[[headline-2, left-mobile]ONFI Demonstrated Significant Reductions in Seizures Associated With LGS as Adjunctive Therapy]^1-3

[[accent,center]PRIMARY ENDPOINT]

[[color-black]Increased efficacy with increased dosage]

[[color-green]REDUCTIONS IN MEAN WEEKLY RATE OF DROP SEIZURES (ATONIC, TONIC, OR MYOCLONIC) BY DOSE (N=217, mlTT)]^1,2

Study Design: CONTAIN (Cl O bazam in Patie NT s with Lennox-G A staut Sy N drome) was a randomized, double-blind, placebo-controlled study consisting of a 4-week baseline period followed by a 3-week titration period and a 12-week maintenance period (N=238, randomized). Patients age 2 to 54 years with a current or prior diagnosis of LGS were stratified into 2 weight groups (12.5 kg to ≤30 kg or >30 kg), and then randomized to placebo or 1 of 3 target maintenance doses of ONFI. The dosage groups were: placebo (n=59); low-dose (5 mg/10 mg, n=58); medium-dose (10 mg/20 mg, n=62); and high-dose (20 mg/40 mg, n=59). Doses above 5 mg/day were administered in 2 divided doses. The primary endpoint was the percentage reduction in mean weekly rate of drop seizures (atonic, tonic, or myoclonic) from the 4-week baseline period to the 12-week maintenance period.

• Drop seizures were defined as drop attacks or spells that involved the entire body, trunk, or head, and¹:

  • Led to a fall or injury, slumping in a chair, or hitting the head on a surface
  • Could have led to a fall or injury, depending on the position of the patient at the time of the attack or spell

• Patients in the trial experienced ≥2 drop seizures per week during the 4-week baseline period, while receiving stable doses of 1 to 3 antiepileptic drugs (AEDs) ≥30 days prior to screening¹

• ONFI causes somnolence and sedation. In clinical trials, somnolence or sedation was reported at all effective doses and was dose-related. In general, somnolence and sedation begin within the first month of treatment and may diminish with continued treatment. Monitor patients for somnolence and sedation, particularly with concomitant use of other CNS depressants²

• Most common AEs (≥10% in any treatment group and ≥5% greater than placebo, respectively) were somnolence or sedation (32% vs. 15%), somnolence (25% vs. 12%), pyrexia (17% vs. 3%), lethargy (15% vs. 5%), aggression (14% vs. 5%), drooling (14% vs. 3%), irritability (11% vs. 5%), ataxia (10% vs. 3%), and constipation (10% vs. 0%)²

[[color-grey,center]Key enrollment criteria]¹

• Age: 2 to 60 years
• LGS onset before 11 years of age
• Documentation of EEG with slow spike-and-wave (SSW) (<2.5 Hz) at some point in the patient's history