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A Clinical Study to Evaluate the Effects of Estrogen in Healthy Postmenopausal Women

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ClinicalTrials.gov Identifier: NCT00820664
Recruitment Status : Completed
First Posted : January 12, 2009
Results First Posted : May 7, 2010
Last Update Posted : January 22, 2016
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Diagnostic
Condition Postmenopausal Symptoms
Interventions Drug: Comparator: Estrace 0.5 mg
Drug: Comparator: Estrace 2 mg
Drug: Comparator: Placebo
Enrollment 29
Recruitment Details Patients were recruited through advertisement and review of patient databases at Comprehensive Phase I, USA, between December 2008 and April 2009.
Pre-assignment Details Major entry criteria - healthy postmenopausal women within 10 years of attaining menopause as determined by follicle-stimulating hormone (FSH) and estradiol levels within range of postmenopause, and other criteria. Normal transvaginal ultrasound at screening with endometrial thickening at < 5.0 mm.
Arm/Group Title 17β-estradiol 2.0 Milligrams 17β-estradiol 0.5 Milligrams Placebo
Hide Arm/Group Description Estrace 2.0 mg tablet Estrace 0.5 mg tablet [Not Specified]
Period Title: Overall Study
Started 9 11 9
Completed 9 11 9
Not Completed 0 0 0
Arm/Group Title 17β-estradiol 2.0 Milligrams 17β-estradiol 0.5 Milligrams Placebo Total
Hide Arm/Group Description Estrace 2.0 mg tablet Estrace 0.5 mg tablet [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 9 11 9 29
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 11 participants 9 participants 29 participants
54.11  (3.76) 53.91  (5.65) 55.33  (3.04) 54.41  (4.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 11 participants 9 participants 29 participants
Female
9
 100.0%
11
 100.0%
9
 100.0%
29
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 11 participants 9 participants 29 participants
Black 1 0 0 1
White 8 11 9 28
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 9 participants 11 participants 9 participants 29 participants
27.87  (3.95) 28.69  (2.74) 27.43  (1.98) 28.05  (2.92)
1.Primary Outcome
Title Immunohistochemistry (IHC) Proliferative Effects Measurement
Hide Description Ratio of the total number of positively stained cell nuclei to the total number of cell nuclei. Proliferating endometrial cells express the Ki-67 antigen. The ratio was converted to a percent proliferating cells by taking the number of Ki-67 positive stained nuclei in a given field and dividing by the total number of nuclei in that field and multiplying by 100. At least 5 high power fields were scored in this manner and an aggregate percent Ki-67 positive cells was reported. Square root transformation was taken to make it approximately normally distributed for an ANOVA model to apply.
Time Frame 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Though 29 subjects were enrolled, only 20 subjects had biopsy samples that were deemed adequate for Ki-67 immunohistochemical analysis at Week 4.
Arm/Group Title 17β-estradiol 2.0 Milligrams 17β-estradiol 0.5 Milligrams Placebo
Hide Arm/Group Description:
Estrace 2.0 mg tablet
Estrace 0.5 mg tablet
[Not Specified]
Overall Number of Participants Analyzed 6 8 6
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Square root of % positive stained cells
0.73
(0.61 to 0.86)
0.43
(0.32 to 0.54)
0.25
(0.12 to 0.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 17β-estradiol 2.0 Milligrams, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 1-sided, alpha=0.05
Method ANOVA
Comments A one-way ANOVA model with term treatment was fit to the square root transformed response.
Method of Estimation Estimation Parameter Least Squares Mean
Estimated Value 0.49
Confidence Interval 95%
0.31 to 1.00
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 17β-estradiol 0.5 Milligrams, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.032
Comments 1-sided, alpha=0.05
Method ANOVA
Comments A one-way ANOVA model with term treatment was fit to the square root transformed response.
Method of Estimation Estimation Parameter Least Squares Mean
Estimated Value 0.19
Confidence Interval 95%
0.02 to 1.00
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Gene Expression Intensity After 4 Weeks of Either 0.5 or 2 mg Estrace Compared to Placebo.
Hide Description [Not Specified]
Time Frame 4 weeks
Outcome Measure Data Not Reported
Time Frame Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment.
Adverse Event Reporting Description Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
 
Arm/Group Title 17β-estradiol 2.0 Milligrams 17β-estradiol 0.5 Milligrams Placebo
Hide Arm/Group Description Estrace 2.0 mg tablet Estrace 0.5 mg tablet [Not Specified]
All-Cause Mortality
17β-estradiol 2.0 Milligrams 17β-estradiol 0.5 Milligrams Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
17β-estradiol 2.0 Milligrams 17β-estradiol 0.5 Milligrams Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/11 (0.00%)   0/9 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
17β-estradiol 2.0 Milligrams 17β-estradiol 0.5 Milligrams Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/9 (77.78%)   6/11 (54.55%)   6/9 (66.67%) 
Eye disorders       
Vision Blurred * 1  1/9 (11.11%)  0/11 (0.00%)  0/9 (0.00%) 
Gastrointestinal disorders       
Abdominal Discomfort * 1  2/9 (22.22%)  0/11 (0.00%)  0/9 (0.00%) 
Abdominal Distension * 1  1/9 (11.11%)  0/11 (0.00%)  0/9 (0.00%) 
Abdominal Pain * 1  2/9 (22.22%)  2/11 (18.18%)  2/9 (22.22%) 
Abdominal Pain Lower * 1  1/9 (11.11%)  1/11 (9.09%)  1/9 (11.11%) 
Diarrhoea * 1  1/9 (11.11%)  0/11 (0.00%)  0/9 (0.00%) 
Frequent Bowel Movements * 1  0/9 (0.00%)  1/11 (9.09%)  0/9 (0.00%) 
General disorders       
Feeling Cold * 1  0/9 (0.00%)  0/11 (0.00%)  1/9 (11.11%) 
Infections and infestations       
Pharyngitis * 1  0/9 (0.00%)  0/11 (0.00%)  1/9 (11.11%) 
Viral Upper Respiratory Tract Infection * 1  1/9 (11.11%)  0/11 (0.00%)  0/9 (0.00%) 
Investigations       
Blood Pressure Increased * 1  0/9 (0.00%)  0/11 (0.00%)  2/9 (22.22%) 
Musculoskeletal and connective tissue disorders       
Back Pain * 1  0/9 (0.00%)  2/11 (18.18%)  0/9 (0.00%) 
Groin Pain * 1  0/9 (0.00%)  0/11 (0.00%)  1/9 (11.11%) 
Pain In Extremity * 1  0/9 (0.00%)  1/11 (9.09%)  1/9 (11.11%) 
Nervous system disorders       
Dizziness * 1  1/9 (11.11%)  2/11 (18.18%)  1/9 (11.11%) 
Headache * 1  2/9 (22.22%)  1/11 (9.09%)  1/9 (11.11%) 
Somnolence * 1  1/9 (11.11%)  0/11 (0.00%)  0/9 (0.00%) 
Psychiatric disorders       
Insomnia * 1  0/9 (0.00%)  1/11 (9.09%)  0/9 (0.00%) 
Renal and urinary disorders       
Pollakiuria * 1  0/9 (0.00%)  0/11 (0.00%)  1/9 (11.11%) 
Urinary Retention * 1  0/9 (0.00%)  1/11 (9.09%)  0/9 (0.00%) 
Reproductive system and breast disorders       
Endometrial Hyperplasia * 1  0/9 (0.00%)  1/11 (9.09%)  0/9 (0.00%) 
Menorrhagia * 1  0/9 (0.00%)  1/11 (9.09%)  0/9 (0.00%) 
Ovarian Cyst * 1  0/9 (0.00%)  1/11 (9.09%)  0/9 (0.00%) 
Pelvic Pain * 1  0/9 (0.00%)  0/11 (0.00%)  1/9 (11.11%) 
Postmenopausal Haemorrhage * 1  1/9 (11.11%)  0/11 (0.00%)  0/9 (0.00%) 
Vaginal Discharge * 1  1/9 (11.11%)  0/11 (0.00%)  0/9 (0.00%) 
Vaginal Haemorrhage * 1  4/9 (44.44%)  1/11 (9.09%)  0/9 (0.00%) 
Vulvovaginal Pruritus * 1  2/9 (22.22%)  0/11 (0.00%)  0/9 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  0/9 (0.00%)  0/11 (0.00%)  3/9 (33.33%) 
Respiratory Tract Congestion * 1  0/9 (0.00%)  0/11 (0.00%)  1/9 (11.11%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
The registered secondary outcome: "Mean gene expression intensity after 4 weeks of either 0.5 or 2 mg Estrace compared to placebo" results are not available because of inadequate quantity and quality of tissue samples that were obtained.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Executive Vice President, Clinical and Quantitative Sciences
Organization: Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00820664    
Other Study ID Numbers: 0000-122
2009_505
First Submitted: January 8, 2009
First Posted: January 12, 2009
Results First Submitted: April 13, 2010
Results First Posted: May 7, 2010
Last Update Posted: January 22, 2016