AGN-241751 in the Treatment of Major Depressive Disorder

• Sponsor: Gate Neurosciences, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03586427
• Collaborator: (none)
• Enrollment: 251
• Locations: 25
• Arms: 5
• Actual Duration (Months): 14.3
• Patients Per Site: 10
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy at 1 day post initial oral dose of AGN-241751 compared with placebo in participants with Major Depressive Disorder (MDD).

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder, Major	Drug: AGN-241751; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 251 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo-Controlled, Fixed-Dose Study of AGN-241751 in Adult Participants With Major Depressive Disorder
• Actual Study Start Date: Jun 13, 2018
• Actual Primary Completion Date: Jul 22, 2019
• Actual Study Completion Date: Aug 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AGN-241751 Dose 1 AGN-241751 Dose 1 administered as 1 tablet taken orally every day	Drug: AGN-241751; AGN-241751 administered orally as a single tablet
Experimental: AGN-241751 Dose 2 AGN-241751 Dose 2 administered as 1 tablet taken orally every day	Drug: AGN-241751; AGN-241751 administered orally as a single tablet
Experimental: AGN-241751 Dose 3 AGN-241751 Dose 3 administered as 1 tablet taken orally every day	Drug: AGN-241751; AGN-241751 administered orally as a single tablet
Experimental: AGN-241751 Dose 4 AGN-241751 Dose 4 administered as 1 tablet taken orally every day	Drug: AGN-241751; AGN-241751 administered orally as a single tablet
Placebo Comparator: Placebo Placebo administered as 1 tablet taken orally every day	Drug: Placebo; Placebo administered orally as a single tablet

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [Baseline to Day 1]

   The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.

Secondary Outcome Measures

1. Change From Baseline in MADRS Total Score at Week 3 [Baseline to Week 3]

   The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent from the participant has been obtained prior to any study -related procedures (as described in Appendix 3).

• Male or female participants must be 18 to 65 years of age, inclusive, at the time of signing the informed consent.

• Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for MDD (based on confirmation from the modified Structured Clinical Interview for DSM disorders [SCID]), with a current major depressive episode of at least 8 weeks and not exceeding 18 months in duration at Visit 1.

• Have a minimum score of 26 on the rater-administered Montgomery-Asberg depression rating scale (MADRS) and a minimum score of 24 on the computer-administered MADRS at both Visit 1 (Screening) and Visit 2 (Baseline).

• Have a difference of no greater than 7 points between the rater-administered MADRS and computer-administered MADRS at both Visit 1 (Screening) and Visit 2 (Baseline).

• Have a clinical global impression-severity (CGI-S) score ≥ 4 at both Visit 1 (Screening) and Visit 2 (Baseline).

• Have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test if a woman of childbearing potential (WOCBP).

• Female participants willing to minimize the risk of becoming pregnancy for the duration of the clinical study and follow-up period. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

• not a WOCBP OR

• A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 of protocol during the treatment period and for at least 5 terminal half-lives after the last dose of study treatment.

• Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. A male participant must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 5 terminal half-lives after the last dose of study treatment and refrain from donating sperm during this period.

• Able, as assessed by the investigator, and willing to follow study instructions and likely to complete all required study visits.

• Normal physical-examination findings, clinical-laboratory test results, and electrocardiogram (ECG) results from Visit 1 (Screening) or abnormal results that are determined to be not clinically significant by the investigator.

• Body mass index (BMI) within the range 18 and 40 kg/m^2 (inclusive).

• Eligibility confirmed through a formal adjudication process (see Section 9 Diagnostic Assessments).

Exclusion Criteria:

Psychiatric and Treatment-Related Criteria

• DSM-5-based diagnosis of any disorder other than MDD that was the primary focus of treatment within 6 months before Visit 1. Comorbid generalized anxiety disorder, social anxiety disorder, or specific phobias are acceptable provided they play a secondary role in the balance of symptoms and are not the primary driver of treatment decisions.

• Lifetime history of meeting DSM-5 criteria for:

• Schizophrenia spectrum or other psychotic disorder

• Bipolar or related disorder

• Major neurocognitive disorder

• Neurodevelopmental disorder of greater than mild severity or of a severity that impacts the participant's ability to consent, follow study directions, or otherwise safely participate in the study

• Dissociative disorder

• Posttraumatic stress disorder

• MDD with psychotic features

• History of meeting DSM-5 criteria for alcohol or substance use disorder (other than nicotine or caffeine) within the 6 months before Visit 1.

• DSM-5-based diagnosis of any personality disorder of sufficient severity to interfere with participation in this study in the opinion of the investigator.

• History (based on participant report and/or medical records, and investigator judgment) of:

• Inadequate response to electroconvulsive therapy (ECT), a monoamine oxidase inhibitor, ketamine, or adjunctive treatment with an antipsychotic

• Treatment with clozapine or any depot antipsychotic

• ECT, vagus nerve stimulation, transcranial magnetic stimulation, or any experimental central nervous system treatment during the current episode or in the 6 months before Visit 1 (whichever is longer)

• Tardive dyskinesia, serotonin syndrome, or neuroleptic malignant syndrome

• Having received:

• Anticonvulsant/mood stabilizer, within 1 year prior to Visit 1

• Antipsychotic in the current episode, with the exception of quetiapine given for insomnia ≤ 50 mg/day provided it can be safely discontinued prior to Visit 2

• Combination therapy of 2 or more antidepressant therapies (ADTs) in the current episode if given for depression at adequate dose and duration

• ADT augmentation agent in the current episode

• Lifetime history of nonresponse to ≥ 2 antidepressants after adequate trials (adequate treatment is defined as at least 6 weeks at an adequate dose(s) based on approved package insert recommendations) or a non-response to an antidepressant after adequate treatment for the current major depressive episode.

• Positive result at Visit 1 from the urine drug screen (UDS) test for any prohibited medication. Exception: participants with a positive UDS at Visit 1 for opiates, cannabinoids, or episodic use of benzodiazepines may be allowed in the study provided:

• The drug was used for a legitimate medical purpose;

• The drug can be discontinued prior to participation in the study (except for episodic use of benzodiazepines which may be continued); and

• A repeat UDS is negative for these substances prior to enrollment (except for episodic use of benzodiazepines which may be continued)

• Suicide risk, as determined by meeting any of the following criteria:

• A suicide attempt within the past year

• Significant risk, as judged by the investigator, based on the psychiatric interview or information collected in the C-SSRS at Visit 1 (Screening) or Visit 2 (Baseline)

• MADRS Item 10 score ≥ 5 at Visit 1 (Screening) or Visit 2 (Baseline) on the MADRS

• At imminent risk of injuring self or others or causing significant damage to property, as judged by the investigator.

• Requiring concomitant treatment with any of the prohibited medications, supplements, or herbal products listed in Appendix 6 of protocol, including any psychotropic drug or any drug with psychotropic activity, except as described in Section 7.7.2. of protocol.

• Prior participation in any investigational study of AGN-241751.

• Initiation or termination of psychotherapy for depression within the 3 months preceding Visit 1, or plans to initiate, terminate, or change such therapy during the course of the study. (Support meetings or counselling [eg, marital counselling] are allowed provided they are no more frequent than weekly and do not have treatment of depression as their objective).

• Ongoing treatment with phototherapy, or termination of phototherapy within 1 month of Visit 1.

• Known allergy or sensitivity to the study medication or its components.

Other Medical Criteria

• BMI < 18 kg/m^{2 or > 40 kg/m}2 at screening.

• Females who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study.

• WOCBP and male partners of WOCBP, not using a reliable means of contraception (Appendix 5 of protocol).

• Participant has a condition or is in a situation which, in the investigator's opinion, may put the participant at significant risk, may confound the study results, or may interfere significantly with the participant's participation in the study.

• Any cardiovascular disease that is clinically significant, unstable, or decompensated.

• Heart rate (supine) of ≤ 45 beats per minute (bpm) or ≥ 120 bpm, or any heart rate that is clinically symptomatic at Visit 1 or Visit 2 based upon vital signs.

• Any systolic and/or diastolic blood pressure (BP) that is symptomatic or clinically significant in the opinion of the investigator.

• History of congenital QTc prolongation or QTc prolongation (screening ECG with QTcF ≥ 450 msec for men and QTcF ≥ 470 msec for women).

• Hypothyroidism or hyperthyroidism, unless stabilized on appropriate pharmacotherapy with no change in dosage for at least 1 month before Visit 1.

• History of seizure disorder, stroke, significant head injury, tumor of the central nervous system, or any other condition that predisposes to seizure.

• Known human immunodeficiency virus (HIV) infection.

• Positive hepatitis C antibody on screening, with the exception of participants for whom the reflex hepatitis C virus ribonucleic acid (HCV RNA) test is negative.

• Positive test for hepatitis B surface antigen and/or hepatitis B core antibody immunoglobulin M.

• Screening liver enzyme test (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) results > 2 times the upper limit of normal (ULN).

Other Criteria

• Current enrollment in an investigational drug or device study or participation in such a study within 6 months of entry into this study.

• Employee, or immediate relative of an employee, of the sponsor, any of its affiliates or partners, or the study center.

• Inability to speak, read, and understand the English language sufficiently to understand the nature of the study, to provide written informed consent, or to allow the completion of all study assessments.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Health Initiatives Research PLLC	Fayetteville	Arkansas	United States	72703
2	Synexus US - Cerritos	Cerritos	California	United States	90703
3	Wake Research - Pharmacology Research Institute	Encino	California	United States	91316
4	Wake Research - Pharmacology Research Institute	Newport Beach	California	United States	92660
5	Pacific Research Partners, LLC	Oakland	California	United States	94607
6	North County Clinical Research, Inc.	Oceanside	California	United States	92054
7	Collaborative Neuroscience Network	Torrance	California	United States	90502
8	Elite Clinical Trials, Inc.	Wildomar	California	United States	92595
9	Synexus US - Atlanta	Atlanta	Georgia	United States	30328
10	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30331
11	Pillar Clinical Research	Lincolnwood	Illinois	United States	60712
12	Boston Clinical Trials	Boston	Massachusetts	United States	02131
13	Hassman Research Institute	Berlin	New Jersey	United States	08009
14	Center for Emotional Fitness	Cherry Hill	New Jersey	United States	08002
15	Neurobehavioral Research, Inc	Cedarhurst	New York	United States	11516
16	Synexus US - Queens	Jamaica	New York	United States	11432
17	Eastside Comprehensive Medical Center	New York	New York	United States	10128
18	Finger Lakes Clinical Research	Rochester	New York	United States	14618
19	Neuro-Behavioral Clinical Research, Inc	North Canton	Ohio	United States	44720
20	IPS Research	Oklahoma City	Oklahoma	United States	73106
21	Clinical Neuroscience Solutions, Inc - Memphis, TN	Memphis	Tennessee	United States	38119
22	Research Strategies of Memphis, LLC	Memphis	Tennessee	United States	38119
23	Donald J. Garcia, Jr., MD, PA	Austin	Texas	United States	78737
24	FutureSearch Trials of Dallas, LP	Dallas	Texas	United States	75231
25	Northwest Clinical Research Center	Bellevue	Washington	United States	98007

Sponsors and Collaborators

• Gate Neurosciences, Inc

Investigators

• Study Director: Ronald M Burch, MD PhD, Gate Neurosciences, Inc

Study Documents (Full-Text)

• Study Protocol - May 1, 2019
• Statistical Analysis Plan - Aug 3, 2018

More Information

Publications

None provided.

• Responsible Party: Gate Neurosciences, Inc
• ClinicalTrials.gov Identifier: NCT03586427
• Other Study ID Numbers: 3125-201-002
• First Posted: Jul 13, 2018
• Last Update Posted: Aug 3, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

Participant Flow

Pre-assignment Detail	After providing written consent, participants entered a single-blind placebo lead-in screening period of up to 7 days. Participants received single-blind placebo during the screening period. Participants meeting the eligibility criteria at the end of the screening period were randomized into one of the 5 treatment groups and entered the double-blind treatment period.

Arm/Group Title	AGN-241751 Dose 1	AGN-241751 Dose 2	AGN-241751 Dose 3	AGN-241751 Dose 4	Placebo
Arm/Group Description	AGN-241751 Dose Level 1: 0.25 mg weekly for 3 weeks	AGN-241751 Dose Level 2: 1 mg weekly for 3 weeks	AGN-241751 Dose Level 3: 3 mg weekly for 3 weeks	AGN-241751 Dose Level 4: 10 mg weekly for 3 weeks	Placebo: Placebo administered weekly as a single tablet and daily to all groups except for drug day one time each week
Period Title: Overall Study
STARTED	48	50	52	50	51
COMPLETED	48	46	46	46	46
NOT COMPLETED	0	4	6	4	5

Baseline Characteristics

Arm/Group Title	AGN-241751 Dose 1	AGN-241751 Dose 2	AGN-241751 Dose 3	AGN-241751 Dose 4	Placebo	Total
Arm/Group Description	AGN-241751 0.25 mg administered as 1 tablet taken orally one time each week for 3 weeks Placebo administered as 1 tablet taken orally every day except days AGN-214751 was taken	AGN-241751 1 mg administered as 1 tablet taken orally one time each week for 3 weeks Placebo administered as 1 tablet taken orally every day except days AGN-214751 was taken	AGN-241751 3 mg administered as 1 tablet taken orally one time each week for 3 weeks Placebo administered as 1 tablet taken orally every day except days AGN-214751 was taken	AGN-241751 10 mg administered as 1 tablet taken orally one time each week for 3 weeks Placebo administered as 1 tablet taken orally every day except days AGN-214751 was taken	Placebo administered as 1 tablet taken orally every day	Total of all reporting groups
Overall Participants	48	50	52	50	51	251
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.8 (14.02)	41.8 (13.53)	42.2 (14.23)	42.9 (13.48)	40.0 (14.49)	41.7 (13.88)
Sex: Female, Male (Count of Participants)
Female	33 68.8%	15 30%	16 30.8%	20 40%	30 58.8%	114 45.4%
Male	15 31.3%	35 70%	36 69.2%	30 60%	21 41.2%	137 54.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	1 2%	1 0.4%
Asian	3 6.3%	1 2%	1 1.9%	2 4%	1 2%	8 3.2%
Native Hawaiian or Other Pacific Islander	1 2.1%	0 0%	0 0%	0 0%	0 0%	1 0.4%
Black or African American	18 37.5%	24 48%	22 42.3%	15 30%	20 39.2%	99 39.4%
White	24 50%	24 48%	28 53.8%	32 64%	27 52.9%	135 53.8%
More than one race	1 2.1%	1 2%	1 1.9%	0 0%	2 3.9%	5 2%
Unknown or Not Reported	1 2.1%	0 0%	0 0%	1 2%	0 0%	2 0.8%
Region of Enrollment (participants) [Number]
United States	48 100%	50 100%	52 100%	50 100%	51 100%	251 100%
Current antidepressant usage (Count of Participants)
Count of Participants [Participants]	7 14.6%	13 26%	13 25%	13 26%	11 21.6%	57 22.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Description	The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.
Time Frame	Baseline to Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AGN-241751 Dose 1	AGN-241751 Dose 2	AGN-241751 Dose 3	AGN-241751 Dose 4	Placebo
Arm/Group Description	AGN-241751 Dose 1 administered as 1 tablet taken orally every day AGN-241751: AGN-241751 administered orally as a single tablet	AGN-241751 Dose 2 administered as 1 tablet taken orally every day AGN-241751: AGN-241751 administered orally as a single tablet	AGN-241751 Dose 3 administered as 1 tablet taken orally every day AGN-241751: AGN-241751 administered orally as a single tablet	AGN-241751 Dose 4 administered as 1 tablet taken orally every day AGN-241751: AGN-241751 administered orally as a single tablet	Placebo administered as 1 tablet taken orally every day Placebo: Placebo administered orally as a single tablet
Measure Participants	48	50	52	50	51
Least Squares Mean (Standard Error) [score on a scale]	-8.6 (1.21)	-8.0 (1.19)	-9.5 (1.18)	-10.6 (1.18)	-7.7 (1.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AGN-241751 Dose 1, AGN-241751 Dose 2, AGN-241751 Dose 3, AGN-241751 Dose 4, Placebo
	Comments	Each dose group was compared to placebo
	Type of Statistical Test	Other
	Comments	Mixed model of repeated measures least square estimates of change compared to placebo
Statistical Test of Hypothesis	p-Value	>0.05
	Comments	Comparison of each dose level change from baseline to placebo baseline yielded P values >0.05
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Change From Baseline in MADRS Total Score at Week 3
Description	The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.
Time Frame	Baseline to Week 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AGN-241751 Dose 1	AGN-241751 Dose 2	AGN-241751 Dose 3	AGN-241751 Dose 4	Placebo
Arm/Group Description	AGN-241751 Dose Level 1: 0.25 mg weekly for 3 weeks	AGN-241751 Dose Level 2: 1 mg weekly for 3 weeks	AGN-241751 Dose Level 3: 3 mg weekly for 3 weeks	AGN-241751 Dose Level 4: 10 mg weekly for 3 weeks	Placebo: Placebo administered weekly as a single tablet and daily to all groups except for drug day one time each week
Measure Participants	48	50	52	50	51
Least Squares Mean (Standard Error) [score on a scale]	-11.5 (1.56)	-12.5 (1.54)	-14.1 (1.55)	-13.5 (1.54)	-13.6 (1.54)

Adverse Events

Time Frame	4 weeks
Arm/Group Title	AGN-241751 Dose 1		AGN-241751 Dose 2		AGN-241751 Dose 3		AGN-241751 Dose 4		Placebo
Arm/Group Description	AGN-241751 Dose Level 1: 0.25 mg weekly for 3 weeks		AGN-241751 Dose Level 2: 1 mg weekly for 3 weeks		AGN-241751 Dose Level 3: 3 mg weekly for 3 weeks		AGN-241751 Dose Level 4: 10 mg weekly for 3 weeks		Placebo: Placebo administered weekly as a single tablet and daily to all groups except for drug day one time each week
All Cause Mortality
	AGN-241751 Dose 1		AGN-241751 Dose 2		AGN-241751 Dose 3		AGN-241751 Dose 4		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		0/50 (0%)		0/52 (0%)		0/50 (0%)		0/51 (0%)
Serious Adverse Events
	AGN-241751 Dose 1		AGN-241751 Dose 2		AGN-241751 Dose 3		AGN-241751 Dose 4		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		0/50 (0%)		0/52 (0%)		0/50 (0%)		0/51 (0%)
Other (Not Including Serious) Adverse Events
	AGN-241751 Dose 1		AGN-241751 Dose 2		AGN-241751 Dose 3		AGN-241751 Dose 4		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/48 (35.4%)		18/50 (36%)		12/52 (23.1%)		19/50 (38%)		16/51 (31.4%)
Gastrointestinal disorders
Nausea	1/48 (2.1%)	1	3/50 (6%)	3	2/52 (3.8%)	2	1/50 (2%)	1	2/51 (3.9%)	2
Dry Mouth	0/48 (0%)	0	1/50 (2%)	1	0/52 (0%)	0	3/50 (6%)	3	1/51 (2%)	1
Diarrhea	2/48 (4.2%)	2	0/50 (0%)	0	0/52 (0%)	0	1/50 (2%)	1	0/51 (0%)	0
Infections and infestations
Upper Respiratory Tract Infection	2/48 (4.2%)	2	1/50 (2%)	1	1/52 (1.9%)	1	2/50 (4%)	2	1/51 (2%)	1
Nasopharyngitis	1/48 (2.1%)	1	2/50 (4%)	2	0/52 (0%)	0	2/50 (4%)	2	1/51 (2%)	1
Viral Upper Respiratory Infection	2/48 (4.2%)	2	0/50 (0%)	0	0/52 (0%)	0	0/50 (0%)	0	0/51 (0%)	0
Nervous system disorders
Headache	3/48 (6.3%)	3	3/50 (6%)	3	3/52 (5.8%)	3	2/50 (4%)	2	4/51 (7.8%)	4
Somnolence	2/48 (4.2%)	2	1/50 (2%)	1	0/52 (0%)	0	1/50 (2%)	1	2/51 (3.9%)	2
Dizziness	2/48 (4.2%)	2	0/50 (0%)	0	3/52 (5.8%)	3	3/50 (6%)	3	2/51 (3.9%)	2
Sedation	2/48 (4.2%)	2	0/50 (0%)	0	0/52 (0%)	0	1/50 (2%)	1	2/51 (3.9%)	2
Insomnia	0/48 (0%)	0	5/50 (10%)	5	0/52 (0%)	0	1/50 (2%)	1	1/51 (2%)	1
Psychiatric disorders
Anxiety	0/48 (0%)	0	1/50 (2%)	1	3/52 (5.8%)	3	1/50 (2%)	1	0/51 (0%)	0
Abnormal dreams	0/48 (0%)	0	1/50 (2%)	1	0/52 (0%)	0	2/50 (4%)	2	0/51 (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.