Levonorgestrel in Preventing Ovarian Cancer in Patients at High Risk for Ovarian Cancer

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00445887
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 60
• Locations: 66
• Arms: 2
• Patients Per Site: 0.9

Study Details

Study Description

Brief Summary

This randomized phase II trial is studying how well levonorgestrel works in preventing ovarian cancer in patients at high risk for ovarian cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of levonorgestrel may prevent ovarian cancer.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Carcinoma	Other: Laboratory Biomarker Analysis; Drug: Levonorgestrel; Other: Placebo	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the impact of levonorgestrel on the relative frequency of apoptosis in the ovarian epithelium of patients at high risk for ovarian cancer.

SECONDARY OBJECTIVES:

1. Estimate the impact of this drug on proliferation and transforming growth factor-beta (TGF-beta) expression in the ovarian epithelium of these patients.

2. Assess the safety of this drug in these patients.

OUTLINE: This is a prospective, randomized, placebo-controlled, double-blind study. Patients are stratified according to menopausal status (premenopausal vs postmenopausal). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral levonorgestrel once daily.

ARM II: Patients receive oral placebo once daily.

In both arms, treatment continues for 4-6 weeks in the absence of disease progression or unacceptable toxicity, including on the day of surgery. Patients then undergo prophylactic salpingo-oophorectomy. After completion of study therapy, patients are followed at 1 year.

NOTE: * Patients who are unable to have surgery completed during the expected 4-6 weeks, may continue levonorgestrel or placebo for a time period no > 5 months. Patients unable to undergo surgery within 5 months are removed from the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Phase II Double Blind Randomized Trial Evaluating the Biologic Effect of Levonorgestrel on the Double Blind Randomized Trial Evaluating the Biologic Effect of Levonorgestrel on the Ovarian Epithelium in Women at High Risk for Ovarian Cancer
• Actual Study Start Date: Mar 10, 2008
• Actual Primary Completion Date: Dec 11, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (levonorgestrel) Patients receive oral levonorgestrel once daily.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Levonorgestrel; Given orally; Other Names: 18-Methylnorethisterone D-(-)-Norgestrel L-norgestrel Mirena Norplant Plan B
Placebo Comparator: Arm II (placebo) Patients receive oral placebo once daily.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Levonorgestrel; Given orally; Other Names: 18-Methylnorethisterone D-(-)-Norgestrel L-norgestrel Mirena Norplant Plan B ; Other: Placebo; Given orally; Other Names: placebo therapy PLCB sham therapy

Outcome Measures

Primary Outcome Measures

1. Median Proportion Cells That Are Apoptotic in Epithelial Ovarian Tissue [Surgical specimen (4 - 6 weeks after entry)]

   The median proportion of cells that are considered to be apoptotic are counted in the ovarian tissue sample, among the total number of cells available in the sample slide.

2. Number of Participants With Adverse Events According to Grade as Determined by NCI CTCAE v.3.0 [Up to 20 weeks]

   Participants were graded using CTCAE v.30 criteria. Grade 1 is the least severe grade. Each adverse event lists criteria for grading, grade 1 being mild, up to grade 5. Grade 4 is generally life threatening. Grade 5 is death.

Secondary Outcome Measures

1. Proportion of Proliferation as Measured by Ki-67 [Time of surgery (4 to 6 weeks after entry)]

2. Patients With High Expression of Transforming Growth Factor-beta 1 [Baseline to time of surgery (4 to 6 weeks)]

Other Outcome Measures

1. Median Proportion Cells That Are Apoptotic in Fallopian Tube Tissue [Surgical specimen (4-6 weeks after entry)]

   The median proportion of cells that are considered to be apoptotic are counted in the fallopian tube tissue sample, among the total number of cells available in the sample slide

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• At increased genetic risk for ovarian cancer AND planning to undergo risk-reducing salpingo-oophorectomy (RRSO)

• Has ≥ 1 intact ovary

• Patients enrolled on clinical trial GOG-0199 and planning to undergo RRSO allowed

• Submission of fixed ovarian tissue (FN01) required

• Must meet 1 of the following additional criteria:

• Family of the patient has a documented deleterious BRCA1 or BRCA2 mutation and either the patient herself has tested positive for a deleterious BRCA1 or BRCA2 mutation or the patient has a first- or second-degree relative with a deleterious BRCA1 or BRCA2 mutation

• No patient with a deleterious BRCA1 or BRCA2 mutation whose first- or second-degree relative has tested negative for the exact same mutation

• The family contains members with ≥ 2 ovarian* and/or breast cancers among the first- or second-degree relatives (male relatives must be counted) of the patient within the same lineage (this condition may be satisfied by multiple primary cancers in the same person or, where breast cancer is required to meet this criterion, ≥ 1 breast cancer must have been diagnosed prior to menopause or at age ≤ 50 years if age at menopause is unknown)

• The patient is of Ashkenazi Jewish ethnicity (lineage via the mother) with one first- degree or two second-degree maternal relatives with breast and/or ovarian cancer* (where breast cancer is required to meet this criterion, ≥ 1 breast cancer must have been diagnosed prior to menopause or at age ≤ 50 years if age at menopause is unknown)

• The probability of carrying a BRCA1 or BRCA2 mutation, given the family pedigree of breast and ovarian cancers, exceeds 20%, as calculated by BRCAPRO

• No prior history of ovarian cancer, including low malignant potential cancers, or primary papillary serous carcinoma of the peritoneum

• No prior or concurrent history of breast cancer, including ductal carcinoma in situ (DCIS) of the breast

• Women with a history of hormone receptor-negative breast cancer (both estrogen receptor-negative and progesterone receptor-negative) are eligible

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective nonhormonal contraception prior to the prophylactic salpingo-oophorectomy

• No prior history of deep vein thrombosis, stroke, liver disease, or heart attack

• No prior history of myocardial infarction

• No known bleeding disorders or hypercoagulable states

• No other malignancy, including ductal carcinoma in situ, within 1 year of systemic therapy, except for nonmelanoma skin cancer

• No prior chemotherapy regimen lasting ≥ 12 months

• No oral or intrauterine hormonal contraception or hormonal replacement therapy within the past 3 months or injectable medroxyprogesterone within the past 12 months

• No intraperitoneal surgery within the past 3 months (including laparoscopy)

• No prior or concurrent radiotherapy to the pelvis

• No concurrent hormonal contraception

• No concurrent tamoxifen, raloxifene, estrogen, progesterone-like hormones, or other hormonal medication (including hormone replacement therapy)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
3	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
4	University of California San Diego	San Diego	California	United States	92103
5	Colorado Gynecologic Oncology Group	Aurora	Colorado	United States	80010
6	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
7	Northwestern University	Chicago	Illinois	United States	60611
8	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
9	Hinsdale Hematology Oncology Associates Incorporated	Hinsdale	Illinois	United States	60521
10	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
11	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
12	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana	United States	46514
13	Elkhart General Hospital	Elkhart	Indiana	United States	46515
14	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
15	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
16	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
17	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545
18	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
19	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana	United States	46563
20	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
21	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
22	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
23	Michiana Hematology Oncology PC-Westville	Westville	Indiana	United States	46391
24	Saint Elizabeth Medical Center South	Edgewood	Kentucky	United States	41017
25	Baptist Health Lexington	Lexington	Kentucky	United States	40503
26	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
27	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
28	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
29	Lakeland Hospital Niles	Niles	Michigan	United States	49120
30	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan	United States	49085
31	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
32	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
33	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
34	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
35	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
36	CoxHealth South Hospital	Springfield	Missouri	United States	65807
37	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
38	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
39	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
40	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
41	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
42	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
43	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina	United States	27215
44	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
45	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
46	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
47	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio	United States	45219
48	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio	United States	45220
49	Case Western Reserve University	Cleveland	Ohio	United States	44106
50	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
51	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
52	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
53	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
54	Miami Valley Hospital	Dayton	Ohio	United States	45409
55	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
56	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
57	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
58	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
59	The Don and Sybil Harrington Cancer Center	Amarillo	Texas	United States	79106
60	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
61	University of Texas Medical Branch	Galveston	Texas	United States	77555-0565
62	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
63	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
64	Carilion Clinic Gynecological Oncology	Roanoke	Virginia	United States	24016
65	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
66	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449

Sponsors and Collaborators

• Gynecologic Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Gustavo C Rodriguez, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT00445887
• Other Study ID Numbers: GOG-0214; NCI-2009-00588; 10-01367; CDR0000532268; GOG-0214; GOG-0214; GOG-0214; GOG-0214; U10CA101165
• First Posted: Mar 9, 2007
• Last Update Posted: Nov 19, 2019
• Last Verified: Nov 1, 2019

• Additional relevant MeSH terms: Ovarian Neoplasms; Levonorgestrel; Norgestrel

Study Results

Participant Flow

Recruitment Details	The protocol opened to accrual 03/10/2008 and closed 11/26/2012Women who were are at increased risk for ovarian cancer and were intending to undergo prophylactic salpingo-oopherectomy were randomized to Levenorgestrel (0.15 mg/day) or Placebo for 4 to 6 weeks.

Arm/Group Title	Arm I (Levenorgestrel)	Arm II (Placebo)
Arm/Group Description	Levenorgestrel (0.15 mg/day) for 4 to 6 weeks for 4 to 6 weeks	Placebo for 4 to 6 weeks
Period Title: Overall Study
STARTED	33	31
COMPLETED	33	31
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I (Levenorgestrel)	Arm II (Placebo)	Total
Arm/Group Description	Levenorgestrel (0.15 mg/day) for 4 to 6 weeks for 4 to 6 weeks	Placebo for 4 to 6 weeks	Total of all reporting groups
Overall Participants	33	31	64
Age, Customized (Count of Participants)
20-29 years	0 0%	0 0%	0 0%
30-39 years	4 12.1%	6 19.4%	10 15.6%
40-49 years	14 42.4%	13 41.9%	27 42.2%
50-59 years	14 42.4%	9 29%	23 35.9%
60-69 years	1 3%	3 9.7%	4 6.3%
Sex: Female, Male (Count of Participants)
Female	33 100%	31 100%	64 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Median Proportion Cells That Are Apoptotic in Epithelial Ovarian Tissue
Description	The median proportion of cells that are considered to be apoptotic are counted in the ovarian tissue sample, among the total number of cells available in the sample slide.
Time Frame	Surgical specimen (4 - 6 weeks after entry)

Outcome Measure Data

Analysis Population Description

Patients with evaluable slides. 14 of the cases did not have ovarian tissue available for evaluation. 50 cases were available for the primary analysis.

Arm/Group Title	Arm I (Levenorgestrel)	Arm II (Placebo)
Arm/Group Description	Levenorgestrel (0.15 mg/day) for 4 to 6 weeks for 4 to 6 weeks	Placebo for 4 to 6 weeks
Measure Participants	26	24
Median (Inter-Quartile Range) [proportion of total cells]	.093	.115

2. Primary Outcome

Title	Number of Participants With Adverse Events According to Grade as Determined by NCI CTCAE v.3.0
Description	Participants were graded using CTCAE v.30 criteria. Grade 1 is the least severe grade. Each adverse event lists criteria for grading, grade 1 being mild, up to grade 5. Grade 4 is generally life threatening. Grade 5 is death.
Time Frame	Up to 20 weeks

Outcome Measure Data

Analysis Population Description

All eligible and treated patients who had toxicity on study.

Arm/Group Title	Grade 1 CTCAE v 3.0 Arm I (Levonorgestrel)	Grade 2 CTCAE v 3.0 Arm 1 (Levonorgestrel)	Grade 3 CTCAE v 3.0 Arm 1 (Levonorgestrel)	Grade 4 CTCAE v3.0 Arm 1 Levonorgestrel)	Grade 5 CTCAE v3.0 Arm I (Levonorgestrel)	Grade 1 CTCAE 3.0 Arm II (Placebo)	Grade 2 CTCAE 3.0 Arm II (Placebo)	Grade 3 CTCAE 3.0 Arm II (Placebo)	Grade 4 CTCAE 3.0 Arm II (Placebo)	Grade 5 CTCAE 3.0 Arm II (Placebo)
Arm/Group Description	Number of patients on arm 1 who experienced a grade 1 event using CTCAE v 3.0	Number of patients on arm 1 who experienced a grade 2 event using CTCAE v 3.0	Number of patients on arm 1 who experienced a grade 3 event using CTCAE v 3.0	Number of patients on arm ! who experienced a grade 4 event using CTCAE v. 3.0	Number of patients on arm I who experienced a grade 5 event using CTCAE v. 3.0	Number of patients on arm II who experienced a grade 1 event using CTCAE v.30	Number of patients on arm II who experienced a grade 2 event using CTCAE 3.0	Number of patients on arm II who experienced a grade 3 event using CTCAE 3.0	Number of patients on arm II who experienced a grade 4 event using CTCAE 3.0	Number of patients on arm II who experienced a grade 5 event using CTCAE 3.0
Measure Participants	33	33	33	33	33	31	31	31	31	31
Allergy/Immunology	1 3%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Constitutional Symptoms	1 3%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Cardiac	1 3%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Dermatology/Skin	2 6.1%	0 0%	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Endocrine	1 3%	0 0%	0 0%	0 NaN	0 NaN	2 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Gastrointestinal	1 3%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Renal/Genitourinary	2 6.1%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Hemorrhage/Bleeding	3 9.1%	0 0%	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Blood/Bone Marrow	5 15.2%	2 6.5%	0 0%	0 NaN	0 NaN	3 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Infection	0 0%	0 0%	1 1.6%	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Metabolic/Laboratory	2 6.1%	0 0%	0 0%	0 NaN	0 NaN	2 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Neurology	0 0%	0 0%	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Pulmonary/Upper Respiratory	1 3%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Pain	3 9.1%	1 3.2%	0 0%	0 NaN	0 NaN	2 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Sexual/Reproductive Function	3 9.1%	0 0%	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN

3. Secondary Outcome

Title	Proportion of Proliferation as Measured by Ki-67
Time Frame	Time of surgery (4 to 6 weeks after entry)

Outcome Measure Data

Analysis Population Description

All eligible, treated patients with an evaluable sample.

Arm/Group Title	Arm I (Levenorgestrel)	Arm II (Placebo)
Arm/Group Description	Levenorgestrel (0.15 mg/day) for 4 to 6 weeks for 4 to 6 weeks	Placebo for 4 to 6 weeks
Measure Participants	32	30
Median (Inter-Quartile Range) [Proportion of cells exhibiting Ki-67]	.003	.008

4. Secondary Outcome

Title	Patients With High Expression of Transforming Growth Factor-beta 1
Time Frame	Baseline to time of surgery (4 to 6 weeks)

Outcome Measure Data

Analysis Population Description

All eligible, treated and evaluable for Transforming Growth factor-beta

Arm/Group Title	Arm I (Levenorgestrel)	Arm II (Placebo)
Arm/Group Description	Levenorgestrel (0.15 mg/day) for 4 to 6 weeks for 4 to 6 weeks	Placebo for 4 to 6 weeks
Measure Participants	29	20
Count of Participants [Participants]	6 18.2%	3 9.7%

5. Other Pre-specified Outcome

Title	Median Proportion Cells That Are Apoptotic in Fallopian Tube Tissue
Description	The median proportion of cells that are considered to be apoptotic are counted in the fallopian tube tissue sample, among the total number of cells available in the sample slide
Time Frame	Surgical specimen (4-6 weeks after entry)

Outcome Measure Data

Analysis Population Description

Patients with evaluable slides

Arm/Group Title	Arm I (Levenorgestrel)	Arm II (Placebo)
Arm/Group Description	Levenorgestrel (0.15 mg/day) for 4 to 6 weeks for 4 to 6 weeks	Placebo for 4 to 6 weeks
Measure Participants	32	30
Median (Inter-Quartile Range) [proportion of total cells]	.205	.079

Adverse Events

Time Frame	Study Treatment - 4 - 6 weeks from enrollment
Arm/Group Title	Arm I (Levenorgestrel)		Arm II (Placebo)
Arm/Group Description	Levenorgestrel (0.15 mg/day) for 4 to 6 weeks for 4 to 6 weeks		Placebo for 4 to 6 weeks
All Cause Mortality
	Arm I (Levenorgestrel)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Levenorgestrel)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (Levenorgestrel)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/33 (48.5%)		14/31 (45.2%)
Blood and lymphatic system disorders
Neutrophils	1/33 (3%)		0/31 (0%)
Blood/Bone Marrow - Other	0/33 (0%)		1/31 (3.2%)
Leukocytes	0/33 (0%)		2/31 (6.5%)
Hemoglobin	6/33 (18.2%)		3/31 (9.7%)
Cardiac disorders
Hypertension	1/33 (3%)		0/31 (0%)
Endocrine disorders
Hot Flashes	1/33 (3%)		2/31 (6.5%)
Hyperthyroidism	0/33 (0%)		1/31 (3.2%)
Gastrointestinal disorders
Flatulence	0/33 (0%)		1/31 (3.2%)
Distention	0/33 (0%)		1/31 (3.2%)
Constipation	1/33 (3%)		0/31 (0%)
General disorders
Sweating	1/33 (3%)		0/31 (0%)
Fever	0/33 (0%)		1/31 (3.2%)
Pain: Chest /Thorax Nos	1/33 (3%)		0/31 (0%)
Pain: Head/Headache	2/33 (6.1%)		2/31 (6.5%)
Pain: Back	0/33 (0%)		1/31 (3.2%)
Pain: Bladder	1/33 (3%)		0/31 (0%)
Pain: Abdominal Pain Nos	1/33 (3%)		1/31 (3.2%)
Immune system disorders
Allergy/Immunology - Other	1/33 (3%)		0/31 (0%)
Rhinitis	0/33 (0%)		1/31 (3.2%)
Infections and infestations
Infection - Other	1/33 (3%)		0/31 (0%)
Inf Unknown Anc: Bronchus	0/33 (0%)		1/31 (3.2%)
Inf Unknown Anc: Urinary Tract Nos	1/33 (3%)		0/31 (0%)
Inf Unknown Anc: Colon	1/33 (3%)		0/31 (0%)
Metabolism and nutrition disorders
Hypocalcemia	1/33 (3%)		1/31 (3.2%)
Hyperglycemia	1/33 (3%)		0/31 (0%)
Hypokalemia	0/33 (0%)		1/31 (3.2%)
Nervous system disorders
Dizziness	0/33 (0%)		1/31 (3.2%)
Renal and urinary disorders
Urinary Retention	1/33 (3%)		0/31 (0%)
Urinary Frequency	1/33 (3%)		0/31 (0%)
Reproductive system and breast disorders
Sexual/Reproductive Function: Other	1/33 (3%)		1/31 (3.2%)
Vaginal Discharge	2/33 (6.1%)		0/31 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/33 (3%)		0/31 (0%)
Skin and subcutaneous tissue disorders
Acne	2/33 (6.1%)		0/31 (0%)
Dermatology/Skin - Other	0/33 (0%)		1/31 (3.2%)
Vascular disorders
Hemorrhage, Gu - Vagina	3/33 (9.1%)		1/31 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.