Endometrial Safety Study of Transdermal Testosterone (300 Mcg/Day) in Naturally Postmenopausal Women

• Sponsor: Warner Chilcott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00467259
• Collaborator: (none)
• Enrollment: 1,271
• Locations: 115
• Arms: 2
• Duration (Months): 21.1
• Patients Per Site: 11.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study is designed to evaluate the endometrial safety of a testosterone patch as treatment for low libido in naturally postmenopausal women.

Condition or Disease	Intervention/Treatment	Phase
Hypoactive Sexual Desire Disorder	Drug: Testosterone Transdermal System; Drug: Placebo patch	Phase 3

Detailed Description

Naturally postmenopausal women with hypoactive sexual desire disorder (HSDD) will be randomized into a 52-week, multicenter, double-blind (DB), parallel-group, placebo-controlled study. Patients will be stratified based on whether they use concomitant estrogen/progestin therapy and then randomized in a 4:1 ration to receive either testosterone transdermal system (300 mcg/day) or placebo. Patients using estrogen/progestin at the start of the study should maintain this therapy throughout the study; patients not using estrogen/progestin at the start of the study should not initiate estrogen/progestin therapy throughout the study. Endometrial biopsies and transvaginal ultrasounds will be collected/performed at screening and study exit for all patients. Safety will be assessed by adverse events, reports of vaginal bleeding, lipids, serum chemistry, and hematology. Physical exams, pap smears, and mammograms will be monitored.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1271 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-controlled, Multicenter, 52-week Study to Evaluate the Endometrial Safety of Transdermal Testosterone (300 Mcg/Day) in Naturally Postmenopausal Women With Hypoactive Sexual Desire Disorder.
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 28 cm² Placebo patch	Drug: Placebo patch; placebo patch, changed twice a week for 52 weeks
Experimental: Testosterone Testosterone patch, 300 mcg/day, change patch twice a week for 52 weeks	Drug: Testosterone Transdermal System; Testosterone patch, 300 mcg/day, change patch twice a week for 52 weeks

Outcome Measures

Primary Outcome Measures

1. Incidence of Endometrial Hyperplasia in Naturally Postmenopausal Women With Hypoactive Sexual Desire Disorder (HSDD) Not Using Concomitant Estrogen and Progestin, Year 1 [52 weeks]

   Incidence measured is number of patients with endometrial hyperplasia/number of patients with evaluable biopsies

Secondary Outcome Measures

1. Incidence of Endometrial Hyperplasia in Naturally Postmenopausal Women With HSDD Using Concomitant Estrogen and Progestin, Year 1 [52 weeks]

   Incidence measured is number of patients with endometrial hyperplasia/number of patients with evaluable biopsies

2. Incidence Endometrial Hyperplasia in Naturally Postmenopausal Women With HSDD Using Concomitant Estrogen & Progestin Combined With Those Not Using Estrogen & Progestin Therapy, Year 1 [52 weeks]

   Incidence measured is number of patients with endometrial hyperplasia/number of patients with evaluable biopsies

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women will be screened for study participation and must be at least one year post menopausal, 45-70 years old, in general good health, and may or may not be on hormone therapy, and must have low sexual desire which causes distress.

Exclusion Criteria:

• Women will be screened for study participation and must not be using androgen therapy or have any medical, physical, psychological, or pharmacological condition that could make participation unsafe or confound the safety evaluation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Study Facility	Birmingham	Alabama	United States	35209
2	Research Facility	Birmingham	Alabama	United States	35233
3	Research Facility	Mobile	Alabama	United States	36617
4	Research Facility	Montgomery	Alabama	United States	36116
5	Test Facility	Chandler	Arizona	United States	85225
6	Study Facility	Peoria	Arizona	United States	85381
7	Research Facility	Phoenix	Arizona	United States	85015
8	Research Facility	Phoenix	Arizona	United States	85032
9	Research Facility	Scottsdale	Arizona	United States	85251
10	Research Site	Tucson	Arizona	United States	85712
11	Research Facility	Tucson	Arizona	United States	85715
12	Study Facility	Tuscon	Arizona	United States	85741
13	Site Facility	Jonesboro	Arkansas	United States	72401
14	Site Facility	Little Rock	Arkansas	United States	72223
15	Research Facility	Anaheim	California	United States	92805
16	Research Site	Berkeley	California	United States	94705
17	Research Facility	Palm Desert	California	United States	92260
18	Research Facility	Pasadena	California	United States	91106
19	Research Facility	San Diego	California	United States	92123
20	Research Facility	San Ramon	California	United States	94583
21	Test Facility	Santa Rosa	California	United States	95405
22	Site Facility	Upland	California	United States	91786
23	Research Facility	Vista	California	United States	92083
24	Site Facility	Vista	California	United States	92083
25	Site Facility	Westlake Village	California	United States	91361
26	Test Facility	Denver	Colorado	United States	80218
27	Research Facility	Longmont	Colorado	United States	80501
28	Test Facility	New London	Connecticut	United States	06320
29	Study Facility	Waterbury	Connecticut	United States	06708
30	Research Facility	Washington	District of Columbia	United States	20036
31	Research Facility	Boynton Beach	Florida	United States	33437
32	Site Facility	Clearwater	Florida	United States	33759
33	Site Facility	Daytona Beach	Florida	United States	32114
34	Research Facility	Gainesville	Florida	United States	32601
35	Research Site	Jacksonville	Florida	United States	32207
36	Site Facility	Jupiter	Florida	United States	33458
37	Test Facility	Miami	Florida	United States	33156
38	Research Facility	Pinellas Park	Florida	United States	33781
39	Research Facility	Plantation	Florida	United States	33324
40	Study Facility	South Miami	Florida	United States	33143
41	Research Site	Tampa	Florida	United States	33606
42	Test Facility	Vero Beach	Florida	United States	32960
43	Research Facility	West Palm Beach	Florida	United States	33409
44	Research Facility	Weston	Florida	United States	33326
45	Research Facility	Alpharetta	Georgia	United States	30005
46	Research Facility	Atlanta	Georgia	United States	30342
47	Site Facility	Decatur	Georgia	United States	30034
48	Site Facility	Douglasville	Georgia	United States	30134
49	Site Facility	Roswell	Georgia	United States	30075
50	Test Facility	Savannah	Georgia	United States	31405
51	Study Facility	Idaho Falls	Idaho	United States	83404
52	Test Facility	Champaign	Illinois	United States	61820
53	Test Facility	Chicago	Illinois	United States	60610
54	Test Facility	Indianapolis	Indiana	United States	46250
55	Research Facility	Overland Park	Kansas	United States	66202
56	Site Facility	Louisville	Kentucky	United States	40291
57	Study Facility	Baltimore	Maryland	United States	21229
58	Research Facility	Baltimore	Maryland	United States	21285-6815
59	Study Facility	Boston	Massachusetts	United States	02114
60	Research Facility	Bingham Farm	Michigan	United States	48025
61	Study Facility	Paw Paw	Michigan	United States	49079
62	Test Facility	Saginaw	Michigan	United States
63	Research Facility	Edina	Minnesota	United States	55435
64	Research Site	Jackson	Mississippi	United States	39216
65	Test Facility	St Louis	Missouri	United States	63141
66	Site Facility	Billings	Montana	United States	59102
67	Research Site	Omaha	Nebraska	United States	68124
68	Site Facility	Las Vegas	Nevada	United States	89146
69	Test Facility	Reno	Nevada	United States	89502
70	Test Facility	Moorestown	New Jersey	United States	08057
71	Research Facility	New York	New York	United States	10016
72	Test Facility	Raleigh	North Carolina	United States	27609
73	Study Facility	Winston Salem	North Carolina	United States	27103
74	Site Facility	Winston-Salem	North Carolina	United States	27103
75	Research Facility	Beachwood	Ohio	United States	44122
76	Test Facility	Centerville	Ohio	United States	45459
77	Research Facility	Cincinnati	Ohio	United States	45219
78	Study Facility	Cincinnati	Ohio	United States	45249
79	Research Facility	Cincinnati	Ohio	United States	45267-0457
80	Research Site	Cleveland	Ohio	United States	44106
81	Site Facility	Cleveland	Ohio	United States	44122
82	Test Facility	Columbus	Ohio	United States	43212
83	Test Facility	Columbus	Ohio	United States	43231
84	Research Facility	Dayton	Ohio	United States	45409
85	Test Facility	Englewood	Ohio	United States	45322
86	Test Facility	Oklahoma City	Oklahoma	United States
87	Test Facility	Tulsa	Oklahoma	United States	74104
88	Site Facility	Eugene	Oregon	United States	97401
89	Research Facility	Philadelphia	Pennsylvania	United States	19114
90	Study Facility	Bristol	Tennessee	United States	37620
91	Research Facility	Chattanooga	Tennessee	United States	37404
92	Research Facility	Nashville	Tennessee	United States	37203
93	Site Facility	Austin	Texas	United States	78705
94	Research Facility	Carrolton	Texas	United States	75007
95	Site Facility	Corpus Christi	Texas	United States	78414
96	Research Facility	Dallas	Texas	United States	75231
97	Test Facility	Farmers Branch	Texas	United States	75234
98	Research Facility	Houston	Texas	United States	77030
99	Research Facility	Irving	Texas	United States	75061
100	Research Facility	Midland	Texas	United States	79705
101	Research Facility	Richardson	Texas	United States	75082
102	Site Facility	San Antonio	Texas	United States	78229
103	Test Facility	San Antonio	Texas	United States	78229
104	Study Facility	Salt Lake City	Utah	United States	84117
105	Research Facility	West Valley City	Utah	United States	84120
106	Research Facility	Newport News	Virginia	United States	23606
107	Study Facility	Richmond	Virginia	United States	23229
108	Test Facility	Richmond	Virginia	United States	23229
109	Site Facility	Richmond	Virginia	United States	23294
110	Research Facility	Virginia Beach	Virginia	United States	23452
111	Research Facility	Virginia Beach	Virginia	United States	23456
112	Site Facility	Seattle	Washington	United States	98105
113	Research Facility	Tacoma	Washington	United States	98405
114	Test Facility	Tacoma	Washington	United States	98405
115	Research Site	Charleston	West Virginia	United States	25301

Sponsors and Collaborators

• Warner Chilcott

Investigators

• Study Director: Johna Lucas, MD, Procter and Gamble

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Warner Chilcott
• ClinicalTrials.gov Identifier: NCT00467259
• Other Study ID Numbers: 2007004
• First Posted: Apr 30, 2007
• Last Update Posted: Dec 15, 2011
• Last Verified: Nov 1, 2011

• Keywords provided by Warner Chilcott: Natural Menopause
• Additional relevant MeSH terms: Hypokinesia; Sexual Dysfunctions, Psychological; Testosterone

Study Results

Participant Flow

Recruitment Details	Screening began 14 May 2007
Pre-assignment Detail	Randomized 1127 women not using concomitant estrogen & progestin (E&P) therapy. An additional 134 women using concomitant estrogen & progestin therapy were randomized. Subjects were stratified by using or not using E&P by site and then randomized 4:1 300 mcg/d TTS or placebo.

Arm/Group Title	Placebo	Testosterone
Arm/Group Description	Placebo patch	Testosterone patch, 300 mcg/day, change patch twice a week for 52 weeks
Period Title: Overall Study
STARTED	251	1020
ITT Population	251	1019
COMPLETED	176	778
NOT COMPLETED	75	242

Baseline Characteristics

Arm/Group Title	Placebo	Testosterone	Total
Arm/Group Description	Placebo patch	Testosterone patch, 300 mcg/day, change patch twice a week for 52 weeks	Total of all reporting groups
Overall Participants	251	1020	1271
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.5 (4.8)	55.8 (4.9)	55.7 (4.9)
Age, Customized (Number) [Number]
40-49 years old	21 8.4%	95 9.3%	116 9.1%
50-59 years old	182 72.5%	700 68.6%	882 69.4%
60-65 years old	39 15.5%	189 18.5%	228 17.9%
66 + years old	9 3.6%	35 3.4%	44 3.5%
Sex: Female, Male (Count of Participants)
Female	251 100%	1020 100%	1271 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Number) [Number]
Hispanic or Latino	14 5.6%	50 4.9%	64 5%
Not Hispanic or Latino	237 94.4%	969 95%	1206 94.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
Indian (American)	1 0.4%	3 0.3%	4 0.3%
Asian (Oriental)	3 1.2%	6 0.6%	9 0.7%
Black or African American	9 3.6%	82 8%	91 7.2%
Caucasian	231 92%	920 90.2%	1151 90.6%
Hispanic	1 0.4%	3 0.3%	4 0.3%
Indian (Asian)	0 0%	1 0.1%	1 0.1%
Latino	0 0%	2 0.2%	2 0.2%
Mexican	1 0.4%	0 0%	1 0.1%
Multi-Racial	4 1.6%	1 0.1%	5 0.4%
Hawaiian / Pacific Islander	0 0%	1 0.1%	1 0.1%
Spanish	1 0.4%	0 0%	1 0.1%
Region of Enrollment (participants) [Number]
United States	251 100%	1020 100%	1271 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Endometrial Hyperplasia in Naturally Postmenopausal Women With Hypoactive Sexual Desire Disorder (HSDD) Not Using Concomitant Estrogen and Progestin, Year 1
Description	Incidence measured is number of patients with endometrial hyperplasia/number of patients with evaluable biopsies
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Subjects with evaluable endometrial biopsies.

Arm/Group Title	Placebo	Testosterone
Arm/Group Description	Placebo patch	Testosterone patch, 300 mcg/day, change patch twice a week for 52 weeks
Measure Participants	137	580
Number (95% Confidence Interval) [# Endometrial Hyperplasia/Evaluable Biop]	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Testosterone
	Comments	1000 naturally postmenopausal women not on concomitant E+P therapy at baseline were to be randomized (800 TTS; 200 placebo). It was assumed 60% would complete 1 year and 80% of these would have evaluable biopsies. Of the 800 randomized to TTS approximately 380 were expected to have evaluable biopsies at 1 year. 380 patients on TTS with evaluable biopsies at 1 year would provide 90% power to rule out an incidence of hyperplasia of 2% using the upper bound of a 2-sided 95% CI.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Fisher Exact
	Comments	p-value obtained from Fisher's exact test and corresponds to the test of the null hypothesis of no treatment difference.

2. Secondary Outcome

Title	Incidence of Endometrial Hyperplasia in Naturally Postmenopausal Women With HSDD Using Concomitant Estrogen and Progestin, Year 1
Description	Incidence measured is number of patients with endometrial hyperplasia/number of patients with evaluable biopsies
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Subjects with evaluable endometrial biopsies.

Arm/Group Title	Placebo	Testosterone
Arm/Group Description	Placebo patch	Testosterone patch, 300 mcg/day, change patch twice a week for 52 weeks
Measure Participants	10	68
Number (95% Confidence Interval) [# Endometrial Hyperplasia/Evaluable Biop]	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Testosterone
	Comments	1000 naturally postmenopausal women not on concomitant E+P therapy at baseline were to be randomized (800 TTS; 200 placebo). It was assumed 60% would complete 1 year and 80% of these would have evaluable biopsies. Of the 800 randomized to TTS approximately 380 were expected to have evaluable biopsies at 1 year. 380 patients on TTS with evaluable biopsies at 1 year would provide 90% power to rule out an incidence of hyperplasia of 2% using the upper bound of a 2-sided 95% CI.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Fisher Exact
	Comments	p-value obtained from Fisher's exact test and corresponds to the test of the null hypothesis of no treatment difference.

3. Secondary Outcome

Title	Incidence Endometrial Hyperplasia in Naturally Postmenopausal Women With HSDD Using Concomitant Estrogen & Progestin Combined With Those Not Using Estrogen & Progestin Therapy, Year 1
Description	Incidence measured is number of patients with endometrial hyperplasia/number of patients with evaluable biopsies
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Subjects with evaluable endometrial biopsies.

Arm/Group Title	Placebo	Testosterone
Arm/Group Description	Placebo patch	Testosterone patch, 300 mcg/day, change patch twice a week for 52 weeks
Measure Participants	147	648
Number (95% Confidence Interval) [# Endometrial Hyperplasia/Evaluable Biop]	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Testosterone
	Comments	1000 naturally postmenopausal women not on concomitant E+P therapy at baseline were to be randomized (800 TTS; 200 placebo). It was assumed 60% would complete 1 year and 80% of these would have evaluable biopsies. Of the 800 randomized to TTS approximately 380 were expected to have evaluable biopsies at 1 year. 380 patients on TTS with evaluable biopsies at 1 year would provide 90% power to rule out an incidence of hyperplasia of 2% using the upper bound of a 2-sided 95% CI.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Fisher Exact
	Comments	p-value obtained from Fisher's Exact test and corresponds to the test of the null hypothesis of no treatment difference.

Adverse Events

Time Frame	52 week treatment period
Adverse Event Reporting Description	Vaginal bleeding that worsens from baseline will only be recorded on vaginal bleeding page, not as an AE. However, if vaginal bleeding results in study withdrawal or meets the ICH definition of a "serious" AE it will be recorded as an AE.
Arm/Group Title	Placebo		Testosterone
Arm/Group Description	Placebo patch		Testosterone patch, 300 mcg/day, change patch twice a week for 52 weeks
All Cause Mortality
	Placebo		Testosterone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Testosterone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/251 (4%)		33/1019 (3.2%)
Cardiac disorders
Coronary Artery Disease	0/251 (0%)		1/1019 (0.1%)
Congenital, familial and genetic disorders
Congenital Cerebrovascular Anomaly	0/251 (0%)		1/1019 (0.1%)
Gastrointestinal disorders
Pancreatitis Acute	0/251 (0%)		1/1019 (0.1%)
Abdominal Pain Lower	1/251 (0.4%)		0/1019 (0%)
Oesophageal Spasm	1/251 (0.4%)		0/1019 (0%)
Small Intestine Haemorrhage	1/251 (0.4%)		0/1019 (0%)
Appendicitis Perforated	0/251 (0%)		1/1019 (0.1%)
Gastrointestinal Haemorrhage	1/251 (0.4%)		0/1019 (0%)
General disorders
Chest Pain	0/251 (0%)		1/1019 (0.1%)
Hepatobiliary disorders
Cholecystitis Acute	0/251 (0%)		1/1019 (0.1%)
Infections and infestations
Appendicitis	0/251 (0%)		1/1019 (0.1%)
Diverticulitis	1/251 (0.4%)		1/1019 (0.1%)
Cellulitis	0/251 (0%)		1/1019 (0.1%)
Joint Abscess	0/251 (0%)		1/1019 (0.1%)
Device Related Infection	1/251 (0.4%)		0/1019 (0%)
Urinary Tract Infection	0/251 (0%)		1/1019 (0.1%)
Injury, poisoning and procedural complications
Sternal Injury	0/251 (0%)		1/1019 (0.1%)
Hip Fracture	0/251 (0%)		1/1019 (0.1%)
Tibia Fracture	0/251 (0%)		1/1019 (0.1%)
Head Injury	0/251 (0%)		1/1019 (0.1%)
Spinal Fracture	0/251 (0%)		2/1019 (0.2%)
Radius Fracture	1/251 (0.4%)		0/1019 (0%)
Ulna Fracture	1/251 (0.4%)		0/1019 (0%)
Upper Limb Fracture	0/251 (0%)		1/1019 (0.1%)
Musculoskeletal and connective tissue disorders
Arthritis Reactive	0/251 (0%)		1/1019 (0.1%)
Back Pain	1/251 (0.4%)		0/1019 (0%)
Pain in Extremity	0/251 (0%)		1/1019 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	1/251 (0.4%)		1/1019 (0.1%)
Breast Cancer in Situ	0/251 (0%)		1/1019 (0.1%)
Hodgkin's Disease	0/251 (0%)		1/1019 (0.1%)
Leiomyosarcoma	1/251 (0.4%)		0/1019 (0%)
Leiomyosarcoma Metastatic	1/251 (0.4%)		0/1019 (0%)
Colon Adenoma	1/251 (0.4%)		0/1019 (0%)
Metastases to Liver	1/251 (0.4%)		0/1019 (0%)
Brain Neoplasm	0/251 (0%)		1/1019 (0.1%)
Acoustic Neuroma	0/251 (0%)		1/1019 (0.1%)
Oesophageal Carcinoma	1/251 (0.4%)		0/1019 (0%)
Nervous system disorders
Guillain-Barre Syndrome	0/251 (0%)		1/1019 (0.1%)
Carotid Artery Occlusion	0/251 (0%)		1/1019 (0.1%)
Cerebrovascular Accident	0/251 (0%)		1/1019 (0.1%)
Hypertensive Encephalopathy	0/251 (0%)		1/1019 (0.1%)
Hypoaesthesia	0/251 (0%)		1/1019 (0.1%)
Transient Ischaemic Attack	0/251 (0%)		3/1019 (0.3%)
Psychiatric disorders
Affective Disorder	0/251 (0%)		1/1019 (0.1%)
Renal and urinary disorders
Stress Urinary Incontinence	0/251 (0%)		1/1019 (0.1%)
Glomerulonephritis Minimal Lesion	0/251 (0%)		1/1019 (0.1%)
Renal Failure	1/251 (0.4%)		0/1019 (0%)
Nephrolithiasis	0/251 (0%)		1/1019 (0.1%)
Reproductive system and breast disorders
Ovarian Cyst	1/251 (0.4%)		0/1019 (0%)
Uterine Prolapse	0/251 (0%)		1/1019 (0.1%)
Vascular disorders
Deep Vein Thrombosis	0/251 (0%)		2/1019 (0.2%)
Hypertension	1/251 (0.4%)		1/1019 (0.1%)
Other (Not Including Serious) Adverse Events
	Placebo		Testosterone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	125/251 (49.8%)		472/1019 (46.3%)
Gastrointestinal disorders
Diarrhoea	6/251 (2.4%)	6	8/1019 (0.8%)	9
Nausea	5/251 (2%)	5	10/1019 (1%)	11
General disorders
Application Site Reaction	47/251 (18.7%)	50	180/1019 (17.7%)	196
Infections and infestations
Nasopharyngitis	11/251 (4.4%)	12	22/1019 (2.2%)	26
Sinusitis	5/251 (2%)	5	25/1019 (2.5%)	27
Upper Respiratory Tract Infection	10/251 (4%)	11	28/1019 (2.7%)	32
Urinary Tract Infection	2/251 (0.8%)	2	24/1019 (2.4%)	31
Investigations
Weight Increased	5/251 (2%)	5	51/1019 (5%)	51
Nervous system disorders
Headache	8/251 (3.2%)	8	22/1019 (2.2%)	26
Psychiatric disorders
Depression	9/251 (3.6%)	10	13/1019 (1.3%)	14
Skin and subcutaneous tissue disorders
Hirsutism	4/251 (1.6%)	4	41/1019 (4%)	48
Vascular disorders
Hot Flush	5/251 (2%)	5	21/1019 (2.1%)	21
Hypertension	8/251 (3.2%)	8	27/1019 (2.6%)	27

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.