ONFI® (clobazam) is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older.

Increased efficacy with increased dosage

REDUCTIONS IN MEAN WEEKLY RATE OF DROP SEIZURES (ATONIC, TONIC, OR MYOCLONIC) BY DOSE (N=217, mlTT)1,2

ONFI® (clobazam) CIV CONTAIN Trial efficacy chart of weekly drop seizure response by dose in patients 2 years of age or older with LGS. See full Prescribing Information, including Boxed Warning for risks from concomitant use with opioids.
-12.1
-41.2
-49.4
-68.3

Study Design: CONTAIN (ClObazam in PatieNTs with Lennox-GAstaut SyNdrome) 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

Key enrollment criteria1

  • 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

Dose-ranging trial

MEDIAN PERCENTAGE REDUCTION IN WEEKLY RATE OF DROP SEIZURES3

Dose-Ranging Trial of ONFI® (clobazam) CIV Efficacy chart of Median Percentage Reduction in Weekly Rate of Drop Seizures in patients 2 years of age or older with LGS. See full Prescribing Information, including Boxed Warning for risks from concomitant use with opioids
29%
93%

Study Design: This dose-ranging study was a randomized, double-blind comparison study of high- and low-dose ONFI, consisting of a 4-week baseline period followed by a 3-week titration period and a 4-week maintenance period (N=68). Patients age 2 to 25 years with a current or prior diagnosis of LGS were stratified by weight, randomized to either a low§- or high-dose of ONFI, and then entered a 3-week titration period. The primary efficacy measure was the percent reduction in the weekly frequency of drop seizures (atonic, tonic, or myoclonic), also known as drop attacks, from the 4-week baseline period to the 4-week maintenance period.

  • Adverse events experienced by ≥5% of patients in either treatment group included somnolence, lethargy, sedation, salivary hypersecretion, constipation, aggression, hypomania, and insomnia3

§Low-dose of ONFI: target of 0.25 mg/kg/day (with maximum of 10 mg/day) for weight ≤37.6 kg, fixed dose of 10 mg/day for weight >37.6 kg. High-dose of ONFI: target of 1.0 mg/kg/day (with maximum of 40 mg/day) for weight ≤37.6 kg, fixed dose of 40 mg/day for weight >37.6 kg.

READ MORE CLINICAL TRIAL RESULTS

Download the CONTAIN Trial abstract to see an overview of results with ONFI.

DOWNLOAD TRIAL RESULTS

IDENTIFY MORE PATIENTS APPROPRIATE FOR ONFI

Dr. Abdelmoity discusses the broad range of LGS features that can present in patients

LEARN ABOUT FLEXIBLE
DOSING FORMULATIONS

Two dosing formulations,
including an oral suspension

ONFI SUPPORT CENTER

Completing the ONFI Insurance Information Form will allow the ONFI Support Center to confirm insurance coverage for ONFI

Complete Terms and Conditions for the 14-Day Trial and Commercial Copay Assistance Programs are available here.

Complete Terms and Conditions for other patient support programs are available here.

IMPORTANT SAFETY INFORMATION

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS

See full Prescribing Information for complete boxed warning.

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
  • Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
  • Limit dosages and durations to the minimum required.
  • Follow patients for signs and symptoms of respiratory depression and sedation.

Contraindication: Hypersensitivity

ONFI is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients. Hypersensitivity reactions have included serious dermatological reactions.

Risks from Concomitant Use with Opioids (see Boxed Warning)

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe ONFI concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use. Advise both patients and caregivers about the risks of respiratory depression and sedation when ONFI is used with opioids.

Potentiation of Sedation from Concomitant Use with Central Nervous System (CNS) Depressants

ONFI has a CNS depressant effect. Caution patients or their caregivers against simultaneous use with other CNS depressant drugs or alcohol and that the effects of other CNS depressant drugs or alcohol may be potentiated.

Somnolence or Sedation

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 depressants. Caution patients against engaging in hazardous activities that require mental alertness, such as operating dangerous machinery or motor vehicles, until the effect of ONFI is known.

Withdrawal Symptoms

As with all antiepileptic drugs (AEDs), withdraw ONFI gradually to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus. Withdrawal symptoms occurred following abrupt discontinuation of ONFI; the risk of withdrawal symptoms is greater with higher doses.

Serious Dermatological Reactions

Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with ONFI in both children and adults during the post-marketing period. Discontinue ONFI at the first sign of rash, unless the rash is clearly not drug-related.

Physical and Psychological Dependence

Carefully monitor patients with a history of substance abuse when receiving ONFI or other psychotropic agents because of the predisposition of such patients to habituation and dependence. In clinical trials, cases of dependency were reported following abrupt discontinuation of ONFI. The risk of dependence increases with increasing dose and duration of treatment.

Suicidal Behavior and Ideation

AEDs, including ONFI, increase the risk of suicidal thoughts or behavior in patients. Inform patients, their caregivers, and families of the risk and advise them to monitor and report any emergence or worsening of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm. If these symptoms occur, consider whether it may be related to the AED or illness, because epilepsy itself can increase these risks.

Pregnancy, Registry and Nursing Mothers

Adverse Reactions

The most commonly observed adverse reactions reported in an LGS randomized, double-blind, placebo-controlled, parallel group clinical trial of patients who received clobazam as adjunctive therapy (≥10% in any treatment group and at least 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%).

For more information, please see the full Prescribing Information, including Boxed Warning for risks from concomitant use with opioids; Medication Guide; and Instructions for Use.

IMPORTANT SAFETY INFORMATION

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS

See full Prescribing Information for complete boxed warning.

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
  • Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
  • Limit dosages and durations to the minimum required.
  • Follow patients for signs and symptoms of respiratory depression and sedation.

Contraindication: Hypersensitivity

ONFI is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients. Hypersensitivity reactions have included serious dermatological reactions.

Risks from Concomitant Use with Opioids (see Boxed Warning)

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe ONFI concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use. Advise both patients and caregivers about the risks of respiratory depression and sedation when ONFI is used with opioids.

Potentiation of Sedation from Concomitant Use with Central Nervous System (CNS) Depressants

ONFI has a CNS depressant effect. Caution patients or their caregivers against simultaneous use with other CNS depressant drugs or alcohol and that the effects of other CNS depressant drugs or alcohol may be potentiated.

Somnolence or Sedation

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 depressants. Caution patients against engaging in hazardous activities that require mental alertness, such as operating dangerous machinery or motor vehicles, until the effect of ONFI is known.

Withdrawal Symptoms

As with all antiepileptic drugs (AEDs), withdraw ONFI gradually to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus. Withdrawal symptoms occurred following abrupt discontinuation of ONFI; the risk of withdrawal symptoms is greater with higher doses.

Serious Dermatological Reactions

Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with ONFI in both children and adults during the post-marketing period. Discontinue ONFI at the first sign of rash, unless the rash is clearly not drug-related.

Physical and Psychological Dependence

Carefully monitor patients with a history of substance abuse when receiving ONFI or other psychotropic agents because of the predisposition of such patients to habituation and dependence. In clinical trials, cases of dependency were reported following abrupt discontinuation of ONFI. The risk of dependence increases with increasing dose and duration of treatment.

Suicidal Behavior and Ideation

AEDs, including ONFI, increase the risk of suicidal thoughts or behavior in patients. Inform patients, their caregivers, and families of the risk and advise them to monitor and report any emergence or worsening of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm. If these symptoms occur, consider whether it may be related to the AED or illness, because epilepsy itself can increase these risks.

Pregnancy, Registry and Nursing Mothers

Adverse Reactions

The most commonly observed adverse reactions reported in an LGS randomized, double-blind, placebo-controlled, parallel group clinical trial of patients who received clobazam as adjunctive therapy (≥10% in any treatment group and at least 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%).

For more information, please see the full Prescribing Information, including Boxed Warning for risks from concomitant use with opioids; Medication Guide; and Instructions for Use.

References
  • Ng YT, Conry JA, Drummond R, et al. Randomized, phase Ill study results of clobazam in Lennox-Gastaut syndrome. Neurology. 2011;77(15):1473-1481.
  • ONFI [package insert]. Deerfield, IL: Lundbeck.
  • Conry JA, Ng YT, Paolicchi JM, et al. Clobazam in the treatment of Lennox-Gastaut syndrome. Epilepsia. 2009;50(5):1158-1166.