Erythromycin in Parkinson's Disease

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02005029
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 26
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Gastroparesis (slow stomach emptying) is a common feature of Parkinson's Disease. Levodopa (Sinemet), a common medication for Parkinson's Disease, can make gastroparesis worse. Gastroparesis effects how the levodopa is absorbed and used by the body. This study will explore the possibility of using Erythromycin, a drug commonly used (off label) for gastroparesis, along with levodopa to determine if there is improved levodopa absorption and motor function.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease; Levodopa	Drug: Erythromycin; Drug: placebo	N/A

Detailed Description

Participants will be required to make four visits for evaluation. Visit 1 is a screening visit, participants will receive the study drug or a placebo during visits 2 and 3, and visit 4 is a follow up visit. Participants will provide blood and urine samples during the visits. Participants will also be required to complete questionnaires and a series of motor tests.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Erythromycin in Parkinson's Disease: A Pilot Study of Its Effects on Levodopa Pharmacokinetics and Pharmacodynamics
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo One time IV dose of placebo	Drug: placebo
Experimental: Erythromycin One time IV dose of 100 mg Erythromycin	Drug: Erythromycin

Outcome Measures

Primary Outcome Measures

1. Gastric Emptying Time [2 weeks, between visits 2 and 3]

   Mean gastric emptying time in minutes as measured by SmartPill

2. Area Under the Curve 0-4 Hours for Plasma Levodopa After Erythromycin Versus Placebo [2 weeks, between visits 2 and 3]

   Mean Area under the Curve 0-4 hours for plasma levodopa after erythromycin versus placebo. Plasma samples were collected at the following times post-levodopa dose: 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, and 240 minutes.

Secondary Outcome Measures

1. 9-hole Peg Test Right Hand [2 weeks, between visits 2 and 3]

   Change in motor function as assessed by 9-hole peg test for upper extremity manipulation/dexterity. This test measures the total time required to place and remove 9 holes in a pegboard. Each hand is tested separately.

2. 9-hole Peg Test Left Hand [2 weeks, between visits 2 and 3]

   Change in motor function as assessed by 9-hole peg test for upper extremity manipulation/dexterity. This test measures the total time required to place and remove 9 holes in a pegboard. Each hand is tested separately.

3. Five Times Sit-to-stand Test [2 weeks, between visits 2 and 3]

   Change in motor function as measured by Five times sit-to-stand test. This test measures the total time to complete 5 repetitions of sit to stand.

4. Comfortable 20 Feet Gait Speed (CGS) [2 weeks, between visits 2 and 3]

   Change in motor function as assessed by comfortable 20 feet gait speed (CGS)

5. Timed up and go Test (TUAG) Comfortable Speed [2 weeks, between visits 2 and 3]

   Change in motor function as assessed by timed up and go test (comfortable speed). This test measures the total time to stand from a chair, walk 10 feet, and return to sitting.

6. Timed up and go Test (TUAG) Fast Speed [2 weeks, between visits 2 and 3]

   Change in motor function as assessed by timed up and go test (fast speed). This test measures the total time to stand from a chair, walk 10 feet, and return to sitting.

7. Change in Dyskinesia [2 weeks, between visits 2 and 3]

   Mean total AIMS (Abnormal Involuntary Movements Scale) score after receiving erythromycin minus mean total AIMS score after receiving placebo. The AIMS test has a total of twelve items rating involuntary movements of various areas of the patient's body. Ten of the items are rated on a five-point scale of severity from 0-4. The scale is rated from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). Two of the items are not scored. Total score range is from 0 to 40. Higher scores represent more severe dyskinesia (a worse outcome).

8. MDS-UPDRS Part 3 (Movement Disorders Society- Unified Parkinson's Disease Rating Scale) [2 weeks, between visits 2 and 3]

   Part 3 of this scale is a standardized physical assessment that quantifies the total burden of motor symptoms in Parkinson's disease patients. Each of the 18 items on the scale is rated from 0 (none, 1 (slight), 2 (mild), 3 (moderate) and 4 (severe). Scores range from 0-72. Higher scores represent a more severe burden of motor symptoms (a worse outcome).

9. Mean Cmax of Plasma Levodopa After Erythromycin Versus Placebo [2 weeks, between visits 2 and 3]

   Mean Cmax of plasma levodopa after erythromycin versus placebo. Plasma samples were collected at the following times post-levodopa dose: 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, and 240 minutes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have a definitive diagnosis of Parkinson's Disease (per United Kingdom brain bank criteria), Hoehn and Yahr stage 1-3,

• must exhibit unequivocal levodopa responsiveness

• must be able to distinguish between the "off" versus "on" state

• Subjects must be on a stable dose of levodopa for at least 28 days prior to enrollment and should be anticipated to maintain a stable dose throughout both study periods

• Subjects may be on concomitant therapy with Monoamine oxidase B inhibitors, entacapone, and amantadine, though the doses of these medications must have remained stable for at least 28 days prior to enrollment and must be expected to remain stable throughout both study periods.

Exclusion Criteria:

• History of deep brain stimulation for Parkinson Disease

• History of ablative (tissue removal) surgery for Parkinson Disease

• Presence of dementia (MMSE<25)

• Presence of active psychosis

• History of any chronic gastrointestinal diseases

• History of any prior gastrointestinal surgeries except for appendectomy, cholecystectomy, and hysterectomy

• Any gastrointestinal surgeries in the past 3 months

• Severe dysphagia (difficulty swallowing) to pills or food

• History of physiological or mechanical gastrointestinal obstruction

• History of strictures or fistulae (abnormal or narrow connections) along the gastrointestinal tract

• History of gastric bezoars (undigested mass)

• Allergy to wheat, soy, milk, or nuts

• Presence of portable electromechanical devices such as pacemaker, defibrillator, or infusion pump

• Female subjects who are pregnant or lactating

• Symptomatic orthostatic hypotension (low blood pressure)

• Diabetes

• Presence of symptomatic anemia

• Abnormal liver or kidney function

• Cardiac arrhythmia (past or present) or abnormal QT interval on entrance EKG

• Known hypersensitivity to any of the study drugs

• Subjects receiving certain medications during specified time frames

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Virginia Commonwealth University Parkinson's Center	Richmond	Virginia	United States	23230

Sponsors and Collaborators

• Virginia Commonwealth University

Investigators

• Principal Investigator: Leslie J Cloud, M.D., Virginia Commonwealth University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT02005029
• Other Study ID Numbers: HM15105
• First Posted: Dec 9, 2013
• Last Update Posted: Feb 3, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by Virginia Commonwealth University: Parkinson's Disease; Levodopa; motor fluctuations; gastroparesis
• Additional relevant MeSH terms: Parkinson Disease; Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Erythromycin stearate

Study Results

Participant Flow

Recruitment Details	Eighteen patients were screened for eligibility between April 2013 and June 2015 at the Virginia Commonwealth University Parkinson's and Movement Disorders Center.
Pre-assignment Detail	10 of 18 participants were randomized. Of those not randomized, 7 did not meet eligibility criteria and 1 was withdrawn by the principal investigator prior to randomization due to noncompliance with the protocol.

Arm/Group Title	Placebo First Then Erythromycin	Erythromycin Then Placebo
Arm/Group Description	One time IV dose of placebo followed by 1 time IV dose of Erythromycin (after 2 week washout)	One time IV dose of 100 mg Erythromycin followed by 1 time IV dose of placebo (after 2 week washout)
Period Title: First Intervention (1 Day)
STARTED	5	5
COMPLETED	4	5
NOT COMPLETED	1	0
Period Title: First Intervention (1 Day)
STARTED	4	5
COMPLETED	4	5
NOT COMPLETED	0	0
Period Title: First Intervention (1 Day)
STARTED	4	5
COMPLETED	4	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo First Then Erythromycin	Erythromycin Then Placebo	Total
Arm/Group Description	One time IV dose of placebo followed by 1 time IV dose of Erythromycin (after 2 week washout)	One time IV dose of 100 mg Erythromycin followed by 1 time IV dose of placebo (after 2 week washout)	Total of all reporting groups
Overall Participants	5	5	10
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	64.6	64.0	64.3
Gender (Count of Participants)
Female	1 20%	1 20%	2 20%
Male	4 80%	4 80%	8 80%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 100%	5 100%	10 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	5 100%	5 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Gastric Emptying Time
Description	Mean gastric emptying time in minutes as measured by SmartPill
Time Frame	2 weeks, between visits 2 and 3

Outcome Measure Data

Analysis Population Description

Of the original ten participants; one participant's data was excluded due to symptomatic orthostasis which likely confounded her results, one participant was withdrawn early due to noncompliance, and four participants were unable to complete a SmartPill evaluation.

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Mean gastric emptying time for participants receiving erythromycin	Mean gastric emptying time for participants receiving placebo
Measure Participants	4	4
Mean (Standard Deviation) [minutes]	105 (66.5)	180 (40.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.036
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Area Under the Curve 0-4 Hours for Plasma Levodopa After Erythromycin Versus Placebo
Description	Mean Area under the Curve 0-4 hours for plasma levodopa after erythromycin versus placebo. Plasma samples were collected at the following times post-levodopa dose: 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, and 240 minutes.
Time Frame	2 weeks, between visits 2 and 3

Outcome Measure Data

Analysis Population Description

Of the original ten participants; one participant's data was excluded due to symptomatic orthostasis which likely confounded her results, one participant was withdrawn early due to noncompliance, and one participant had undetectable plasma levodopa levels through out the study and was thus excluded from the pharmacokinetic analysis.

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Area under the curve 0-4 hours for plasma levodopa after erythromycin	Area under the curve 0-4 hours for plasma levodopa after placebo
Measure Participants	7	7
Mean (Standard Deviation) [ng/mL*min]	123237 (137561)	103584 (106271)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Erythromycin:Placebo AUC ratio
	Estimated Value	1.07
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.43
	Estimation Comments

3. Secondary Outcome

Title	9-hole Peg Test Right Hand
Description	Change in motor function as assessed by 9-hole peg test for upper extremity manipulation/dexterity. This test measures the total time required to place and remove 9 holes in a pegboard. Each hand is tested separately.
Time Frame	2 weeks, between visits 2 and 3

Outcome Measure Data

Analysis Population Description

Of the original 10 participants, one participant's data was excluded due to symptomatic orthostasis which likely confounded her results and one participant was withdrawn early due to noncompliance.

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Mean time for right hand after erythromycin	Mean time for right hand after placebo
Measure Participants	8	8
Mean (Standard Deviation) [seconds]	25.36 (4.37)	25.80 (4.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	9-hole Peg Test Left Hand
Description	Change in motor function as assessed by 9-hole peg test for upper extremity manipulation/dexterity. This test measures the total time required to place and remove 9 holes in a pegboard. Each hand is tested separately.
Time Frame	2 weeks, between visits 2 and 3

Outcome Measure Data

Analysis Population Description

Of the original 10 participants, one participant's data was excluded due to symptomatic orthostasis which likely confounded her results and one participant was withdrawn early due to noncompliance.

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Mean time for right hand after erythromycin	Mean time for right hand after placebo
Measure Participants	8	8
Mean (Standard Deviation) [seconds]	29.36 (6.27)	27.33 (6.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Five Times Sit-to-stand Test
Description	Change in motor function as measured by Five times sit-to-stand test. This test measures the total time to complete 5 repetitions of sit to stand.
Time Frame	2 weeks, between visits 2 and 3

Outcome Measure Data

Analysis Population Description

Of the original 10 participants, one participant's data was excluded due to symptomatic orthostasis which likely confounded her results and one participant was withdrawn early due to noncompliance.

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Five times sit-to-stand for all participants receiving erythromycin	Five times sit-to-stand for all participants receiving placebo
Measure Participants	8	8
Mean (Standard Deviation) [seconds]	11.09 (2.24)	10.09 (2.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4405
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Comfortable 20 Feet Gait Speed (CGS)
Description	Change in motor function as assessed by comfortable 20 feet gait speed (CGS)
Time Frame	2 weeks, between visits 2 and 3

Outcome Measure Data

Analysis Population Description

Of the original 10 participants, one participant's data was excluded due to symptomatic orthostasis which likely confounded her results and one participant was withdrawn early due to noncompliance.

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Mean CGS for all participants receiving erythromycin	Mean CGS for all participants receiving placebo
Measure Participants	8	8
Mean (Standard Deviation) [seconds]	4.26 (0.44)	4.10 (0.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6011
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Timed up and go Test (TUAG) Comfortable Speed
Description	Change in motor function as assessed by timed up and go test (comfortable speed). This test measures the total time to stand from a chair, walk 10 feet, and return to sitting.
Time Frame	2 weeks, between visits 2 and 3

Outcome Measure Data

Analysis Population Description

Of the original 10 participants, one participant's data was excluded due to symptomatic orthostasis which likely confounded her results and one participant was withdrawn early due to noncompliance.

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	TUAG (comfortable speed) after erythromycin	TUAG (comfortable speed) after placebo
Measure Participants	8	8
Mean (Standard Deviation) [seconds]	8.67 (1.33)	8.26 (1.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8923
	Comments
	Method	t-test, 2 sided
	Comments

8. Secondary Outcome

Title	Timed up and go Test (TUAG) Fast Speed
Description	Change in motor function as assessed by timed up and go test (fast speed). This test measures the total time to stand from a chair, walk 10 feet, and return to sitting.
Time Frame	2 weeks, between visits 2 and 3

Outcome Measure Data

Analysis Population Description

Of the original 10 participants, one participant's data was excluded due to symptomatic orthostasis which likely confounded her results and one participant was withdrawn early due to noncompliance.

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	TUAG (fast speed) after erythromycin	TUAG (fast speed) after placebo
Measure Participants	8	8
Mean (Standard Deviation) [seconds]	6.79 (0.927)	6.85 (1.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.832
	Comments
	Method	t-test, 2 sided
	Comments

9. Secondary Outcome

Title	Change in Dyskinesia
Description	Mean total AIMS (Abnormal Involuntary Movements Scale) score after receiving erythromycin minus mean total AIMS score after receiving placebo. The AIMS test has a total of twelve items rating involuntary movements of various areas of the patient's body. Ten of the items are rated on a five-point scale of severity from 0-4. The scale is rated from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). Two of the items are not scored. Total score range is from 0 to 40. Higher scores represent more severe dyskinesia (a worse outcome).
Time Frame	2 weeks, between visits 2 and 3

Outcome Measure Data

Analysis Population Description

Of the original 10 participants, one participant's data was excluded due to symptomatic orthostasis which likely confounded her results and one participant was withdrawn early due to noncompliance.

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	AIMS after receiving erythromycin	AIMS after receiving placebo
Measure Participants	8	8
Mean (Standard Deviation) [units on a scale]	0.875 (1.458)	0.375 (1.061)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1546
	Comments
	Method	t-test, 2 sided
	Comments

10. Secondary Outcome

Title	MDS-UPDRS Part 3 (Movement Disorders Society- Unified Parkinson's Disease Rating Scale)
Description	Part 3 of this scale is a standardized physical assessment that quantifies the total burden of motor symptoms in Parkinson's disease patients. Each of the 18 items on the scale is rated from 0 (none, 1 (slight), 2 (mild), 3 (moderate) and 4 (severe). Scores range from 0-72. Higher scores represent a more severe burden of motor symptoms (a worse outcome).
Time Frame	2 weeks, between visits 2 and 3

Outcome Measure Data

Analysis Population Description

One participant's data was excluded due to symptomatic orthostasis which likely confounded her results and one participant was withdrawn early due to noncompliance.

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description
Measure Participants	8	8
Before or "off" levodopa	30.75 (13.26)	25.37 (11.09)
After or "on" levodopa	17.13 (11.48)	16.50 (8.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0314
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.75
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 5.00
	Estimation Comments	Mean difference in "on" score versus "off" score from the MDS UPDRS Part 3 on day of erythromycin minus the mean difference in 'on" score versus "off" score on day of placebo.

11. Secondary Outcome

Title	Mean Cmax of Plasma Levodopa After Erythromycin Versus Placebo
Description	Mean Cmax of plasma levodopa after erythromycin versus placebo. Plasma samples were collected at the following times post-levodopa dose: 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, and 240 minutes.
Time Frame	2 weeks, between visits 2 and 3

Outcome Measure Data

Analysis Population Description

Of the original ten participants; one participant's data was excluded due to symptomatic orthostasis which likely confounded her results, one participant was withdrawn early due to noncompliance, and one participant had undetectable plasma levodopa levels throughout the study and was thus excluded from the pharmacokinetic analysis.

Arm/Group Title	Erythromycin	Placebo
Arm/Group Description	Cmax of plasma levodopa after erythromycin	Cmax of plasma levodopa after placebo
Measure Participants	7	7
Mean (Standard Deviation) [ng/mL]	1267 (1012)	1395 (1015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erythromycin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Erythromycin:Placebo Cmax ratio
	Estimated Value	0.83
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.24
	Estimation Comments

Adverse Events

Time Frame	1 year, 10 months
Adverse Event Reporting Description	Participants were followed from the beginning to the end of their active participation or the resolution of any adverse events.
Arm/Group Title	Erythromycin		Placebo
Arm/Group Description	Participants who received a one time dose of IV erythromycin		Participants who received a one time dose of placebo
All Cause Mortality
	Erythromycin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Erythromycin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Erythromycin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/9 (44.4%)		2/10 (20%)
Cardiac disorders
symptomatic orthostasis	1/9 (11.1%)	1	1/10 (10%)	1
Gastrointestinal disorders
diarrhea	1/9 (11.1%)	1	0/10 (0%)	0
Hepatobiliary disorders
transaminitis	0/9 (0%)	0	1/10 (10%)	1
Nervous system disorders
akathisia	1/9 (11.1%)	1	0/10 (0%)	0
Renal and urinary disorders
possible hematuria	1/9 (11.1%)	1	0/10 (0%)	0

Limitations/Caveats

An overall limitation was the small sample size.

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.