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Evaluating the Impact of Caffeine on the Incidence of Adverse Events During Treatment with Viloxazine Extended-Release (Qelbree®) in Adults with ADHD
- Azmi Nasser, Roberto Gomeni, Joseph Hull, Zulane Maldonado-Cruz, Jami Earnest, Jonathan Rubin
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- Journal:
- CNS Spectrums / Volume 28 / Issue 2 / April 2023
- Published online by Cambridge University Press:
- 14 April 2023, pp. 234-235
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Introduction
Viloxazine ER (viloxazine extended-release capsules (Qelbree®) is a novel, nonstimulant, FDA-approved treatment for attention-deficit/hyperactivity disorder (ADHD) in adults and children ≥6 years of age. Viloxazine ER inhibits cytochrome P450-1A2, the enzyme responsible for caffeine metabolism. In a Phase 1 study, the peak exposure (Cmax) of caffeine was unchanged, while the systemic total exposure (AUC) was shown to increase ~5-fold following coadministration of caffeine (200mg) with viloxazine ER (900 mg/day x 4 days) compared to caffeine alone. Except for insomnia (44.4%), and possibly dizziness (8.3%), the incidence of adverse events (AEs) was not notably higher following coadministration vs. either caffeine or viloxazine ER alone. The objective of this analysis was to evaluate the impact of caffeine consumption on the incidence of AEs in adults with ADHD treated with viloxazine ER.
MethodsData were analyzed from the Phase 3, double-blind (DB), placebo-controlled trial (NCT04016779) and ensuing (ongoing) open-label extension (OLE) safety trial (NCT04143217) supporting the viloxazine ER indication for adults with ADHD. Participants reported caffeine intake during the past week at each study visit.
Correlation was assessed between viloxazine ER dose (mg/day) and weekly total caffeine consumption (mg) and between ADHD Investigator Symptom Rating Scale (AISRS) Total score and caffeine consumption. Fifteen AE preferred terms, known to be associated with caffeine consumption, were evaluated. For viloxazine ER-treated subjects (200–600 mg/day) who experienced a potentially caffeine-associated AE, the probability the AE occurred as a function of viloxazine ER dose and caffeine consumption during the DB or OLE trials was estimated using a logistic regression model for AEs with an incidence ≥5%.
ResultsOf 372 enrolled subjects ~85% reported caffeine use during the DB trial; mean caffeine use was 1034 mg/week for the placebo group and 859 mg/week for the viloxazine ER group. There was no correlation between viloxazine ER dose and caffeine consumption (p=0.73), nor between AISRS total score and caffeine consumption (p=0.908). Of subjects reporting caffeine use, 44 (DB placebo), 79 (DB viloxazine ER), and 33 (OLE viloxazine ER) reported any of the pre-identified caffeine- associated AEs and were included in the regression analysis. For these subjects, insomnia-related AEs, fatigue, nausea, headache-related AEs, decreased appetite, and somnolence-related AEs occurred in ≥5% of viloxazine ER-treated subjects. Based on the regression analysis, caffeine consumption significantly increased the probability of experiencing insomnia-related AEs only (p=0.02).
ConclusionsThis analysis suggests using caffeine concomitantly with viloxazine ER does not increase the likelihood of experiencing caffeine-related AEs except for insomnia. Still patients should be aware of the potential for viloxazine ER to augment caffeine exposure.
FundingSupernus Pharmaceuticals, Inc.
Effects of Viloxazine ER (Qelbree®) on Weight and Height Trajectories: Interim Results From a Long-term, Open-Label Extension Trial in Pediatric ADHD
- Azmi Nasser, Joseph Hull, Jami Earnest, Jennifer Koch, Tesfaye Liranso, Zulane Maldonado-Cruz, Jonathan Rubin, Ann Childress
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- Journal:
- CNS Spectrums / Volume 28 / Issue 2 / April 2023
- Published online by Cambridge University Press:
- 14 April 2023, p. 218
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Introduction
Stimulant medications and the norepinephrine reuptake inhibitor, atomoxetine, contain warnings regarding potential for slowing of growth (weight and height) in children and recommend monitoring of growth when using these medications for pediatric ADHD. Viloxazine ER (viloxazine extended-release capsules; Qelbree®), is a nonstimulant medication, FDA-approved for ADHD in adults and children (≥6 years of age). Viloxazine ER has pharmacologic differences from other approved ADHD medications and might not affect growth in the same manner as other therapies. A safety analysis was conducted to determine viloxazine ER effects on growth and weight trajectories in pediatric ADHD patients with long-term use.
MethodsData were evaluated from five DBPC, phase 2 and 3 clinical trials and an ongoing long-term, open-label extension (OLE) trial (NCT02736656). Viloxazine ER doses during the trials ranged from 100–400 mg/day (age 6–11 yrs) or 100–600 mg/day (age 12–17 yrs). Height and weight were evaluated pretreatment in both DB and OLE every 3 months during the OLE, and converted into percentile values and corresponding z-scores using Centers for Disease Control (CDC) normal growth curves to evaluate growth trajectories. The incidence of weight- and growth-related adverse events (AEs) terms were also evaluated.
ResultsAt the time of data cut (31 July 2019), 1097 subjects had received at least one dose of viloxazine ER in the OLE (66% male, mean (SD) age 10.8 (3.06), 59% age 6–11, mean (SD) BMI 18.8 (3.42) kg/m2, height 146.7 (17.46) cm, weight 42.1 (16.01) kg. During the OLE, mean (SE) z-scores for height and weight were between -1 and 1 for all timepoints, indicating growth measures within a normal range compared with expected values. Similar results were observed when weight and height were analyzed by sex and by age categories. Growth data were available for 338 subjects at 12 months. Among these subjects, the mean (SD) change from baseline in weight-for-age z-score was -0.2 (0.5) and height-for-age z-score was -0.14 (1.1). Adverse events relevant to weight and growth in the DB trials (incidence ≥ 1%) included (viloxazine ER [100–600 mg/day] n=1117 vs. placebo n=487): decreased appetite (8.1% vs. 0.8%), nausea (5.1% vs. 2.7%), vomiting (4.7% vs. 1.4%), weight increase (0.4% vs. 1.2%) and weight decrease (1.3% vs. 0.4%), and increased appetite (0.2% vs. 1.2%). During the OLE weight-and growth-related AEs reported for ≥ 1% of subjects were: decreased appetite 5.8%, vomiting 2.7%, nausea 2.4%, weight decreased 2.3%, and weight increased 2.0%.
ConclusionsOver time, pediatric subjects taking viloxazine ER, on average, maintained normal weight and height relative to the CDC’s child growth charts. However, because Qelbree may affect weight, it is recommended that healthcare providers check patient weight before starting and while using viloxazine ER.
FundingSupernus Pharmaceuticals, Inc.