Influence of Progesterone Administration on Drug-Induced QT Interval Lengthening

• Sponsor: Indiana University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01929083
• Collaborator: American Heart Association (Other)
• Enrollment: 19
• Locations: 2
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Female sex is an independent risk factor for the potentially fatal drug-induced arrhythmia (irregular heartbeat) known as torsades de pointes (TdP), which is associated with prolongation of the corrected QT (QTc) interval on the electrocardiogram (ECG). Mechanisms for this increased risk in women are not well-understood. QTc interval duration has been shown to fluctuate throughout the phases of the menstrual cycle. Evidence indicates that the QTc interval response to drugs that may cause TdP is greater during the menses and ovulation phases of the menstrual cycle, during which serum progesterone concentrations are lowest, and lesser during the luteal phase, during which serum progesterone concentrations are highest. Additional evidence from our laboratory suggests that progesterone may be protective against TdP. Specific Aim 1: Establish the influence of oral progesterone administration as a preventive method by which to diminish the degree of drug-induced QT interval prolongation in women. Working hypothesis: Oral progesterone administration effectively attenuates enhanced drug-induced QT interval response in women. To test this hypothesis, progesterone or placebo will be administered in a crossover fashion to women during the menses phase of the menstrual cycle. QTc interval response to low-dose ibutilide, a drug known to lengthen the QT interval, will be assessed. The primary endpoint will be individually-corrected QT interval (QTcI) response to ibutilide, in the presence and absence of progesterone, which will be assessed by: 1) Effect on maximum change in QTcI, and 2) Area under the QTcI interval-time curves (AUEC). At the conclusion of this study, we will have established that oral progesterone administration is a safe and effective method of attenuating drug-induced QT interval prolongation.

Condition or Disease	Intervention/Treatment	Phase
Prolonged QT Interval in EKG and Sudden Death	Drug: Progesterone; Drug: Placebo; Drug: Ibutilide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Influence of Progesterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Progesterone Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days	Drug: Progesterone; Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days; Drug: Ibutilide; Ibutilide 0.003 mg/kg administered to all subjects to moderately lengthen the QT interval
Placebo Comparator: Placebo Subjects will receive oral placebo, two capsules once daily every evening for 7 days	Drug: Placebo; Subjects will receive oral placebo two capsules once daily every evening for 7 days; Drug: Ibutilide; Ibutilide 0.003 mg/kg administered to all subjects to moderately lengthen the QT interval

Outcome Measures

Primary Outcome Measures

1. Baseline (Pre-Ibutilide) QTcI Intervals [After 7 days of progesterone or placebo, prior to receiving IV ibutilide]

2. Maximum Individual-corrected QT Interval (QTcI) [0, 15 & 30 minutes, and 1, 2, 4, 6, 8, and 12 hours post-ibutilide administration]

   QT intervals will be corrected as follows: Prior to randomization, subjects will come to the Indiana Clinical Research Center for a 12-hour stay, during which three ECGs, one minute apart, will be obtained at the following times: 0, 15 & 30 minutes, and 1, 2, 4, 6, 8, and 12 hours. Subjects will be discharged, and then return then next morning for the 24 hour ECG. QT and RR intervals will be used to determine each subject's individual rate-corrected QT interval (QTcI) using the parabolic model QT = β•RRα, where RR is the interval between adjacent QRS complexes, and α and β are subject-specific correction factors.

3. Maximum % Change From Baseline in QTcI Intervals Following Ibutilide Administration [After 7 days of progesterone or placebo]

4. Area Under the QTcI - Time Curve (AUEC) [From beginning of 10-minute ibutilide infusion to 1 hour following ibutilide infusion]

Secondary Outcome Measures

1. Incidence of Progesterone-associated Adverse Effects Compared to Placebo [During 7 days of treatment with oral progesterone or placebo]

Other Outcome Measures

1. Adverse Effects Associated With Ibutilide in the Progesterone and Placebo Phases [Within 8 hours following ibutilide administration]

2. Maximum (Peak) Serum Ibutilide Concentrations During Progesterone and Placebo Phases [Within 1 hour following ibutilide administration (0, 15 & 30 minutes and 1 hours.)]

3. Serum Estradiol Concentrations During the Progesterone and Placebo Phases [Following 7 days of progesterone or placebo]

4. Serum Progesterone Concentrations During Progesterone and Placebo Phases [After 7 days of progesterone or placebo]

5. Ratio of Serum Progesterone:Estradiol Concentrations During the Progesterone and Placebo Phases [After 7 days of progesterone or placebo]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Female

• Age 21-40 years

• Premenopausal

Exclusion Criteria:

Serum potassium ,< 3.6 meq/l

• Serum magnesium < 1.8 mg/dl

• Serum hemoglobin < 9.0 mg/dl

• Serum hematocrit < 26%

• Hypertension

• Coronary artery disease

• Heart failure

• Liver disease

• Kidney disease

• Serum creatinine > 1.5 mg/dl

• Taking hormone contraceptives

• Baseline Bazett's correct QTc interval > 450 ms

• Family history of long-QT syndrome, arrhythmias, sudden cardiac death

• Concomitant use of any QT prolonging drug

• Pregnancy

• weight < 45 kg

• Unwillingness to use non-hormonal forms of birth control during the study period

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana Clinical Research Center	Indianapolis	Indiana	United States	46202
2	Purdue University	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Indiana University
• American Heart Association

Investigators

• Principal Investigator: James E Tisdale, BSc, PharmD, Purdue University & Indiana University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: James E. Tisdale, Professor of Pharmacy Practice, Purdue University
• ClinicalTrials.gov Identifier: NCT01929083
• Other Study ID Numbers: 12GRNT12060187
• First Posted: Aug 27, 2013
• Last Update Posted: Oct 30, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by James E. Tisdale, Professor of Pharmacy Practice, Purdue University: Torsades de pointes; Progesterone; Clinical trial; Risk reduction; Electrocardiography
• Additional relevant MeSH terms: Torsades de Pointes; Long QT Syndrome; Jervell-Lange Nielsen Syndrome; Death, Sudden; Ibutilide; Progesterone

Study Results

Participant Flow

Recruitment Details	Subjects recruited from a) INResearch database, maintained by Indiana Clinical Translational Research Institute (CTSI), and b) Hard copy and electronic advertisements on the IUPUI and Purdue University campuses Participants were recruited between October 2012 and February 2014
Pre-assignment Detail	n=333 subjects assessed for eligibility; n=27 consented, n=306 excluded (n=108 did not meet inclusion criteria, n=198 declined to participate); of n=27 consented, n=19 enrolled, n=8 excluded because they met one or more exclusion criteria

Arm/Group Title	Progesterone First, Then Placebo	Placebo First, Then Progesterone
Arm/Group Description	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days	Subjects will receive oral placebo, two capsules once daily every evening for 7 days Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days
Period Title: Intervention 1
STARTED	10	9
Returned for 1st Ibutilide Administratio	7	9
COMPLETED	7	9
NOT COMPLETED	3	0
Period Title: Intervention 1
STARTED	7	9
Returned for 2nd Ibutilide Administratio	7	8
COMPLETED	7	8
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	n=15 subjects who completed the study
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29 (5)
Sex: Female, Male (Count of Participants)
Female	15 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Baseline (Pre-Ibutilide) QTcI Intervals
Time Frame	After 7 days of progesterone or placebo, prior to receiving IV ibutilide

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days	Subjects will receive oral placebo, two capsules once daily every evening for 7 days Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days
Measure Participants	15	15
Mean (Standard Deviation) [ms]	412 (15)	419 (14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test

2. Primary Outcome

Title	Maximum Individual-corrected QT Interval (QTcI)
Description	QT intervals will be corrected as follows: Prior to randomization, subjects will come to the Indiana Clinical Research Center for a 12-hour stay, during which three ECGs, one minute apart, will be obtained at the following times: 0, 15 & 30 minutes, and 1, 2, 4, 6, 8, and 12 hours. Subjects will be discharged, and then return then next morning for the 24 hour ECG. QT and RR intervals will be used to determine each subject's individual rate-corrected QT interval (QTcI) using the parabolic model QT = β•RRα, where RR is the interval between adjacent QRS complexes, and α and β are subject-specific correction factors.
Time Frame	0, 15 & 30 minutes, and 1, 2, 4, 6, 8, and 12 hours post-ibutilide administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days	Subjects will receive oral placebo, two capsules once daily every evening for 7 days Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days
Measure Participants	15	15
Mean (Standard Deviation) [ms]	443 (17)	458 (19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test

3. Secondary Outcome

Title	Incidence of Progesterone-associated Adverse Effects Compared to Placebo
Time Frame	During 7 days of treatment with oral progesterone or placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days	Subjects will receive oral placebo, two capsules once daily every evening for 7 days Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days
Measure Participants	16	17
Fatigue/general malaise	38 253.3%	6 NaN
Headache	13 86.7%	6 NaN
Mood changes	13 86.7%	0 NaN
Breast tenderness	13 86.7%	0 NaN
Hypotension	6 40%	0 NaN
Vertigo requiring discontinuation	6 40%	0 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments	P value for incidence of fatigue/malaise
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.60
	Comments	p values for incidence of headache
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments	p value for incidence of mood changes
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments	p value for incidence of breast tenderness
	Method	Fisher Exact
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments	p value for incidence of hypotension
	Method	Fisher Exact
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments	p value for incidence of vertigo requiring discontinuation of therapy
	Method	Fisher Exact
	Comments

4. Primary Outcome

Title	Maximum % Change From Baseline in QTcI Intervals Following Ibutilide Administration
Time Frame	After 7 days of progesterone or placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days	Subjects will receive oral placebo, two capsules once daily every evening for 7 days Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days
Measure Participants	15	15
Mean (Standard Deviation) [percentage change from baseline value]	7.5 (2.4)	9.3 (3.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test

5. Primary Outcome

Title	Area Under the QTcI - Time Curve (AUEC)
Time Frame	From beginning of 10-minute ibutilide infusion to 1 hour following ibutilide infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days	Subjects will receive oral placebo, two capsules once daily every evening for 7 days Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days
Measure Participants	15	15
Mean (Standard Deviation) [ms*hr]	497 (13)	510 (16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test

6. Other Pre-specified Outcome

Title	Adverse Effects Associated With Ibutilide in the Progesterone and Placebo Phases
Time Frame	Within 8 hours following ibutilide administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days	Subjects will receive oral placebo, two capsules once daily every evening for 7 days Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days
Measure Participants	15	17
Bradycardia (HR < 60 bpm)	20 133.3%	12 NaN
Burning at infusion site	7 46.7%	6 NaN
Transient QTc interval > 500 ms	0 0%	6 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments	p value for bradycardia
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.99
	Comments	p value for burning at infusion site
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> 0.99
	Comments	p value for transient QTc interval > 500 ms
	Method	Fisher Exact
	Comments

7. Other Pre-specified Outcome

Title	Maximum (Peak) Serum Ibutilide Concentrations During Progesterone and Placebo Phases
Time Frame	Within 1 hour following ibutilide administration (0, 15 & 30 minutes and 1 hours.)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days	Subjects will receive oral placebo, two capsules once daily every evening for 7 days Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days
Measure Participants	15	15
Mean (Standard Deviation) [pg/mL]	1247 (770)	1172 (709)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test

8. Other Pre-specified Outcome

Title	Serum Estradiol Concentrations During the Progesterone and Placebo Phases
Time Frame	Following 7 days of progesterone or placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days	Subjects will receive oral placebo, two capsules once daily every evening for 7 days Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days
Measure Participants	15	15
Mean (Standard Deviation) [pg/mL]	89.3 (62.8)	71.8 (31.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test

9. Other Pre-specified Outcome

Title	Serum Progesterone Concentrations During Progesterone and Placebo Phases
Time Frame	After 7 days of progesterone or placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days	Subjects will receive oral placebo, two capsules once daily every evening for 7 days Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days
Measure Participants	15	15
Mean (Standard Deviation) [ng/mL]	16.2 (11.0)	1.2 (1.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test

10. Other Pre-specified Outcome

Title	Ratio of Serum Progesterone:Estradiol Concentrations During the Progesterone and Placebo Phases
Time Frame	After 7 days of progesterone or placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days	Subjects will receive oral placebo, two capsules once daily every evening for 7 days Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days
Measure Participants	15	15
Mean (Standard Deviation) [Ratio]	205 (40)	18 (16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progesterone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test

Adverse Events

Time Frame	During 7 days of therapy with progesterone or placebo
Arm/Group Title	Progesterone		Placebo
Arm/Group Description	Subjects will receive treatment with oral progesterone 400 mg once daily (two x 200 mg capsules) every evening for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days		Subjects will receive oral placebo, two capsules once daily every evening for 7 days Placebo: Subjects will receive oral placebo two capsules once daily every evening for 7 days
All Cause Mortality
	Progesterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Progesterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		0/17 (0%)
Ear and labyrinth disorders
Vertigo requiring discontinuation of therapy	1/16 (6.3%)	1	0/17 (0%)	0
Other (Not Including Serious) Adverse Events
	Progesterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/16 (56.3%)		2/17 (11.8%)
Endocrine disorders
Breast tenderness	2/16 (12.5%)	2	0/17 (0%)	0
General disorders
Fatigue/general malaise	6/16 (37.5%)	6	1/17 (5.9%)	1
Headache	2/16 (12.5%)	2	1/17 (5.9%)	1
Mood changes	2/16 (12.5%)	2	0/17 (0%)	0
Hypotension	1/16 (6.3%)	1	0/17 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.