A Double-blind, Randomized, Multi-center Study to Investigate the Endometrial Safety of a Continuous, Combined, Oral Estrogen/Progestin Preparation (17b-estradiol [E2] / Drospirenone [DRSP]) and to Compare the Bleeding Pattern of Subjects Treated With E2 / DRSP With the Bleeding Pattern of Subjects Treated With E2 / Norethisterone Acetate (NETA) When Used for Hormone Therapy (HT) for 1 Year in Post-menopausal Women
| Registry | NCT00522873 |
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| Status | Completed |
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| Phase | Phase 3 |
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| Study type | Interventional; randomized, parallel, masking: triple, treatment |
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| Enrollment | 662 (Actual) |
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| Sponsor | Bayer (Industry); collaborators: Laboratorium für Klinische Forschung, Diagnostic Cytology Laboratory, University of California, San Francisco |
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| Conditions | Postmenopause |
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| Interventions | 0.25mg DRSP / 0.5mg E2 (BAY86-4891), 0.5mg NETA / 1.0mg E2 (Activella) (Drug) |
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| Dates | start 2007-08-01, primary completion 2009-08-01, completion 2009-08-01, first posted 2007-08-30, last updated 2014-12-31 |
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| Locations | 59 sites in United States, Argentina, Austria, Brazil, Denmark, Italy, Mexico, Russia |
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Related Papers Related Patents Related Grants Related Experts
All trials for Postmenopause All trials of 0.25mg DRSP / 0.5mg E2 (BAY86-4891) All trials of 0.5mg NETA / 1.0mg E2 (Activella)
-Summary
The study is designed to investigate the safety of the investigational product for the lining of the uterus (endometrium).
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+Arms and interventions
| Arm | Type | Interventions | Description |
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| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Experimental | Drug: 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) | Active comparator | Drug: 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). |
- 0.25mg DRSP / 0.5mg E2 (BAY86-4891) (Drug): 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) (Drug): One capsule \[0.5mg norethisterone acetate/1.0mg 17β-estradiol (NETA/E2)\] per day taken orally for 13 cycles (28 days per cycle).
+Outcome measures
Primary outcomes
- 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) [Up to one year]: 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.
Secondary outcomes
- Number of Participants With Amenorrhea During Month 1 to 3 of Treatment [Month 1 to Month 3]: 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.
- Number of Participants With Amenorrhea During Month 10 to 12 of Treatment [Month 10 to Month 12]: 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.
+Eligibility
Sex: Female, ages: 40 Years to 65 Years
Inclusion Criteria:
* Postmenopausal women between 40 and 65 years of age with hormone therapy indication (symptoms and need for treatment)
* Non-hysterectomized women.
Exclusion Criteria:
* Usual exclusion criteria for hormone therapy apply.
+Posted results
Participant flow
| Milestone | 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | 0.5mg NETA / 1.0mg E2 (Activella) |
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| Started | 490 | 172 |
| Received treatment | 489 | 172 |
| Completed | 394 | 128 |
| Not completed | 96 | 44 |
Outcome results
- 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) (Primary), Number, Participants: 0.25mg DRSP / 0.5mg E2 (BAY86-4891) 0
- Number of Participants With Amenorrhea During Month 1 to 3 of Treatment (Secondary), Number, Participants: 0.25mg DRSP / 0.5mg E2 (BAY86-4891) 255; 0.5mg NETA / 1.0mg E2 (Activella) 67
- Number of Participants With Amenorrhea During Month 10 to 12 of Treatment (Secondary), Number, Participants: 0.25mg DRSP / 0.5mg E2 (BAY86-4891) 280; 0.5mg NETA / 1.0mg E2 (Activella) 89
Adverse events
| Arm | Deaths | Serious adverse events | Other adverse events |
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| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | 0 | 16/489 (3.3%) | 172/489 (35.2%) |
| 0.5mg NETA / 1.0mg E2 (Activella) | 0 | 6/172 (3.5%) | 63/172 (36.6%) |
Serious adverse events by term
| Term | Organ system | 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | 0.5mg NETA / 1.0mg E2 (Activella) |
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| Lymphadenopathy | Blood and lymphatic system disorders | 1/489 | 0/172 |
| Deafness neurosensory | Ear and labyrinth disorders | 0/489 | 1/172 |
| Hyperparathyroidism | Endocrine disorders | 0/489 | 1/172 |
| Retinal vascular thrombosis | Eye disorders | 0/489 | 1/172 |
| Abdominal pain lower | Gastrointestinal disorders | 1/489 | 0/172 |
| Constipation | Gastrointestinal disorders | 1/489 | 0/172 |
| Faecaloma | Gastrointestinal disorders | 1/489 | 0/172 |
| Large intestinal haemorrhage | Gastrointestinal disorders | 1/489 | 0/172 |
| Pancreatitis acute | Gastrointestinal disorders | 1/489 | 0/172 |
| Cholecystitis | Hepatobiliary disorders | 1/489 | 0/172 |
| Cholelithiasis | Hepatobiliary disorders | 1/489 | 0/172 |
| Appendicitis | Infections and infestations | 0/489 | 1/172 |
| Cellulitis | Infections and infestations | 1/489 | 0/172 |
| Pneumonia | Infections and infestations | 1/489 | 0/172 |
| Splenic rupture | Injury, poisoning and procedural complications | 1/489 | 0/172 |
| Hyperglycaemia | Metabolism and nutrition disorders | 1/489 | 0/172 |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 1/489 | 0/172 |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/489 | 1/172 |
| Colon adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/489 | 0/172 |
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/489 | 0/172 |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/489 | 0/172 |
| Lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/489 | 0/172 |
| Salivary gland adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/489 | 0/172 |
| Carpal tunnel syndrome | Nervous system disorders | 1/489 | 0/172 |
| Grand mal convulsion | Nervous system disorders | 0/489 | 1/172 |
| Transient ischaemic attack | Nervous system disorders | 1/489 | 0/172 |
| Anxiety | Psychiatric disorders | 1/489 | 0/172 |
| Self-injurious ideation | Psychiatric disorders | 1/489 | 0/172 |
| Urinary incontinence | Renal and urinary disorders | 1/489 | 0/172 |
| Asthma | Respiratory, thoracic and mediastinal disorders | 1/489 | 0/172 |
| Hip arthroplasty | Surgical and medical procedures | 1/489 | 0/172 |
Other adverse events by term
| Term | Organ system | 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | 0.5mg NETA / 1.0mg E2 (Activella) |
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| Abdominal pain | Gastrointestinal disorders | 6/489 | 4/172 |
| Influenza | Infections and infestations | 21/489 | 6/172 |
| Nasopharyngitis | Infections and infestations | 18/489 | 2/172 |
| Urinary tract infection | Infections and infestations | 9/489 | 4/172 |
| Weight increased | Investigations | 17/489 | 3/172 |
| Back pain | Musculoskeletal and connective tissue disorders | 17/489 | 2/172 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 12/489 | 0/172 |
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 16/489 | 4/172 |
| Headache | Nervous system disorders | 32/489 | 7/172 |
| Depression | Psychiatric disorders | 9/489 | 6/172 |
| Breast pain | Reproductive system and breast disorders | 21/489 | 10/172 |
| Breast tenderness | Reproductive system and breast disorders | 9/489 | 5/172 |
| Cervical dysplasia | Reproductive system and breast disorders | 11/489 | 7/172 |
| Endometrial hypertrophy | Reproductive system and breast disorders | 13/489 | 4/172 |
| Postmenopausal haemorrhage | Reproductive system and breast disorders | 14/489 | 9/172 |
| Hypertension | Vascular disorders | 15/489 | 5/172 |
+Locations (59)
| Facility | City | Country | Status |
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| Chandler, Arizona | United States | |
| San Diego, California | United States | |
| San Diego, California | United States | |
| Denver, Colorado | United States | |
| Greenwood Village, Colorado | United States | |
| Boynton Beach, Florida | United States | |
| Clearwater, Florida | United States | |
| Boise, Idaho | United States | |
| Amite, Louisiana | United States | |
| Marrero, Louisiana | United States | |
| Las Vegas, Nevada | United States | |
| Cleveland, Ohio | United States | |
| Philadelphia, Pennsylvania | United States | |
| Columbia, South Carolina | United States | |
| Corpus Christi, Texas | United States | |
| Richmond, Virginia | United States | |
| Seattle, Washington | United States | |
| Lanús Oeste, Buenos Aires | Argentina | |
| San Isidro, Buenos Aires | Argentina | |
| Buenos Aires, Ciudad Auton. de Buenos Aires | Argentina | |
| Buenos Aires, Ciudad Auton. de Buenos Aires | Argentina | |
| Mödling, Lower Austria | Austria | |
| Wiener Neustadt, Lower Austria | Austria | |
| Fürstenfeld, Styria | Austria | |
| Wörgl, Tyrol | Austria | |
| Bregenz, Vorarlberg | Austria | |
| Innsbruck | Austria | |
| Klagenfurt | Austria | |
| Mürzzuschlag | Austria | |
| Sankt Pölten | Austria | |
| Vienna | Austria | |
| Vienna | Austria | |
| Vienna | Austria | |
| Vienna | Austria | |
| Zeltweg | Austria | |
| Goiânia, Goiás | Brazil | |
| Curitiba, Paraná | Brazil | |
| Porto Alegre, Rio Grande do Sul | Brazil | |
| São Paulo, São Paulo | Brazil | |
| Aalborg | Denmark | |
| Ballerup Municipality | Denmark | |
| Vejle | Denmark | |
| Bologna | Italy | |
| Cagliari | Italy | |
| Modena | Italy | |
| Novara | Italy | |
| Parma | Italy | |
| Pisa | Italy | |
| Sassari | Italy | |
| Siena | Italy | |
| Mexico City, Mexico City | Mexico | |
| México | Mexico | |
| México, D.F. | Mexico | |
| Monterrey | Mexico | |
| Moscow | Russia | |
| Moscow | Russia | |
| Moskva | Russia | |
| Moskva | Russia | |
| Moskva | Russia | |
+Publications
- Results publication: Genazzani AR, Schmelter T, Schaefers M, Gerlinger C, Gude K. One-year randomized study of the endometrial safety and bleeding pattern of 0.25 mg drospirenone/0.5 mg 17beta-estradiol in postmenopausal women. Climacteric. 2013 Aug;16(4):490-8. doi: 10.3109/13697137.2013.783797. Epub 2013 May 11. PMID 23531117
+Investigators
- Bayer Study Director, Study director, Bayer