Abstract | BACKGROUND AND OBJECTIVE: METHODS: This was a phase III, randomized, double-blind, placebo-controlled, two-arm trial in adults (18-65 years of age) with attention-deficit/hyperactivity disorder. Eligible subjects were randomized 1:1 to viloxazine ER (flexible dose of 200-600 mg/day) or matched placebo. The primary efficacy endpoint was the change from baseline at end of study (week 6) in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score. The key secondary endpoint was the change from baseline at end of study in the Clinical Global Impressions-Severity of Illness (CGI-S) score. Additional secondary outcome measures included the AISRS Inattention and Hyperactivity/Impulsivity subscales, the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A), the Generalized Anxiety Disorder-7 Item (GAD-7), and the Clinical Global Impressions-Improvement (CGI-I); each was analyzed at end of study. Responder rates on CGI scales and the AISRS were also assessed. RESULTS: A total of 374 subjects were randomized. At end of study, the mean viloxazine ER dose was 504 mg. The reduction in the change from baseline at end of study AISRS total score (least-square means ± standard error) was significantly greater in subjects treated with viloxazine ER (-15.5 ± 0.91) compared with placebo (-11.7 ± 0.90), p = 0.0040. The reduction in the CGI-S score was also significantly greater in subjects treated with viloxazine ER (-1.4 ± 0.10) compared with placebo (-1.0 ± 0.10), p = 0.0023. The viloxazine ER group demonstrated significantly greater improvements in the AISRS Inattention (p = 0.0015) and Hyperactivity/Impulsivity (p = 0.0380) subscales, the CGI-I (p = 0.0076), and the BRIEF-A Global Executive Composite (p = 0.0468) and Metacognition Index (p = 0.0100). Analysis of categorical secondary endpoints revealed that the viloxazine ER group had a significantly higher AISRS 30% response rate compared with placebo (p = 0.0395); all other comparisons were not significant. Many treatment effects (including the primary and key secondary endpoints) were significant by week 2. The most common treatment-related adverse events that occurred in ≥5% of subjects receiving viloxazine ER were insomnia (14.8%), fatigue (11.6%), nausea (10.1%), decreased appetite (10.1%), dry mouth (9.0%), and headache (9.0%). Viloxazine ER was well tolerated, with a 9.0% discontinuation rate due to adverse events compared with 4.9% in the placebo group. CONCLUSIONS: CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04016779.
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Authors | Azmi Nasser, Joseph T Hull, Soumya A Chaturvedi, Tesfaye Liranso, Oyinkansola Odebo, Alisa R Kosheleff, Nicholas Fry, Andrew J Cutler, Jonathan Rubin, Stefan Schwabe, Ann Childress |
Journal | CNS drugs
(CNS Drugs)
Vol. 36
Issue 8
Pg. 897-915
(08 2022)
ISSN: 1179-1934 [Electronic] New Zealand |
PMID | 35896943
(Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | © 2022. The Author(s). |
Chemical References |
- Capsules
- Central Nervous System Stimulants
- Delayed-Action Preparations
- Viloxazine
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Topics |
- Adult
- Attention Deficit Disorder with Hyperactivity
(diagnosis, drug therapy)
- Capsules
(therapeutic use)
- Central Nervous System Stimulants
(therapeutic use)
- Child
- Delayed-Action Preparations
(therapeutic use)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Humans
- Treatment Outcome
- Viloxazine
(therapeutic use)
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