SPRAVATO(esketamine)nasal spray(十九)
NCT02493868) was a long-term randomized, double-blind, parallel-group, multicentermaintenance-of-effect study in adults 18 to <65 years of age who were known remitters andresponders to SPRAVATO. Patients in this study were responders in one of two short-term
controlled trials (Study 1 and another 4-week study) or in an open-label direct-enrollment studyin which they received flexibly-dosed SPRAVATO (56 mg or 84 mg twice weekly) plus dailyoral AD in an initial 4-week phase.
Stable remission was defined as a MADRS total score ≤ 12 for at least 3 of the last 4 weeks.
Stable response was defined as a MADRS total score reduction ≥ 50% for at least 3 of the last4 weeks and not in remission. After at least 16 initial weeks of treatment with SPRAVATO andan oral AD, stable remitters and stable responders were randomized separately to continueintranasal treatment with SPRAVATO or switch to placebo nasal spray, in both cases withcontinuation of their oral AD. The primary study endpoint was time to relapse in the stableremitter group. Relapse was defined as a MADRS total score ≥22 for 2 consecutive weeks orhospitalization for worsening depression or any other clinically relevant event indicative ofrelapse.
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The demographic and baseline disease characteristics of the two groups were similar. Patientshad a median age of 48 years (range 19 to 64 years) and were 66% female, 90% Caucasian, and4% Black.
Patients in stable remission who continued treatment with SPRAVATO plus oral ADexperienced a statistically significantly longer time to relapse of depressive symptoms than didpatients on placebo nasal spray plus an oral AD (see Figure 5).
Figure 5: Time to Relapse in Patients with TRD in Stable Remission in Study 2* (Full Analysis Set)。
* Note: The estimated hazard ratio (95% CI) of SPRAVATO + Oral AD relative to Placebo nasal spray + Oral AD based on weighted estimateswas 0.49 (95% CI: 0.29, 0.84). However, the hazard ratio did not appear constant throughout the trial.
Time to relapse was also significantly delayed in the stable responder population. These patientsexperienced a statistically significantly longer time to relapse of depressive symptoms thanpatients on placebo nasal spray plus oral AD (see Figure 6).
Figure 6: Time to Relapse in Patients in Stable Response in TRD Patients in Study 2* (Full Analysis Set)
* Note: The estimated hazard ratio (95% CI) of SPRAVATO + Oral AD relative to Placebo nasal spray + Oral AD based on Cox proportionalhazards model was 0.30 (95% CI: 0.16, 0.55).
In Study 2, based on depressive symptomatology, the majority of stable remitters (69%) receivedevery-other-week dosing for the majority of time during the maintenance phase; 23% of stableremitters received weekly dosing. Among stable responders, 34% received every-other-weekdosing and 55% received weekly dosing the majority of time during the maintenance phase. Ofthe patients randomized to SPRAVATO, 39% received the 56 mg dose and 61% received the84 mg dose.
14.3 Effects on Driving
Two studies were conducted to assess the effects of SPRAVATO on driving skills; one study inadult patients with major depressive disorder (Study 3) and one study in healthy subjects (Study4). On-road driving performance was assessed by the mean standard deviation of the lateralposition (SDLP), a measure of driving impairment.
A single-blind, placebo-controlled study in 25 adult patients with major depressive disordereva luated the effects of a single 84-mg dose of intranasal SPRAVATO on next |
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