Long-Term Safety Data for Adult ADHD Treatment Option

DATA UPDATE

Long-term Qelbree Treatment in Adults with ADHD:
SAFETY and EFFICACY DATA¹

Data update including long-term safety and efficacy data for adult patients with ADHD 18 years of age and older.


INDICATION

Qelbree is indicated for the treatment of ADHD in adults and pediatric patients 6 years and older.

Please see full Important Safety Information to the top left.

Qelbree is a first-line, FDA-approved, nonstimulant treatment option for adults and pediatric patients 6 years and older with ADHD.¹

This is the first nonstimulant ADHD treatment option to be approved for adults (18 years and older) in 20 years.¹ 

Four clinical studies evaluated the efficacy and safety of Qelbree for ADHD treatment in patients 6 years and older.^1,2
 

Qelbree phase III adult trial: study design and methodology^1,2

The adult phase III pivotal trial (Figure 1) was a randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of Qelbree 200 mg/day to 600 mg/day in adults (18 to 65 years of age) with ADHD. Eligible subjects were randomized 1:1 to either the Qelbree or matched placebo arms. Subjects in the Qelbree arm received 200 mg/day of Qelbree during the first week and 400 mg/day of Qelbree during the second week. At study visits from week 3 through week 6, the investigators adjusted the doses, either increasing or decreasing them, based on the subject’s clinical response and tolerability. The primary efficacy endpoint was CFB at EOS (Week 6) in the AISRS Total Score. The key secondary endpoint was CFB at EOS in the CGI-S score. Additional secondary outcomes were measured.
 

^{*No study visit was scheduled/performed at week 5. 
Abbreviations: AISRS, Adult Investigator Symptom Rating Scale; CGI-S, Clinical Global Impression-Severity; CFB, change from baseline; EOS, end of study; FDA, Food and Drug Administration.}

CONTRAINDICATIONS

• Concomitant administration of a monoamine oxidase inhibitor (MAOI), or dosing within 14 days after discontinuing an MAOI, because of an increased risk of hypertensive crisis
• Concomitant administration of sensitive CYP1A2 substrates or CYP1A2 substrates with a narrow therapeutic range

Please see full Important Safety Information to the top left.

Qelbree Phase III Adult Trial Results¹:
Qelbree met the primary endpoint (change from baseline in the AISRS Total Score at EOS) in the adult phase III pivotal trial. The LS mean (±SE) change from baseline in AISRS Total Score at EOS was -15.5 (±0.91) in the Qelbree group and -11.7 (±0.90) in the placebo group (P=.004; Figure 2). Qelbree delivered significant symptom score reductions in the AISRS Total Score, which measures both inattention and hyperactivity/impulsivity symptoms in adults. The change from baseline (reduction) in the CGI-S score was statistically significantly greater in adults treated with Qelbree than in adults taking placebo.
 

IMPORTANT SAFETY INFORMATION

• Suicidal thoughts and behaviors: Closely monitor all Qelbree-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes

Please see full Important Safety Information to the top left.

Qelbree Long-term, Open-Label Treatment in Adults (P311) with ADHD: Study Design and Methodology³

Adult patients who completed the phase III trial were eligible to enroll in an ongoing, long-term, OLE safety trial (Figure 4). For patients with a rollover from the phase III trials <7 days, all efficacy and safety assessments collected at the subject’s EOS visit served as their efficacy and safety assessments for visit 1 of the OLE. For rollover >7 days, a screening visit for eligibility was scheduled and visit 1 baseline efficacy and safety assessments were collected.

After completing the 6-week phase III trial, subjects were given 200 mg/day of Qelbree for the first 2 weeks in the OLE. At visit 2 (week 2) and all subsequent visits, investigators could adjust the dose of Qelbree in increments/decrements of 50 mg/day to 200 mg/day each week to a target dose between 200 mg/day and 600 mg/day, based on the subject’s clinical response and tolerability. The primary objective of the OLE trial was to monitor and collect long-term safety data on the use of Qelbree monotherapy for the treatment of ADHD in the adult population. To evaluate the secondary efficacy objective, patients underwent AISRS and CGI-S assessments at study visits.
 

IMPORTANT SAFETY INFORMATION

• Heart rate, blood pressure increases: Qelbree can cause an increase in diastolic blood pressure and heart rate. Assess these measures prior to starting therapy, following increases in dosage, and periodically during therapy

Please see full Important Safety Information to the top left.

Qelbree OLE treatment in adults with ADHD: safety analysis (Figure 5)³

The primary objective of the Qelbree adult OLE trial was safety. The trial found no new safety signals for adults taking Qelbree long term. The most common AEs were consistent with those seen in the phase III trial: insomnia, headache, somnolence, fatigue, nausea, decreased appetite, dry mouth, and constipation. Twenty-eight patients (17.6%) discontinued due to AEs. The OLE trial followed 159 patients for up to 3 years, subject to the commercial availability of the product. Following treatment with once-daily Qelbree: 

• At week 12 of the OLE (n=102), the mean dose of Qelbree was 434 mg/day, and 72% of patients were receiving ≥400 mg/day
• At week 52 of the OLE (n=39), the mean dose of Qelbree was 427 mg/day, and 67% of patients were receiving ≥400 mg/day

IMPORTANT SAFETY INFORMATION

• Somnolence and fatigue: Patients should not perform activities requiring mental alertness, such as operating a motor vehicle or hazardous machinery, due to potential somnolence (including sedation or lethargy) and fatigue, until they know how they will be affected by Qelbree

Please see full Important Safety Information to the top left.

• Data and calculations from patients in the OLE are descriptive only. There is no placebo group from which to draw a comparison of changes from baseline in AISRS Total Score or make any other long-term safety or efficacy conclusions³
• Enrollment in the OLE safety trial was temporarily closed due to COVID-19 pandemic restrictions; therefore some subjects did not roll over into the OLE immediately after the DB week 6 (EOS) visit³

IMPORTANT SAFETY INFORMATION

• Activation of mania or hypomania: Noradrenergic drugs may induce a manic or mixed episode in patients with bipolar disorder. Prior to initiating treatment with Qelbree, screen patients to determine if they are at risk for bipolar disorder. Screening should include a detailed psychiatric history, including a personal or family history of suicide, bipolar disorder, and depression

Please see full Important Safety Information to the top left.

Please see full Prescribing Information, including Boxed Warning.

Learn more about Qelbree, an extended-release, nonstimulant medication for ADHD: https://www.QelbreeHCP.com/

References: 

1. Qelbree [package insert]. Rockville, MD: Supernus Pharmaceuticals, Inc. 
2. Nasser A, Hull JT, Chaturvedi SA, et al. A phase III, randomized, double-blind, placebo-controlled trial assessing the safety and efficacy of viloxazine extended-release capsules in adults with attention-deficit/hyperactivity disorder. CNS Drugs. 2022;36(8):897-915.  
3. Data on file, Supernus Pharmaceuticals. 

QBE.2023-0210 V2