Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette's Disorder

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01904773
• Collaborator: (none)
• Enrollment: 29
• Locations: 7
• Arms: 3
• Duration (Months): 18
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a two-part, randomized, multi-center, blinded study in adolescents with Tourette's Disorder. There will be an up to 21-day screening period in which subject eligibility will be determined. In Part 1 of the study, the safety, tolerability and pharmacokinetics of AZD5213 will be assessed during a 1- week period.

In Part 2 of the study, the safety, tolerability, and preliminary efficacy of two doses (depending on tolerability in Part 1 of the study) of AZD5213 and placebo will be assessed through six consecutive four-week crossover periods. Each subject will receive both AZD5213 and placebo. A follow-up vist will take place at 14 (±) 7 days following the last dose of study drug.

Condition or Disease	Intervention/Treatment	Phase
Tourette Syndrome	Drug: AZD5213 and placebo	Phase 2

Detailed Description

This is a multicenter, randomized, two-part study of AZD5213 in adolescents (ages 12-17 years) with Tourette's Disorder.

In Part 1 of the study, following an up to 21-day screening period, on Day 1, after baseline procedures are performed, eligible subjects will receive a single, low dose of AZD5213, in-clinic.

After study drug dosing on Day 1, safety and tolerability will be assessed in-clinic, and blood samples will be taken for pharmacokinetic (PK) analysis. On Days 2, 3, 4, 5, 6 and 7 subjects will take study drug, and will be contacted via telephone and adverse events and concomitant medications will be assessed. On Day 8, safety, tolerability, and blood sampling for PK analysis (predose and 2-4 hours post-dose) will be performed in-clinic. Part 2 of the study will consist of six consecutive crossover periods. In Part 2 of the study, each study drug will be administered in two 4-week periods (six treatment periods, total). Each study drug will be received in one of Periods 1-3, and again in one of Periods 4-6. Approximately 24 subjects will receive study drug in Part 1 of this study in order to complete approximately 18 subjects in Part 2.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A 6-month, Multicenter, Randomized, Safety, Tolerability, Pharmacokinetic, and Preliminary Efficacy Study of AZD5213 in Adolescents With Tourette's Disorder
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: AZD5213 and placebo; low dose AZD5213 capsules; high dose AZD5213 capsules; placebo capsules
Experimental: low dose AZD5213	Drug: AZD5213 and placebo; low dose AZD5213 capsules; high dose AZD5213 capsules; placebo capsules
Experimental: high dose AZD5213	Drug: AZD5213 and placebo; low dose AZD5213 capsules; high dose AZD5213 capsules; placebo capsules

Outcome Measures

Primary Outcome Measures

1. Total Tic Severity Score (Part 2 Only) Crossover Analysis Over 6 Periods [3 week period of treatment]

   Total Tic Severity Score on the the Yale Global Tic Severity Scale - Part 2 only (lower is better), range 0 - 50

2. Pharmacokinetics : Maximum Plasma Concentration (ng/ml) - Part 1 Only [Day 1]

   Pharmacokinetics Part 1 only: Maximum plasma Concentration (ng/ml) Single dose Day 1 AZD5213 0.5 mg

3. Pharmacokinetics : Time to Maximum Concentration (hr) - Part 1 Only [Day 1]

   Pharmacokinetics Part 1 only: Time to maximum plasma concentration (hr)Single dose Day 1 AZD5213 0.5 mg

4. Pharmacokinetics : AUC (h*ng/ ml) - Part 1 Only [Day 1]

   Pharmacokinetics Part 1 only: Single dose Day 1 AZD5213 0.5 mg Area Under the Concentration time curve (AUC) 0 to infinity (h*ng/ml)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female, between the ages of ≥ 12 and < 18 years at baseline (Day 1).

2. Meets Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for Tourette's Disorder, as assessed by the Kiddie-SADS (Schedule for Affective Disorders and Schizophrenia)-Present and Lifetime Version (K-SADS-PL) Tic Disorder Supplement and clinical interview.

3. Yale Global Tic Severity Scale (YGTSS) Total Tic Severity Score (TTS) ≥ 20 at Screen and baseline (Day 1).

4. Symptoms of Tourette's Disorder must impair school, occupational, and/or social function.

5. Written informed assent or consent provided by the subject, and written informed consent provided by the parent(s)/guardians(s), as appropriate per the Institutional Review Board/Ethics Committee. 6. Weight ≥ 40 kg at the screening and baseline (Day 1) visits.

6. In the opinion of the investigator, the subject and designated guardian(s) and/or parent(s) must be considered likely to comply with the study protocol and to have a high probability of completing the study.

Exclusion Criteria:

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

1. Prior participation in any AZD5213 study.

2. Acute suicidality as evidenced by answering "yes" for question #4 or question #5 on the Columbia-Suicide Severity Rating Scale (C-SSRS), indicating active suicidal ideation with any intent to act, at Screen or baseline (Day 1).

3. Pregnant or breast-feeding females.

4. History of seizure disorder other than a single childhood febrile seizure.

5. Presence of any psychiatric or neurologic disorder or symptom, if, in the judgment of the investigator, the psychiatric or neurologic disorder or symptom is likely to confound interpretation of drug effect or affect the subject's ability to complete the study. 6. Any clinically important abnormality as determined by the investigator at Screen or baseline (Day 1) in physical or neurologic examination, vital sign, ECG, or clinical laboratory test results that could be detrimental to the subject or could affect the subject's ability to complete the study.

6. History or presence of any clinically important medical condition that, in the judgement of the investigator, is likely to deteriorate, could be detrimental to the subject, or could affect the subject's ability to complete the study.

7. History or presence of a clinically important sleep disorder.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Orange	California	United States
2	Research Site	St. Petersburg	Florida	United States
3	Research Site	Summit	New Jersey	United States
4	Research Site	New York	New York	United States
5	Research Site	Cincinnati	Ohio	United States
6	Research Site	Orem	Utah	United States
7	Research Site	Salt Lake City	Utah	United States

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01904773
• Other Study ID Numbers: D3032C00001
• First Posted: Jul 22, 2013
• Last Update Posted: Sep 23, 2016
• Last Verified: Sep 1, 2016

• Keywords provided by AstraZeneca: Combined Multiple Motor and Vocal Tic Disorder; Tourette Disorder; Gilles de la Tourette Syndrome; Tourette Disease
• Additional relevant MeSH terms: Tourette Syndrome

Study Results

Participant Flow

Recruitment Details	Subjects between the ages of 12 and 17 with Tourette's Disorder
Pre-assignment Detail	There were 29 screening visits for 28 subjects, 1 subject was initially screen failed for exclusion 32 but rescreened and qualified and entered Part 1 of the study(104-4003 rescreened and qualified as 104-4004). Eligible subjects participated in Part 1 and then continued into a randomized 6 period crossover Part 2 of the study

Arm/Group Title	Initial Study	Part 2 -Sequence BBABBA	Part 2- Sequence BABBAB	Part 2 - Sequence ABCACB	Part 2- Sequence ACBABC	Part 2- Sequence BACCAB	Part 2- Sequence BCACBA	Part 2 Sequence CABBAC	Part 2- Seqence CBABCA
Arm/Group Description	Initial Screen, Part 1: AZD5213 0.5 mg single dose Day 1, AZD5213 2 mg dose Days 6-8	B=AZD5213 0.5 mg, A=Placebo (did not tolerate 2.0 mg in Part 1)	B=AZD5213 0.5 mg, A=Placebo (did not tolerate 2.0 mg in Part 1)	A=Placebo, B=AZD5213 0.5 mg, C=AZD5213 2.0 mg	A= Placebo, B=AZD5213 0.5 mg, C=AZD5213 2.0 mg	A=Placebo, B=AZD5213 0.5 mg, C=AZD5213 2.0 mg	A=Placebo, B=AZD5213 0.5 mg, C=AZD5213 2.0 mg	A=Placebo, B=AZD5213 0.5 mg, C=AZD5213 2.0 mg	A=Placebo, B=AZD5213 0.5 mg, C=AZD5213 2.0 mg
Period Title: Screen
STARTED	28	0	0	0	0	0	0	0	0
COMPLETED	24	0	0	0	0	0	0	0	0
NOT COMPLETED	4	0	0	0	0	0	0	0	0
Period Title: Screen
STARTED	24	0	0	0	0	0	0	0	0
COMPLETED	24	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Screen
STARTED	24	0	0	0	0	0	0	0	0
Tolerated 2.0 mg in Part 1	20	0	0	0	0	0	0	0	0
Did Not Tolerate 2.0 mg in Part 1	4	0	0	0	0	0	0	0	0
COMPLETED	23	0	0	0	0	0	0	0	0
NOT COMPLETED	1	0	0	0	0	0	0	0	0
Period Title: Screen
STARTED	0	2	1	2	3	4	4	3	4
COMPLETED	0	2	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	1	0	0
Period Title: Screen
STARTED	0	2	1	2	3	4	3	3	4
COMPLETED	0	1	1	2	3	4	3	3	4
NOT COMPLETED	0	1	0	0	0	0	0	0	0
Period Title: Screen
STARTED	0	1	1	2	3	4	3	3	4
COMPLETED	0	1	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Screen
STARTED	0	1	1	2	3	4	3	3	4
COMPLETED	0	1	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Screen
STARTED	0	1	1	2	3	4	3	3	4
COMPLETED	0	1	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Screen
STARTED	0	1	1	2	3	4	3	3	4
COMPLETED	0	1	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Screen
STARTED	0	1	1	2	3	4	3	3	4
COMPLETED	0	1	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Screen
STARTED	0	1	1	2	3	4	3	3	4
COMPLETED	0	1	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Screen
STARTED	0	1	1	2	3	4	3	3	4
COMPLETED	0	1	1	2	3	4	3	2	4
NOT COMPLETED	0	0	0	0	0	0	0	1	0
Period Title: Screen
STARTED	0	1	1	2	3	4	3	2	4
COMPLETED	0	0	1	2	3	4	3	2	4
NOT COMPLETED	0	1	0	0	0	0	0	0	0
Period Title: Screen
STARTED	0	0	1	2	3	4	3	2	4
COMPLETED	0	0	1	2	3	4	3	2	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	Part 1 & Part 2
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.6 (1.76)
Sex: Female, Male (Count of Participants)
Female	4 16.7%
Male	20 83.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 12.5%
Not Hispanic or Latino	21 87.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 8.3%
White	21 87.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Nicotine use (Number) [Number]
Current	0 0%
Never	24 100%
Past	0 0%
Tourette's Disorder Duration (months) [Median (Full Range) ]
Median (Full Range) [months]	75

Outcome Measures

1. Primary Outcome

Title	Total Tic Severity Score (Part 2 Only) Crossover Analysis Over 6 Periods
Description	Total Tic Severity Score on the the Yale Global Tic Severity Scale - Part 2 only (lower is better), range 0 - 50
Time Frame	3 week period of treatment

Outcome Measure Data

Analysis Population Description

All Part 2 participants

Arm/Group Title	AZD5213 0.5 mg	AZD5213 2.0 mg	Placebo
Arm/Group Description	Part 1 single dose, Part 2 - multiple 3 week treatment periods in a randomized 6 period crossover design	Part 2 - multiple 3 week treatment periods in a randomized 6 period crossover design	Part 2 - multiple 3 week treatment periods in a randomized 6- period crossover design
Measure Participants	23	19	21
Least Squares Mean (Standard Error) [Total Tic Severity Score]	24.32 (2.01)	25.41 (2.05)	22.99 (2.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AZD5213 2.0 mg, Placebo
	Comments	Comparison with placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0087
	Comments	Bonferroni-Holm adjustment, compared with 0.025
	Method	ANCOVA
	Comments	Each subject received each treatment multiple times in a crossover design
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.42
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.90
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	AZD5213 0.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1198
	Comments	Bonferroni-Holm compared with 0.025
	Method	ANCOVA
	Comments	Each subject received each treatment multiple times in a crossover design
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	1.34
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.85
	Estimation Comments

2. Primary Outcome

Title	Pharmacokinetics : Maximum Plasma Concentration (ng/ml) - Part 1 Only
Description	Pharmacokinetics Part 1 only: Maximum plasma Concentration (ng/ml) Single dose Day 1 AZD5213 0.5 mg
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	AZD5213 0.5 mg
Arm/Group Description	Part 1 single dose, Part 2 - multiple 3 week treatment periods in a randomized 6 period crossover design
Measure Participants	23
Mean (Standard Deviation) [Plasma concentration (ng/ml)]	3.690 (1.405)

3. Primary Outcome

Title	Pharmacokinetics : Time to Maximum Concentration (hr) - Part 1 Only
Description	Pharmacokinetics Part 1 only: Time to maximum plasma concentration (hr)Single dose Day 1 AZD5213 0.5 mg
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	AZD5213 0.5 mg
Arm/Group Description	Part 1 single dose, Part 2 - multiple 3 week treatment periods in a randomized 6 period crossover design
Measure Participants	23
Mean (Standard Deviation) [Time (hr)]	2.112 (1.004)

4. Primary Outcome

Title	Pharmacokinetics : AUC (h*ng/ ml) - Part 1 Only
Description	Pharmacokinetics Part 1 only: Single dose Day 1 AZD5213 0.5 mg Area Under the Concentration time curve (AUC) 0 to infinity (h*ng/ml)
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	AZD5213 0.5 mg
Arm/Group Description	Part 1 single dose, Part 2 - multiple 3 week treatment periods in a randomized 6 period crossover design
Measure Participants	23
Mean (Standard Deviation) [AUC (h*ng/ml)]	26.356 (9.155)

Adverse Events

Time Frame	176 days
Adverse Event Reporting Description	Part 1 - Single dose Day 1 - multiple dose day 6-8 Part 2 - Six period crossover Day 9 -176
Arm/Group Title	Overall Study		Part 1 - AZD5213 0.5 mg		Part 1 - AZD5213 2.0 mg		Part 2 - AZD5213 0.5 mg		Part 2 - AZD5213 2.0 mg		Part 2 - Placebo		Part 1 - Placebo
Arm/Group Description	Part 1 & Part 2		Part 1 - Day 1, AZD5213 0.5 mg		Part 1 - Days 6-8, AZD5213 2.0 mg		Part 2 - AZD5213, 0.5 mg periods (2-4 periods)		Part 2 - AZD5213, 2.0 mg periods (2 periods)		Part 2 - Placebo periods (2 periods)		Part 1 - Placebo, Days 2-5, washout after 0.5 mg single dose
All Cause Mortality
	Overall Study		Part 1 - AZD5213 0.5 mg		Part 1 - AZD5213 2.0 mg		Part 2 - AZD5213 0.5 mg		Part 2 - AZD5213 2.0 mg		Part 2 - Placebo		Part 1 - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Overall Study		Part 1 - AZD5213 0.5 mg		Part 1 - AZD5213 2.0 mg		Part 2 - AZD5213 0.5 mg		Part 2 - AZD5213 2.0 mg		Part 2 - Placebo		Part 1 - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/24 (8.3%)		0/24 (0%)		1/24 (4.2%)		0/23 (0%)		0/19 (0%)		1/21 (4.8%)		0/24 (0%)
Nervous system disorders
Convulsion	1/24 (4.2%)	1	0/24 (0%)	0	1/24 (4.2%)	1	0/23 (0%)	0	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Reproductive system and breast disorders
Testicular torsion (Part 2)	1/23 (4.3%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Other (Not Including Serious) Adverse Events
	Overall Study		Part 1 - AZD5213 0.5 mg		Part 1 - AZD5213 2.0 mg		Part 2 - AZD5213 0.5 mg		Part 2 - AZD5213 2.0 mg		Part 2 - Placebo		Part 1 - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/24 (91.7%)		1/24 (4.2%)		7/24 (29.2%)		16/23 (69.6%)		9/19 (47.4%)		11/21 (52.4%)		5/24 (20.8%)
Cardiac disorders
Palpitations	1/24 (4.2%)	5	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	2	1/19 (5.3%)	1	1/21 (4.8%)	1	1/24 (4.2%)	1
Eye disorders
Vision blurred	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	3/24 (12.5%)	3	0/24 (0%)	0	1/24 (4.2%)	1	2/23 (8.7%)	2	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Dry mouth	2/24 (8.3%)	2	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	1/19 (5.3%)	1	1/21 (4.8%)	1	0/24 (0%)	0
Gastroesophageal reflux disease	1/24 (4.2%)	2	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Constipation	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Diarrhoea	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Tooth impacted	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	1/19 (5.3%)	1	0/21 (0%)	0	0/24 (0%)	0
Vomiting	2/24 (8.3%)	2	0/24 (0%)	0	1/24 (4.2%)	1	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Nausea	1/24 (4.2%)	2	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
General disorders
Fatigue	2/24 (8.3%)	8	0/24 (0%)	0	2/24 (8.3%)	3	1/23 (4.3%)	1	1/19 (5.3%)	1	1/21 (4.8%)	1	1/24 (4.2%)	2
Feeling abnormal	2/24 (8.3%)	2	0/24 (0%)	0	0/24 (0%)	0	2/23 (8.7%)	2	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Asthenia	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Irritability	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	1/19 (5.3%)	1	0/21 (0%)	0	0/24 (0%)	0
Medical device complication	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Non-cardiac chest pain	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Pain	2/24 (8.3%)	2	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	1/24 (4.2%)	1
Pyrexia	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Thirst	1/24 (4.2%)	1	0/24 (0%)	0	1/24 (4.2%)	1	0/23 (0%)	0	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Infections and infestations
Nasopharyngitis	6/24 (25%)	6	0/24 (0%)	0	1/24 (4.2%)	1	2/23 (8.7%)	2	2/19 (10.5%)	2	1/21 (4.8%)	1	0/24 (0%)	0
Gastroenteritis	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Gastroenteritis viral	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Upper respiratory tract infection	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Viral upper respiratory tract infection	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Influenza	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Injury, poisoning and procedural complications
Chemical burn of skin	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Contusion	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Procedural pain	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	1/19 (5.3%)	1	0/21 (0%)	0	0/24 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	3/24 (12.5%)	3	0/24 (0%)	0	1/24 (4.2%)	1	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	1/24 (4.2%)	1
Musculoskeletal and connective tissue disorders
Tendonitis	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	1/19 (5.3%)	1	0/21 (0%)	0	0/24 (0%)	0
Nervous system disorders
Headache	9/24 (37.5%)	17	0/24 (0%)	0	2/24 (8.3%)	2	5/23 (21.7%)	8	2/19 (10.5%)	3	2/21 (9.5%)	2	2/24 (8.3%)	2
Dizziness	3/24 (12.5%)	5	0/24 (0%)	0	1/24 (4.2%)	1	1/23 (4.3%)	2	0/19 (0%)	0	1/21 (4.8%)	1	1/24 (4.2%)	1
Somnolence	1/24 (4.2%)	2	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	1/19 (5.3%)	1	0/21 (0%)	0	0/24 (0%)	0
Disturbance in attention	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Tremor	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Psychiatric disorders
Anxiety	2/24 (8.3%)	2	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	1/19 (5.3%)	1	1/21 (4.8%)	1	0/24 (0%)	0
Confusional State	1/24 (4.2%)	3	0/24 (0%)	0	1/24 (4.2%)	1	0/23 (0%)	0	1/19 (5.3%)	1	1/21 (4.8%)	1	0/24 (0%)	0
Initial insomnia	3/24 (12.5%)	4	0/24 (0%)	0	1/24 (4.2%)	1	1/23 (4.3%)	1	1/19 (5.3%)	1	0/21 (0%)	0	1/24 (4.2%)	1
Tic	2/24 (8.3%)	3	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	1/19 (5.3%)	1	1/21 (4.8%)	2	0/24 (0%)	0
Abnormal behavior	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Agitation	2/24 (8.3%)	2	0/24 (0%)	0	1/24 (4.2%)	1	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Depressed mood	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Impulsive behavior	1/24 (4.2%)	1	0/24 (0%)	0	1/24 (4.2%)	1	0/23 (0%)	0	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Hypervigilance	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Mood swings	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Nightmare	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	1/19 (5.3%)	1	0/21 (0%)	0	0/24 (0%)	0
Sexually inappropriate behavior	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Sleep disorder	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Insomnia	6/24 (25%)	10	1/24 (4.2%)	1	3/24 (12.5%)	3	1/23 (4.3%)	4	1/19 (5.3%)	1	1/21 (4.8%)	1	0/24 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	2/24 (8.3%)	2	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Dyspnoea	1/24 (4.2%)	2	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Epistaxis	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Nasal congestion	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/19 (0%)	0	1/21 (4.8%)	1	0/24 (0%)	0
Nasal septum deviation	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	1/19 (5.3%)	1	0/21 (0%)	0	0/24 (0%)	0
Orapharangeal pain	2/24 (8.3%)	2	0/24 (0%)	0	0/24 (0%)	0	2/23 (8.7%)	2	0/18 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Skin and subcutaneous tissue disorders
Hyperkeratosis	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0
Cold Sweats	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/19 (0%)	0	0/21 (0%)	0	0/24 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.