SAPS: A Pilot Study to Determine the Feasibility and Utility of Implementing of the Full Scale TOM Trial

• Sponsor: University of California, San Diego (Other)
• Overall Status: Completed
• CT.gov ID: NCT01696214
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 20
• Location: 1
• Arms: 4
• Duration (Months): 49
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The primary aim of the pilot (SAPS) protocol is to determine the feasibility and utility of implementing the provisional design of the full scale TOM trial (e.g., the six month treatment period, the impact of the smoking cessation intervention).

There is no active hypothesis for the Vanguard Protocol.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Fluticasone 250 mg/salmeterol 50 mg; Drug: Montelukast 10mg; Drug: Theophylline 400 mg; Drug: ipratropium	Phase 4

Detailed Description

The protocol is a small scale pilot of the full-scale TOM trial, and it will utilize a placebo design and incorporates 4 treatment arms. In the Vanguard Protocol all participants are to complete a 4 week run-in with Advair 100/50, followed by randomization to 1 of 4 arms of study treatment. The 4 drug treatment combinations are (2 inhalers, 2 pills):

• Advair 250/50, Placebo, Placebo, Placebo

• Advair 100/50 and montelukast, Placebo, Placebo

• Advair 100/50 and theophylline, Placebo, Placebo

• Advair 100/50 and ipratropium, Placebo, Placebo The 24 week treatment phase will be followed by a 4 week washout period on Advair 100/50. There is no crossover.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: SAPS:Smoking Asthmatics Pilot Study:
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Ipratropium Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 2.5 mL, 0.02% 3 times daily via mini nebulizer with placebo theophylline and placebo montelukast.	Drug: ipratropium; Participants will be assigned to ipratropium 2.5 mL of 0.02% solution via mini nebulizer 3 times a day day for 24 weeks.; Other Names: Atrovent
Placebo Comparator: Theophylline Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and placebo montelukast.	Drug: Theophylline 400 mg; Participants will be assigned to theophylline once a day for 24 weeks
Placebo Comparator: Montelukast Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and placebo ipratropium.	Drug: Montelukast 10mg; Participants will be assigned to montelukast once a day for 24 weeks.; Other Names: Singulair
Placebo Comparator: fluticasone 250 mg/salmeterol 50mg Participants will be assigned to inhaled fluticasone 250/salmeterol 50 twice a day for 24 weeks with placebo theophylline, placebo ipratropium, and placebo montelukast.	Drug: Fluticasone 250 mg/salmeterol 50 mg; Drug: Fluticasone 250 mg/salmeterol 50 mg Participants will be assigned to a 24 week treatment with inhaled fluticasone/salmeterol or matching placebo; Other Names: Advair(fluticasone/salmeterol)250/50

Outcome Measures

Primary Outcome Measures

1. Asthma Control Test [Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks and at follow-up visit 1 month off study drug. Median scores over the 24 weeks of treatment were compared.]

   The primary symptomatic measure, the Asthma Control Test (ACT), has been shown to be valid for measuring poor asthma control in asthmatic children and non-smoking adults. The ACT is a tool developed by Nathan and collaborators a decade ago for evaluating asthma control. It consists of five questions with five possible answers each. A maximum score of 25 points indicates complete asthma control. A score between 20 and 24 represents partially controlled asthma, while a score 19 or below indicates poorly controlled asthma and a score <16 indicates uncontrolled asthma. The minimally important clinical difference has been determined to be 3.

Secondary Outcome Measures

1. The Asthma Symptom Utility Index (ASUI) [Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks and a follow-up visit 1 month off study drug. Median scores, change from initial visit and end of treatment, were compared]

   The Asthma Symptom Utility Index (ASUI), an important secondary outcome in the proposed full-scale TOM Trial, has also been shown to be useful in tracking the frequency and severity of asthma-related symptoms in non-smoking asthmatics. ASUI is a brief, interviewer-administered, patient preference-based scale assessing frequency and severity of selected asthma-related symptoms and treatment side effects. 11 items are reviewed, with 2-week recall to assess four symptoms (cough, wheeze, shortness of breath, and awakening at night) and medication side-effects each on two dimensions (frequency and severity). 4-point Likert scale is used to assess frequency (not at all, 1 to 3 days, 4 to 7 days, and 8 to 14 days) and severity (not applicable, mild, moderate and severe). Scores range from 0 (worst possible symptoms) to 1 (no symptoms). The change between two time points, initial visit and after 24 weeks of treatment, is reported. The median value is reported with the standard deviation.

2. Percent (%) Perdicted FEV1 Changes [Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks. Median scores over the 24 weeks of treatment were compared]

   Physiologic measures of % predicted FEV1

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Gender and Age:

• Males and females, ages 18- 50

Current Smoker:

• Smoke at least 5 cigarettes per day for at least 5 years

• Positive urine cotinine test

Asthma:

• Physician diagnosed asthma

• Symptomatic, as evidenced by

• Use of SABA two or more times per week for relief of asthma symptoms, or

• One or more nocturnal awakenings per week for asthma symptoms ACRC - SC MEETING - 19 MAY 2012 SAPS │ 25 Confidential, not for attribution or citation.

• Pre-BD FEV1 greater than or equal to 40% predicted

• Asthma diagnosis confirmed by either

• albuterol reversibility of FEV1 by 12% or more, or

• 20% fall in FEV1 at 8mg or less of methacholine

• If over age 45, a DLco greater than 80% predicted

• Females of childbearing potential: not pregnant, not lactating and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study.

Exclusion Criteria:

• Diagnosis of COPD or emphysema

• Other major chronic illnesses in the opinion of the investigator that might interfere with the study:

• e.g. including but not limited to uncontrolled diabetes, uncontrolled HIV infection or other immune system disorder, hyperthyroidism, seizure disorders, renal failure, liver disease, non-skin cancer, unstable psychiatric illness.

• Recent active substance abuse (in past 6 months)

• Lung disease other than asthma including COPD, bronchiectasis, sarcoidosis, or other significant lung disease

• Unstable cardiac disease (decompensated CHF, unstable angina, recent MI, atrial fibrillation, supraventricular or ventricular tachycardia, congenital heart disease, or severe uncontrolled hypertension).

• High risk of near fatal or fatal asthma as defined by the following 1-3

• ICU admission of asthma in the past year

• more than 2 hospitalizations for asthma in the previous year

• more than 3 ED visits for asthma in the previous year

• intubation or ICU admission for asthma in the past 2 years

• use of more than 2 canisters of inhaled short-acting beta2-agonist in past month

• Acute asthma exacerbation in the past 4 weeks (treatment with systemic corticosteroids)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Airway Research & Clinical Trials Center	San Diego	California	United States	92103

Sponsors and Collaborators

• University of California, San Diego
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Joe Ramsdell, MD, UCSD

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joe Ramsdell, Medical Doctor, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT01696214
• Other Study ID Numbers: ARCTC-09; IR34HL109482-01A1
• First Posted: Sep 28, 2012
• Last Update Posted: Jan 23, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Joe Ramsdell, Medical Doctor, University of California, San Diego: asthma,smokers
• Additional relevant MeSH terms: Asthma; Fluticasone; Xhance; Theophylline; Salmeterol Xinafoate; Ipratropium; Fluticasone-Salmeterol Drug Combination; Montelukast

Study Results

Participant Flow

Arm/Group Title	Ipratropium	Theophylline	Montelukast	Fluticasone 250 mg/Salmeterol 50mg
Arm/Group Description	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 0.02% solution, 2.5 ml via mini nebulizer for 24 weeks with placebo theophylline and placebo montelukast. Ipratropium: Participants will be assigned to ipratropium 0.02% solution, 2.5 ml via mini nebulizer 3 times	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and placebo montelukast. Theophylline: Participants will be assigned to theophylline 400 mg once a day for 24 weeks	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and placebo ipratropium. Montelukast 10mg: Participants will be assigned to montelukast 10 mg once a day for 24 weeks.	Participants will be assigned to inhaled fluticasone 250 mg/salmeterol 50 mg twice a day for 24 weeks with placebo theophylline, placebo ipratropium, and placebo montelukast. Fluticasone 250 mg/salmeterol 50 mg: Participants will be assigned to a 24 week treatment with inhaled fluticasone 250 mg /salmeterol 50
Period Title: Overall Study
STARTED	5	5	5	5
COMPLETED	4	5	5	5
NOT COMPLETED	1	0	0	0

Baseline Characteristics

Arm/Group Title	Ipratropium	Theophylline	Montelukast	Fluticasone 250 mg/Salmeterol 50mg	Total
Arm/Group Description	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 0.02% solution, 2.5 ml via mini nebulizer for 24 weeks with placebo theophylline and montelukast. Ipratropium: Participants will be assigned to ipratropium 0.02% solution, 2.5 ml via mini nebulizer 3 times	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 300 mg once a day for 24 weeks with placebo tiotroprium and montelukast. Theophylline: Participants will be assigned to theophylline 300 mg once a day for 24 weeks	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and tiotroprium. Montelukast 10mg: Participants will be assigned to montelukast 10 mg once a day for 24 weeks.	Participants will be assigned to inhaled fluticasone 250 mg/salmeterol 50 mg twice a day for 24 weeks with placebo theophylline, tiotroprium, and montelukast. Fluticasone 250 mg/salmeterol 50 mg: Participants will be assigned to a 24 week treatment with inhaled fluticasone 250 mg /salmeterol 50	Total of all reporting groups
Overall Participants	4	5	5	5	19
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	5 100%	5 100%	5 100%	19 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	49	48	39	28	41
Sex: Female, Male (Count of Participants)
Female	4 100%	2 40%	3 60%	1 20%	10 52.6%
Male	0 0%	3 60%	2 40%	4 80%	9 47.4%
Region of Enrollment (participants) [Number]
United States	4 100%	5 100%	5 100%	5 100%	19 100%

Outcome Measures

1. Primary Outcome

Title	Asthma Control Test
Description	The primary symptomatic measure, the Asthma Control Test (ACT), has been shown to be valid for measuring poor asthma control in asthmatic children and non-smoking adults. The ACT is a tool developed by Nathan and collaborators a decade ago for evaluating asthma control. It consists of five questions with five possible answers each. A maximum score of 25 points indicates complete asthma control. A score between 20 and 24 represents partially controlled asthma, while a score 19 or below indicates poorly controlled asthma and a score <16 indicates uncontrolled asthma. The minimally important clinical difference has been determined to be 3.
Time Frame	Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks and at follow-up visit 1 month off study drug. Median scores over the 24 weeks of treatment were compared.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ipratropium	Theophylline	Montelukast	Fluticasone 250 mg/Salmeterol 50mg
Arm/Group Description	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 2.5 mL, 0.02% 3 times daily via mini nebulizer with placebo theophylline and montelukast. ipratropium: Participants will be assigned to ipratropium 2.5 mL of 0.02% solution via mini nebulizer 3 times a day day for 24 weeks.	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and montelukast. Theophylline 400 mg: Participants will be assigned to Theophylline once a day for 24 weeks	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and ipratropium. Montelukast 10mg: Participants will be assigned to Leukotriene receptor antagonist once a day for 24 weeks.	Participants will be assigned to inhaled fluticasone 250/salmeterol 50 twice a day for 24 weeks with placebo theophylline, ipratropium, and montelukast. Fluticasone 250 mg/salmeterol 50 mg: Drug: Fluticasone 250 mg/salmeterol 50 mg Participants will be assigned to a 24 week treatment with inhaled fluticasone/salmeterol or matching placebo
Measure Participants	4	5	5	5
Median (Full Range) [units on a scale]	17.5	13	12	10

2. Secondary Outcome

Title	The Asthma Symptom Utility Index (ASUI)
Description	The Asthma Symptom Utility Index (ASUI), an important secondary outcome in the proposed full-scale TOM Trial, has also been shown to be useful in tracking the frequency and severity of asthma-related symptoms in non-smoking asthmatics. ASUI is a brief, interviewer-administered, patient preference-based scale assessing frequency and severity of selected asthma-related symptoms and treatment side effects. 11 items are reviewed, with 2-week recall to assess four symptoms (cough, wheeze, shortness of breath, and awakening at night) and medication side-effects each on two dimensions (frequency and severity). 4-point Likert scale is used to assess frequency (not at all, 1 to 3 days, 4 to 7 days, and 8 to 14 days) and severity (not applicable, mild, moderate and severe). Scores range from 0 (worst possible symptoms) to 1 (no symptoms). The change between two time points, initial visit and after 24 weeks of treatment, is reported. The median value is reported with the standard deviation.
Time Frame	Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks and a follow-up visit 1 month off study drug. Median scores, change from initial visit and end of treatment, were compared

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ipratropium	Theophylline	Montelukast	Fluticasone 250 mg/Salmeterol 50mg
Arm/Group Description	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 2.5 mL, 0.02% 3 times daily via mini nebulizer with placebo theophylline and placebo montelukast. ipratropium: Participants will be assigned to ipratropium 2.5 mL of 0.02% solution via mini nebulizer 3 times a day day for 24 weeks.	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and placebo montelukast. Theophylline 400 mg: Participants will be assigned to theophylline once a day for 24 weeks	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and placebo ipratropium. Montelukast 10mg: Participants will be assigned to montelukast once a day for 24 weeks.	Participants will be assigned to inhaled fluticasone 250/salmeterol 50 twice a day for 24 weeks with placebo theophylline, placebo ipratropium, and placebo montelukast. Fluticasone 250 mg/salmeterol 50 mg: Drug: Fluticasone 250 mg/salmeterol 50 mg Participants will be assigned to a 24 week treatment with inhaled fluticasone/salmeterol or matching placebo
Measure Participants	4	5	5	5
Median (Standard Deviation) [units on a scale]	0.16 (0.07)	0.24 (0.20)	0.14 (0.15)	0.13 (0.18)

3. Secondary Outcome

Title	Percent (%) Perdicted FEV1 Changes
Description	Physiologic measures of % predicted FEV1
Time Frame	Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks. Median scores over the 24 weeks of treatment were compared

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ipratropium	Theophylline	Montelukast	Fluticasone 250 mg/Salmeterol 50mg
Arm/Group Description	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 0.02% solution, 2.5 ml via mini nebulizer for 24 weeks with placebo theophylline and placebo montelukast. Ipratropium: Participants will be assigned to ipratropium 0.02% solution, 2.5 ml via mini nebulizer 3 times	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and placebo montelukast. Theophylline: Participants will be assigned to theophylline 400 mg once a day for 24 weeks	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and placebo ipratropium. Montelukast 10mg: Participants will be assigned to montelukast 10 mg once a day for 24 weeks.	Participants will be assigned to inhaled fluticasone 250 mg/salmeterol 50 mg twice a day for 24 weeks with placebo theophylline, placebo ipratropium, and placebo montelukast. Fluticasone 250 mg/salmeterol 50 mg: Participants will be assigned to a 24 week treatment with inhaled fluticasone 250 mg /salmeterol 50
Measure Participants	4	5	5	5
Median (Standard Deviation) [percent predicted FEV1]	-1.62 (7.89)	4.73 (7.72)	0.87 (10.57)	-5.71 (5.24)

Adverse Events

Time Frame	1 year
Arm/Group Title	Ipratropium		Theophylline		Montelukast		Fluticasone 250 mg/Salmeterol 50mg
Arm/Group Description	Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 0.02% solution, 2.5 ml via mini nebulizer for 24 weeks with placebo theophylline and montelukast. Ipratropium: Participants will be assigned to ipratropium 0.02% solution, 2.5 ml via mini nebulizer 3 times		Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 300 mg once a day for 24 weeks with placebo tiotroprium and montelukast. Theophylline: Participants will be assigned to theophylline 300 mg once a day for 24 weeks		Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and tiotroprium. Montelukast 10mg: Participants will be assigned to montelukast 10 mg once a day for 24 weeks.		Participants will be assigned to inhaled fluticasone 250 mg/salmeterol 50 mg twice a day for 24 weeks with placebo theophylline, tiotroprium, and montelukast. Fluticasone 250 mg/salmeterol 50 mg: Participants will be assigned to a 24 week treatment with inhaled fluticasone 250 mg /salmeterol 50
All Cause Mortality
	Ipratropium		Theophylline		Montelukast		Fluticasone 250 mg/Salmeterol 50mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ipratropium		Theophylline		Montelukast		Fluticasone 250 mg/Salmeterol 50mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)
Respiratory, thoracic and mediastinal disorders
asthma exacerbation	0/4 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Social circumstances
death	0/4 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Other (Not Including Serious) Adverse Events
	Ipratropium		Theophylline		Montelukast		Fluticasone 250 mg/Salmeterol 50mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		5/5 (100%)		5/5 (100%)		5/5 (100%)
Cardiac disorders
tachycardia	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	1/5 (20%)	1
Eye disorders
iritis	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Gastrointestinal disorders
nausea	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	1/5 (20%)	1
diarrhea	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
constipation	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
General disorders
drowsiness	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0
dry mouth	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
edema	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Infections and infestations
viral infection	4/5 (80%)	4	1/5 (20%)	1	1/5 (20%)	1	3/5 (60%)	3
Musculoskeletal and connective tissue disorders
back pain	1/5 (20%)	2	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
chest pain	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
headache	0/5 (0%)	0	1/5 (20%)	1	1/5 (20%)	1	1/5 (20%)	1
swollen hand	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
sprained finger	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0
Nervous system disorders
migraine headache	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Renal and urinary disorders
urinary tract infection	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Skin and subcutaneous tissue disorders
rash	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0
skin lesion	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
pruritus	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0
Social circumstances
motor vehicle accident	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0

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.