Interventional, Randomised, Double-blind, Placebo-controlled, Fixed-dose Study of Vortioxetine in Adults With Attention Deficit Hyperactivity Disorder (ADHD)
Overview
- Phase
- Phase 2
- Intervention
- vortioxetine 10 mg tablet
- Conditions
- Attention Deficit Hyperactivity Disorder
- Sponsor
- H. Lundbeck A/S
- Enrollment
- 227
- Locations
- 15
- Primary Endpoint
- Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose is to determine the effect of vortioxetine treatment on ADHD symptoms in adult patients with ADHD in a 12 weeks study.
Detailed Description
The study employed the Sequential Parallel Comparison Design (SPCD), a clinical study design which intend to increase signal detection by using two stages of treatment: * Stage 1 - first 6 weeks of the 12-weeks treatment period (Visit 2/Baseline 1 to Visit 5/Week 6) * Stage 2 - last 6 weeks of the 12-weeks treatment period (Visit 5/Baseline 2 to Visit 8/Week 12) In Stage 1, patients were randomized to placebo or vortioxetine 10 or 20mg. Patients on vortioxetine 10 or 20mg/day during Stage 1 remained on the same treatment in Stage 2. Responders to placebo in Stage 1 remained on Placebo in Stage 2. Patients who were placebo non-responders during Stage 1, defined as patients with a \<30% reduction in AISRS total score from Baseline 1, were re-randomized to placebo or vortioxetine 10 or 20mg/day in Stage 2.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The patient is willing and able to attend study appointments within the specified time windows.
- •The patient is an outpatient.
- •The patient is diagnosed with a primary diagnosis of ADHD according to the DSM-5™ classification.
- •The patient has an AISRS total score ≥
- •The patient has a CGI-S rating ≥4 (moderately ill or worse).
Exclusion Criteria
- •The patient has previously been treated with vortioxetine.
- •The patient has any current psychiatric disorder (DSM-IV-TR™ criteria), other than ADHD, as assessed using the Mini International Neuropsychiatric Interview (MINI).
- •The patient has a known first-degree relative with bipolar disorder.
- •The patient suffers from intellectual disability as evaluated by the Wechsler Abbreviated Scale of Intelligence (WASI) II vocabulary and matrix.
- •The patient suffers from organic mental disorders, or mental disorders due to a general medical condition (DSM-5™ criteria).
- •The patient has reported current use of, or has tested positive for, drugs of abuse (opiates, methadone, cocaine, amphetamines \[including ecstasy\], barbiturates, benzodiazepines, and cannabinoids). If a patient tests positive for opiates due to incidental use of codeine containing medication, as assessed in a clinical interview, the drug screen may be repeated up to three weeks later but the retest result must be available from the central laboratory latest at Visit 2 and has to be negative for this patient to be eligible for enrolment. If a patient tests positive for amphetamines due to his/her ADHD current treatment, as confirmed by a clinical interview, the patient is eligible for enrolment provided this treatment is discontinued two weeks prior to the Baseline Visit.
- •The patient has a history of two prior failed (\<50% improvement in symptoms) adequate trials of ADHD treatment.
- •The patient has any other disorder for which the treatment takes priority over treatment of ADHD or is likely to interfere with study treatment or impair treatment compliance.
- •The patient has a history of moderate or severe head trauma or other neurological disorders or systemic medical diseases that are, in the investigator's opinion, likely to affect central nervous system functioning.
- •The patient has attempted suicide within the last 6 months or is at significant risk of suicide (either in the opinion of the Investigator or defined as a "yes" to suicidal ideation questions 4 or 5 or answering "yes" to suicidal behaviour on the Columbia-Suicide Rating Scale (C-SSRS) within the last 12 months).
Arms & Interventions
vortioxetine 10 mg tablet
In Stage 1, patients will receive vortioxetine 10mg/day for 6 weeks. In Stage 2, patients who received vortioxetine 10mg/day in Stage 1 will continue on the same treatment for additionally 6 weeks. Placebo non-responders will be re-randomized to placebo, or vortioxetine 10 or 20mg/day for additionally 6 weeks.
Intervention: vortioxetine 10 mg tablet
vortioxetine 20 mg tablet
In Stage 1, patients will receive vortioxetine 20mg/day for 6 weeks. In Stage 2, patients who received vortioxetine 20mg/day in Stage 1 will continue on the same treatment for additionally 6 weeks. Placebo non-responders will be re-randomized to placebo, or vortioxetine 10 or 20mg/day for additionally 6 weeks.
Intervention: vortioxetine 20 mg tablet
Placebo tablet
In Stage 1, the patients will receive placebo for 6 weeks. In Stage 2, placebo responders will continue on placebo for additionally 6 weeks. Placebo non-responders will be re-randomized to placebo, or vortioxetine 10 or 20mg/day for additionally 6 weeks.
Intervention: Placebo tablet
Outcomes
Primary Outcomes
Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score
Time Frame: Baseline to Week 6
AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). AISRS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher score corresponded to a worse severity of ADHD.
Secondary Outcomes
- Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index(Baseline to Week 6)
- Change in AISRS Inattention Sub-score(Baseline to Week 6)
- Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score(Baseline to Week 6)
- Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score(Baseline to Week 6)
- Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score(Baseline to Week 6)
- Change AISRS Hyperactivity/Impulsivity Sub-score(Baseline to Week 6)
- Percentage of Patients Responding (Response Defined as 30% or Greater Reduction From Baseline in AISRS Total Score)(Baseline to Week 6)
- Change in Adult ADHD Self-Report Scale (ASRS) Total Score(Baseline to Week 6)
- Change in Clinical Global Impression - Severity of Illness (CGI-S) Score(Baseline to Week 6)
- Clinical Global Impression - Global Improvement (CGI-I) Score(Week 6)
- Response (Defined as a CGI-I Score of 1 or 2), Stage 1(Week 6)
- Change in BRIEF-A Using the Behavioural Regulation Index(Baseline to Week 6)
- Change in BRIEF-A Subscales - Inhibit(Baseline to Week 6)
- Change BRIEF-A Subscales - Initiate(Baseline to Week 6)
- Change in BRIEF-A Subscales - Organization of Materials(Baseline to Week 6)
- Change in BRIEF-A Subscales - Planning/Organize(Baseline to Week 6)
- Change in BRIEF-A Subscales - Shift(Baseline to Week 6)
- Change in BRIEF-A Subscales - Self Monitor(Baseline to Week 6)
- Change in BRIEF-A Subscales - Task Monitor(Baseline to Week 6)
- Change in BRIEF-A Subscales - Working Memory(Baseline to Week 6)
- Change in BRIEF-A Subscales - Emotional Control(Baseline to Week 6)
- Change in Perceived Deficits Questionnaire - Depression (PDQ-D) Total Score(Baseline to Week 6)
- Change in PDQ-D Subscales - Attention and Concentration Sub-score(Baseline to Week 6)
- Change in PDQ-D Sub-scales - Retrospective Memory Sub-score(Baseline to Week 6)
- Change in PDQ-D Sub-scales - Prospective Memory Sub-score(Baseline to Week 6)
- Change in PDQ-D Sub-scales - Planning and Organisation Sub-score(Baseline to Week 6)
- Change in SDS Item Scores - Family(Baseline to Week 6)
- Change in SDS Item Scores - Work(Baseline to Week 6)
- Change in SDS Item Scores - Social Life(Baseline to Week 6)
- Change in SDS Item Scores - Number of Days Lost(Baseline to Week 6)
- Change in SDS Item Scores - Number of Underproductive Days(Baseline to Week 6)
- Change in WLQ Using the Global Productivity Index(Baseline to Week 6)
- Change in WLQ Domain Scores - Limitations Handling Time(Baseline to Week 6)
- Change in WLQ Domain Scores - Mental-Interpersonal Work Demands(Baseline to Week 6)
- Change in WLQ Domain Scores - Physical Demands(Baseline to Week 6)
- Change in WLQ Domain Scores - Output Demands(Baseline to Week 6)
- Change in Adult ADHD Quality of Life Measure (AAQoL) Total Score(Baseline to Week 6)
- Change in AAQoL Subscales - Life Productivity Sub-score(Baseline to Week 6)
- Change in AAQoL Subscales - Psychological Health Sub-score(Baseline to Week 6)
- Change in AAQoL Subscales - Life Outlook Sub-score(Baseline to Week 6)
- Change in AAQoL Subscales - Relationships Sub-score(Baseline to Week 6)