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A Study of Duloxetine in Elderly Generalized Anxiety Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01118780
First received: May 5, 2010
Last updated: June 25, 2013
Last verified: June 2013
  Purpose

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).


Condition Intervention Phase
Generalized Anxiety Disorder
Drug: Duloxetine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Duloxetine Versus Placebo in the Treatment of Elderly Patients With Generalized Anxiety Disorder

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change From Baseline to Week 10 in Hamilton Anxiety Rating Scale (HAMA) Total Score [ Time Frame: Baseline, Week 10 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Change From Baseline to Week 10 in Sheehan Disability Scale (SDS) Global Functional Impairment Score [ Time Frame: Baseline, Week 10 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Week 10 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 10 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 10 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 10 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline through 10 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline, Week 10 ] [ Designated as safety issue: No ]
    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 Response or Remission at Week 10 (Response and Remission Rates) [ Time Frame: Baseline, Week 10 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Functional Remission at Week 10 (Functional Remission Rate) [ Time Frame: Week 10 ] [ Designated as safety issue: No ]
    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) [ Time Frame: (Baseline through 10 weeks) and (Baseline, Week 2 through Week 10) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline through 10 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline through 10 weeks ] [ Designated as safety issue: Yes ]
    The percentage of participants who reported 1 or more falls at or before Week 10.

  • Time to First Response [ Time Frame: Baseline through 10 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline through 10 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline through 10 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline through 10 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline through 10 weeks ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Number of Participants Experiencing a Treatment-Emergent Adverse Event (AE) During the Taper Period [ Time Frame: 2 weeks during the taper period ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 291
Study Start Date: October 2010
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Duloxetine 30 milligrams (mg) -120 mg Drug: Duloxetine
Administered by mouth, daily for 10 weeks
Other Names:
  • Cymbalta
  • Duloxetine Hydrochloride
  • LY248686
Placebo Comparator: Placebo Drug: Placebo
Administered by mouth, daily for 10 weeks

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01118780

  Show 25 Study Locations
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01118780     History of Changes
Other Study ID Numbers: 12866, F1J-MC-HMGF
Study First Received: May 5, 2010
Results First Received: June 25, 2013
Last Updated: June 25, 2013
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Austria: Federal Office for Safety in Health Care
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
Mexico: Federal Commission for Sanitary Risks Protection
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Eli Lilly and Company:
GAD
Generalized Anxiety Disorder
Anxiety

Additional relevant MeSH terms:
Anxiety Disorders
Disease
Mental Disorders
Pathologic Processes
Duloxetine
Adrenergic Agents
Adrenergic Uptake Inhibitors
Analgesics
Antidepressive Agents
Central Nervous System Agents
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014