Novel neuroplastogen for PTSD clears phase 2 trial

The highly selective, rapid-acting neuroplastogen TSND-201 appears to be efficacious and well tolerated in the treatment of post-traumatic stress disorder (PTSD), according to the results of a phase 2 trial.

The trial included 65 adults (mean age 43.7 years, 60 percent female) with PTSD who had been showing symptoms (Clinician-Administered PTSD Scales for DSM-5 [CAPS-5] ≥35) for at least 6 months. These participants were randomly assigned to receive TSND-201 or placebo. Treatment consisted of four once-weekly oral dosing sessions (150 mg followed by 100 mg or placebo). No psychotherapy was provided. All participants were followed up for 6 weeks after the last dose.

The change in the CAPS-5 total severity score from baseline to day 64 was the primary endpoint. Secondary endpoints included changes in PTSD Checklist for DSM-5 (PCL-5), Sheehan Disability Scale (SDS), and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Response (≥50-percent improvement from baseline), remission (≤11 total severity score), loss of PTSD diagnosis, changes in CAPS-5 symptom clusters, and treatment-emergent adverse events (TEAEs) were also assessed.

Compared with placebo, TSND-201 was associated with significantly greater improvement in CAPS-5 total score at day 64 (least-squares [LS] mean difference, 9.64, 90 percent confidence interval [CI], −16.48 to −2.80; p=0.01).

TSND-201 was also associated with more favourable changes in PCL-5 (−28.46 vs −19.47; LS mean treatment difference, −8.99), SDS (−8.29 vs −3.57; LS mean treatment difference, −4.72), and MADRS (−13.94 vs −7.73; LS mean treatment difference, −6.21) scores relative to placebo.

Headache, decreased appetite, nausea, dizziness, blood pressure increased, dry mouth, and insomnia were the most frequent TEAEs reported in the TSND-201 group.