Supernus Announces P304 Phase III Data Confirming Positive Results from Previous Three Phase III Studies on SPN-812 in ADHD
- 400 mg dose reached statistical significance compared to placebo, consistent with previous Phase III studies:
• Change versus baseline in ADHD Rating Scale 5, p-value = 0.0082
• Effect size of 0.66
• CGI-I secondary endpoint, p-value = 0.0051
• Hyperactivity/Impulsivity subscale, p-value = 0.0484
• Inattention subscale, p-value = 0.0042
- 600 mg dose narrowly missed statistical significance with p-value = 0.0712
- SPN-812 was well-tolerated with low incidence of adverse events and low discontinuation rates consistent with previous Phase III studies
- Complete Phase III program consists of robust Phase III data on 100 mg, 200 mg, and 400 mg doses in more than 1,000 patients with supporting data from two Phase II studies
- New Drug Application (NDA) continues to be on track for 2H 2019 submission
P304 is the fourth clinical trial in the SPN-812 Phase III program. Positive data from three successful pivotal trials (P301, P302, and P303) were reported in
“We are pleased with the final data confirming the positive results we announced in the previous Phase III studies on SPN-812 last year in December. We now have robust data on 100 mg, 200 mg and 400 mg doses from all four Phase III clinical trials with SPN-812 in patients with ADHD. The data are consistent in showing a clinically meaningful reduction in the symptoms of ADHD, with a favorable safety and tolerability profile,” stated
About the P304 Phase III Study
The study is a randomized, double-blind, placebo controlled, multicenter, parallel group clinical trial in adolescents 12 to 17 years of age diagnosed with ADHD. Each treatment was administered orally once a day over seven weeks, including one week of titration for 400 mg and two weeks of titration for 600 mg.
A total of 297 patients were randomized across placebo and two doses of SPN-812 (400 mg/600 mg). The primary objective was to assess the effect of SPN-812 in reducing the symptoms of ADHD in adolescents 12-17 years old. The primary outcome measure was the change from baseline to the end of the study in the ADHD-RS-5 total score tested on the 600 mg followed by the 400 mg in the statistical plan. Safety and tolerability of SPN-812 were assessed by the monitoring of adverse events (AEs), clinical laboratory tests, vital signs, ECGs, suicidality and physical examinations. Patients who completed the study were offered the opportunity to continue into an open-label phase that is currently on-going.
P304 Phase III Topline Results
At the end of the study (EOS), SPN-812 400 mg reached statistical significance compared to placebo in the primary endpoint. Patients receiving SPN-812 400 mg had an -18.3 LS Mean change from baseline (p=0.0082) vs. LS Mean change of-13.2 from baseline for placebo at week 7. With respect to SPN-812 600 mg, the LS Mean change of -16.7 (p=0.0712) from baseline in the primary endpoint was observed at week 7.
The result, based on Mixed Model Repeated Measures (MMRM) analysis in the Intent-To-Treat (ITT) population, was consistent with the results from sensitivity analyses using Analysis of Covariance (ANCOVA) (400 mg, p=0.0191; 600 mg, p=0.1002) at week 7 (EOS) with placebo based imputation for missing data.
At the 400 mg dose, SPN-812 demonstrated statistically significant onset of action starting week 2 (p=0.0063), which continued to the end of study at week 7 (p=0.0082). At 600 mg dose, SPN-812 demonstrated statistically significant difference from placebo in the primary endpoint during the last week of titration (week 2 dosed at 400 mg, p=0.0456) and the first week of maintenance (week 3 dosed at 600 mg, p=0.0238).
Similar to the first three studies (P301, P302 and P303), at the end of the P304 study, SPN-812 400 mg reached statistical significance compared to placebo on the hyperactivity/impulsivity and inattention subscales of the ADHD-RS-5 scale with p-values of 0.0484 and 0.0042, respectively.
In addition, SPN-812 400 mg dose met the Clinical Global Impression-Improvement secondary endpoint with p-value of 0.0051 compared to placebo.
While the 600 mg dose did not reach statistical significance, it is not needed for the submission or approvability of the NDA for children and adolescents. It was included to check for a potentially higher level of efficacy, to help in identifying the maximum effective dose, and to help in designing our trials for the adult population.
Overall, the trial exhibited favorable tolerability and safety profiles consistent with the other Phase III trials with low incidence of AEs across all doses. AEs were mild leading to low discontinuation rates of 4.0% to 5.1%. Treatment related AEs that reported at more than or equal to 5% for SPN-812 were somnolence, fatigue, decreased appetite, headache and nausea.
“In addition to the consistent and clinically meaningful efficacy data, we continue to be encouraged by the safety and tolerability of SPN-812 especially that the 600 mg dose showed a similar profile to the 400 mg dose. We believe this compelling safety profile at a wide range of doses should provide physicians with dosing flexibility,” stated Dr.
With the completion of the P304 study, the Company now has a robust clinical data package in more than 1,000 children and adolescent patients across all three doses of SPN-812: 100 mg, 200 mg and 400 mg. The Company continues to be focused on putting together the NDA for submission to the
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SPN-812 is a serotonin norepinephrine modulating agent (SNMA) that Supernus is developing as a novel non-stimulant for the treatment of ADHD. Based on data generated to date, the Company believes SPN-812 could be a well-differentiated ADHD treatment compared to other non-stimulant treatments for ADHD due to its different pharmacological and pharmacokinetic profile. The active ingredient in SPN-812, viloxazine hydrochloride, has an extensive safety record in
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