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

Study identifier:D3032C00001

ClinicalTrials.gov identifier:NCT01904773

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A 6-month, Multicenter, Randomized, Safety, Tolerability, Pharmacokinetic, and Preliminary Efficacy Study of AZD5213 in Adolescents with Tourette's Disorder

Medical condition

Tourette Syndrome

Phase

Phase 2

Healthy volunteers

Study drug

AZD5213 and placebo

Sex

All

Actual Enrollment

Study type

Interventional

Age

12 Years - 17 Years

Date

Study Start Date: 01 Aug 2013

Primary Completion Date: 01 Feb 2015

Study Completion Date: 01 Feb 2015

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Sept 2016 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

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

Location

Research Site

Summit, NJ, United States

Location

Research Site

Cincinnati, OH, United States

Location

Research Site

New York, NY, United States

Location

Research Site

St. Petersburg, FL, United States

Location

Research Site

Orange, CA, United States

Location

Research Site

Salt Lake City, Utah, United States

Location

Research Site

Orem, UT, United States

Arms	Assigned Interventions
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

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects between the ages of 12 and 17 with Tourette's Disorder

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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

Reporting Groups

	Description
Initial study	Initial Screen, Part 1: AZD5213 0.5 mg single dose Day 1, AZD5213 2 mg dose Days 6-8
Part 2 -Sequence BBABBA	B=AZD5213 0.5 mg, A=Placebo (did not tolerate 2.0 mg in Part 1)
Part 2- Sequence BABBAB	B=AZD5213 0.5 mg, A=Placebo (did not tolerate 2.0 mg in Part 1)
Part 2 - Sequence ABCACB	A=Placebo, B=AZD5213 0.5 mg, C=AZD5213 2.0 mg
Part 2- Sequence ACBABC	A= Placebo, B=AZD5213 0.5 mg, C=AZD5213 2.0 mg
Part 2- Sequence BACCAB	A=Placebo, B=AZD5213 0.5 mg, C=AZD5213 2.0 mg
Part 2- Sequence BCACBA	A=Placebo, B=AZD5213 0.5 mg, C=AZD5213 2.0 mg
Part 2 Sequence CABBAC	A=Placebo, B=AZD5213 0.5 mg, C=AZD5213 2.0 mg
Part 2- Seqence CBABCA	A=Placebo, B=AZD5213 0.5 mg, C=AZD5213 2.0 mg

Participant Flow for 14 periods

Period 1: Screen

	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
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
Screen failure	3	0	0	0	0	0	0	0	0
Withdrawal by Subject	1	0	0	0	0	0	0	0	0

Period 2: Part 1 - Single dose- AZD5213 0.5 mg

	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
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 3: Part 1 - Multiple dose AZD5213 2.0 mg

	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
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
Adverse Event	1	0	0	0	0	0	0	0	0

Period 4: First Intervention

	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
STARTED	2	1	2	3	4	4	3	4
COMPLETED	2	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	1	0	0
Adverse Event	0	0	0	0	0	1	0	0

Period 5: Placebo washout first intervention

	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
STARTED	2	1	2	3	4	3	3	4
COMPLETED	1	1	2	3	4	3	3	4
NOT COMPLETED	1	0	0	0	0	0	0	0
Condition worsened	1	0	0	0	0	0	0	0

Period 6: Second Intervention

	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
STARTED	1	1	2	3	4	3	3	4
COMPLETED	1	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0

Period 7: Placebo washout Second Intervention

	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
STARTED	1	1	2	3	4	3	3	4
COMPLETED	1	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0

Period 8: Third Intervention

	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
STARTED	1	1	2	3	4	3	3	4
COMPLETED	1	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0

Period 9: Placebo washout Third Intervention

	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
STARTED	1	1	2	3	4	3	3	4
COMPLETED	1	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0

Period 10: Fourth Intervention

	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
STARTED	1	1	2	3	4	3	3	4
COMPLETED	1	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0

Period 11: Placebo washout Fourth Intervention

	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
STARTED	1	1	2	3	4	3	3	4
COMPLETED	1	1	2	3	4	3	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0

Period 12: Fifth Intervention

	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
STARTED	1	1	2	3	4	3	3	4
COMPLETED	1	1	2	3	4	3	2	4
NOT COMPLETED	0	0	0	0	0	0	1	0
Adverse Event	0	0	0	0	0	0	1	0

Period 13: Placebo washout Fifth Intervention

	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
STARTED	1	1	2	3	4	3	2	4
COMPLETED	0	1	2	3	4	3	2	4
NOT COMPLETED	1	0	0	0	0	0	0	0
Study specific withdrawal criteria	1	0	0	0	0	0	0	0

Period 14: Sixth Intervention

	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
STARTED	1	2	3	4	3	2	4
COMPLETED	1	2	3	4	3	2	4
NOT COMPLETED	0	0	0	0	0	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

All patients enrolled in Part 1 of the study, 23 of whom continued into Part 2

Reporting Groups

	Description
Overall Study	Part 1 & Part 2

Baseline Measures

	Overall Study
Number of Participants [units: Participants]	24
Gender, Male/Female [units: Participants]
Female	4
Male	20
Age Continuous ^[1] [units: years] Mean ± Standard Deviation	14.6 ± 1.76
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0
Asian	1
Native Hawaiian or Other Pacific Islander	0
Black or African American	2
White	21
More than one race	0
Unknown or Not Reported	0
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	3
Not Hispanic or Latino	21
Unknown or Not Reported	0
Nicotine use ^[2] [units: Participants]
Current	0
Never	24
Past	0
Tourette's Disorder Duration ^[3] [units: months] Median ( Full Range )	75 (29.8 to 159.4)

Outcome Measures

1. Primary Outcome Measure: Total Tic Severity Score (Part 2 only) crossover analysis over 6 periods [ Time Frame: 3 week period of treatment ]

Measure Type	Primary
Measure Name	Total Tic Severity Score (Part 2 only) crossover analysis over 6 periods
Measure 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
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Part 2 participants

Reporting Groups

	Description
AZD5213 0.5 mg	Part 1 single dose, Part 2 - multiple 3 week treatment periods in a randomized 6 period crossover design
AZD5213 2.0 mg	Part 2 - multiple 3 week treatment periods in a randomized 6 period crossover design
Placebo	Part 2 - multiple 3 week treatment periods in a randomized 6- period crossover design

Measured Values

	AZD5213 0.5 mg	AZD5213 2.0 mg	Placebo
Number of Participants Analyzed [units:participants]	23	19	21
Total Tic Severity Score (Part 2 only) crossover analysis over 6 periods [units: Total Tic Severity Score] Least Squares Mean (Standard Error)	24.32 (2.01)	25.41 (2.05)	22.99 (2.03)

Statistical Analysis 1 for Total Tic Severity Score (Part 2 only) crossover analysis over 6 periods

Groups^[1]	AZD5213 2.0 mg, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0087
Mean Difference (Net)^[5]	2.42
Standard Error of the mean	± 0.90

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison with placebo
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Each subject received each treatment multiple times in a crossover design
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Bonferroni-Holm adjustment, compared with 0.025
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Total Tic Severity Score (Part 2 only) crossover analysis over 6 periods

Groups^[1]	AZD5213 0.5 mg, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.1198
Median Difference (Net)^[5]	1.34
Standard Error of the mean	± 0.85

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Each subject received each treatment multiple times in a crossover design
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Bonferroni-Holm compared with 0.025
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Pharmacokinetics : Maximum Plasma concentration (ng/ml) - Part 1 only [ Time Frame: Day 1 ]

Measure Type	Primary
Measure Name	Pharmacokinetics : Maximum Plasma concentration (ng/ml) - Part 1 only
Measure Description	Pharmacokinetics Part 1 only: Maximum plasma Concentration (ng/ml) Single dose Day 1 AZD5213 0.5 mg
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic population

Reporting Groups

	Description
AZD5213 0.5 mg	Part 1 single dose, Part 2 - multiple 3 week treatment periods in a randomized 6 period crossover design

Measured Values

	AZD5213 0.5 mg
Number of Participants Analyzed [units:participants]	23
Pharmacokinetics : Maximum Plasma concentration (ng/ml) - Part 1 only [units: Plasma concentration (ng/ml)] Mean (Standard Deviation)	3.690 (1.405)

No statistical analysis provided for Pharmacokinetics : Maximum Plasma concentration (ng/ml) - Part 1 only

3. Primary Outcome Measure: Pharmacokinetics : Time to Maximum concentration (hr) - Part 1 only [ Time Frame: Day 1 ]

Measure Type	Primary
Measure Name	Pharmacokinetics : Time to Maximum concentration (hr) - Part 1 only
Measure Description	Pharmacokinetics Part 1 only: Time to maximum plasma concentration (hr)Single dose Day 1 AZD5213 0.5 mg
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic population

Reporting Groups

	Description
AZD5213 0.5 mg	Part 1 single dose, Part 2 - multiple 3 week treatment periods in a randomized 6 period crossover design

Measured Values

	AZD5213 0.5 mg
Number of Participants Analyzed [units:participants]	23
Pharmacokinetics : Time to Maximum concentration (hr) - Part 1 only [units: Time (hr)] Mean (Standard Deviation)	2.112 (1.004)

No statistical analysis provided for Pharmacokinetics : Time to Maximum concentration (hr) - Part 1 only

4. Primary Outcome Measure: Pharmacokinetics : AUC (h*ng/ ml) - Part 1 only [ Time Frame: Day 1 ]

Measure Type	Primary
Measure Name	Pharmacokinetics : AUC (h*ng/ ml) - Part 1 only
Measure 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
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic population

Reporting Groups

	Description
AZD5213 0.5 mg	Part 1 single dose, Part 2 - multiple 3 week treatment periods in a randomized 6 period crossover design

Measured Values

	AZD5213 0.5 mg
Number of Participants Analyzed [units:participants]	23
Pharmacokinetics : AUC (hng/ ml) - Part 1 only [units: AUC (hng/ml)] Mean (Standard Deviation)	26.356 (9.155)

No statistical analysis provided for Pharmacokinetics : AUC (h*ng/ ml) - Part 1 only

Serious Adverse Events

Time Frame	176 days
Additional Description	Part 1 - Single dose Day 1 - multiple dose day 6-8 Part 2 - Six period crossover Day 9 -176

Reporting Groups

	Description
Overall Study	Part 1 & Part 2
Part 1 - AZD5213 0.5 mg	Part 1 - Day 1, AZD5213 0.5 mg
Part 1 - AZD5213 2.0 mg	Part 1 - Days 6-8, AZD5213 2.0 mg
Part 2 - AZD5213 0.5 mg	Part 2 - AZD5213, 0.5 mg periods (2-4 periods)
Part 2 - AZD5213 2.0 mg	Part 2 - AZD5213, 2.0 mg periods (2 periods)
Part 2 - Placebo	Part 2 - Placebo periods (2 periods)
Part 1 - Placebo	Part 1 - Placebo, Days 2-5, washout after 0.5 mg single dose

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

Total, serious adverse events

# participants affected / at risk

2/24 (8.33%)

0/24 (0.00%)

1/24 (4.17%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

Reproductive system and breast disorders

Testicular torsion (Part 2)¹
Surgical orchiectomy required, treatment continued (placebo treatment period)

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Nervous system disorders

Convulsion¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/24 (4.17%)

0/23 (0.00%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA Version 16.0

Other Adverse Events

Time Frame	176 days
Additional Description	Part 1 - Single dose Day 1 - multiple dose day 6-8 Part 2 - Six period crossover Day 9 -176

Frequency Threshold

Threshold above which other adverse events are reported	1%

Reporting Groups

	Description
Overall Study	Part 1 & Part 2
Part 1 - AZD5213 0.5 mg	Part 1 - Day 1, AZD5213 0.5 mg
Part 1 - AZD5213 2.0 mg	Part 1 - Days 6-8, AZD5213 2.0 mg
Part 2 - AZD5213 0.5 mg	Part 2 - AZD5213, 0.5 mg periods (2-4 periods)
Part 2 - AZD5213 2.0 mg	Part 2 - AZD5213, 2.0 mg periods (2 periods)
Part 2 - Placebo	Part 2 - Placebo periods (2 periods)
Part 1 - Placebo	Part 1 - Placebo, Days 2-5, washout after 0.5 mg single dose

Other 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

Total, other (not including serious) adverse events

# participants affected / at risk

22/24 (91.67%)

1/24 (4.17%)

7/24 (29.17%)

16/23 (69.57%)

9/19 (47.37%)

11/21 (52.38%)

5/24 (20.83%)

Psychiatric disorders

Anxiety¹

# participants affected / at risk

2/24 (8.33%)

0/24 (0.00%)

0/23 (0.00%)

1/19 (5.26%)

1/21 (4.76%)

0/24 (0.00%)

# events

Psychiatric disorders

Confusional State¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/24 (4.17%)

0/23 (0.00%)

1/19 (5.26%)

1/21 (4.76%)

0/24 (0.00%)

# events

Psychiatric disorders

Initial insomnia¹

# participants affected / at risk

3/24 (12.50%)

0/24 (0.00%)

1/24 (4.17%)

1/23 (4.35%)

1/19 (5.26%)

0/21 (0.00%)

1/24 (4.17%)

# events

Psychiatric disorders

Tic¹

# participants affected / at risk

2/24 (8.33%)

0/24 (0.00%)

0/23 (0.00%)

1/19 (5.26%)

1/21 (4.76%)

0/24 (0.00%)

# events

Psychiatric disorders

Abnormal behavior¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Psychiatric disorders

Agitation¹

# participants affected / at risk

2/24 (8.33%)

0/24 (0.00%)

1/24 (4.17%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Psychiatric disorders

Depressed mood¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Psychiatric disorders

Impulsive behavior¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/24 (4.17%)

0/23 (0.00%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Psychiatric disorders

Hypervigilance¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Psychiatric disorders

Mood swings¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Psychiatric disorders

Nightmare¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

1/19 (5.26%)

0/21 (0.00%)

0/24 (0.00%)

# events

Psychiatric disorders

Sexually inappropriate behavior¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Psychiatric disorders

Sleep disorder¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Nervous system disorders

Headache¹

# participants affected / at risk

9/24 (37.50%)

0/24 (0.00%)

2/24 (8.33%)

5/23 (21.74%)

2/19 (10.53%)

2/21 (9.52%)

2/24 (8.33%)

# events

Nervous system disorders

Dizziness¹

# participants affected / at risk

3/24 (12.50%)

0/24 (0.00%)

1/24 (4.17%)

1/23 (4.35%)

0/19 (0.00%)

1/21 (4.76%)

1/24 (4.17%)

# events

Nervous system disorders

Somnolence¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

1/19 (5.26%)

0/21 (0.00%)

0/24 (0.00%)

# events

Nervous system disorders

Disturbance in attention¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Nervous system disorders

Tremor¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain upper¹

# participants affected / at risk

3/24 (12.50%)

0/24 (0.00%)

1/24 (4.17%)

2/23 (8.70%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Gastrointestinal disorders

Dry mouth¹

# participants affected / at risk

2/24 (8.33%)

0/24 (0.00%)

0/23 (0.00%)

1/19 (5.26%)

1/21 (4.76%)

0/24 (0.00%)

# events

Gastrointestinal disorders

Gastroesophageal reflux disease¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Gastrointestinal disorders

Constipation¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Gastrointestinal disorders

Tooth impacted¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

1/19 (5.26%)

0/21 (0.00%)

0/24 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

2/24 (8.33%)

0/24 (0.00%)

1/24 (4.17%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Tendonitis¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

1/19 (5.26%)

0/21 (0.00%)

0/24 (0.00%)

# events

Infections and infestations

Nasopharyngitis¹

# participants affected / at risk

6/24 (25.00%)

0/24 (0.00%)

1/24 (4.17%)

2/23 (8.70%)

2/19 (10.53%)

1/21 (4.76%)

0/24 (0.00%)

# events

Infections and infestations

Gastroenteritis¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Infections and infestations

Gastroenteritis viral¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Infections and infestations

Upper respiratory tract infection¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Infections and infestations

Viral upper respiratory tract infection¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹

# participants affected / at risk

2/24 (8.33%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Epistaxis¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Injury, poisoning and procedural complications

Chemical burn of skin¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Injury, poisoning and procedural complications

Contusion¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Injury, poisoning and procedural complications

Procedural pain¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

1/19 (5.26%)

0/21 (0.00%)

0/24 (0.00%)

# events

Eye disorders

Vision blurred¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹

# participants affected / at risk

3/24 (12.50%)

0/24 (0.00%)

1/24 (4.17%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

1/24 (4.17%)

# events

General disorders

Fatigue¹

# participants affected / at risk

2/24 (8.33%)

0/24 (0.00%)

2/24 (8.33%)

1/23 (4.35%)

1/19 (5.26%)

1/21 (4.76%)

1/24 (4.17%)

# events

General disorders

Feeling abnormal¹

# participants affected / at risk

2/24 (8.33%)

0/24 (0.00%)

2/23 (8.70%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

General disorders

Asthenia¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

General disorders

Irritability¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

1/19 (5.26%)

0/21 (0.00%)

0/24 (0.00%)

# events

General disorders

Medical device complication¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

General disorders

Non-cardiac chest pain¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

General disorders

Pain¹

# participants affected / at risk

2/24 (8.33%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

1/24 (4.17%)

# events

General disorders

Pyrexia¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

General disorders

Thirst¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/24 (4.17%)

0/23 (0.00%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal septum deviation¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

0/23 (0.00%)

1/19 (5.26%)

0/21 (0.00%)

0/24 (0.00%)

# events

Infections and infestations

Influenza¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Cardiac disorders

Palpitations¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

1/19 (5.26%)

1/21 (4.76%)

1/24 (4.17%)

# events

Skin and subcutaneous tissue disorders

Hyperkeratosis¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Skin and subcutaneous tissue disorders

Cold Sweats¹

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/23 (4.35%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Orapharangeal pain¹

# participants affected / at risk

2/24 (8.33%)

0/24 (0.00%)

2/23 (8.70%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

# events

Psychiatric disorders

Insomnia¹

# participants affected / at risk

6/24 (25.00%)

1/24 (4.17%)

3/24 (12.50%)

1/23 (4.35%)

1/19 (5.26%)

1/21 (4.76%)

0/24 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA Version 16.0

Certain Agreements

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

There IS 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.

The agreement is:

	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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact

Name/Title:	Joel Posener, MD - Head, Early Clinical Development
Organization:	AstraZeneca Pharmaceuticals LP, Neuroscience Innovative Medicines Unit
E-mail:	[email protected]