE
|
7.5%
5/67 • Number of events 11 • from enrollment through Recovery Cycle 8, up to 8 months
|
3.0%
2/66 • Number of events 11 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.2%
4/64 • Number of events 11 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Gastrointestinal disorders
VOMITING
|
3.0%
2/67 • Number of events 10 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.1%
4/66 • Number of events 10 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.2%
4/64 • Number of events 10 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Reproductive system and breast disorders
VULVOVAGINAL PRURITUS
|
3.0%
2/67 • Number of events 10 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.1%
4/66 • Number of events 10 • from enrollment through Recovery Cycle 8, up to 8 months
|
6.2%
4/64 • Number of events 10 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Nervous system disorders
Headache
|
41.8%
28/67 • Number of events 62 • from enrollment through Recovery Cycle 8, up to 8 months
|
30.3%
20/66 • Number of events 62 • from enrollment through Recovery Cycle 8, up to 8 months
|
21.9%
14/64 • Number of events 62 • from enrollment through Recovery Cycle 8, up to 8 months
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
23.9%
16/67 • Number of events 43 • from enrollment through Recovery Cycle 8, up to 8 months
|
19.7%
13/66 • Number of events 43 • from enrollment through Recovery Cycle 8, up to 8 months
|
21.9%
14/64 • Number of events 43 • from enrollment through Recovery Cycle 8, up to 8 months
|
Additional Information
Kimberly Myer, Sr. Program Director, NIH
Premier Research
Phone: 984-238-1297
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place