Clinical trial NCT00744627: Efficacy and Safety of Vortioxetine (Lu AA21004) for Treatment of Generalized Anxiety Disorder in Adults.
Official title: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed-Dose Study Comparing the Efficacy and Safety of a Single Dose 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
Anxiety Disorders
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: H. Lundbeck A/S
First posted: 2008-09-01
Enrollment: 301
Sex: ALL
Minimum age (years): 18
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 evaluate the efficacy and safety of vortioxetine, once daily (QD), in adults with Generalized Anxiety Disorders.

Detailed description: The drug that was tested in this study is called Vortioxetine. Vortioxetine is being tested to treat anxiety in adults who have general anxiety disorder (GAD). This study looked at GAD relief in people who took vortioxetine.

The study enrolled 301 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):

* Vortioxetine 5 mg
* Placebo (dummy inactive pill) - this was a capsule that looked like the study drug but had no active ingredient.

All participants were asked to take one capsule at the same time each day throughout the study.

This multi-center trial was conducted in Europe. The overall time to participate in this study was up to 13 weeks. Participants made 7 visits to the clinic, and were contacted by telephone 4 weeks after the last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

* Suffers from a primary diagnosis of Generalized Anxiety Disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
* Has a Hamilton Anxiety Scale total score ≥20 at Screening and Baseline.
* Has a Hamilton Anxiety Scale score ≥2 on both Item 1 (anxious mood) and Item 2 (tension) at Screening and Baseline.
* Has a Montgomery-Åsberg Depression Rating Scale total score ≤16 at Screening and Baseline.
* Male and females of childbearing potential who are sexually active agree to use adequate contraception from Screening throughout the duration of the study and for 1 month after the last dose of study medication.

Exclusion Criteria:

* Has received any investigational compound \<30 days before Screening or 5 half-lives prior to Screening.
* Has received Lu AA21004 in a previous clinical study or as a therapeutic agent.
* Has 1 or more of the following:

  * Any current psychiatric disorder other than Generalized Anxiety Disorder as defined in the DSM-IV-TR.
  * 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.
  * Presence or history of a clinically significant neurological disorder (including epilepsy).
  * Neurodegenerative disorder (Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington disease, etc).
  * Any Axis II disorder that might compromise the study.
* Is required to take excluded medications or it is anticipated that the participant will require treatment with at least 1 of the disallowed concomitant medications during the study including:

  * Nonsteroidal anti-inflammatory drugs
  * Rifampin
  * Macrolide antibiotics
  * Hormones
  * Hypoglycemic agents and Insulin
  * Systemic steroids
  * Antineoplastics
  * Antiobesity agents
  * Antidiarrheal agents (episodic use allowed)
  * Antifungal agents (episodic topical use allowed)
  * Antihistamines (episodic use of loratadine, desloratadine, cetirizine allowed)
  * Cough/cold agents (episodic use allowed but preparations containing pseudoephedrine and narcotics are NOT allowed)
  * Diuretics (episodic use allowed)
* 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 inhibitors 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 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 bilirubin level \>1.5 times the upper limits of normal.
* Has a serum creatinine of \>1.5 times the upper limits of normal.
* Has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication. This criterion does not include those participants with basal cell or stage I squamous cell carcinoma of the skin.
* Has clinically significant abnormal vital signs as determined by the investigator.
* Has 1 or more laboratory values outside the normal range, based on the blood or urine samples taken at Screening, that are considered by the investigator to be clinically significant.
* Has thyroid stimulating hormone value outside the normal range at Screening and is deemed clinically significant by the investigator.
* Has an abnormal electrocardiogram as determined by the central reader and confirmed as clinically significant by the investigator.
* Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.
* Has previously participated in this study.

Primary outcomes:
measure: Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Week 8
timeFrame: Baseline to Week 8
Secondary outcomes:
measure: Change From Baseline in the Hospital Anxiety and Depression (HAD) Anxiety Subscale at Week 8
timeFrame: Baseline to Week 8
measure: Clinical Global Impression Scale-Global Improvement at Week 8
timeFrame: Baseline to Week 8
measure: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8
timeFrame: Baseline to Week 8
measure: Percentage of Responders in HAM-A Total Score at Week 8
timeFrame: Baseline and 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 36-Item Short-Form Health Survey (SF-36) Social Functioning Subscore at Week 8
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 the Hospital Anxiety and Depression (HAD) Anxiety Subscale at Other Weeks Assessed
timeFrame: Baseline to Weeks 1 and 4
measure: Clinical Global Impression Scale-Global Improvement at Other Weeks Assessed
timeFrame: Baseline to Weeks 1, 2, 4 and 6
measure: Change From Baseline in Sheehan Disability Scale (SDS) Total Score 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 at Each Week Assessed
timeFrame: Baseline to Weeks 1, 2, 4, 6 and 8
measure: Change From Baseline in the Hospital Anxiety and Depression (HAD) Depression Subscale at Each Week Assessed
timeFrame: Baseline to Weeks 1, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Social Functioning Subscore at Other Weeks Assessed
timeFrame: Baseline to Weeks 2 and 4
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Functioning Subscore at Each Week Assessed
timeFrame: Baseline to Weeks 2, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Role-Physical Subscore at Each Week Assessed
timeFrame: Baseline to Weeks 2, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Bodily Pain Subscore at Each Week Assessed
timeFrame: Baseline to Weeks 2, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) General Health Subscore at Each Week Assessed
timeFrame: Baseline to Weeks 2, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Vitality Subscore at Each Week Assessed
timeFrame: Baseline to Weeks 2, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Role-Emotional Subscore at Each Week Assessed
timeFrame: Baseline to Weeks 2, 4 and 8
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Mental Health Subscore at Each Week Assessed
timeFrame: Baseline to Weeks 2, 4 and 8
measure: Health Care Resource Utilization as Assessed by the Health Economic Assessment Questionnaire
timeFrame: Baseline and Week 8
Other outcomes:
Locations:
city: Tallinn
country: Estonia
city: Viljandi
country: Estonia
city: Bad Saarow
country: Germany
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Huettenberg
country: Germany
city: Rodgau
country: Germany
city: Schwerin
country: Germany
city: Wiesbaden
country: Germany
city: Liepaja
country: Latvia
city: Riga
country: Latvia
city: Sigulda
country: Latvia
city: Kaunas
country: Lithuania
city: Palanga
country: Lithuania
city: Vilnius
country: Lithuania
city: Białystok
country: Poland
city: Gdynia
country: Poland
city: Gorlice
country: Poland
city: Leszno
country: Poland
city: Skórzewo
country: Poland
city: Toruń
country: Poland
city: Tuszyn
country: Poland
city: Bucharest
country: Romania
city: Oradea
country: Romania
city: Ekaterinburg
country: Russian Federation
city: Kazan
country: Russian Federation
city: Lipetsk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Rostov-on-Don
country: Russian Federation
city: Samara
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Stavropol
country: Russian Federation
city: Dnepropetrovsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Liev
country: Ukraine
city: Lugansk
country: Ukraine
city: Simferopol
country: Ukraine
Study officials:
affiliation: Takeda
name: Medical Director, Clinical Science
role: STUDY_DIRECTOR
References:
citation: Bidzan L, Mahableshwarkar AR, Jacobsen P, Yan M, Sheehan DV. Vortioxetine (Lu AA21004) in generalized anxiety disorder: results of an 8-week, multinational, randomized, double-blind, placebo-controlled clinical trial. Eur Neuropsychopharmacol. 2012 Dec;22(12):847-57. doi: 10.1016/j.euroneuro.2012.07.012. Epub 2012 Aug 14.
citation: Christensen MC, Loft H, Florea I, McIntyre RS. Efficacy of vortioxetine in working patients with generalized anxiety disorder. CNS Spectr. 2019 Apr;24(2):249-257. doi: 10.1017/S1092852917000761. Epub 2017 Oct 30.