CS201: Study of Dexpramipexole Chronic Sinusitis With Nasal Polyps and Eosinophilia

• Sponsor: Knopp Biosciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02217332
• Collaborator: (none)
• Enrollment: 20
• Locations: 7
• Arm: 1
• Duration (Months): 29.7
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Phase 2, open-label, multi-center study to evaluate the clinical effects of oral administration of dexpramipexole for 6 months in subjects with chronic sinusitis with nasal polyps and eosinophilia.

Condition or Disease	Intervention/Treatment	Phase
Chronic Sinusitis With Nasal Polyps and Eosinophilia	Drug: dexpramipexole	Phase 2

Detailed Description

This open-labelled study will evaluate the safety and preliminary efficacy of dexpramipexole for reducing the number of eosinophils in the peripheral blood and in improving nasal polyp score when administered to 20 subjects with chronic sinusitis with nasal polyps and eosinophilia.

Subjects will received dexpramipexole for up to 6 months and will have safety tests performed monthly and will have efficacy evaluations performed at month 1, month 3, and month 6 after beginning study drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Preliminary Efficacy of Dexpramipexole in Patients With Chronic Sinusitis With Nasal Polyps and Eosinophilia (CSNP-E)
• Study Start Date: Aug 1, 2014
• Actual Primary Completion Date: Dec 14, 2016
• Actual Study Completion Date: Jan 20, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dexpramipexole dexpramipexole 150 mg BID	Drug: dexpramipexole; Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day); Other Names: KNS-760704 BIIB050 RPPX

Outcome Measures

Primary Outcome Measures

1. Ratio to Baseline in Peripheral Blood Eosinophil Counts After 6 Months of Treatment [Baseline and Month 6]

   Change in peripheral blood eosinophil (measured in cells/μL) from baseline to month 6 is presented as ratio to baseline.

2. Change From Baseline in Total Polyp Score (TPS) After 6 Months of Treatment [Baseline and Month 6]

   The change in Nasal Polyp Score (NPS) score after 6 months of treatment is presented. A blinded Central Endoscopy Rater determined the NPS for each nare on a scale of 0 to 4, and the bilateral NPS scores were added to generate the Total Polyp Score (TPS) on a scale of 0 to 8. A lower TPS corresponds to a lower polyp burden.

Secondary Outcome Measures

1. Number of Subjects With Potentially Clinically Significant Values in Clinical Laboratory Evaluations [6 months]

   Summary of subjects from the safety population who experienced potentially clinically significant values in hand serum chemistry results

2. Number of Subjects With Potentially Clinically Significant Values in Vital Signs and Weight [6 months]

   Summary of subjects from the safety population who experienced potentially clinically significant values or changes in vital signs or weight

3. Number of Subjects With Potentially Significant Values in Electrocardiogram Parameters [6 months]

   Summary of subjects from the safety population who experienced potentially significant values in electrocardiogram parameters

4. Ratio to Baseline in Peripheral Blood Eosinophil Counts After 3 Months of Treatment [Baseline and Month 3]

   Change in peripheral blood eosinophil (measured in cells/μL) from baseline to month 3 is presented as ratio to baseline.

5. Change From Baseline in TPS After 3 Months of Treatment [Baseline and Month 3]

   The change in Nasal Polyp Score (NPS) score after 3 months of treatment is presented. A blinded Central Endoscopy Rater determined the NPS for each nare on a scale of 0 to 4, and the bilateral NPS scores were added to generate the Total Polyp Score (TPS) on a scale of 0 to 8. A lower TPS corresponds to a lower polyp burden.

Other Outcome Measures

1. Ratio to Baseline in Polyp Tissue Eosinophil Count After 6 Months of Treatment [Baseline and Month 6]

   Change in polyp tissue eosinophil count measured as eosinophils/hpf (high powered field) from baseline to month 6 is presented as ratio to baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female >18 or <70 years of age

• Willing to practice effective contraception during the study and be willing and able to continue contraception for 1 month (females) or 3 months (males) after the last dose of study treatment

• Confirmed diagnosis of chronic sinusitis with nasal polyps

• Documented history of nasal eosinophilia

• Documented peripheral absolute eosinophil count >300 cells/μL

• Bilateral total polyp score of >4

• Sino-nasal outcome test (SNOT-22) score of >7

• Using an intranasal corticosteroid spray or irrigation (< 1000 μg/day beclomethasone or equivalent)

Exclusion Criteria:

• Acute sinusitis, concurrent nasal infection, or subjects who have had a nasal or upper respiratory tract infection within 2 weeks prior to baseline

• CT scan suggestive of allergic fungal rhinosinusitis

• Nasal septal deviation that would occlude at least one nostril

• Nasal surgery (including polypectomy) within 6 months prior to baseline

• History of more than 5 sinonasal surgeries requiring general anesthesia

• History of more than 2 sinonasal surgeries that changed the lateral wall of the nose

• History of cystic fibrosis, primary ciliary's dysfunction or Kartagener's syndrome

• History of diagnosis with a parasitic infection

• Hospitalization or emergency treatment for the treatment of asthma two or more times in the 12 months prior to baseline

• Hospitalization for an acute asthmatic attack within 4 weeks prior to baseline

• Forced expiratory volume (FEV1) of <60% of predicted normal range

• Treatment with a systemic corticosteroid or intra-polyp corticosteroid within 8 weeks prior to baseline or anticipated need for systemic corticosteroids during the study treatment period

• Utilization of rescue oral corticosteroids for asthma or chronic sinusitis exacerbation more than one time within the past 1 year

• Treatment with an investigational drug in the previous 30 days or 5-half-lives, whichever is longer

• Treatment with a monoclonal antibody therapy including omalizumab (Xolair®), within 5-half-lives

• Treatment with zileuton (Zyflo®) within 4 weeks of baseline

• Treatment with pramipexole (Mirapex®) within 4 weeks of baseline

• History of malignancy, including solid tumors and hematologic malignancies (except basal cell and squamous cell cancers of the skin that have been completely excised and cured)

• History of human immunodeficiency virus (HIV) or hepatitis B or C

• History of unstable or severe cardiac, hepatic, or renal disease, or other medically significant illness

• Medical or other condition likely to interfere with subject's ability to undergo study procedures, adhere to visit schedule or comply with study requirements

• Absolute neutrophil count <2000 cells/μL at screening, or any documented history of neutropenia

• Total IgE >1500 IU/ml at any visit prior to baseline

• Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) of ≤80 mg/dL at screening (estimation of creatinine clearance using the MDRD formula)

• History of long QT syndrome or arrhythmia

• Prolongation of QT/QTc interval (e.g., repeated demonstration of a QT/QTc interval

450 ms) at screening or pre-dose on day 1

• Clinically important abnormalities in resting ECG that may interfere with the interpretation of QTc interval changes at screening or pre-dose on day 1, including any of the following:

• PR interval >210 ms;

• QRS >110 ms;

• Heart rate <45 bpm or >100 bpm (average of 3 assessments).

• Pregnant women or women breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ENT Associates of South Florida	Boca Raton	Florida	United States	33487
2	Johns Hopkins University	Baltimore	Maryland	United States	21205
3	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
4	Wake Research Associates	Raleigh	North Carolina	United States	27612
5	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
6	University of Pittsburgh School of Medicine	Pittsburgh	Pennsylvania	United States	15213
7	University of Virginia	Charlottesville	Virginia	United States	22903

Sponsors and Collaborators

• Knopp Biosciences

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Knopp Biosciences
• ClinicalTrials.gov Identifier: NCT02217332
• Other Study ID Numbers: KNS-76704-CS201
• First Posted: Aug 15, 2014
• Last Update Posted: May 18, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by Knopp Biosciences: Sinusitis; Rhinosinusitis; CRS; CRSwNP; CSNP-E; Nasal polyps; Nasal polyposis; Eosinophilia; Asthma
• Additional relevant MeSH terms: Sinusitis; Nasal Polyps; Eosinophilia; Polyps; Chronic Disease; Pramipexole

Study Results

Participant Flow

Pre-assignment Detail	During a screening period of between 14 and 21 days, subjects were monitored symptoms of sinusitis and asthma. Subject who failed to meet the eligibility criteria during the screening period were disqualified.

Arm/Group Title	Dexpramipexole
Arm/Group Description	dexpramipexole 150 mg BID dexpramipexole: Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)
Period Title: Overall Study
STARTED	20
COMPLETED	13
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Dexpramipexole
Arm/Group Description	dexpramipexole 150 mg BID dexpramipexole: Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.1 (9.78)
Age, Customized (Count of Participants)
< 50 years	14 70%
50 to 65 years	5 25%
> 65 years	1 5%
Sex: Female, Male (Count of Participants)
Female	8 40%
Male	12 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	19 95%
Unknown or Not Reported	1 5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 15%
White	17 85%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	20 100%
CSNP-E Symptoms (Count of Participants)
Anterior and/or posterior mucopurulent drainage	20 100%
Sinonasal obstruction/congestion	20 100%
Decreased sense of smell (anosmia)	20 100%
Duration of Symptoms (months) (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	112.4 (138.13)
Duration of symptoms (Count of Participants)
≤ 1 year	3 15%
> 1 year to ≤ 5 years	6 30%
> 5 years to ≤ 10 years	6 30%
> 10 years	5 25%

Outcome Measures

1. Primary Outcome

Title	Ratio to Baseline in Peripheral Blood Eosinophil Counts After 6 Months of Treatment
Description	Change in peripheral blood eosinophil (measured in cells/μL) from baseline to month 6 is presented as ratio to baseline.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

All subjects who had a Month 3 evaluation (on study drug Day 77 or later) for TPS and peripheral blood eosinophil count. Last observation carried forward (LOCF) was used to replace missing data due to drop out. Only Month 3 data or later (assessment date Day 77 or later and within 7 days of last dose) were used.

Arm/Group Title	Dexpramipexole
Arm/Group Description	dexpramipexole 150 mg BID dexpramipexole: Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)
Measure Participants	16
Geometric Mean (95% Confidence Interval) [ratio to baseline]	0.06

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexpramipexole
	Comments	Null hypothesis is the ratio of Month 6 to Baseline within the dexpramipexole group equals '1'.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test comparing baseline to month 6 on log scale within the dexpramipexole treatment group.

2. Primary Outcome

Title	Change From Baseline in Total Polyp Score (TPS) After 6 Months of Treatment
Description	The change in Nasal Polyp Score (NPS) score after 6 months of treatment is presented. A blinded Central Endoscopy Rater determined the NPS for each nare on a scale of 0 to 4, and the bilateral NPS scores were added to generate the Total Polyp Score (TPS) on a scale of 0 to 8. A lower TPS corresponds to a lower polyp burden.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

All subjects who had a Month 3 evaluation (on study drug Day 77 or later) for TPS and peripheral blood eosinophil count. Last observation carried forward (LOCF) was used to replace missing data due to drop out. Only Month 3 data or later (assessment date Day 77 or later and within 7 days of last dose) were used.

Arm/Group Title	Dexpramipexole
Arm/Group Description	dexpramipexole 150 mg BID dexpramipexole: Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)
Measure Participants	15
Mean (Standard Deviation) [units on a scale]	0.07 (1.751)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexpramipexole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.885
	Comments	Month 6/LOCF was used for the analysis of change from Baseline to Month 6 within the dexpramipexole group.
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Number of Subjects With Potentially Clinically Significant Values in Clinical Laboratory Evaluations
Description	Summary of subjects from the safety population who experienced potentially clinically significant values in hand serum chemistry results
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The safety population included all subjects who received at least 1 dose of study treatment.

Arm/Group Title	Dexpramipexole
Arm/Group Description	dexpramipexole 150 mg BID dexpramipexole: Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)
Measure Participants	20
LOW: Albumin <= 25 g/L	0 0%
HIGH: Alanine aminotransferase (ALT) >= 1.5 x ULN	1 5%
HIGH: Aspartate aminotransferase (AST) >= 1.5 x ULN	0 0%
HIGH: Total bilirubin >= 1.5 x ULN	0 0%
HIGH: Glucose>= 9.7 mmol/L	1 5%
LOW: Glucose <= 2.2 mmol/L	1 5%
HIGH: Eosinophils > 1.6 x 10(9)/L	1 5%
HIGH: Hematocrit - Females >=54%	0 0%
LOW: Hematocrit - Females <= 32%	2 10%
HIGH: Hemoglobin - Females >=175g/L	0 0%
LOW: Hemoglobin - Females <= 95g/L	2 10%
HIGH: Lymphocytes > 12 x 10(9)/L	0 0%
LOW: Lymphocytes < 0.8 x 10(9)/L	2 10%
LOW: Neutrophils < 1.5 x 10(9)/L	0 0%

4. Secondary Outcome

Title	Number of Subjects With Potentially Clinically Significant Values in Vital Signs and Weight
Description	Summary of subjects from the safety population who experienced potentially clinically significant values or changes in vital signs or weight
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The safety population included all subjects who received at least 1 dose of study treatment.

Arm/Group Title	Dexpramipexole
Arm/Group Description	dexpramipexole 150 mg BID dexpramipexole: Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)
Measure Participants	20
Systolic Blood Pressure: >180 mmHg	0 0%
Systolic Blood Pressure: increase from pre-dosing of more than 40 mmHg	0 0%
Systolic Blood Pressure: <90 mmHg	0 0%
Systolic Blood Pressure: decrease from pre-dosing of more than 30 mmHg	0 0%
Diastolic Blood Pressure: >105 mmHg	0 0%
Diastolic Blood Pressure: increase from pre-dosing of more than 30 mmHg	0 0%
Diastolic Blood Pressure: <50 mmHg	0 0%
Diastolic Blood Pressure: decrease from pre-dosing of more than 20 mmHg	0 0%
Heart Rate: >120 beats per minute	0 0%
Heart Rate: increase from pre-dosing of more than 20 beats per minute	1 5%
Heart Rate: <50 beats per minute	0 0%
Heart Rate: decrease from pre-dosing of more than 20 beats per minute	0 0%
Temperature: >38ºC and an increase from pre-dosing of at least 1ºC	0 0%
Body Weight: >7% increase from baseline value	0 0%
Body Weight: <=7% decrease from baseline value	0 0%

5. Secondary Outcome

Title	Number of Subjects With Potentially Significant Values in Electrocardiogram Parameters
Description	Summary of subjects from the safety population who experienced potentially significant values in electrocardiogram parameters
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The safety population included all subjects who received at least 1 dose of study treatment.

Arm/Group Title	Dexpramipexole
Arm/Group Description	dexpramipexole 150 mg BID dexpramipexole: Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)
Measure Participants	20
QTcF: >450 msec	2 10%
QTcF: >480 msec	0 0%
QTcF: > 450 msec and ≤ 450 msec at baseline	1 5%
QTcF: > 480 msec and ≤ 480 msec at baseline	0 0%
QTcF: > 450 msec and change from baseline > 30 msec	0 0%
QTcF: > 480 msec and change from baseline > 30 msec	0 0%
QTcF change from baseline: >30 msec	1 5%
QTcF change from baseline: >60 msec	0 0%
Rhythm abnormalities: Sinus rhythm	17 85%
Rhythm abnormalities: Sinus bradycardia	3 15%
Rhythm abnormalities: Premature atrial complexes, conducted or non-conducted sinus rhythm	1 5%
ST-T abnormalities: Nonspecific T wave abnormality	3 15%
ST-T abnormalities: Early repolarization	1 5%
ST-T abnormalities: Early repolarization, considered normal variant	1 5%
ST-T abnormalities: Nonspecific ST deviation	1 5%
ST-T abnormalities: Nonspecific ST deviation, prolonged QTcF interval	1 5%
ST-T abnormalities: Nonspecific T wave abnormality, prolonged QTcF interval	1 5%
ST-T abnormalities: Prolonged QTcF interval	1 5%
Conduction abnormality: First degree AV block	2 10%
Conduction abnormality: Complete right bundle branch block	1 5%
Conduction abnormality: Complete right bundle branch block first degree AV block	1 5%

6. Secondary Outcome

Title	Ratio to Baseline in Peripheral Blood Eosinophil Counts After 3 Months of Treatment
Description	Change in peripheral blood eosinophil (measured in cells/μL) from baseline to month 3 is presented as ratio to baseline.
Time Frame	Baseline and Month 3

Outcome Measure Data

Analysis Population Description

All subjects who had a Month 3 evaluation (on study drug Day 77 or later) for total eosinophil count

Arm/Group Title	Dexpramipexole
Arm/Group Description	dexpramipexole 150 mg BID dexpramipexole: Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)
Measure Participants	16
Geometric Mean (95% Confidence Interval) [ratio]	0.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexpramipexole
	Comments	Null hypothesis is the ratio of Month 3 to Baseline within the dexpramipexole group equals '1'.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	t-test, 2 sided
	Comments	Paired t-test comparing baseline to month 3 on log scale within the dexpramipexole treatment group.

7. Secondary Outcome

Title	Change From Baseline in TPS After 3 Months of Treatment
Description	The change in Nasal Polyp Score (NPS) score after 3 months of treatment is presented. A blinded Central Endoscopy Rater determined the NPS for each nare on a scale of 0 to 4, and the bilateral NPS scores were added to generate the Total Polyp Score (TPS) on a scale of 0 to 8. A lower TPS corresponds to a lower polyp burden.
Time Frame	Baseline and Month 3

Outcome Measure Data

Analysis Population Description

All subjects who had a Month 3 evaluation (on study drug Day 77 or later) for total eosinophil count and total polyp score

Arm/Group Title	Dexpramipexole
Arm/Group Description	dexpramipexole 150 mg BID dexpramipexole: Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)
Measure Participants	16
Mean (Standard Deviation) [units on a scale]	0.0 (1.414)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexpramipexole
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments	Month 3/LOCF was used for the analysis of change from Baseline to Month 3 within the dexpramipexole group.
	Method	t-test, 2 sided
	Comments	Paired t-test comparing baseline to month 3 within the dexpramipexole treatment group

8. Other Pre-specified Outcome

Title	Ratio to Baseline in Polyp Tissue Eosinophil Count After 6 Months of Treatment
Description	Change in polyp tissue eosinophil count measured as eosinophils/hpf (high powered field) from baseline to month 6 is presented as ratio to baseline.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

All subjects who had a Month 3 evaluation (on study drug Day 77 or later) for TPS and peripheral blood eosinophil count (Efficacy Population). Additionally, subjects with <5 eos/hpf at screening or baseline visit are not included in this analysis.

Arm/Group Title	Dexpramipexole
Arm/Group Description	dexpramipexole 150 mg BID dexpramipexole: Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)
Measure Participants	12
Geometric Mean (68% Confidence Interval) [ratio to baseline]	0.03

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexpramipexole
	Comments	Null hypothesis is the ratio of Month 6 to Baseline within the dexpramipexole group equals '1'; 68% confidence interval is equal to plus/minus 1 standard error
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Wilcoxon Signed Rank Test (paired)
	Comments

Adverse Events

Time Frame	6 months on treatment
Arm/Group Title	Dexpramipexole
Arm/Group Description	dexpramipexole 150 mg BID dexpramipexole: Dexpramipexole capsule-shaped film-coated tablets at the dose strength of 150 mg administered orally as 1 tablet twice daily (300 mg/day)
All Cause Mortality
	Dexpramipexole
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Serious Adverse Events
	Dexpramipexole
	Affected / at Risk (%)	# Events
Total	1/20 (5%)
Metabolism and nutrition disorders
biliary dyskinesia	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Dexpramipexole
	Affected / at Risk (%)	# Events
Total	18/20 (90%)
Ear and labyrinth disorders
Ear pain	1/20 (5%)	1
Vertigo	1/20 (5%)	1
Gastrointestinal disorders
Abdominal distension	1/20 (5%)	1
Abdominal pain	1/20 (5%)	1
Constipation	1/20 (5%)	1
Diarrhoea	1/20 (5%)	1
Dyspepsia	1/20 (5%)	1
Eosinophilic oesophagitis	1/20 (5%)	1
Flatulence	1/20 (5%)	1
Gastrooesophageal reflux disease	2/20 (10%)	2
General disorders
Fatigue	1/20 (5%)	1
Oedema	1/20 (5%)	1
Xerosis	1/20 (5%)	1
Hepatobiliary disorders
Biliary dyskinesia	1/20 (5%)	1
Infections and infestations
Ear infection	1/20 (5%)	1
Folliculitis	1/20 (5%)	1
Nasopharyngitis	3/20 (15%)	4
Onychomycosis	1/20 (5%)	1
Oral candidiasis	1/20 (5%)	1
Otitis media	1/20 (5%)	1
Rhinitis	1/20 (5%)	1
Sinusitis	8/20 (40%)	12
Subcutaneous abscess	1/20 (5%)	1
Upper respiratory tract infection	1/20 (5%)	1
Metabolism and nutrition disorders
Decreased appetite	2/20 (10%)	2
Hyperglycemia	1/20 (5%)	1
Hypoglycemia	1/20 (5%)	1
Polydipsia	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/20 (10%)	2
Pain in extremity	1/20 (5%)	1
Tendonitis	1/20 (5%)	1
Nervous system disorders
Headache	1/20 (5%)	1
Sinus headache	1/20 (5%)	1
Psychiatric disorders
Anxiety	1/20 (5%)	1
Middle insomnia	1/20 (5%)	1
Sleep disorder	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/20 (10%)	2
Dyspnoea	1/20 (5%)	1
Epistaxis	1/20 (5%)	1
Intranasal paraesthesia	1/20 (5%)	1
Nasal congestion	3/20 (15%)	4
Nasal septum ulceration	1/20 (5%)	1
Rales	1/20 (5%)	1
Rhinitis allergic	1/20 (5%)	1
Upper-airway cough syndrome	1/20 (5%)	1
Wheezing	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Dermatitis	1/20 (5%)	1
Skin hyperpigmentation	1/20 (5%)	1
Stasis dermatitis	1/20 (5%)	1
Urticaria	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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