A Study to Evaluate the Safety and Effectiveness of Asoprisnil and Estrogen Administration to Postmenopausal Women

Official Title: “A Phase II Pilot Study to Evaluate the Safety and Efficacy of J867 Administered With Estrogen to Postmenopausal Women”

The objective of this study is to determine the safety and effectiveness of 3 asoprisnil doses when administered to postmenopausal women with Premarin® 0.625 mg.

The objective of this study is to determine the safety and effectiveness of asoprisnil 5, 10, and 25 mg, compared to placebo, when administered to postmenopausal women, with Premarin® 0.625 mg, for 12 weeks. Pharmacodynamic effects to be assessed include bleeding pattern, endometrial biopsy results, and endometrial thickness. Safety assessments will include clinical laboratory results, physical examination with vital signs, pelvic and breast examinations, ultrasound results, and adverse events

Intervention(s) in this Clinical Trial

• Drug: Asoprisnil/Premarin
  • Asoprisnil 5mg and Premarin 0.625 mg Tablets, oral Daily for 12 weeks
• Drug: Asoprisnil/Premarin
  • Asoprisnil 10mg and Premarin 0.625 mg Tablets, oral Daily for 12 weeks
• Drug: Asoprisnil/Premarin
  • Asoprisnil 25mg and Premarin 0.625 mg Tablets, oral Daily for 12 weeks
• Drug: Placebo and Premarin
  • Placebo and Premarin 0.625 mg Tablets, oral Daily for 12 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Experimental: 2
• Experimental: 3
• Placebo Comparator: 4

Primary Measures

• Assessment of endometrium by endometrial biopsy
  • Time Frame: Week 12
    Safety Issue?: Yes
• Change from baseline in endometrial thickness as assessed by ultrasound
  • Time Frame: Week 12
    Safety Issue?: No

Secondary Measures

• Frequency and amount of vaginal bleeding via patient diary.
  • Time Frame: Week 4, 8, and 12
    Safety Issue?: No
• Incidence of hot flushes
  • Time Frame: Week 4, 8, and 12
    Safety Issue?: No
• Presence or absence of endometrial hyperplasia.
  • Time Frame: Week 12
    Safety Issue?: Yes
• Response to global efficacy question regarding improvement in menopause symptoms.
  • Time Frame: Week 12
    Safety Issue?: No

Inclusion Criteria:

• Postmenopausal women with an intact uterus
• Body mass index (BMI) between 18.0 - 33.0
• Good general health
• Endometrial thickness ≤ 4 mm by TVU
• No history or suspected endometrial hyperplasia
• Negative urine pregnancy test
• Pap smear in last 6 months with no evidence of malignancy or pre-malignant changes
• Mammogram without suspicion of malignancy within last 6 months
• Endometrial biopsy with no evidence of pathologic changes within last 6 months

Exclusion Criteria:

• Any abnormal lab result the study-doctor considers significant
• History of severe reaction to hormone therapy
• Receiving hormone therapy
• Currently using phytoestrogenic compounds, such as red clover, black cohosh (Promensil and Remifemin), dong quai, ginseng and soy isoflavones
• History or known or suspected cancer other than basal cell carcinoma
• Stenosis of the cervix
• History of reproductive endocrine disorder
• Washout requirement for hormonal therapy not met
• Ovarian mass
• Submucus or other symptomatic fibroid which would confound efficacy

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 48 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Abbott Industry

Overall Clinical Trial Officials and Contacts

Medical Director Study Chair Abbott  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00152282

Study ID Number: M00-198

ClinicalTrials.gov Identifier: NCT00152282

Health Authority: United States: Food and Drug Administration