Gigi is living with CDD.
DEMONSTRATED SAFETY PROFILE IN PATIENTS 2 YEARS AND OLDER WITH CDKL5 DEFICIENCY DISORDER (CDD)1
Most common adverse reactions in the pivotal trial
Adverse reactions that occurred in ZTALMY-treated patients with seizures associated with CDD at a rate ≥3% and greater than that with placebo
| Adverse Reaction | ZTALMY (n=50) | Placebo (n=51) |
|---|---|---|
| Somnolence*† | 38% | 20% |
| Pyrexia | 18% | 8%0 |
| Upper respiratory tract infection | 10% | 6%0 |
| Sedation† | 6% | 4%0 |
| Salivary hypersecretion | 6% | 2%0 |
| Seasonal allergy | 6% | 00% |
| Bronchitis | 4% | 00% |
| Influenza | 4% | 2%0 |
| Gait disturbance | 4% | 2%0 |
| Nasal congestion | 4% | 2%0 |
*Includes the terms lethargy and hypersomnia.
†Adverse reactions that occurred with a 21-day titration; somnolence and sedation are expected to be reduced with the recommended 28-day titration.
The most frequent adverse reactions leading to a dose interruption or reduction in ZTALMY-treated patients were somnolence (10%) and sedation (2%).
Somnolence and Sedation
ZTALMY can cause somnolence and sedation. In a clinical study somnolence and sedation appeared early during treatment and were generally dose related. Other CNS depressants, including opioids, antidepressants, and alcohol, could potentiate these effects. Monitor patients for these effects and advise them not to drive or operate machinery until they have gained sufficient experience with ZTALMY.1
CNS=central nervous system.
Fewer patients taking ZTALMY discontinued treatment compared with placebo2
Incidence of discontinuation due to adverse reactions in the pivotal trial2
of patients given ZTALMY
of patients given placebo
The adverse reactions leading to discontinuation in the ZTALMY group were somnolence and seizure (1 patient) and seizure (1 patient).1
Withdrawal of antiepileptic drugs (AEDs)
As with most AEDs, withdraw ZTALMY gradually to minimize the risk of increased seizure frequency and status epilepticus. If withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.1
Most adverse events were mild or moderate in severity2
Summary of TEAEs* over 17 weeks2
| Severity† | ZTALMY (n=50) | Placebo (n=51) |
|---|---|---|
| Mild | 32% | 52.9% |
| Moderate | 52% | 29.4% |
| Severe | 2% | 5.9%0 |
*TEAE=treatment-emergent adverse event, defined as an AE that occurred or worsened on the day of or after the first dose of study drug.2
†Highest severity for subjects.2
Note: If a subject experienced more than 1 adverse event in a category, the subject was counted only once in that category.2
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including ZTALMY, increase the risk of suicidal thoughts or behavior. Monitor patients taking ZTALMY for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior.1
About the study population
The pivotal trial was a double-blind, randomized, placebo-controlled study of 101 patients with CDD aged 2 to 19 years.1
- Patients had tried and discontinued a median of 7 ASMs2
- Patients were taking a median of 2 concomitant ASMs2*
- Patients had a median of 50 major motor seizures per 28 days2
ASMs=antiseizure medications.
*96% of patients were taking at least 1 ASM. The most frequently used (by ≥20% of patients) concomitant ASMs were valproate, levetiracetam, clobazam, and vigabatrin.1
ZTALMY was administered concomitantly
with commonly used ASMs in CDD1,3,4
of patients taking ZTALMY received concomitant ASM treatment2
The most common ASMs (used by ≥20% of patients) were2:
- valproate
- levetiracetam
- clobazam
- vigabatrin
of patients taking ZTALMY used other concomitant medications2
The most common concomitant non-ASM medications were2:
- acetaminophen (n=15)
- polyethylene glycol (PEG) (n=5)
CYP3A4 inducers and UGT inhibitors
Cytochrome P450 inducers will decrease ganaxolone exposure. Avoid concomitant use with strong or moderate CYP3A4 inducers; if unavoidable, consider a dosage increase of ZTALMY, but do not exceed the maximum recommended dosage.
UGT inhibitors may increase ganaxolone exposure. Consider a reduction of ZTALMY maintenance dose when initiating UGT inhibitors.1
Results from an open-label extension study
Following the pivotal trial, an open-label extension (OLE) study was conducted in patients taking ZTALMY. The secondary objectives of the OLE study were to assess the long-term efficacy, safety, and tolerability of ZTALMY. Safety findings in the OLE study were consistent with those observed in the pivotal study.
