A Study in Pediatric Participants With Generalized Anxiety Disorder

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01226511
• Collaborator: (none)
• Enrollment: 281
• Locations: 24
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 11.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to find out if duloxetine [30-120 milligrams (mg)] given once a day by mouth for 10 weeks to children and adolescents, is better than placebo when treating Generalized Anxiety Disorder (GAD).

Condition or Disease	Intervention/Treatment	Phase
Anxiety Neuroses; Anxiety States, Neurotic; Neuroses, Anxiety	Drug: Duloxetine; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 281 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Efficacy and Safety Study of Duloxetine Versus Placebo in the Treatment of Children and Adolescents With Generalized Anxiety Disorder
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Duloxetine 30-120 mg flexible dosing once daily for 10 weeks. At the end of the 10 week blinded treatment period, participants may participate in an 18 week extension	Drug: Duloxetine; Administered orally; Other Names: Cymbalta LY248686
Placebo Comparator: Placebo Administered once daily for 10 weeks. At the end of the 10 week blinded treatment period, placebo participants receive duloxetine in the 18 week extension	Drug: Duloxetine; Administered orally; Other Names: Cymbalta LY248686 ; Drug: Placebo; Administered orally

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to 10-Week Endpoint in the Pediatric Anxiety Rating Scale (PARS) Severity Score Evaluated for Symptoms Identified on the Generalized Anxiety Subsection of the PARS Symptom Checklist [Baseline, 10 weeks]

   PARS severity score for GAD was assessed for all symptoms identified in the generalized anxiety section of the PARS symptom checklist. PARS severity score for GAD was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 7); each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity scores for GAD ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for baseline, pooled investigator, age category, visit, treatment, treatment*visit, age category*visit, and baseline*visit.

Secondary Outcome Measures

1. Response Rate at Endpoint for Generalized Anxiety Disorder (GAD) Using Pediatric Anxiety Rating Scale (PARS) Severity Score for GAD [Baseline, 10 weeks]

   Response rate was defined as the percentage of participants having a 50% improvement from baseline to endpoint on the PARS severity score for GAD. PARS severity score for GAD was assessed for all symptoms identified in the generalized anxiety section of the PARS symptom checklist. PARS severity score for GAD was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 7); each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity scores for GAD ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity.

2. Change From Baseline to 10-Week Endpoint on the Pediatric Anxiety Rating Scale (PARS) Severity Total Score Evaluated for All Symptoms Identified on the PARS Symptom Checklist Symptoms [Baseline, 10 weeks]

   PARS severity total score was assessed for all symptoms identified on the PARS symptom checklist. PARS severity total score was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 7); each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity total scores ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for treatment, pooled investigator, visit, baseline, age category, treatment*visit, baseline*visit, and age category*visit.

3. Change From Baseline to 10-Week Endpoint on the Clinical Global Impression of Severity (CGI-S) Scale [Baseline, 10 weeks]

   The CGI-S scale evaluated the severity of illness at the time of assessment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicated a greater severity of illness. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for treatment, pooled investigator, visit, baseline, age category, treatment*visit, baseline*visit, and age category*visit.

4. Remission Rate at Endpoint for Generalized Anxiety Disorder (GAD) Using Clinical Global Impressions of Severity (CGI-S) Scale [10 weeks]

   Remission rate was defined as the percentage of participants having a CGI-S score ≤2 at endpoint. The CGI-S scale evaluated the severity of illness at the time of assessment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicated a greater severity of illness.

5. Change From Baseline to 10-Week Endpoint in the Children's Global Assessment Scale (CGAS) [Baseline, 10 weeks]

   The CGAS was a clinician-rated assessment of general functioning. CGAS raw scores ranged from 1 (greatest impairment) to 100 (superior functioning). Lower scores indicated a lower level of functioning and greater impairment. Least squares (LS) mean from an analysis of covariance (ANCOVA) was adjusted for treatment, pooled investigator, baseline, and age category.

6. Percentage of Participants During the 10-Week Period With Treatment-Emergent (New or Worsening) Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) [Baseline up to 10 weeks]

   The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Results reported as percentage of participants with treatment-emergent (new or worsening) suicidal ideation from baseline=(number of participants with changes compared to baseline/total number of participants at risk)*100.

7. Percentage of Participants During the 10-Week Period With Treatment-Emergent (New or Worsening) Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) [Baseline up to 10 weeks]

   The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Reported as percentage of participants with treatment-emergent (new or worsening) suicidal behavior from baseline=(number of participants with changes compared to baseline/total number of participants at risk)*100.

8. Change From 10-Week to 28-Week Endpoint in the Pediatric Anxiety Rating Scale (PARS) Severity Score Evaluated for Symptoms Identified on the Generalized Anxiety Subsection of the PARS Symptom Checklist [10 weeks, 28 weeks]

   PARS severity score for GAD was assessed for all symptoms identified in the generalized anxiety section of the PARS symptom checklist. PARS severity score for GAD was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 7); each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity scores for GAD ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for pooled investigator, visit, baseline, age category, baseline*visit, and age category*visit within reporting groups.

9. Change From 10-Week to 28-Week Endpoint on the Pediatric Anxiety Rating Scale (PARS) Severity Total Score Evaluated for All Symptoms Identified on the PARS Symptom Checklist Symptoms [10 weeks, 28 weeks]

   PARS severity total score was assessed for all symptoms identified on the PARS symptom checklist. PARS severity total score was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 7); each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity total scores ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for pooled investigator, visit, baseline, age category, baseline*visit, and age category*visit within reporting groups.

10. Change From 10-Week to 28-Week Endpoint on the Clinical Global Impression of Severity (CGI-S) Scale [10 weeks, 28 weeks]

    The CGI-S scale evaluated the severity of mental illness at the time of assessment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicated a greater severity of illness. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for pooled investigator, visit, baseline, age category, baseline*visit, and age category*visit within reporting groups.

11. Change From 10-Week to 28-Week Endpoint in the Children's Global Assessment Scale (CGAS) [10 weeks, 28 weeks]

    The CGAS was a clinician-rated assessment of general functioning. CGAS raw scores ranged from 1 (greatest impairment) to 100 (superior functioning). Lower scores indicated a lower level of functioning and greater impairment. Least squares (LS) mean from an analysis of covariance (ANCOVA) was adjusted for pooled investigator, baseline, and age category within reporting groups.

12. Percentage of Participants During the 18-Week Extension Period With Treatment-Emergent (New or Worsening) Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) [10 weeks up to 28 weeks]

    The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Results reported as percentage of participants with treatment-emergent (new or worsening) suicidal ideation from baseline=(number of participants with changes compared to baseline/total number of participants at risk)*100.

13. Percentage of Participants During the 18-Week Extension Period With Treatment-Emergent (New or Worsening) Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) [10 weeks up to 28 weeks]

    The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Reported as percentage of participants with treatment-emergent (new or worsening) suicidal behavior from baseline=(number of participants with changes compared to baseline/total number of participants at risk)*100.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with GAD on clinical exam as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and supported by the Mini International Neuropsychiatric Interview for children and adolescents (MINI-Kid)

• Diagnosis of moderate or greater severity of GAD as determined by the following:

• Presence of 4 or more symptoms identified on the generalized anxiety subsection of the Pediatric Anxiety Rating Scale (PARS) symptom checklist at screening and randomization. Two of which are excessive worry and dread or fearful anticipation (nonspecific)

• PARS severity score of 15 or more at screening and randomization for symptoms identified on the generalized anxiety subsection of PARS symptom checklist at screening and randomization

• Clinical Global Impressions of Severity (CGI-S) rating of 4 or more at screening and randomization

• Presence of significant social, academic, and/or familial dysfunction as determined by the Children's Global Assessment Scale (CGAS) score of 60 or less at screening and randomization

• Female participants must test negative for pregnancy during screening Furthermore, female participants must agree to abstain from sexual activity or to use a reliable method of birth control as determined by the investigator during the study

• Participant's parent/legal representative and participant, if capable, are judged to be reliable by the investigator to keep all appointments for clinical visits, tests, and procedures required by the protocol

• Participant's parent/legal representative and participant, if capable, must have a degree of understanding such that they can communicate intelligently with the investigator and study coordinator

• Participants must be capable of swallowing study drug whole (without opening the capsule, crushing, dissolving, dividing, et cetera)

• Participants must have venous access sufficient to allow blood sampling and are compliant with blood draws as per the protocol

Exclusion Criteria:

• Current diagnosis of major depressive disorder (MDD)

• Participants for whom the primary focus of treatment is separation anxiety or social phobia (participants with secondary separation anxiety or social phobia are allowed to participate)

• Have current primary diagnosis of any DSM-IV-TR Axis I disorder except GAD, or a current secondary DSM-IV-TR Axis 1 disorder that requires any pharmacologic treatment (other than those disorders listed below). Primary is defined as the disorder that is the primary focus of treatment

• Have a history of DSM-IV-TR-defined substance abuse or dependence within the past year, excluding caffeine and nicotine

• Have a current or previous diagnosis of bipolar disorder, psychotic depression, schizophrenia or other psychotic disorder, anorexia, bulimia, obsessive compulsive disorder, post-traumatic stress disorder, panic disorder, or pervasive development disorder, as judged by the investigator

• Have 1 or more first-degree relatives (parents or siblings) with diagnosed bipolar I disorder

• Have a serious or unstable medical illness, psychological condition, clinically significant laboratory or electrocardiogram (ECG) result, hypersensitivity to duloxetine, or its active ingredients, frequent or severe allergic reactions to multiple medications, uncontrolled narrow-angle glaucoma, acute liver injury (for example, hepatitis) or severe cirrhosis (Child-Pugh Class C), or a history of any seizure disorder (other than febrile seizures)

• Have a significant suicide attempt within 1 year of screening or are currently at risk of suicide in the opinion of the investigator

• Have initiated, stopped, or changed the type or intensity of psychotherapy within 6 weeks prior to screening. Participants who require a change to psychotherapy between weeks 1 through 10 will be excluded

• Have a weight less than 20 kilograms at any time during the screening period

• Female participants who are pregnant, nursing or have recently given birth

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hialeah	Florida	United States	33013
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Smyrna	Georgia	United States	30080
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Libertyville	Illinois	United States	60048
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lexington	Kentucky	United States	40509
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Troy	Michigan	United States	48083
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gladstone	Missouri	United States	64118
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Omaha	Nebraska	United States	68198
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cherry Hill	New Jersey	United States	08002
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	New York	New York	United States	10032
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rochester	New York	United States	14618
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cincinnati	Ohio	United States	45219
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cleveland	Ohio	United States	44106
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oklahoma City	Oklahoma	United States	73103
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Richmond	Virginia	United States	23230
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bellevue	Washington	United States	98007
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Spokane	Washington	United States	99202
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Insurgentes Cuicuilco		Mexico	04530
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mexico City		Mexico	14080
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Monterrey		Mexico	64060
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	San Luis Potosi		Mexico	78200
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Zona Centro		Mexico	37000
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bloemfontein		South Africa	9301
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cape Town		South Africa	7530
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pretoria		South Africa	0042

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01226511
• Other Study ID Numbers: 12929; F1J-MC-HMGI
• First Posted: Oct 22, 2010
• Last Update Posted: Mar 5, 2014
• Last Verified: Jan 1, 2014

• Additional relevant MeSH terms: Anxiety Disorders; Neurotic Disorders; Duloxetine Hydrochloride

Study Results

Participant Flow

Pre-assignment Detail	This study had 4 periods: Screening period (1-week), acute treatment period (10-week, double-blind period with flexible duloxetine dosing), extension treatment (18-week period, of which 16 weeks were open-label treatment with flexible duloxetine dosing), and a taper period (2 weeks recommended at discontinuation from study any point after Week 2).

Arm/Group Title	Duloxetine/Duloxetine	Placebo/Duloxetine
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period. Duloxetine was provided in 30-mg capsules. Participants who received higher doses of duloxetine at the end of treatment period participation received gradually lower doses of duloxetine over the 2-week recommended tapering period, and participants who received the lowest dose of duloxetine or placebo at the end of treatment period participation received placebo over the 2-week recommended tapering period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period. Duloxetine was provided in 30-mg capsules. Participants who received higher doses of duloxetine at the end of treatment period participation received gradually lower doses of duloxetine over the 2-week recommended tapering period, and participants who received the lowest dose of duloxetine or placebo at the end of treatment period participation received placebo over the 2-week recommended tapering period.
Period Title: Acute Treatment Period
STARTED	140	141
COMPLETED	108	110
NOT COMPLETED	32	31
Period Title: Acute Treatment Period
STARTED	108	110
COMPLETED	81	83
NOT COMPLETED	27	27
Period Title: Acute Treatment Period
STARTED	51	57
COMPLETED	46	54
NOT COMPLETED	5	3

Baseline Characteristics

Arm/Group Title	Duloxetine/Duloxetine	Placebo/Duloxetine	Total
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period. Duloxetine was provided in 30-mg capsules. Participants who received higher doses of duloxetine at the end of treatment period participation received gradually lower doses of duloxetine over the 2-week recommended tapering period, and participants who received the lowest dose of duloxetine or placebo at the end of treatment period participation received placebo over the 2-week recommended tapering period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period. Duloxetine was provided in 30-mg capsules. Participants who received higher doses of duloxetine at the end of treatment period participation received gradually lower doses of duloxetine over the 2-week recommended tapering period, and participants who received the lowest dose of duloxetine or placebo at the end of treatment period participation received placebo over the 2-week recommended tapering period.	Total of all reporting groups
Overall Participants	135	137	272
Age, Customized (participants) [Number]
7 to 11 years	62 45.9%	66 48.2%	128 47.1%
12 to 17 years	73 54.1%	71 51.8%	144 52.9%
Sex: Female, Male (Count of Participants)
Female	70 51.9%	75 54.7%	145 53.3%
Male	65 48.1%	62 45.3%	127 46.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	37 27.4%	40 29.2%	77 28.3%
Not Hispanic or Latino	88 65.2%	88 64.2%	176 64.7%
Unknown or Not Reported	10 7.4%	9 6.6%	19 7%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	7 5.2%	6 4.4%	13 4.8%
Asian	1 0.7%	1 0.7%	2 0.7%
Black or African American	9 6.7%	10 7.3%	19 7%
White	112 83%	111 81%	223 82%
More than 1 race	6 4.4%	9 6.6%	15 5.5%
Region of Enrollment (participants) [Number]
United States	98 72.6%	99 72.3%	197 72.4%
Mexico	26 19.3%	26 19%	52 19.1%
South Africa	11 8.1%	12 8.8%	23 8.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to 10-Week Endpoint in the Pediatric Anxiety Rating Scale (PARS) Severity Score Evaluated for Symptoms Identified on the Generalized Anxiety Subsection of the PARS Symptom Checklist
Description	PARS severity score for GAD was assessed for all symptoms identified in the generalized anxiety section of the PARS symptom checklist. PARS severity score for GAD was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 7); each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity scores for GAD ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for baseline, pooled investigator, age category, visit, treatment, treatment*visit, age category*visit, and baseline*visit.
Time Frame	Baseline, 10 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a baseline and at least 1 post-baseline PARS severity score for GAD during the acute treatment period, excluding 9 participants from 1 site with major quality issues.

Arm/Group Title	Duloxetine (Acute Treatment)	Placebo (Acute Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period.
Measure Participants	135	133
Least Squares Mean (Standard Error) [units on a scale]	-9.70 (0.502)	-7.05 (0.500)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Duloxetine (Acute Treatment), Placebo (Acute Treatment)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least squares (LS) mean difference
	Estimated Value	-2.65
	Confidence Interval	(2-Sided) 95%; -4.03 to -1.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.700
	Estimation Comments

2. Secondary Outcome

Title	Response Rate at Endpoint for Generalized Anxiety Disorder (GAD) Using Pediatric Anxiety Rating Scale (PARS) Severity Score for GAD
Description	Response rate was defined as the percentage of participants having a 50% improvement from baseline to endpoint on the PARS severity score for GAD. PARS severity score for GAD was assessed for all symptoms identified in the generalized anxiety section of the PARS symptom checklist. PARS severity score for GAD was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 7); each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity scores for GAD ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity.
Time Frame	Baseline, 10 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a baseline and at least 1 post-baseline PARS severity score for GAD [last observation carried forward (LOCF)] during the acute treatment period, excluding 9 participants from 1 site with major quality issues.

Arm/Group Title	Duloxetine (Acute Treatment)	Placebo (Acute Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period.
Measure Participants	135	133
Number [percentage of participants]	51 (4.8) 37.8%	37 (4.8) 27%

3. Secondary Outcome

Title	Change From Baseline to 10-Week Endpoint on the Pediatric Anxiety Rating Scale (PARS) Severity Total Score Evaluated for All Symptoms Identified on the PARS Symptom Checklist Symptoms
Description	PARS severity total score was assessed for all symptoms identified on the PARS symptom checklist. PARS severity total score was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 7); each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity total scores ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for treatment, pooled investigator, visit, baseline, age category, treatment*visit, baseline*visit, and age category*visit.
Time Frame	Baseline, 10 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a baseline and at least 1 post-baseline PARS severity total score during the acute treatment period, excluding 9 participants from 1 site with major quality issues.

Arm/Group Title	Duloxetine (Acute Treatment)	Placebo (Acute Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period.
Measure Participants	135	133
Least Squares Mean (Standard Error) [units on a scale]	-9.15 (0.479)	-6.36 (0.477)

4. Secondary Outcome

Title	Change From Baseline to 10-Week Endpoint on the Clinical Global Impression of Severity (CGI-S) Scale
Description	The CGI-S scale evaluated the severity of illness at the time of assessment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicated a greater severity of illness. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for treatment, pooled investigator, visit, baseline, age category, treatment*visit, baseline*visit, and age category*visit.
Time Frame	Baseline, 10 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a baseline and at least 1 post-baseline CGI-S score during the acute treatment period, excluding 9 participants from 1 site with major quality issues.

Arm/Group Title	Duloxetine (Acute Treatment)	Placebo (Acute Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period.
Measure Participants	135	133
Least Squares Mean (Standard Error) [units on a scale]	-1.93 (0.114)	-1.38 (0.113)

5. Secondary Outcome

Title	Remission Rate at Endpoint for Generalized Anxiety Disorder (GAD) Using Clinical Global Impressions of Severity (CGI-S) Scale
Description	Remission rate was defined as the percentage of participants having a CGI-S score ≤2 at endpoint. The CGI-S scale evaluated the severity of illness at the time of assessment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicated a greater severity of illness.
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with at least 1 post-baseline CGI-S score [last observation carried forward (LOCF)] during the acute treatment period, excluding 9 participants from 1 site with major quality issues.

Arm/Group Title	Duloxetine (Acute Treatment)	Placebo (Acute Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period.
Measure Participants	135	133
Number [percentage of participants]	45 33.3%	30 21.9%

6. Secondary Outcome

Title	Change From Baseline to 10-Week Endpoint in the Children's Global Assessment Scale (CGAS)
Description	The CGAS was a clinician-rated assessment of general functioning. CGAS raw scores ranged from 1 (greatest impairment) to 100 (superior functioning). Lower scores indicated a lower level of functioning and greater impairment. Least squares (LS) mean from an analysis of covariance (ANCOVA) was adjusted for treatment, pooled investigator, baseline, and age category.
Time Frame	Baseline, 10 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a baseline and at least 1 post-baseline [last observation carried forward (LOCF)] CGAS score during the acute treatment period, excluding 9 participants from 1 site with major quality issues.

Arm/Group Title	Duloxetine (Acute Treatment)	Placebo (Acute Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period.
Measure Participants	123	124
Least Squares Mean (Standard Error) [units on a scale]	17.14 (1.232)	12.16 (1.219)

7. Secondary Outcome

Title	Percentage of Participants During the 10-Week Period With Treatment-Emergent (New or Worsening) Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description	The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Results reported as percentage of participants with treatment-emergent (new or worsening) suicidal ideation from baseline=(number of participants with changes compared to baseline/total number of participants at risk)*100.
Time Frame	Baseline up to 10 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a baseline and at least 1 post-baseline C-SSRS suicidal ideation score during the acute treatment period, whose baseline maximum C-SSRS suicidal ideation score was <5. Nine (9) participants from 1 site with major quality issues were excluded.

Arm/Group Title	Duloxetine (Acute Treatment)	Placebo (Acute Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period.
Measure Participants	135	134
Number [percentage of participants]	5.9 4.4%	5.2 3.8%

8. Secondary Outcome

Title	Percentage of Participants During the 10-Week Period With Treatment-Emergent (New or Worsening) Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description	The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Reported as percentage of participants with treatment-emergent (new or worsening) suicidal behavior from baseline=(number of participants with changes compared to baseline/total number of participants at risk)*100.
Time Frame	Baseline up to 10 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a baseline and at least 1 post-baseline C-SSRS suicidal behavior score during the acute treatment period, excluding 9 participants from 1 site with major quality issues.

Arm/Group Title	Duloxetine (Acute Treatment)	Placebo (Acute Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period.
Measure Participants	135	134
Number [percentage of participants]	0.0 0%	0.0 0%

9. Secondary Outcome

Title	Change From 10-Week to 28-Week Endpoint in the Pediatric Anxiety Rating Scale (PARS) Severity Score Evaluated for Symptoms Identified on the Generalized Anxiety Subsection of the PARS Symptom Checklist
Description	PARS severity score for GAD was assessed for all symptoms identified in the generalized anxiety section of the PARS symptom checklist. PARS severity score for GAD was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 7); each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity scores for GAD ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for pooled investigator, visit, baseline, age category, baseline*visit, and age category*visit within reporting groups.
Time Frame	10 weeks, 28 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a PARS severity score for GAD during the acute treatment period and at least 1 PARS severity score for GAD during the extension treatment period, excluding 9 participants from 1 site with major quality issues.

Arm/Group Title	Duloxetine/Duloxetine (Extension Treatment)	Placebo/Duloxetine (Extension Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period.
Measure Participants	104	105
Least Squares Mean (Standard Error) [units on a scale]	-3.33 (0.352)	-5.15 (0.452)

10. Secondary Outcome

Title	Change From 10-Week to 28-Week Endpoint on the Pediatric Anxiety Rating Scale (PARS) Severity Total Score Evaluated for All Symptoms Identified on the PARS Symptom Checklist Symptoms
Description	PARS severity total score was assessed for all symptoms identified on the PARS symptom checklist. PARS severity total score was derived by summing 5 of 7 severity/impairment/interference items (2, 3, 5, 6, 7); each item ranged from 0 (none) to 5 (extreme severity/impairment/interference). PARS severity total scores ranged from 0 (none) to 25 (extreme severity), with a score of 15 indicating moderate illness severity. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for pooled investigator, visit, baseline, age category, baseline*visit, and age category*visit within reporting groups.
Time Frame	10 weeks, 28 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a PARS severity total score during the acute treatment period and at least 1 PARS severity total score during the extension treatment period, excluding 9 participants from 1 site with major quality issues.

Arm/Group Title	Duloxetine/Duloxetine (Extension Treatment)	Placebo/Duloxetine (Extension Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period.
Measure Participants	104	105
Least Squares Mean (Standard Error) [units on a scale]	-3.32 (0.357)	-5.26 (0.432)

11. Secondary Outcome

Title	Change From 10-Week to 28-Week Endpoint on the Clinical Global Impression of Severity (CGI-S) Scale
Description	The CGI-S scale evaluated the severity of mental illness at the time of assessment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicated a greater severity of illness. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach adjusted for pooled investigator, visit, baseline, age category, baseline*visit, and age category*visit within reporting groups.
Time Frame	10 weeks, 28 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a CGI-S score during the acute treatment period and at least 1 CGI-S score during the extension treatment period, excluding 9 participants from 1 site with major quality issues.

Arm/Group Title	Duloxetine/Duloxetine (Extension Treatment)	Placebo/Duloxetine (Extension Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period.
Measure Participants	104	105
Least Squares Mean (Standard Error) [units on a scale]	-0.76 (0.093)	-1.17 (0.088)

12. Secondary Outcome

Title	Change From 10-Week to 28-Week Endpoint in the Children's Global Assessment Scale (CGAS)
Description	The CGAS was a clinician-rated assessment of general functioning. CGAS raw scores ranged from 1 (greatest impairment) to 100 (superior functioning). Lower scores indicated a lower level of functioning and greater impairment. Least squares (LS) mean from an analysis of covariance (ANCOVA) was adjusted for pooled investigator, baseline, and age category within reporting groups.
Time Frame	10 weeks, 28 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a CGAS score during the acute treatment period and at least 1 CGAS score during the extension treatment period [last observation carried forward (LOCF)], excluding 9 participants from 1 site with major quality issues.

Arm/Group Title	Duloxetine/Duloxetine (Extension Treatment)	Placebo/Duloxetine (Extension Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period.
Measure Participants	103	105
Least Squares Mean (Standard Error) [units on a scale]	7.32 (1.19)	10.48 (1.03)

13. Secondary Outcome

Title	Percentage of Participants During the 18-Week Extension Period With Treatment-Emergent (New or Worsening) Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description	The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Results reported as percentage of participants with treatment-emergent (new or worsening) suicidal ideation from baseline=(number of participants with changes compared to baseline/total number of participants at risk)*100.
Time Frame	10 weeks up to 28 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a C-SSRS suicidal ideation score <5 at the last 2 visits in the acute treatment period and at least 1 C-SSRS suicidal ideation score during the extension treatment period. Nine (9) participants from 1 site with major quality issues were excluded.

Arm/Group Title	Duloxetine/Duloxetine (Extension Treatment)	Placebo/Duloxetine (Extension Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period.
Measure Participants	104	105
Number [percentage of participants]	3 2.2%	3 2.2%

14. Secondary Outcome

Title	Percentage of Participants During the 18-Week Extension Period With Treatment-Emergent (New or Worsening) Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description	The C-SSRS captured occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Reported as percentage of participants with treatment-emergent (new or worsening) suicidal behavior from baseline=(number of participants with changes compared to baseline/total number of participants at risk)*100.
Time Frame	10 weeks up to 28 weeks

Outcome Measure Data

Analysis Population Description

Randomized participants with a C-SSRS suicidal behavior score at the last 2 visits in the acute treatment period and at least 1 C-SSRS suicidal behavior score during the extension treatment period, excluding 9 participants from 1 site with major quality issues.

Arm/Group Title	Duloxetine/Duloxetine (Extension Treatment)	Placebo/Duloxetine (Extension Treatment)
Arm/Group Description	Participants received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period.	Participants received placebo capsules orally, QD for 10 weeks during the acute treatment period and flexible doses of duloxetine 30 to 120 mg orally, QD for 18 weeks during the optional extension treatment period.
Measure Participants	104	105
Number [percentage of participants]	0 0%	2 1.5%

Adverse Events

Adverse Event Reporting Description	Serious adverse events (SAEs) and non-serious AEs were reported for all randomized participants, excluding 9 participants from 1 site with major quality issues.
Arm/Group Title	Duloxetine		Placebo		Duloxetine/Duloxetine-Extension Treatment		Placebo/Duloxetine-Extension Treatment		Duloxetine-Taper		Placebo-Taper
Arm/Group Description	Adverse events (AEs) during the acute treatment period for participants who received flexible doses of duloxetine 30 to 120 milligrams (mg) orally, once daily (QD) for 10 weeks.		AEs during the acute treatment period for participants who received placebo capsules orally, QD for 10 weeks.		AEs during the extension treatment period for participants who received flexible doses of duloxetine 30 to 120 mg orally, QD during both the acute and extension treatment periods (up to 28 weeks).		AEs during the extension treatment period for participants who received placebo capsules orally, QD during the acute treatment period (10 weeks) and flexible doses of duloxetine 30 to 120 mg orally, QD during the extension treatment period (up to 18 weeks).		AEs during the taper period for participants who were dispensed duloxetine prior to entering the taper phase. Participants who received higher doses of duloxetine at the end of treatment period participation received gradually lower doses of duloxetine over the 2-week recommended tapering period.		AEs during the taper period for participants who were dispensed placebo prior to entering the taper phase. Participants who received the lowest dose of duloxetine or placebo at the end of treatment period participation received placebo over the 2-week recommended tapering period.
All Cause Mortality
	Duloxetine		Placebo		Duloxetine/Duloxetine-Extension Treatment		Placebo/Duloxetine-Extension Treatment		Duloxetine-Taper		Placebo-Taper
	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)
Serious Adverse Events
	Duloxetine		Placebo		Duloxetine/Duloxetine-Extension Treatment		Placebo/Duloxetine-Extension Treatment		Duloxetine-Taper		Placebo-Taper
	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	1/135 (0.7%)		0/137 (0%)		2/104 (1.9%)		2/106 (1.9%)		1/97 (1%)		1/7 (14.3%)
Infections and infestations
Adenoiditis	0/135 (0%)	0	0/137 (0%)	0	1/104 (1%)	1	0/106 (0%)	0	0/97 (0%)	0	0/7 (0%)	0
Tonsillitis	0/135 (0%)	0	0/137 (0%)	0	1/104 (1%)	1	0/106 (0%)	0	0/97 (0%)	0	0/7 (0%)	0
Psychiatric disorders
Acute psychosis	0/135 (0%)	0	0/137 (0%)	0	0/104 (0%)	0	1/106 (0.9%)	1	0/97 (0%)	0	0/7 (0%)	0
Bipolar disorder	0/135 (0%)	0	0/137 (0%)	0	0/104 (0%)	0	1/106 (0.9%)	1	0/97 (0%)	0	0/7 (0%)	0
Self-injurious ideation	1/135 (0.7%)	1	0/137 (0%)	0	0/104 (0%)	0	0/106 (0%)	0	0/97 (0%)	0	0/7 (0%)	0
Suicidal ideation	1/135 (0.7%)	1	0/137 (0%)	0	1/104 (1%)	1	0/106 (0%)	0	1/97 (1%)	1	1/7 (14.3%)	1
Other (Not Including Serious) Adverse Events
	Duloxetine		Placebo		Duloxetine/Duloxetine-Extension Treatment		Placebo/Duloxetine-Extension Treatment		Duloxetine-Taper		Placebo-Taper
	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	106/135 (78.5%)		90/137 (65.7%)		73/104 (70.2%)		73/106 (68.9%)		12/97 (12.4%)		1/7 (14.3%)
Cardiac disorders
Palpitations	6/135 (4.4%)	6	0/137 (0%)	0	0/104 (0%)	0	0/106 (0%)	0	0/97 (0%)	0	0/7 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	3/135 (2.2%)	3	4/137 (2.9%)	4	0/104 (0%)	0	0/106 (0%)	0	1/97 (1%)	2	0/7 (0%)	0
Abdominal pain upper	13/135 (9.6%)	15	9/137 (6.6%)	10	5/104 (4.8%)	6	7/106 (6.6%)	7	2/97 (2.1%)	2	0/7 (0%)	0
Constipation	5/135 (3.7%)	6	4/137 (2.9%)	4	0/104 (0%)	0	1/106 (0.9%)	1	0/97 (0%)	0	0/7 (0%)	0
Diarrhoea	9/135 (6.7%)	10	6/137 (4.4%)	6	1/104 (1%)	3	5/106 (4.7%)	6	0/97 (0%)	0	0/7 (0%)	0
Flatulence	1/135 (0.7%)	1	0/137 (0%)	0	0/104 (0%)	0	1/106 (0.9%)	1	0/97 (0%)	0	1/7 (14.3%)	1
Nausea	28/135 (20.7%)	35	8/137 (5.8%)	8	10/104 (9.6%)	10	13/106 (12.3%)	16	1/97 (1%)	1	0/7 (0%)	0
Vomiting	22/135 (16.3%)	23	10/137 (7.3%)	10	5/104 (4.8%)	7	6/106 (5.7%)	6	0/97 (0%)	0	0/7 (0%)	0
General disorders
Chest pain	3/135 (2.2%)	3	0/137 (0%)	0	1/104 (1%)	1	0/106 (0%)	0	0/97 (0%)	0	0/7 (0%)	0
Fatigue	11/135 (8.1%)	11	6/137 (4.4%)	6	4/104 (3.8%)	4	9/106 (8.5%)	9	0/97 (0%)	0	0/7 (0%)	0
Irritability	4/135 (3%)	4	6/137 (4.4%)	6	4/104 (3.8%)	4	3/106 (2.8%)	3	1/97 (1%)	1	0/7 (0%)	0
Pyrexia	2/135 (1.5%)	2	4/137 (2.9%)	5	2/104 (1.9%)	2	2/106 (1.9%)	2	0/97 (0%)	0	0/7 (0%)	0
Infections and infestations
Bronchitis	4/135 (3%)	4	4/137 (2.9%)	4	2/104 (1.9%)	2	1/106 (0.9%)	1	0/97 (0%)	0	0/7 (0%)	0
Ear infection	1/135 (0.7%)	1	2/137 (1.5%)	2	3/104 (2.9%)	3	1/106 (0.9%)	1	0/97 (0%)	0	0/7 (0%)	0
Gastroenteritis	1/135 (0.7%)	1	1/137 (0.7%)	1	1/104 (1%)	1	3/106 (2.8%)	3	1/97 (1%)	1	0/7 (0%)	0
Gastroenteritis viral	4/135 (3%)	4	2/137 (1.5%)	2	1/104 (1%)	1	1/106 (0.9%)	1	0/97 (0%)	0	0/7 (0%)	0
Influenza	4/135 (3%)	4	3/137 (2.2%)	3	6/104 (5.8%)	6	4/106 (3.8%)	4	0/97 (0%)	0	0/7 (0%)	0
Nasopharyngitis	4/135 (3%)	4	12/137 (8.8%)	13	4/104 (3.8%)	4	5/106 (4.7%)	5	0/97 (0%)	0	0/7 (0%)	0
Pharyngitis	3/135 (2.2%)	3	1/137 (0.7%)	1	2/104 (1.9%)	2	2/106 (1.9%)	2	0/97 (0%)	0	0/7 (0%)	0
Pharyngitis streptococcal	1/135 (0.7%)	1	2/137 (1.5%)	2	3/104 (2.9%)	3	2/106 (1.9%)	2	0/97 (0%)	0	0/7 (0%)	0
Sinusitis	1/135 (0.7%)	1	4/137 (2.9%)	4	6/104 (5.8%)	6	5/106 (4.7%)	5	0/97 (0%)	0	0/7 (0%)	0
Upper respiratory tract infection	2/135 (1.5%)	2	4/137 (2.9%)	4	3/104 (2.9%)	4	2/106 (1.9%)	2	0/97 (0%)	0	0/7 (0%)	0
Urinary tract infection	1/135 (0.7%)	1	2/137 (1.5%)	2	3/104 (2.9%)	3	0/106 (0%)	0	0/97 (0%)	0	0/7 (0%)	0
Investigations
Weight decreased	5/135 (3.7%)	5	1/137 (0.7%)	1	0/104 (0%)	0	2/106 (1.9%)	2	0/97 (0%)	0	0/7 (0%)	0
Weight increased	2/135 (1.5%)	2	3/137 (2.2%)	3	2/104 (1.9%)	2	0/106 (0%)	0	0/97 (0%)	0	0/7 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	20/135 (14.8%)	21	7/137 (5.1%)	7	1/104 (1%)	1	9/106 (8.5%)	10	0/97 (0%)	0	0/7 (0%)	0
Increased appetite	2/135 (1.5%)	2	4/137 (2.9%)	4	0/104 (0%)	0	0/106 (0%)	0	0/97 (0%)	0	0/7 (0%)	0
Nervous system disorders
Dizziness	10/135 (7.4%)	10	2/137 (1.5%)	2	5/104 (4.8%)	5	7/106 (6.6%)	9	1/97 (1%)	1	0/7 (0%)	0
Headache	27/135 (20%)	37	23/137 (16.8%)	29	13/104 (12.5%)	17	11/106 (10.4%)	13	3/97 (3.1%)	3	0/7 (0%)	0
Paraesthesia	0/135 (0%)	0	3/137 (2.2%)	3	0/104 (0%)	0	2/106 (1.9%)	2	1/97 (1%)	1	0/7 (0%)	0
Psychomotor hyperactivity	3/135 (2.2%)	3	2/137 (1.5%)	2	1/104 (1%)	1	1/106 (0.9%)	1	0/97 (0%)	0	0/7 (0%)	0
Sedation	3/135 (2.2%)	3	0/137 (0%)	0	0/104 (0%)	0	2/106 (1.9%)	2	0/97 (0%)	0	0/7 (0%)	0
Somnolence	16/135 (11.9%)	16	9/137 (6.6%)	9	3/104 (2.9%)	4	8/106 (7.5%)	11	0/97 (0%)	0	0/7 (0%)	0
Tremor	4/135 (3%)	4	1/137 (0.7%)	1	2/104 (1.9%)	2	2/106 (1.9%)	2	1/97 (1%)	1	0/7 (0%)	0
Psychiatric disorders
Insomnia	12/135 (8.9%)	13	7/137 (5.1%)	8	1/104 (1%)	1	3/106 (2.8%)	3	0/97 (0%)	0	0/7 (0%)	0
Intentional self-injury	1/135 (0.7%)	1	1/137 (0.7%)	1	3/104 (2.9%)	3	2/106 (1.9%)	2	0/97 (0%)	0	0/7 (0%)	0
Reproductive system and breast disorders
Dysmenorrhoea	2/70 (2.9%)	3	2/75 (2.7%)	2	0/53 (0%)	0	2/59 (3.4%)	2	0/47 (0%)	0	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	6/135 (4.4%)	6	0/137 (0%)	0	4/104 (3.8%)	4	5/106 (4.7%)	5	0/97 (0%)	0	0/7 (0%)	0
Dyspnoea	3/135 (2.2%)	3	0/137 (0%)	0	0/104 (0%)	0	0/106 (0%)	0	0/97 (0%)	0	0/7 (0%)	0
Oropharyngeal pain	10/135 (7.4%)	10	3/137 (2.2%)	3	1/104 (1%)	1	7/106 (6.6%)	7	0/97 (0%)	0	0/7 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis	3/135 (2.2%)	4	1/137 (0.7%)	2	1/104 (1%)	1	2/106 (1.9%)	4	0/97 (0%)	0	0/7 (0%)	0
Rash	1/135 (0.7%)	1	2/137 (1.5%)	2	1/104 (1%)	1	4/106 (3.8%)	4	0/97 (0%)	0	0/7 (0%)	0
Vascular disorders
Hot flush	2/135 (1.5%)	2	1/137 (0.7%)	1	0/104 (0%)	0	3/106 (2.8%)	3	0/97 (0%)	0	0/7 (0%)	0

Limitations/Caveats

Nine (9) randomized participants (5 duloxetine, 4 placebo) from 1 site were excluded from efficacy and safety analyses due to major quality issues at that site.

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.