Trial Outcomes & Findings for Endometrial Safety Study (NCT NCT00522873)
NCT ID: NCT00522873
Last Updated: 2014-12-31
Results Overview
The number of women who had a biopsy classified as 'hyperplasia or worse' at any time during the study. According to the protocol this endpoint was defined as primary for the DRSP/E2 group only.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
662 participants
Primary outcome timeframe
Up to one year
Results posted on
2014-12-31
Participant Flow
Only non-hysterectomized, postmenopausal women could take part in this study. The women had to have symptoms requiring hormone therapy in the opinion of the investigator. An endometrial biopsy at screening was to show no evidence of endometrial hyperplasia or cancer.
944 women screened, 661 treated. 282 failed screening: consent withdrawn (55), in-/exclusion criteria not met (209), lost to follow-up (3), other (15). 1 woman was randomized but not treated (own decision). 5 women completed the study but not study medication, i.e. they stopped medication early but remained in the study for final assessments.
Participant milestones
| Measure |
0.25mg DRSP / 0.5mg E2 (BAY86-4891)
One capsule \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
0.5mg NETA / 1.0mg E2 (Activella)
One capsule \[0.5mg norethisterone acetate/1.0mg 17β-estradiol (NETA/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
|---|---|---|
|
Overall Study
STARTED
|
490
|
172
|
|
Overall Study
Received Treatment
|
489
|
172
|
|
Overall Study
COMPLETED
|
394
|
128
|
|
Overall Study
NOT COMPLETED
|
96
|
44
|
Reasons for withdrawal
| Measure |
0.25mg DRSP / 0.5mg E2 (BAY86-4891)
One capsule \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
0.5mg NETA / 1.0mg E2 (Activella)
One capsule \[0.5mg norethisterone acetate/1.0mg 17β-estradiol (NETA/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
|---|---|---|
|
Overall Study
Adverse Event
|
41
|
26
|
|
Overall Study
Withdrawal by Subject
|
20
|
9
|
|
Overall Study
Protocol Violation
|
14
|
4
|
|
Overall Study
Lost to Follow-up
|
11
|
3
|
|
Overall Study
Personal Reasons
|
8
|
1
|
|
Overall Study
Medication Errors
|
1
|
1
|
|
Overall Study
Never Received Medication
|
1
|
0
|
Baseline Characteristics
Endometrial Safety Study
Baseline characteristics by cohort
| Measure |
0.25mg DRSP / 0.5mg E2 (BAY86-4891)
n=489 Participants
One capsule \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
0.5mg NETA / 1.0mg E2 (Activella)
n=172 Participants
One capsule \[0.5mg norethisterone acetate/1.0mg 17β-estradiol (NETA/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
Total
n=661 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.5 Years
STANDARD_DEVIATION 5.1 • n=5 Participants
|
53.5 Years
STANDARD_DEVIATION 4.5 • n=7 Participants
|
53.5 Years
STANDARD_DEVIATION 4.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
489 Participants
n=5 Participants
|
172 Participants
n=7 Participants
|
661 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
26.315 kg/m^2
STANDARD_DEVIATION 4.851 • n=5 Participants
|
26.020 kg/m^2
STANDARD_DEVIATION 5.476 • n=7 Participants
|
26.184 kg/m^2
STANDARD_DEVIATION 5.008 • n=5 Participants
|
|
Number of participants with hysterectomy/oophorectomy
Hysterectomized
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Number of participants with hysterectomy/oophorectomy
Oophorectomized
|
25 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Years since last menstruation at baseline
|
5.109 years
STANDARD_DEVIATION 4.528 • n=5 Participants
|
4.807 years
STANDARD_DEVIATION 4.287 • n=7 Participants
|
5.031 years
STANDARD_DEVIATION 4.465 • n=5 Participants
|
PRIMARY outcome
Timeframe: Up to one yearPopulation: For the DRSP/E2 group only - Primary analysis set (PAS): All subjects from the full analysis set (FAS) who either had a biopsy result classified as 'normal' or 'hyperplasia or worse' after a year of treatment or who prematurely discontinued the study before Cycle 13 with a biopsy classified as 'hyperplasia or worse'.
The number of women who had a biopsy classified as 'hyperplasia or worse' at any time during the study. According to the protocol this endpoint was defined as primary for the DRSP/E2 group only.
Outcome measures
| Measure |
0.25mg DRSP / 0.5mg E2 (BAY86-4891)
n=309 Participants
One capsule \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
0.5mg NETA / 1.0mg E2 (Activella)
One capsule \[0.5mg norethisterone acetate/1.0mg 17β-estradiol (NETA/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
|---|---|---|
|
Number of Participants in the DRSP/E2 Group With an Assessment of Endometrial Hyperplasia or Worse at End of Study (EoS) (1 Year of Treatment)
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Month 1 to Month 3Population: Per protocol set (PPS): All subjects from the FAS who had at least 75% overall study drug compliance and no major protocol violations
The women were to record daily in a diary, indicating 'no bleeding', 'spotting', 'light bleeding', 'normal bleeding' or 'heavy bleeding'. Women were considered to have amenorrhea if they had no bleeding and no spotting day within the given time interval.
Outcome measures
| Measure |
0.25mg DRSP / 0.5mg E2 (BAY86-4891)
n=371 Participants
One capsule \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
0.5mg NETA / 1.0mg E2 (Activella)
n=113 Participants
One capsule \[0.5mg norethisterone acetate/1.0mg 17β-estradiol (NETA/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
|---|---|---|
|
Number of Participants With Amenorrhea During Month 1 to 3 of Treatment
|
255 Participants
|
67 Participants
|
SECONDARY outcome
Timeframe: Month 10 to Month 12Population: Per protocol set (PPS): All subjects from the FAS who had at least 75% overall study drug compliance and no major protocol violations
The women were to record any bleeding daily in a diary, indicating 'no bleeding', 'spotting', 'light bleeding', 'normal bleeding' or 'heavy bleeding'. Women were considered to have amenorrhea if they had no bleeding and no spotting day within the given time interval.
Outcome measures
| Measure |
0.25mg DRSP / 0.5mg E2 (BAY86-4891)
n=355 Participants
One capsule \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
0.5mg NETA / 1.0mg E2 (Activella)
n=106 Participants
One capsule \[0.5mg norethisterone acetate/1.0mg 17β-estradiol (NETA/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
|---|---|---|
|
Number of Participants With Amenorrhea During Month 10 to 12 of Treatment
|
280 Participants
|
89 Participants
|
Adverse Events
0.25mg DRSP / 0.5mg E2 (BAY86-4891)
Serious events: 16 serious events
Other events: 172 other events
Deaths: 0 deaths
0.5mg NETA / 1.0mg E2 (Activella)
Serious events: 6 serious events
Other events: 63 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
0.25mg DRSP / 0.5mg E2 (BAY86-4891)
n=489 participants at risk
One capsule \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
0.5mg NETA / 1.0mg E2 (Activella)
n=172 participants at risk
One capsule \[0.5mg norethisterone acetate/1.0mg 17β-estradiol (NETA/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.20%
1/489
|
0.00%
0/172
|
|
Ear and labyrinth disorders
Deafness neurosensory
|
0.00%
0/489
|
0.58%
1/172
|
|
Endocrine disorders
Hyperparathyroidism
|
0.00%
0/489
|
0.58%
1/172
|
|
Eye disorders
Retinal vascular thrombosis
|
0.00%
0/489
|
0.58%
1/172
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.20%
1/489
|
0.00%
0/172
|
|
Gastrointestinal disorders
Constipation
|
0.20%
1/489
|
0.00%
0/172
|
|
Gastrointestinal disorders
Faecaloma
|
0.20%
1/489
|
0.00%
0/172
|
|
Gastrointestinal disorders
Large intestinal haemorrhage
|
0.20%
1/489
|
0.00%
0/172
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.20%
1/489
|
0.00%
0/172
|
|
Hepatobiliary disorders
Cholecystitis
|
0.20%
1/489
|
0.00%
0/172
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.20%
1/489
|
0.00%
0/172
|
|
Infections and infestations
Appendicitis
|
0.00%
0/489
|
0.58%
1/172
|
|
Infections and infestations
Cellulitis
|
0.20%
1/489
|
0.00%
0/172
|
|
Infections and infestations
Pneumonia
|
0.20%
1/489
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
Splenic rupture
|
0.20%
1/489
|
0.00%
0/172
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.20%
1/489
|
0.00%
0/172
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.20%
1/489
|
0.00%
0/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/489
|
0.58%
1/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
|
0.20%
1/489
|
0.00%
0/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.20%
1/489
|
0.00%
0/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.20%
1/489
|
0.00%
0/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma
|
0.20%
1/489
|
0.00%
0/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Salivary gland adenoma
|
0.20%
1/489
|
0.00%
0/172
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.20%
1/489
|
0.00%
0/172
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/489
|
0.58%
1/172
|
|
Nervous system disorders
Transient ischaemic attack
|
0.20%
1/489
|
0.00%
0/172
|
|
Psychiatric disorders
Anxiety
|
0.20%
1/489
|
0.00%
0/172
|
|
Psychiatric disorders
Self-injurious ideation
|
0.20%
1/489
|
0.00%
0/172
|
|
Renal and urinary disorders
Urinary incontinence
|
0.20%
1/489
|
0.00%
0/172
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.20%
1/489
|
0.00%
0/172
|
|
Surgical and medical procedures
Hip arthroplasty
|
0.20%
1/489
|
0.00%
0/172
|
Other adverse events
| Measure |
0.25mg DRSP / 0.5mg E2 (BAY86-4891)
n=489 participants at risk
One capsule \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
0.5mg NETA / 1.0mg E2 (Activella)
n=172 participants at risk
One capsule \[0.5mg norethisterone acetate/1.0mg 17β-estradiol (NETA/E2)\] per day taken orally for 13 cycles (28 days per cycle).
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
1.2%
6/489
|
2.3%
4/172
|
|
Infections and infestations
Influenza
|
4.3%
21/489
|
3.5%
6/172
|
|
Infections and infestations
Nasopharyngitis
|
3.7%
18/489
|
1.2%
2/172
|
|
Infections and infestations
Urinary tract infection
|
1.8%
9/489
|
2.3%
4/172
|
|
Investigations
Weight increased
|
3.5%
17/489
|
1.7%
3/172
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.5%
17/489
|
1.2%
2/172
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.5%
12/489
|
0.00%
0/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
3.3%
16/489
|
2.3%
4/172
|
|
Nervous system disorders
Headache
|
6.5%
32/489
|
4.1%
7/172
|
|
Psychiatric disorders
Depression
|
1.8%
9/489
|
3.5%
6/172
|
|
Reproductive system and breast disorders
Breast pain
|
4.3%
21/489
|
5.8%
10/172
|
|
Reproductive system and breast disorders
Breast tenderness
|
1.8%
9/489
|
2.9%
5/172
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
2.2%
11/489
|
4.1%
7/172
|
|
Reproductive system and breast disorders
Endometrial hypertrophy
|
2.7%
13/489
|
2.3%
4/172
|
|
Reproductive system and breast disorders
Postmenopausal haemorrhage
|
2.9%
14/489
|
5.2%
9/172
|
|
Vascular disorders
Hypertension
|
3.1%
15/489
|
2.9%
5/172
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60