Clinical trial NCT00730691: Efficacy of Vortioxetine (Lu AA21004) in Treating Generalized Anxiety Disorder
Official title: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Active-Referenced, Fixed-Dose Study Comparing the Efficacy and Safety of 3 Doses of Lu AA21004 in Acute Treatment of Adults With Generalized Anxiety Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Generalized Anxiety Disorder
Keywords: Generalized Anxiety Disorder
Mood Disorder
Affective Disorder
Anxiety Disorder
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: H. Lundbeck A/S
First posted: 2008-08-08
Enrollment: 781
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and efficacy of vortioxetine, once daily (QD), in adults with generalized anxiety disorder.

Detailed description: Participants in this study will be randomly assigned to receive either 2.5 mg, 5 mg or 10 mg of vortioxetine, once daily, 60 mg of duloxetine once daily, or a placebo once daily for eight weeks.

Participants will be seen weekly during the first 2 weeks of treatment, and then every 2 weeks up to the end of the 8-week treatment period. Participants who complete the 8-week treatment period will enter a 2-week discontinuation period in order to assess potential discontinuation symptoms. Total commitment time is up to 12 weeks.

Eligibility criteria: Inclusion Criteria:

* Has a primary diagnosis of generalized anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR®) criteria (classification code 300.02).
* Has a Hamilton Anxiety Scale total score ≥ 20. Has a Hamilton Anxiety Scale score ≥2 on both item 1 (anxious mood) and item 2 (tension).
* Has a Montgomery-Åsberg Depression Rating Scale total score ≤16.

Exclusion Criteria:

* Had received any investigational compound \<30 days before Screening or 5 half-lives prior to Screening, whichever is longer.
* Received Lu AA21004 in a previous clinical study.
* Was a study site employee, or an immediate family member (ie, spouse, parent, child, or sibling) of a study site employee involved in conduct of this study.
* Has 1 or more of the following:

  * Any current psychiatric disorder other than Generalized Anxiety Disorder as defined in the DSM-IV-TR® (as assessed by the Mini International Neuropsychiatric Interview \[MINI\]).
  * Current or past history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.
  * Any substance disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR® and must have a negative urine drug screen prior to Baseline.
  * Presence or history of a clinically significant neurological disorder (including epilepsy).
  * Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
  * Any Axis II disorder that might compromise the study.
* Has known sensitivity to duloxetine.
* Is taking excluded medications
* Has a significant risk of suicide according to the investigator's opinion or has a score ≥5 on item 10 (suicidal thoughts) of the Montgomery-Åsberg Depression Rating Scale or has made a suicide attempt in the previous 6 months.
* Has previously failed to respond to adequate treatment with selective serotonin reuptake inhibitor and/or serotonin-norepinephrine reuptake inhibitors.
* Has received electroconvulsive therapy within 6 months prior to Screening.
* Is currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy during the study.
* Has a known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma.
* Has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance.
* Has an alanine aminotransferase, aspartate aminotransferase, or total bilirubin level \>1.5 times the upper limit of normal.
* Has a serum creatinine level \>1.5 upper limit of normal.
* Has a previous history of cancer that had been in remission for less than 5 years.
* Hasclinically significant abnormal vital signs as determined by the investigator.
* Has a history of lack of response to previous adequate treatment with duloxetine for any Generalized Anxiety Disorder episode.
* Has 1 or more laboratory values outside the normal range, based on the blood or urine samples taken at the Screening Visit
* Has a thyroid stimulating hormone value outside the normal range.
* Has an abnormal electrocardiogram.
* has a disease or was taking medications that, in the opinion of the investigator, could have interfered with the assessments of safety, tolerability, or efficacy.
* The patient, in the opinion of the investigator, was unlikely to comply with the clinical study protocol or was unsuitable for any reason.
* Had previously been enrolled in this study.

Primary outcomes:
measure: Change From Baseline in the Hamilton Anxiety (HAM-A) Scale Total Score at Week 8
timeFrame: Baseline to Week 8
Secondary outcomes:
measure: Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Week 8
timeFrame: Baseline to Week 8
measure: Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Week 8
timeFrame: Baseline to Week 8
measure: Change From Baseline in Sheehan Disability Scale (SDS) at Week 8
timeFrame: Baseline to Week 8
measure: Percentage of Responders in HAM-A Total Score at Week 8
timeFrame: Week 8
measure: Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Week 8 in Participants With Baseline HAM-A ≥25
timeFrame: Baseline to Week 8
measure: Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed
timeFrame: Baseline to Weeks 1, 2, 4 and 6
measure: Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed
timeFrame: Baseline to Weeks 1 and 4
measure: Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed
timeFrame: Baseline to Weeks 1, 2, 4 and 6
measure: Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed
timeFrame: Baseline to Weeks 1, 2 and 4
measure: Percentage of Responders in HAM-A Total Score at Other Weeks Assessed
timeFrame: Baseline and Weeks 1, 2, 4 and 6
measure: Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25
timeFrame: Baseline to weeks 1, 2, 4 and 6
measure: Percentage of Participants in HAM-A Remission at Each Week Assessed
timeFrame: Weeks 1, 2, 4, 6 and 8
measure: Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S)
timeFrame: Baseline to Weeks 1, 2, 4, 6 and 8
measure: Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed
timeFrame: Baseline to Weeks 1, 4 and 8
measure: Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire
timeFrame: Baseline and Week 8
Other outcomes:
Locations:
city: Anaheim
country: United States
state: California
city: Beverly Hills
country: United States
state: California
city: Fresno
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Oceanside
country: United States
state: California
city: San Diego
country: United States
state: California
city: Sherman Oaks
country: United States
state: California
city: Widomar
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Farmington
country: United States
state: Connecticut
city: Norwalk
country: United States
state: Connecticut
city: Coral Gables
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Maitland
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Roswell
country: United States
state: Georgia
city: Smyrna
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Oakbrook Ter
country: United States
state: Illinois
city: Terre Haute
country: United States
state: Indiana
city: Owensboro
country: United States
state: Kentucky
city: Shreveport
country: United States
state: Louisiana
city: Rockville
country: United States
state: Maryland
city: Chesterfield
country: United States
state: Missouri
city: St Louis
country: United States
state: Missouri
city: Nashua
country: United States
state: New Hampshire
city: Clementon
country: United States
state: New Jersey
city: Princeton
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Brooklyn
country: United States
state: New York
city: Cedarhurst
country: United States
state: New York
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Staten Island
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Beachwood
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Eugene
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Salem
country: United States
state: Oregon
city: Allentown
country: United States
state: Pennsylvania
city: Media
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Memphis
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: DeSoto
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Lake Jackson
country: United States
state: Texas
city: Wichita Falls
country: United States
state: Texas
city: Midvale
country: United States
state: Utah
city: Woodstock
country: United States
state: Vermont
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Brown Deer
country: United States
state: Wisconsin
city: Middleton
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Mahableshwarkar AR, Jacobsen PL, Chen Y, Simon JS. A randomised, double-blind, placebo-controlled, duloxetine-referenced study of the efficacy and tolerability of vortioxetine in the acute treatment of adults with generalised anxiety disorder. Int J Clin Pract. 2014 Jan;68(1):49-59. doi: 10.1111/ijcp.12328.