655. EXPANDING ACCESS TO KETAMINE THROUGH REFORMULATION

Abstract Background Ketamine, a rapidly acting antidepressant, requires dosing in clinic because of strong symptoms of dissociation and sedation after IV/IN dosing. This need for dosing in clinic limits capacity to treat patients with Treatment Resistant depression (TRD). We hypothesize that ketamine formulations that maximize ketamine’s first pass metabolism and delay absorption will have improved tolerance 1 and could permit dosing at home. Aims & Objectives To evaluate the safety, tolerability and efficacy of an extended-release racemic ketamine tablet in patients with TRD (R-107, developed by Douglas Pharmaceuticals). Method In this phase 2 multicenter clinical trial, adult patients with TRD and Montgomery–Asberg Depression Rating Scale (MADRS) scores ≥20 received open-label R-107 tablets 120 mg per day for 5 days and were assessed on day 8 (enrichment phase). On day 8, responders (MADRS scores ≤12 and reduction ≥50%) were randomized on a 1:1:1:1:1 basis to receive double-blind R-107 doses of 30, 60, 120 or 180 mg, or placebo, twice weekly for a further 12 weeks. Nonresponders on day 8 exited the study. Results 231 patients entered the open-label enrichment phase (days 1–8) and 168 responders were randomized to double-blind treatment. The primary objective was met; the least square mean difference of MADRS score for the 180 mg tablet group and placebo was −6.1 (95% confidence interval 1.0-11.16, P = 0.019) at 13 weeks. Relapse rates during double-blind treatment showed a dose response from 70.6% for placebo to 42.9% for 180 mg. Tolerability was excellent, with no changes in blood pressure, minimal reports of sedation and minimal dissociation. Most patient dosing occurred at home 2. Discussion & Conclusions Extended-release ketamine tablets were acutely effective in 73% of patients with TRD within 1 week. Maintenance of this antidepressant activity was greatest in those receiving 180mg twice weekly over the next 3 months. As predicted, dissociation was minimal, tolerability was good, and most dosing occurred at home. This would expand access to ketamine treatment to a greater number of patients with TRD.