Generalized Anxiety Disorder
Conditions
Keywords
GAD, Generalized Anxiety Disorder, Anxiety
Brief summary
The purpose of this study is to test the safety and efficacy of duloxetine versus placebo in elderly patients suffering from generalized anxiety disorder (GAD).
Interventions
DRUGDuloxetine
Administered by mouth, daily for 10 weeks
DRUGPlacebo
Administered by mouth, daily for 10 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have GAD based on diagnostic criteria and not suffer from an adjustment disorder or anxiety disorder not otherwise specified. Symptoms of GAD should not be situational in nature. * Have a Mini Mental State Examination (MMSE) score of at least 24 at screening. * Have a Clinical Global Impressions of Severity (CGI-Severity) score of greater than or equal to 4 at screening and randomization. * Have a Covi Anxiety Scale (CAS) score of greater than or equal to 9, no item in the Raskin Depression Scale (RDS) may be \>3, and the CAS score must be greater than the RDS at screening. * Have a Hospital Anxiety and Depression Scale (HADS) anxiety subscale score of greater than or equal to 10 at screening. * Have a degree of understanding such that the participant can communicate intelligibly with the investigator and study coordinator. * Are judged to be reliable to keep all appointments and able to swallow all required medication without opening or crushing.
Exclusion criteria
* Have any current and primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revised (DSM-IV TR) Axis I diagnosis other than GAD, with the exception of comorbid social phobia or specific phobia. * major depressive disorder (MDD) within the past 6 months, or * panic disorder, posttraumatic stress disorder (PTSD), or an eating disorder within the past year, or * obsessive compulsive disorder (OCD), bipolar affective disorder, psychosis, factitious disorder, or somatoform disorders during their lifetime. * The presence of an Axis II disorder, or history of antisocial behavior, or participants who, in the opinion of the investigator, are poor medical or psychiatric risks for study compliance. * Have organic mental disorder or mental retardation diagnosis. * Use of benzodiazepine within 14 days prior to randomization. * Are judged clinically to be at serious risk of harm to self or others. * Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. * Have previously completed or withdrawn from this study or any other study investigating duloxetine or have previously been treated with duloxetine within the past year or participants with a lack of response or intolerability to duloxetine (for any approved indication) at a clinically appropriate dose for a minimum of 4 weeks. * Have a history of alcohol or any psychoactive substance abuse or dependence within the past 6 months. * Excessively use caffeine, in the opinion of the investigator. * Have a positive urine drug screen (UDS) for any substances of abuse at screening. * Have a serious medical illness. * Have any acute liver injury or severe cirrhosis. * Have an abnormal thyroid-stimulating hormone (TSH) concentrations. * Have initiated psychotherapy or changed intensity of psychotherapy or other non-drug therapies (such as acupuncture or hypnosis) within 6 weeks prior to enrollment or at any time during the study. * Have taken any excluded medication within 7 days prior to randomization. * Have been treated with a monoamine oxidase inhibitor (MAOI) or fluoxetine within 30 days of randomization or potentially need to use an MAOI during the study or within 5 days of discontinuation of study drug. * Exhibit a lack of response of the current episode of GAD to 2 or more adequate trials of antidepressants, benzodiazepines, or other anxiolytics at a clinically appropriate dose for a minimum of 4 weeks. * Have a history of severe allergies, hypersensitivity to duloxetine or to any of the inactive ingredients; multiple adverse drug reactions; transcranial magnetic stimulation (TMS); history of seizures; or history of psychosurgery or electroconvulsive therapy (ECT) within 12 months. * Have discontinued hormone replacement therapy within the previous 3 months. * Have uncontrolled narrow-angle glaucoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) Total Score | Baseline, Week 10 | The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Global Functional Impairment Score | Baseline, Week 10 | The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Functional Impairment Score (SDS Global Score) was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated a higher functional impairment in the participant's work/social/family life. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit. |
| Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) | Baseline, Week 10 | The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Psychic Anxiety Factor Score was the sum of Items 1 to 6 and Item 14 and could have ranged from 0 to 28. The HAMA Somatic Anxiety Factor Score was the sum of Items 7 to 13 and could have ranged from 0 to 28. The HAMA Anxious Mood Item Score was the score for Item 1 and the HAMA Tension Item Score was the score for Item 2. In each case, higher scores indicated a greater degree of symptom severity. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit. |
| Change From Baseline to Week 10 Endpoint in Hospital Anxiety Depression Scale (HADS) Subscale Scores | Baseline, Week 10 | HADS was a 14-item questionnaire with 2 subscales (anxiety and depression). Each item was rated on a 4-point scale (0 to 3) and higher scores indicated a greater dysfunction. The HADS Anxiety Subscale Score was the sum of the odd numbered items and scores could have ranged from 0 to 21. The HADS Depression Subscale Score was the sum of the even numbered items and scores could have ranged from 0 to 21. Higher scores indicated a greater dysfunction. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit. |
| Clinical Global Impressions of Improvement Scale (CGI-Improvement) at Week 10 | Week 10 | CGI-Improvement measured the clinician's perception of the participant's improvement at the time of assessment compared with the start of treatment. Scores could have ranged from 1 (very much improved) to 7 (very much worse). Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit. |
| Patient's Global Impressions of Improvement Scale (PGI-Improvement) at Week 10 | Week 10 | PGI-Improvement measured the participant's perception of his or her improvement at the time of assessment compared with the start of treatment. Scores could have ranged from 1 (very much better) to 7 (very much worse). Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit. |
| Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Baseline, Week 10 | The BPI-SF Pain Severity Subscale was a participant-rated questionnaire that measured the severity of pain. Severity scores could have ranged from 0 (no pain) to 10 (pain as bad as you can imagine) for questions assessing worst pain, least pain, and average pain in the past 24 hours, and pain right now. The BPI-SF Interference Subscale measured the interference of pain with the participant's ability to function. Interference scores could have ranged from 0 (does not interfere) to 10 (completely interferes) for questions assessing interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Least squares (LS) means were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit. |
| Change From Baseline to Week 10 in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Total Score | Baseline, Week 10 | The Q-LES-Q-SF was a participant-rated questionnaire designed to assess the degree of enjoyment and satisfaction experienced during the past week. The questionnaire consisted of 16 items rated on a 5-point scale ranging from 1 (very poor) to 5 (very good). The total raw score was the sum of Items 1 to 14 and could have ranged from 14 to 70. Total raw scores were converted to, and expressed as, the percentage of the maximum possible score. Percent=100\*(total raw score - 14)/56. Higher scores indicated higher levels of enjoyment/satisfaction. Least squares (LS) mean were calculated and analyzed using analysis of covariance (ANCOVA) adjusted for treatment, pooled investigator, age category, and baseline. |
| Number of Participants With Treatment-Emergent Suicide-Related Ideation and Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Baseline through 10 weeks | The C-SSRS captured the 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. Suicidal behavior: a yes answer to any 1 of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Treatment-emergent was the worsening or new occurrence of suicidal behavior or ideation during treatment compared with baseline (Week 0). |
| Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Work/School, Social Life, and Family/Home Management Individual Impairment Scores | Baseline, Week 10 | The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). Higher values indicated a higher functional impairment in the participant's work/social/family life. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit. |
| Percentage of Participants With Functional Remission at Week 10 (Functional Remission Rate) | Week 10 | Two definitions, using the Sheehan Disability Scale (SDS) Global Functional Impairment Score (SDS Global Score), were used to determine functional remission: Definition 1 (SDS Global Score ≤5 at endpoint) and Definition 2 (SDS Global Score ≤6 at endpoint). The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Score was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated a higher functional impairment in the participant's work/social/family life. |
| Percentage of Participants With Sustained Improvement (Sustained Improvement Rate) | (Baseline through 10 weeks) and (Baseline, Week 2 through Week 10) | Two definitions, using the Hamilton Anxiety Rating Scale (HAMA) Total Score at endpoint compared with baseline, were used to determine sustained improvement: Definition 1 \[sustained improvement overall required a ≥30% improvement (reduction) in the HAMA Total Score at treatment period endpoint, at an earlier visit prior to endpoint, and at all visits in between\] and Definition 2 (sustained improvement from Week 2 required a ≥30% reduction at treatment period endpoint, at Week 2, and at all visits in between). Both definitions required at least 2 post-baseline visits. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity. |
| Adverse Events (AEs) Leading to Discontinuation From Study | Baseline through 10 weeks | The number of participants who discontinued from the study due to an AE (serious or other AE) during the treatment period. A summary of serious and other AEs is located in the Reported Adverse Events module. |
| Percentage of Participants Reporting Falling Down | Baseline through 10 weeks | The percentage of participants who reported 1 or more falls at or before Week 10. |
| Time to First Response | Baseline through 10 weeks | The time (days) to first response, defined as a ≥50% improvement (reduction) from baseline in the Hamilton Anxiety Rating Scale (HAMA) Total Score. Participants who did not have a response were censored at the last treatment period visit. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity. |
| Time to First Remission | Baseline through 10 weeks | The time (days) to first remission. Two definitions, using the Hamilton Anxiety Rating Scale (HAMA) Total Score, were used to determine remission: Definition 1 (HAMA Total Score ≤7 at endpoint) and Definition 2 (HAMA Total Score ≤10 at endpoint). Participants who did not have remission were censored at the last treatment period visit. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity. |
| Time to Sustained Improvement Overall | Baseline through 10 weeks | Time (days) to the earliest visit at which the Hamilton Anxiety Rating Scale (HAMA) Total Score was a ≥30% improvement (reduction) from baseline that was sustained through the last treatment period visit. Participants who did not meet sustained improvement criteria were censored at the last treatment period visit. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity. |
| Time to First Functional Remission | Baseline through 10 weeks | Time (days) to first functional remission. Two definitions, using the Sheehan Disability Scale (SDS) Global Functional Impairment Score (SDS Global Score), were used to determine functional remission: Definition 1 (SDS Global Score ≤5 at endpoint) and Definition 2 (SDS Global Score ≤6 at endpoint). Participants, who did not have an SDS Global Score ≤5 or ≤6, were censored at the last treatment period visit. The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Score was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated a higher functional impairment in the participant's work/social/family life. |
| Time to First Improvement | Baseline through 10 weeks | The time (days) to first improvement, defined as a Clinical Global Impression of Improvement (CGI-Improvement) Score ≤2. Participants who did not have a CGI-I Score ≤2 were censored at the last treatment period visit. CGI-Improvement measured the clinician's perception of the participant's improvement at the time of assessment compared with the start of treatment. Scores could have ranged from 1 (very much improved) to 7 (very much worse). A CGI-Improvement Score of ≤2 was much improved or very much improved. |
| Percentage of Participants With Response or Remission at Week 10 (Response and Remission Rates) | Baseline, Week 10 | Response was a ≥50% improvement (reduction) in the Hamilton Anxiety Rating Scale (HAMA) Total Score at treatment period endpoint compared with baseline. Two definitions were used to determine remission: Definition 1 (HAMA Total Score ≤7 at endpoint) and Definition 2 (HAMA Total Score ≤10 at endpoint). The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | 2 weeks during the taper period | Treatment-emergent AEs were newly occurring AEs or a worsening of AEs during the taper period. A summary of serious AEs and other AEs during the treatment period (baseline through 10 weeks) is located in the Reported Adverse Events module. |
Countries
Argentina, Austria, Canada, Germany, Mexico, Poland, Puerto Rico, United Kingdom, United States
Participant flow
Pre-assignment details
Study had 3 periods: a screening period (3 to 30 days prior to randomization, no study drug administered), a treatment period (10 weeks), and a taper period (2 weeks). Participants who completed the treatment period were considered to have completed the study. Participant Flow and results, unless specified otherwise, are during treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine 30 to 120 milligrams (mg) administered orally, once daily for 10 weeks. Starting dose, 30-mg capsule, once daily for 2 weeks, with option to increase dose (30-mg increments) at Weeks 2, 4, and 7. If participant's Clinical Global Impression of Improvement (CGI-Improvement) Score was ≥3 (minimal improvement, no change, or worse) at Week 2, 4, or 7, the dose was required to be increased by 30 mg. At end of 10-week treatment period, participants had choice to enter 2-week taper period or begin active treatment (duloxetine or other).
Optional taper period: Dosing was dependent on the participant's final dosage during the treatment period. Participants taking duloxetine 120 or 90 mg once daily received duloxetine 60 mg once daily for 1 week followed by 30 mg once daily for 1 week. Participants taking duloxetine 60 mg once daily received duloxetine 30 mg once daily for 1 week followed by placebo for 1 week. Participants taking duloxetine 30 mg once daily received placebo for 2 weeks. | 151 |
| Placebo A placebo capsule administered orally, once daily for 10 weeks. At the end of the 10-week treatment period, participants had choice to enter the 2-week taper period (placebo capsule administered orally, once daily for 2 weeks) or begin active treatment (duloxetine or other). | 140 |
| Total | 291 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 15 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 6 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Violation | 3 | 6 |
| Overall Study | Withdrawal by Subject | 13 | 8 |
Baseline characteristics
| Characteristic | Total | Placebo | Duloxetine |
|---|---|---|---|
| Age Continuous | 71.56 years STANDARD_DEVIATION 5.22 | 71.70 years STANDARD_DEVIATION 5.04 | 71.43 years STANDARD_DEVIATION 5.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 102 Participants | 47 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 189 Participants | 93 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hamilton Anxiety Rating Scale (HAMA) Total Score | 24.49 units on a scale STANDARD_DEVIATION 6.74 | 24.36 units on a scale STANDARD_DEVIATION 7.11 | 24.62 units on a scale STANDARD_DEVIATION 6.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 35 Participants | 18 Participants | 17 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 249 Participants | 120 Participants | 129 Participants |
| Region of Enrollment Argentina | 29 participants | 12 participants | 17 participants |
| Region of Enrollment Austria | 23 participants | 10 participants | 13 participants |
| Region of Enrollment Canada | 18 participants | 8 participants | 10 participants |
| Region of Enrollment Germany | 40 participants | 20 participants | 20 participants |
| Region of Enrollment Mexico | 42 participants | 21 participants | 21 participants |
| Region of Enrollment Poland | 56 participants | 29 participants | 27 participants |
| Region of Enrollment Puerto Rico | 12 participants | 5 participants | 7 participants |
| Region of Enrollment Spain | 18 participants | 9 participants | 9 participants |
| Region of Enrollment United Kingdom | 17 participants | 7 participants | 10 participants |
| Region of Enrollment United States | 36 participants | 19 participants | 17 participants |
| Sex: Female, Male Female | 226 Participants | 112 Participants | 114 Participants |
| Sex: Female, Male Male | 65 Participants | 28 Participants | 37 Participants |
| Years Since Onset of Generalized Anxiety Disorder (GAD) | 12.32 years STANDARD_DEVIATION 15.52 | 11.83 years STANDARD_DEVIATION 14.55 | 12.78 years STANDARD_DEVIATION 16.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 89 / 151 | 71 / 140 |
| serious Total, serious adverse events | 3 / 151 | 0 / 140 |
Outcome results
Primary
Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) Total Score
The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Time frame: Baseline, Week 10
Population: Randomized participants with a baseline and at least 1 post-baseline HAMA Total Score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) Total Score | -15.86 units on a scale | Standard Error 0.63 |
| Placebo | Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) Total Score | -11.69 units on a scale | Standard Error 0.67 |
p-value: <0.00195% CI: [2.47, 5.88]Mixed Models Analysis
Secondary
Adverse Events (AEs) Leading to Discontinuation From Study
The number of participants who discontinued from the study due to an AE (serious or other AE) during the treatment period. A summary of serious and other AEs is located in the Reported Adverse Events module.
Time frame: Baseline through 10 weeks
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine | Adverse Events (AEs) Leading to Discontinuation From Study | 16 participants |
| Placebo | Adverse Events (AEs) Leading to Discontinuation From Study | 15 participants |
Secondary
Change From Baseline to Week 10 Endpoint in Hospital Anxiety Depression Scale (HADS) Subscale Scores
HADS was a 14-item questionnaire with 2 subscales (anxiety and depression). Each item was rated on a 4-point scale (0 to 3) and higher scores indicated a greater dysfunction. The HADS Anxiety Subscale Score was the sum of the odd numbered items and scores could have ranged from 0 to 21. The HADS Depression Subscale Score was the sum of the even numbered items and scores could have ranged from 0 to 21. Higher scores indicated a greater dysfunction. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Time frame: Baseline, Week 10
Population: Randomized participants with a baseline and at least 1 post-baseline HADS Subscale Score.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline to Week 10 Endpoint in Hospital Anxiety Depression Scale (HADS) Subscale Scores | HADS Anxiety Subscale | -7.81 units on a scale | Standard Error 0.37 |
| Duloxetine | Change From Baseline to Week 10 Endpoint in Hospital Anxiety Depression Scale (HADS) Subscale Scores | HADS Depression Subscale | -3.29 units on a scale | Standard Error 0.29 |
| Placebo | Change From Baseline to Week 10 Endpoint in Hospital Anxiety Depression Scale (HADS) Subscale Scores | HADS Depression Subscale | -1.61 units on a scale | Standard Error 0.31 |
| Placebo | Change From Baseline to Week 10 Endpoint in Hospital Anxiety Depression Scale (HADS) Subscale Scores | HADS Anxiety Subscale | -5.62 units on a scale | Standard Error 0.39 |
p-value: <0.00195% CI: [1.2, 3.18]Mixed Models Analysis
p-value: <0.00195% CI: [0.89, 2.49]Mixed Models Analysis
Secondary
Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales
The BPI-SF Pain Severity Subscale was a participant-rated questionnaire that measured the severity of pain. Severity scores could have ranged from 0 (no pain) to 10 (pain as bad as you can imagine) for questions assessing worst pain, least pain, and average pain in the past 24 hours, and pain right now. The BPI-SF Interference Subscale measured the interference of pain with the participant's ability to function. Interference scores could have ranged from 0 (does not interfere) to 10 (completely interferes) for questions assessing interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Least squares (LS) means were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Time frame: Baseline, Week 10
Population: Randomized participants with a baseline and at least 1 post-baseline BPI-SF Pain Severity or Interference Subscale Score.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Mood (n=140, 131) | -1.59 units on a scale | Standard Error 0.22 |
| Duloxetine | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Worst Pain (n=141, 132) | -1.44 units on a scale | Standard Error 0.21 |
| Duloxetine | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Walking Ability (n=140, 131) | -0.91 units on a scale | Standard Error 0.23 |
| Duloxetine | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Least Pain (n=141, 132) | -0.92 units on a scale | Standard Error 0.17 |
| Duloxetine | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Normal Work (n=139, 131) | -1.21 units on a scale | Standard Error 0.23 |
| Duloxetine | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Relations With Other People (n=140, 131) | -0.96 units on a scale | Standard Error 0.21 |
| Duloxetine | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Average Pain (n=141, 132) | -1.10 units on a scale | Standard Error 0.18 |
| Duloxetine | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Sleep (n=140, 131) | -1.58 units on a scale | Standard Error 0.27 |
| Duloxetine | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Pain Right Now (n=141, 132) | -0.81 units on a scale | Standard Error 0.18 |
| Duloxetine | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Enjoyment of Life (n=140, 131) | -1.74 units on a scale | Standard Error 0.23 |
| Duloxetine | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | General Activity (n=140, 131) | -1.45 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Enjoyment of Life (n=140, 131) | -1.24 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Least Pain (n=141, 132) | -0.50 units on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | General Activity (n=140, 131) | -0.92 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Normal Work (n=139, 131) | -0.83 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Average Pain (n=141, 132) | -0.68 units on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Pain Right Now (n=141, 132) | -0.59 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Mood (n=140, 131) | -1.19 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Walking Ability (n=140, 131) | -0.31 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Relations With Other People (n=140, 131) | -0.80 units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Sleep (n=140, 131) | -1.07 units on a scale | Standard Error 0.28 |
| Placebo | Change From Baseline to Week 10 in Brief Pain Inventory-Modified Short Form (BPI-SF) Pain Severity and Interference Subscales | Worst Pain (n=141, 132) | -0.90 units on a scale | Standard Error 0.22 |
p-value: 0.05995% CI: [-0.02, 1.11]Mixed Models Analysis
p-value: 0.07995% CI: [-0.05, 0.89]Mixed Models Analysis
p-value: 0.08995% CI: [-0.06, 0.91]Mixed Models Analysis
p-value: 0.37195% CI: [-0.27, 0.73]Mixed Models Analysis
p-value: 0.06695% CI: [-0.04, 1.09]Mixed Models Analysis
p-value: 0.1495% CI: [-0.13, 0.95]Mixed Models Analysis
p-value: 0.0495% CI: [0.03, 1.18]Mixed Models Analysis
p-value: 0.18795% CI: [-0.19, 0.94]Mixed Models Analysis
p-value: 0.51595% CI: [-0.34, 0.68]Mixed Models Analysis
p-value: 0.14195% CI: [-0.17, 1.18]Mixed Models Analysis
p-value: 0.08895% CI: [-0.07, 1.07]Mixed Models Analysis
Secondary
Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item)
The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Psychic Anxiety Factor Score was the sum of Items 1 to 6 and Item 14 and could have ranged from 0 to 28. The HAMA Somatic Anxiety Factor Score was the sum of Items 7 to 13 and could have ranged from 0 to 28. The HAMA Anxious Mood Item Score was the score for Item 1 and the HAMA Tension Item Score was the score for Item 2. In each case, higher scores indicated a greater degree of symptom severity. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Time frame: Baseline, Week 10
Population: Randomized participants with a baseline and at least 1 post-baseline HAMA factor or item score.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) | HAMA Psychic Anxiety Factor Score (n=143, 131) | -8.59 units on a scale | Standard Error 0.36 |
| Duloxetine | Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) | HAMA Somatic Anxiety Factor Score (n=143, 131) | -7.33 units on a scale | Standard Error 0.33 |
| Duloxetine | Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) | HAMA Anxious Mood Item Score (n=142, 131) | -1.77 units on a scale | Standard Error 0.08 |
| Duloxetine | Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) | HAMA Tension Item Score (n=143, 131) | -1.48 units on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) | HAMA Tension Item Score (n=143, 131) | -1.17 units on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) | HAMA Psychic Anxiety Factor Score (n=143, 131) | -6.19 units on a scale | Standard Error 0.38 |
| Placebo | Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) | HAMA Anxious Mood Item Score (n=142, 131) | -1.24 units on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) (Psychic Anxiety Factor Score, Somatic Anxiety Factor Score, and Individual Item Scores: Anxious Mood Item and Tension Item) | HAMA Somatic Anxiety Factor Score (n=143, 131) | -5.57 units on a scale | Standard Error 0.35 |
p-value: <0.00195% CI: [1.43, 3.37]Mixed Models Analysis
p-value: <0.00195% CI: [0.87, 2.65]Mixed Models Analysis
p-value: <0.00195% CI: [0.3, 0.74]Mixed Models Analysis
p-value: 0.00795% CI: [0.09, 0.53]Mixed Models Analysis
Secondary
Change From Baseline to Week 10 in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Total Score
The Q-LES-Q-SF was a participant-rated questionnaire designed to assess the degree of enjoyment and satisfaction experienced during the past week. The questionnaire consisted of 16 items rated on a 5-point scale ranging from 1 (very poor) to 5 (very good). The total raw score was the sum of Items 1 to 14 and could have ranged from 14 to 70. Total raw scores were converted to, and expressed as, the percentage of the maximum possible score. Percent=100\*(total raw score - 14)/56. Higher scores indicated higher levels of enjoyment/satisfaction. Least squares (LS) mean were calculated and analyzed using analysis of covariance (ANCOVA) adjusted for treatment, pooled investigator, age category, and baseline.
Time frame: Baseline, Week 10
Population: Randomized participants with a baseline and at least 1 post-baseline Q-LES-Q-SF Total Score; Last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline to Week 10 in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Total Score | 15.11 percent of maximum possible score | Standard Error 1.45 |
| Placebo | Change From Baseline to Week 10 in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Total Score | 9.35 percent of maximum possible score | Standard Error 1.52 |
p-value: 0.00295% CI: [-9.4, -2.1]ANCOVA
Secondary
Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Global Functional Impairment Score
The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Functional Impairment Score (SDS Global Score) was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated a higher functional impairment in the participant's work/social/family life. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Time frame: Baseline, Week 10
Population: Randomized participants with a baseline and at least 1 post-baseline SDS Global Functional Impairment Score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Global Functional Impairment Score | -8.60 units on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Global Functional Impairment Score | -5.37 units on a scale | Standard Error 0.64 |
p-value: <0.00195% CI: [1.61, 4.85]Mixed Models Analysis
Secondary
Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Work/School, Social Life, and Family/Home Management Individual Impairment Scores
The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). Higher values indicated a higher functional impairment in the participant's work/social/family life. Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit, baseline score, and baseline-by-visit.
Time frame: Baseline, Week 10
Population: Randomized participants with a baseline and at least 1 post-baseline SDS Work/School, Social Life/Leisure Activities, or Family/Home Management Individual Impairment Scores.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Work/School, Social Life, and Family/Home Management Individual Impairment Scores | Work/School (n=56, 51) | -2.21 units on a scale | Standard Error 0.33 |
| Duloxetine | Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Work/School, Social Life, and Family/Home Management Individual Impairment Scores | Social Life/Leisure Activities (n=140, 131) | -2.84 units on a scale | Standard Error 0.22 |
| Duloxetine | Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Work/School, Social Life, and Family/Home Management Individual Impairment Scores | Family/Home Management (n=140, 131) | -2.82 units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Work/School, Social Life, and Family/Home Management Individual Impairment Scores | Family/Home Management (n=140, 131) | -1.61 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Work/School, Social Life, and Family/Home Management Individual Impairment Scores | Work/School (n=56, 51) | -1.08 units on a scale | Standard Error 0.4 |
| Placebo | Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Work/School, Social Life, and Family/Home Management Individual Impairment Scores | Social Life/Leisure Activities (n=140, 131) | -1.94 units on a scale | Standard Error 0.23 |
p-value: 0.0195% CI: [0.27, 1.98]Mixed Models Analysis
p-value: 0.00295% CI: [0.32, 1.48]Mixed Models Analysis
p-value: <0.00195% CI: [0.61, 1.81]Mixed Models Analysis
Secondary
Clinical Global Impressions of Improvement Scale (CGI-Improvement) at Week 10
CGI-Improvement measured the clinician's perception of the participant's improvement at the time of assessment compared with the start of treatment. Scores could have ranged from 1 (very much improved) to 7 (very much worse). Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit.
Time frame: Week 10
Population: Randomized participants with at least 1 post-baseline CGI-Improvement Score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Clinical Global Impressions of Improvement Scale (CGI-Improvement) at Week 10 | 2.10 units on a scale | Standard Error 0.1 |
| Placebo | Clinical Global Impressions of Improvement Scale (CGI-Improvement) at Week 10 | 2.63 units on a scale | Standard Error 0.1 |
p-value: <0.00195% CI: [0.26, 0.79]Mixed Models Analysis
Secondary
Number of Participants With Treatment-Emergent Suicide-Related Ideation and Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS captured the 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. Suicidal behavior: a yes answer to any 1 of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Treatment-emergent was the worsening or new occurrence of suicidal behavior or ideation during treatment compared with baseline (Week 0).
Time frame: Baseline through 10 weeks
Population: Randomized participants with a baseline and at least 1 post-baseline C-SSRS Score.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants With Treatment-Emergent Suicide-Related Ideation and Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Ideation | 3 participants |
| Duloxetine | Number of Participants With Treatment-Emergent Suicide-Related Ideation and Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Behavior | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Suicide-Related Ideation and Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Ideation | 5 participants |
| Placebo | Number of Participants With Treatment-Emergent Suicide-Related Ideation and Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Behavior | 0 participants |
Secondary
Patient's Global Impressions of Improvement Scale (PGI-Improvement) at Week 10
PGI-Improvement measured the participant's perception of his or her improvement at the time of assessment compared with the start of treatment. Scores could have ranged from 1 (very much better) to 7 (very much worse). Least squares (LS) mean were calculated and analyzed using mixed-model repeated measures (MMRM) adjusted for treatment, pooled investigator, age category, visit, treatment-by-visit.
Time frame: Week 10
Population: Randomized participants with at least 1 post-baseline PGI-Improvement Score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Patient's Global Impressions of Improvement Scale (PGI-Improvement) at Week 10 | 2.35 units on a scale | Standard Error 0.11 |
| Placebo | Patient's Global Impressions of Improvement Scale (PGI-Improvement) at Week 10 | 2.97 units on a scale | Standard Error 0.12 |
p-value: <0.00195% CI: [0.33, 0.91]Mixed Models Analysis
Secondary
Percentage of Participants Reporting Falling Down
The percentage of participants who reported 1 or more falls at or before Week 10.
Time frame: Baseline through 10 weeks
Population: Randomized participants with no falls recorded at Baseline and at least 1 post-baseline assessment for falls.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine | Percentage of Participants Reporting Falling Down | 6.2 percentage of participants |
| Placebo | Percentage of Participants Reporting Falling Down | 3.5 percentage of participants |
Secondary
Percentage of Participants With Functional Remission at Week 10 (Functional Remission Rate)
Two definitions, using the Sheehan Disability Scale (SDS) Global Functional Impairment Score (SDS Global Score), were used to determine functional remission: Definition 1 (SDS Global Score ≤5 at endpoint) and Definition 2 (SDS Global Score ≤6 at endpoint). The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Score was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated a higher functional impairment in the participant's work/social/family life.
Time frame: Week 10
Population: All randomized participants with at least 1 post-baseline SDS Global Score; Last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Percentage of Participants With Functional Remission at Week 10 (Functional Remission Rate) | Functional Remission (SDS Global Score ≤5) | 55.0 percentage of participants |
| Duloxetine | Percentage of Participants With Functional Remission at Week 10 (Functional Remission Rate) | Functional Remission (SDS Global Score ≤6) | 60.9 percentage of participants |
| Placebo | Percentage of Participants With Functional Remission at Week 10 (Functional Remission Rate) | Functional Remission (SDS Global Score ≤5) | 32.9 percentage of participants |
| Placebo | Percentage of Participants With Functional Remission at Week 10 (Functional Remission Rate) | Functional Remission (SDS Global Score ≤6) | 40.7 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Response or Remission at Week 10 (Response and Remission Rates)
Response was a ≥50% improvement (reduction) in the Hamilton Anxiety Rating Scale (HAMA) Total Score at treatment period endpoint compared with baseline. Two definitions were used to determine remission: Definition 1 (HAMA Total Score ≤7 at endpoint) and Definition 2 (HAMA Total Score ≤10 at endpoint). The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.
Time frame: Baseline, Week 10
Population: Randomized participants with a baseline and 1 post-baseline HAMA Total Score; Last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Percentage of Participants With Response or Remission at Week 10 (Response and Remission Rates) | Response | 71.3 percentage of participants |
| Duloxetine | Percentage of Participants With Response or Remission at Week 10 (Response and Remission Rates) | Remission (HAMA Total Score ≤7) | 44.8 percentage of participants |
| Duloxetine | Percentage of Participants With Response or Remission at Week 10 (Response and Remission Rates) | Remission (HAMA Total Score ≤10) | 62.2 percentage of participants |
| Placebo | Percentage of Participants With Response or Remission at Week 10 (Response and Remission Rates) | Remission (HAMA Total Score ≤7) | 29.5 percentage of participants |
| Placebo | Percentage of Participants With Response or Remission at Week 10 (Response and Remission Rates) | Response | 45.5 percentage of participants |
| Placebo | Percentage of Participants With Response or Remission at Week 10 (Response and Remission Rates) | Remission (HAMA Total Score ≤10) | 40.2 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Sustained Improvement (Sustained Improvement Rate)
Two definitions, using the Hamilton Anxiety Rating Scale (HAMA) Total Score at endpoint compared with baseline, were used to determine sustained improvement: Definition 1 \[sustained improvement overall required a ≥30% improvement (reduction) in the HAMA Total Score at treatment period endpoint, at an earlier visit prior to endpoint, and at all visits in between\] and Definition 2 (sustained improvement from Week 2 required a ≥30% reduction at treatment period endpoint, at Week 2, and at all visits in between). Both definitions required at least 2 post-baseline visits. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.
Time frame: (Baseline through 10 weeks) and (Baseline, Week 2 through Week 10)
Population: Randomized participants who had baseline and the required number of post-baseline HAMA Total Scores.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Percentage of Participants With Sustained Improvement (Sustained Improvement Rate) | Sustained Improvement Overall (n=134, 124) | 74.6 percentage of participants |
| Duloxetine | Percentage of Participants With Sustained Improvement (Sustained Improvement Rate) | Sustained Improvement From Week 2 (n=134, 123) | 26.9 percentage of participants |
| Placebo | Percentage of Participants With Sustained Improvement (Sustained Improvement Rate) | Sustained Improvement Overall (n=134, 124) | 55.6 percentage of participants |
| Placebo | Percentage of Participants With Sustained Improvement (Sustained Improvement Rate) | Sustained Improvement From Week 2 (n=134, 123) | 17.9 percentage of participants |
p-value: 0.001Cochran-Mantel-Haenszel
p-value: 0.038Cochran-Mantel-Haenszel
Secondary
Time to First Functional Remission
Time (days) to first functional remission. Two definitions, using the Sheehan Disability Scale (SDS) Global Functional Impairment Score (SDS Global Score), were used to determine functional remission: Definition 1 (SDS Global Score ≤5 at endpoint) and Definition 2 (SDS Global Score ≤6 at endpoint). Participants, who did not have an SDS Global Score ≤5 or ≤6, were censored at the last treatment period visit. The SDS was a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Score was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated a higher functional impairment in the participant's work/social/family life.
Time frame: Baseline through 10 weeks
Population: All randomized participants (pts). Number of pts censored (n)=50 pts in duloxetine treatment arm and n=73 pts in placebo treatment arm for time to first functional remission (SDS Global Score ≤5) and n=37 pts in duloxetine treatment arm and n=60 pts in placebo treatment arm time to first functional remission (SDS Global Score ≤6).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Duloxetine | Time to First Functional Remission | Functional Remission (SDS Global Score ≤5) | 50.00 days |
| Duloxetine | Time to First Functional Remission | Functional Remission (SDS Global Score ≤6) | 31.00 days |
| Placebo | Time to First Functional Remission | Functional Remission (SDS Global Score ≤5) | 72.00 days |
| Placebo | Time to First Functional Remission | Functional Remission (SDS Global Score ≤6) | 71.00 days |
p-value: 0.006Log Rank
p-value: 0.003Log Rank
Secondary
Time to First Improvement
The time (days) to first improvement, defined as a Clinical Global Impression of Improvement (CGI-Improvement) Score ≤2. Participants who did not have a CGI-I Score ≤2 were censored at the last treatment period visit. CGI-Improvement measured the clinician's perception of the participant's improvement at the time of assessment compared with the start of treatment. Scores could have ranged from 1 (very much improved) to 7 (very much worse). A CGI-Improvement Score of ≤2 was much improved or very much improved.
Time frame: Baseline through 10 weeks
Population: All randomized participants. The number of participants censored (n)=37 participants in the duloxetine treatment arm and n=58 participants in the placebo treatment arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duloxetine | Time to First Improvement | 31.00 days |
| Placebo | Time to First Improvement | 52.00 days |
p-value: <0.001Log Rank
Secondary
Time to First Remission
The time (days) to first remission. Two definitions, using the Hamilton Anxiety Rating Scale (HAMA) Total Score, were used to determine remission: Definition 1 (HAMA Total Score ≤7 at endpoint) and Definition 2 (HAMA Total Score ≤10 at endpoint). Participants who did not have remission were censored at the last treatment period visit. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.
Time frame: Baseline through 10 weeks
Population: All randomized participants (pts). The number of censored pts (n)=72 pts in the duloxetine treatment arm and n=92 pts in the placebo treatment arm for time to first remission (HAMA Total Score ≤7) and n=49 pts in the duloxetine treatment arm and n=71 pts in the placebo treatment arm for the time to first remission (HAMA Total Score ≤10).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Duloxetine | Time to First Remission | Remission (HAMA Total Score ≤7) | 71.00 days |
| Duloxetine | Time to First Remission | Remission (HAMA Total Score ≤10) | 51.00 days |
| Placebo | Time to First Remission | Remission (HAMA Total Score ≤7) | NA days |
| Placebo | Time to First Remission | Remission (HAMA Total Score ≤10) | 71.00 days |
p-value: <0.001Log Rank
Secondary
Time to First Response
The time (days) to first response, defined as a ≥50% improvement (reduction) from baseline in the Hamilton Anxiety Rating Scale (HAMA) Total Score. Participants who did not have a response were censored at the last treatment period visit. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. The HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.
Time frame: Baseline through 10 weeks
Population: All randomized participants. The number of censored participants (n)=36 participants in the duloxetine treatment arm and n=60 participants in the placebo treatment arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duloxetine | Time to First Response | 50.00 days |
| Placebo | Time to First Response | 70.00 days |
p-value: 0.005Log Rank
Secondary
Time to Sustained Improvement Overall
Time (days) to the earliest visit at which the Hamilton Anxiety Rating Scale (HAMA) Total Score was a ≥30% improvement (reduction) from baseline that was sustained through the last treatment period visit. Participants who did not meet sustained improvement criteria were censored at the last treatment period visit. The Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) was used to collect HAMA data. HAMA consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAMA Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity.
Time frame: Baseline through 10 weeks
Population: All randomized participants. The number of participants censored (n)=43 participants in the duloxetine treatment arm and n=63 participants in the placebo treatment arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duloxetine | Time to Sustained Improvement Overall | 30.00 days |
| Placebo | Time to Sustained Improvement Overall | 50.00 days |
p-value: 0.001Log Rank
Other Pre-specified
Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period
Treatment-emergent AEs were newly occurring AEs or a worsening of AEs during the taper period. A summary of serious AEs and other AEs during the treatment period (baseline through 10 weeks) is located in the Reported Adverse Events module.
Time frame: 2 weeks during the taper period
Population: Randomized participants who entered the taper period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Nausea | 0 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Pain | 0 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Headache | 0 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Tinnitus | 2 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Oropharyngeal Pain | 0 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Cystitis | 0 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Constipation | 0 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Any Serious AE | 0 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Fatigue | 0 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Vertigo | 1 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Nightmare | 0 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Hyperhidrosis | 0 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Dizziness | 1 participants |
| Duloxetine | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Musculoskeletal Chest Pain | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Constipation | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Any Serious AE | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Pain | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Dizziness | 1 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Fatigue | 1 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Hyperhidrosis | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Nausea | 1 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Tinnitus | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Cystitis | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Headache | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Musculoskeletal Chest Pain | 1 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Nightmare | 1 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Oropharyngeal Pain | 1 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Vertigo | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Headache | 1 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Hyperhidrosis | 2 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Pain | 1 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Musculoskeletal Chest Pain | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Fatigue | 2 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Any Serious AE | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Nightmare | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Dizziness | 1 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Constipation | 1 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Tinnitus | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Vertigo | 0 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Cystitis | 1 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Nausea | 1 participants |
| Placebo | Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period | Non-Serious AE, Oropharyngeal Pain | 0 participants |