Auteurs
ZAKI N.1, POPOVA V.5, CODET M.5, NASH A.2, CHEN N.1, LANE R.1, ZHANG Q.3, RANDALL L.1, SANACORA G.4 , MATHEWS M.1, B. SINGH J.1
- Janssen Research & Development, Titusville, Nj, Etats-Unis
- Janssen Scientific Affairs, Titusville, Nj, Etats-Unis
- Janssen Research & Development, Pennington, Nj, Etats-Unis
- Yale University School of Medicine, New Haven, Ct,, Etats-Unis
- Janssen Research and Development, Beerse, Belgique
Background
Esketamine nasal spray (ESK) plus a newly initiated oral antidepressant (AD) has demonstrated robust efficacy and an acceptable safety profile in managing treatment-resistant depression (TRD). However, long-term (>1 year) safety data are limited.
Methods
This ongoing phase 3, open-label extension study is being conducted to evaluate the long-term safety (and efficacy) of individualized, intermittently-dosed ESK in conjunction with an oral AD in patients with TRD. Patients (≥18 years) who previously participated in 1 of 6 phase 3, “parent” studies of ESK entered either the 4-week induction (IND) phase or the long-term optimization/maintenance (OP/M) phase of this study based on their status at the end of the parent study. Safety evaluations included treatment-emergent adverse events (TEAEs), and cognition. Interim safety results from the extension study are reported herein.
Results
A total of 1148 patients (458 entered at IND; 690 entered at OP/M) were enrolled in the study. Of 458 patients who entered the IND phase, 420 (91.7%) continued to OP/M phase. Of 1110 patients who participated in the OP/M phase, 306 (27.6%) discontinued the study, primarily due to AEs (n=54), lack of efficacy (n=48), and other reasons (n=135; e.g., symptom improvement, scheduling/logistical conflicts, etc.). The median total duration of exposure, including exposure in the preceding parent study, was approximately 3 years (35.8 [range: 0, 57] months). In total, 1064 patients experienced ≥1 TEAEs (IND: 346/458, 75.5%; OP/M: 1024/1110, 92.3%). The most common TEAEs (≥10% of patients) in IND phase were dissociation (21.2%), dizziness (20.5%), nausea (17.7%), vertigo (16.8%), dysgeusia (bad/altered taste) (16.6%), and headache (15.1%) and in OP/M phase were headache (31.2%), dizziness (29.8%), nausea (28.1%), dissociation (22.3%), somnolence (21.8%), nasopharyngitis (21.5%), dysgeusia (18.6%), vertigo (16.8%), anxiety (14.4%), back pain (14.3%), vomiting (13.6%), diarrhea (12.3%), increased blood pressure, urinary tract infection (each 12.1%), upper respiratory tract infection (11.3%), and blurred vision (10.1%). Most TEAEs were mild or moderate in severity. Long-term exposure to ESK did not reveal any additional safety signals of concern related to bladder-, lower urinary tract-, or hepatic-related TEAEs. There were 4 (0.3%) deaths, none considered by the investigator as related to ESK. Cognition remained stable or showed trend for small improvement among all patients during the IND and OP/M phases, with the exception of a slight slowing of reaction times in patients aged ≥65 years, consistent with results of another longitudinal trial.
Conclusion
This interim analysis suggests that long-term treatment (~3 years) with ESK+AD has acceptable safety and tolerability. No new or unexpected safety concerns emerged during 3-year intermittently-dosed treatment with ESK.
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