Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00305695
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 160
• Locations: 95
• Arms: 2
• Patients Per Site: 1.7

Study Details

Study Description

Brief Summary

This randomized phase II trial is studying zoledronate to see how well it works compared to observation in maintaining bone mineral density in patients who are undergoing surgery to remove both ovaries. Zoledronate may prevent bone loss in patients who are undergoing surgery to remove the ovaries.

Condition or Disease	Intervention/Treatment	Phase
Hereditary Breast and Ovarian Cancer Syndrome; Osteoporosis; Ovarian Carcinoma	Other: Laboratory Biomarker Analysis; Drug: Zoledronic Acid	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. Compare the effect of zoledronate vs observation on bone loss associated with surgery (at a minimum, any surgical procedure that results in removal of both ovaries) in patients undergoing excision of both ovaries.

SECONDARY OBJECTIVE:

1. Compare the change in bone mineral density of the bilateral hip in patients treated with these regimens.

TERTIARY OBJECTIVE:

1. Compare the effect of zoledronate vs observation on biochemical markers of bone resorption and bone formation (N-telopeptide and bone specific alkaline phosphatase) during 1 year of treatment.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

All patients undergo surgery, with removal of both ovaries, in month 1. All patients are requested to take calcium supplements twice daily and a multivitamin containing vitamin D once daily beginning in month 1 and continuing for up to 18 months.

ARM I: Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15.

ARM II: Patients are observed for 18 months after surgery.

In both arms, patients complete physical activity questionnaires at baseline and in months 3, 9, 15, and 18. Patients undergo bone mineral density test of lumbar spine and total hip at baseline and in months 9 and 18. Patients also undergo blood collection at baseline and periodically during the study for biomarker studies.

Study Design

• Study Type: Interventional
• Actual Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Phase II Randomized Study of the Effect of Zoledronic Acid Versus Observation on Bone Mineral Density of the Lumbar Spine in Women Who Elect to Undergo Surgery That Results in Removal of Both Ovaries
• Actual Study Start Date: Nov 28, 2005
• Actual Primary Completion Date: Dec 22, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (zoledroic acid) Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Zoledronic Acid; Given IV; Other Names: [1-Hydroxy-2-(1H-imidazol-1-yl)ethylidene]bisphosphonic Acid CGP 42446 CGP42446A NDC-Zoledronate Reclast ZOL 446 Zometa
No Intervention: Arm II (clinical observation) Patients are observed for 18 months after surgery.

Outcome Measures

Primary Outcome Measures

1. Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 9 Months [9 Months]

   To compare the effect of zoledronic acid administered every 6 months on bone loss associated with surgery (at a minimum, any surgical procedure that results in removal of both ovaries), as compared with observation alone. This is to be evaluated by measuring the change from baseline to 9 months in bone mineral density (BMD) of the lumbar spine, specifically L1-L4 dual energy X-ray absorptiometry (DEXA).

2. Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 18 Months [18 months]

   To compare the effect of zoledronic acid administered every 6 months on bone loss associated with surgery (at a minimum, any surgical procedure that results in removal of both ovaries), as compared with observation alone. This is to be evaluated by measuring the change from baseline to 18 months in bone mineral density (BMD) of the lumbar spine, specifically L1-L4 dual energy X-ray absorptiometry (DEXA).

3. Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Right Hip [18 months]

   To compare the effect of zoledronic acid on the change in BMD of the right hip following treatment, evaluated by measuring the change from baseline to 18 months

4. Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Left Hip [18 months]

   To compare the effect of zoledronic acid on the change in BMD of the left hip following treatment, evaluated by measuring the change from baseline to 18 months

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who have elected to undergo, or who have undergone (within 8 weeks) a surgical procedure that results (at minimum) in the absence of both ovaries

• Patients enrolled in the screening arm of GOG-0199 who decide to undergo surgery are potentially eligible for GOG-0215

• Baseline bone mass density (BMD) T-Score ? -1.5 (no more than 1.5 standard deviation below the mean value for young adults) on both the total lumbar spine (L1-L4 region, not individual bones) and bilateral hip

• Patients who had/have at least 1 intact ovary at the time of surgery are eligible

• No prior distant metastatic malignant disease within the past 5 years

• Patients treated for stage M1 (any T, any N) diagnosis in the past 5 years are ineligible

• Patients who achieved a complete response after treatment for rM0 (any T, any N) within the past 5 years are eligible

• Premenopausal*

• Last menstrual cycle occurred < 12 months prior to study enrollment

• GOG performance status 0-2

• Creatinine clearance > 60 mL/min

• No clinical or radiological evidence of existing fracture of the lumbar spine or bilateral hip

• No history of hip of spine fracture with low-intensity trauma or not associated with trauma

• No uncontrolled seizure disorder associated with falls

• No diseases that influence bone metabolism, including any of the following:

• Paget?s disease

• Osteogenesis imperfecta

• Uncontrolled thyroid or parathyroid dysfunction within 12 months prior to study entry

• No other nonmalignant systemic disease, including any of the following:

• Uncontrolled infection

• Uncontrolled type 2 diabetes mellitus

• Cardiovascular, renal, hepatic, or lung disease that would prevent prolonged follow-up

• History of thrombosis or thromboembolism allowed

• No known HIV positivity

• No known hypersensitivity to zoledronate or other bisphosphonates

• No psychiatric, psychological, or other conditions that prevent fully informed consent

• No other active malignancy except nonmelanoma skin cancer

• No history of any medical condition that places the patient at risk for donating blood for research purposes (e.g., chronic infectious diseases, sever anemia, or hemophilia)

• Not pregnant

• Negative pregnancy test

• No current active dental problems, including any of the following:

• Infection of the teeth or jawbone (maxilla or mandible)

• Dental or fixture trauma

• Current or prior diagnosis of osteonecrosis of the jaw

• Exposed bone in the mouth

• Slow healing after dental procedures

• No recent (within 6 weeks) or planned dental or jaw surgery (e.g., extraction or implants)

• No prior treatment for osteoporosis

• No adjuvant radiotherapy within the past 31 days

• No chemotherapy within the past 30 days

• No prior surgery to the hip or spine

• No prior systemic sodium fluoride for > 3 months during the past 2 years

• No more than 30 days use in the past 12 months and no concurrent tamoxifen, raloxifene, or any other selective estrogen-receptor modulator (SERM)

• More than 12 months since prior and no concurrent endocrine therapy

• Insulin and/or oral antidiabetic medications allowed

• Thyroid hormone replacement allowed

• More than 12 months since prior and no concurrent estrogen or hormone replacement therapy (estrogen plus progesterone or estrogen alone)

• Prior or concurrent oral contraceptives allowed

• Systemic (oral) hormone replacement therapy following surgery not allowed

• Vaginal (non-systemic) estrogen allowed

• More than 12 months since prior and no concurrent oral or IV bisphosphonate

• More than 12 months since prior and no concurrent anabolic steroids or growth hormone

• More than 12 months since prior and no concurrent systemic corticosteroids

• Concurrent short term corticosteroid therapy (to prevent/treat chemotherapy-induced nausea/vomiting) allowed

• More than 6 months since prior and no concurrent Tibolone

• More than 2 weeks since prior and no concurrent drugs known to affect the skeleton (e.g., calcitonin, mithramycin, or gallium nitrate)

• No concurrent chemotherapy or radiotherapy

• No concurrent aromatase inhibitors

• Concurrent enrollment on protocol GOG-0199 allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
2	Banner University Medical Center - Tucson	Tucson	Arizona	United States	85719
3	University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
4	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
5	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
6	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
7	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
8	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
9	Stanford Cancer Institute Palo Alto	Palo Alto	California	United States	94304
10	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
11	University of California San Diego	San Diego	California	United States	92103
12	Colorado Gynecologic Oncology Group	Aurora	Colorado	United States	80010
13	Boulder Community Hospital	Boulder	Colorado	United States	80301
14	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
15	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
16	Rose Medical Center	Denver	Colorado	United States	80220
17	North Colorado Medical Center	Greeley	Colorado	United States	80631
18	McKee Medical Center	Loveland	Colorado	United States	80539
19	North Suburban Medical Center	Thornton	Colorado	United States	80229
20	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
21	Hartford Hospital	Hartford	Connecticut	United States	06102
22	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
23	Yale University	New Haven	Connecticut	United States	06520
24	Beebe Medical Center	Lewes	Delaware	United States	19958
25	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
26	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
27	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
28	Jupiter Medical Center	Jupiter	Florida	United States	33458
29	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
30	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
31	University of Illinois	Chicago	Illinois	United States	60612
32	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
33	Carle Cancer Center	Urbana	Illinois	United States	61801
34	Northwestern Medicine Central DuPage Hospital	Winfield	Illinois	United States	60190
35	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
36	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
37	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
38	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
39	Menorah Medical Center	Overland Park	Kansas	United States	66209
40	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
41	Baptist Health Lexington	Lexington	Kentucky	United States	40503
42	Norton Hospital Pavilion and Medical Campus	Louisville	Kentucky	United States	40202
43	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
44	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
45	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
46	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
47	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
48	Mayo Clinic	Rochester	Minnesota	United States	55905
49	Truman Medical Center	Kansas City	Missouri	United States	64108
50	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
51	North Kansas City Hospital	Kansas City	Missouri	United States	64116
52	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
53	Research Medical Center	Kansas City	Missouri	United States	64132
54	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
55	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64507
56	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
57	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri	United States	63141
58	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
59	CoxHealth South Hospital	Springfield	Missouri	United States	65807
60	Sunrise Hospital and Medical Center	Las Vegas	Nevada	United States	89109
61	Center of Hope at Renown Medical Center	Reno	Nevada	United States	89502
62	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
63	Virtua Memorial	Mount Holly	New Jersey	United States	08060
64	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
65	Northwell Health/Center for Advanced Medicine	Lake Success	New York	United States	11042
66	North Shore University Hospital	Manhasset	New York	United States	11030
67	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
68	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
69	Mount Sinai Hospital	New York	New York	United States	10029
70	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina	United States	27215
71	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
72	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
73	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio	United States	45219
74	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio	United States	45220
75	Case Western Reserve University	Cleveland	Ohio	United States	44106
76	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
77	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
78	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
79	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
80	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
81	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
82	Oregon Health and Science University	Portland	Oregon	United States	97239
83	Main Line Health NCORP	Wynnewood	Pennsylvania	United States	19096
84	Women and Infants Hospital	Providence	Rhode Island	United States	02905
85	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
86	Chattanooga's Program in Women's Oncology	Chattanooga	Tennessee	United States	37403
87	Meharry Medical College	Nashville	Tennessee	United States	37208
88	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
89	The Don and Sybil Harrington Cancer Center	Amarillo	Texas	United States	79106
90	University of Vermont Medical Center	Burlington	Vermont	United States	05401
91	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
92	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
93	Carilion Clinic Gynecological Oncology	Roanoke	Virginia	United States	24016
94	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
95	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227

Sponsors and Collaborators

• Gynecologic Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: David S Alberts, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT00305695
• Other Study ID Numbers: GOG-0215; NCI-2009-00589; NCI-P6966; NOVARTIS-GOG-0215; CDR0000462217; NCI-06-C-0204; GOG-0215; GOG-0215; GOG-0215; U10CA101165
• First Posted: Mar 22, 2006
• Last Update Posted: Mar 24, 2020
• Last Verified: Mar 1, 2020

• Additional relevant MeSH terms: Hereditary Breast and Ovarian Cancer Syndrome; Osteoporosis; Zoledronic Acid; Imidazole

Study Results

Participant Flow

Recruitment Details	GOG 0215 accrued 160 patients from November 2005 to April 2010.

Arm/Group Title	Arm I (Zoledroic Acid)	Arm II (Clinical Observation)
Arm/Group Description	Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15. Laboratory Biomarker Analysis: Correlative studies Zoledronic Acid: Given IV	Patients are observed for 18 months after surgery.
Period Title: Overall Study
STARTED	81	79
COMPLETED	40	52
NOT COMPLETED	41	27

Baseline Characteristics

Arm/Group Title	Arm I (Zoledroic Acid)	Arm II (Clinical Observation)	Total
Arm/Group Description	Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15. Laboratory Biomarker Analysis: Correlative studies Zoledronic Acid: Given IV	Patients are observed for 18 months after surgery.	Total of all reporting groups
Overall Participants	80	78	158
Age, Customized (Count of Participants)
20-29 years	3 3.8%	1 1.3%	4 2.5%
30-39 years	9 11.3%	23 29.5%	32 20.3%
40-49 years	57 71.3%	47 60.3%	104 65.8%
50-59 years	11 13.8%	7 9%	18 11.4%
Sex: Female, Male (Count of Participants)
Female	80 100%	78 100%	158 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 9 Months
Description	To compare the effect of zoledronic acid administered every 6 months on bone loss associated with surgery (at a minimum, any surgical procedure that results in removal of both ovaries), as compared with observation alone. This is to be evaluated by measuring the change from baseline to 9 months in bone mineral density (BMD) of the lumbar spine, specifically L1-L4 dual energy X-ray absorptiometry (DEXA).
Time Frame	9 Months

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Arm I (Zoledroic Acid)	Arm II (Clinical Observation)
Arm/Group Description	Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15. Laboratory Biomarker Analysis: Correlative studies Zoledronic Acid: Given IV	Patients are observed for 18 months after surgery.
Measure Participants	51	68
Mean (Full Range) [g/cm2]	-0.025	-0.086

2. Primary Outcome

Title	Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 18 Months
Description	To compare the effect of zoledronic acid administered every 6 months on bone loss associated with surgery (at a minimum, any surgical procedure that results in removal of both ovaries), as compared with observation alone. This is to be evaluated by measuring the change from baseline to 18 months in bone mineral density (BMD) of the lumbar spine, specifically L1-L4 dual energy X-ray absorptiometry (DEXA).
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Arm I (Zoledroic Acid)	Arm II (Clinical Observation)
Arm/Group Description	Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15. Laboratory Biomarker Analysis: Correlative studies Zoledronic Acid: Given IV	Patients are observed for 18 months after surgery.
Measure Participants	40	52
Mean (Full Range) [g/cm2]	-0.001	-0.094

3. Primary Outcome

Title	Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Right Hip
Description	To compare the effect of zoledronic acid on the change in BMD of the right hip following treatment, evaluated by measuring the change from baseline to 18 months
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Eligible and Treated patients

Arm/Group Title	Arm I (Zoledroic Acid)	Arm II (Clinical Observation)
Arm/Group Description	Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15. Laboratory Biomarker Analysis: Correlative studies Zoledronic Acid: Given IV	Patients are observed for 18 months after surgery.
Measure Participants	35	51
Mean (Full Range) [g/cm2]	0.101	-0.052

4. Primary Outcome

Title	Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Left Hip
Description	To compare the effect of zoledronic acid on the change in BMD of the left hip following treatment, evaluated by measuring the change from baseline to 18 months
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Eligible and Treated patients

Arm/Group Title	Arm I (Zoledroic Acid)	Arm II (Clinical Observation)
Arm/Group Description	Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15. Laboratory Biomarker Analysis: Correlative studies Zoledronic Acid: Given IV	Patients are observed for 18 months after surgery.
Measure Participants	40	54
Mean (Full Range) [g/cm2]	-0.003	-0.058

Adverse Events

Time Frame	Up to 18 months
Arm/Group Title	Arm I (Zoledroic Acid)		Arm II (Clinical Observation)
Arm/Group Description	Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15. Laboratory Biomarker Analysis: Correlative studies Zoledronic Acid: Given IV		Patients are observed for 18 months after surgery.
All Cause Mortality
	Arm I (Zoledroic Acid)		Arm II (Clinical Observation)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Zoledroic Acid)		Arm II (Clinical Observation)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/80 (1.3%)		0/78 (0%)
Gastrointestinal disorders
Gastritis	1/80 (1.3%)		0/78 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (Zoledroic Acid)		Arm II (Clinical Observation)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/80 (56.3%)		19/78 (24.4%)
Blood and lymphatic system disorders
Hemoglobin	0/80 (0%)		1/78 (1.3%)
Edema: Limb	1/80 (1.3%)		1/78 (1.3%)
Ear and labyrinth disorders
Tinnitus	2/80 (2.5%)		0/78 (0%)
Endocrine disorders
Hot Flashes	3/80 (3.8%)		6/78 (7.7%)
Hypothyroidism	0/80 (0%)		1/78 (1.3%)
Gastrointestinal disorders
Gastritis	1/80 (1.3%)		0/78 (0%)
Taste Alteration	1/80 (1.3%)		0/78 (0%)
Vomiting	6/80 (7.5%)		0/78 (0%)
Anorexia	2/80 (2.5%)		0/78 (0%)
Constipation	2/80 (2.5%)		3/78 (3.8%)
Nausea	15/80 (18.8%)		1/78 (1.3%)
Gastrointestinal - Other	1/80 (1.3%)		0/78 (0%)
Diarrhea	1/80 (1.3%)		0/78 (0%)
General disorders
Fever	12/80 (15%)		0/78 (0%)
Rigors/Chills	14/80 (17.5%)		1/78 (1.3%)
Fatigue	22/80 (27.5%)		4/78 (5.1%)
Insomnia	0/80 (0%)		4/78 (5.1%)
Pain - Other	1/80 (1.3%)		1/78 (1.3%)
Pain: Pelvis	0/80 (0%)		1/78 (1.3%)
Pain: Vagina	1/80 (1.3%)		1/78 (1.3%)
Pain: Chest /Thorax Nos	1/80 (1.3%)		1/78 (1.3%)
Pain: Head/Headache	6/80 (7.5%)		0/78 (0%)
Pain: Neck	2/80 (2.5%)		0/78 (0%)
Pain: Extremity-Limb	0/80 (0%)		1/78 (1.3%)
Pain: Back	2/80 (2.5%)		1/78 (1.3%)
Pain: Joint	20/80 (25%)		4/78 (5.1%)
Pain: Bone	13/80 (16.3%)		1/78 (1.3%)
Pain: Abdominal Pain Nos	2/80 (2.5%)		2/78 (2.6%)
Pain: External Ear	1/80 (1.3%)		0/78 (0%)
Pain: Muscle	19/80 (23.8%)		1/78 (1.3%)
Flu-Like Syndrome	3/80 (3.8%)		0/78 (0%)
Infections and infestations
Inf Unknown Anc: Sinus	0/80 (0%)		1/78 (1.3%)
Metabolism and nutrition disorders
Creatinine	1/80 (1.3%)		2/78 (2.6%)
Hypocalcemia	1/80 (1.3%)		0/78 (0%)
Hyperglycemia	0/80 (0%)		1/78 (1.3%)
Hypercalcemia	2/80 (2.5%)		0/78 (0%)
Musculoskeletal and connective tissue disorders
Osteoporosis	0/80 (0%)		1/78 (1.3%)
Nervous system disorders
Mental Status	1/80 (1.3%)		0/78 (0%)
Mood Alteration - Depression	0/80 (0%)		3/78 (3.8%)
Mood Alteration - Anxiety	0/80 (0%)		2/78 (2.6%)
Dizziness	1/80 (1.3%)		1/78 (1.3%)
Neuropathy-Sensory	1/80 (1.3%)		0/78 (0%)
Renal and urinary disorders
Incontinence, Urinary	0/80 (0%)		1/78 (1.3%)
Urinary Frequency	0/80 (0%)		1/78 (1.3%)
Reproductive system and breast disorders
Vaginal Dryness	2/80 (2.5%)		3/78 (3.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/80 (1.3%)		0/78 (0%)
Skin and subcutaneous tissue disorders
Rash	1/80 (1.3%)		1/78 (1.3%)
Dry Skin	0/80 (0%)		1/78 (1.3%)
Flushing	0/80 (0%)		1/78 (1.3%)
Vascular disorders
Hemorrhage, Gu - Vagina	0/80 (0%)		1/78 (1.3%)

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.