Clinical Data Efficacy Results
Daily treatment of PRAX-114 in Part B of the Phase 2a study showed a rapid and marked decrease in menopausal symptoms throughout the 14-day treatment period. Treatment with PRAX-114 resulted in mean decreases from baseline at Day 15 of 60% in frequency of moderate-to-severe hot flashes and 68% in the total score of the Perimenopausal Depression Questionnaire (Meno-D)1, a 12-item, self-reported questionnaire assessing the presence and severity of symptoms of PMD. Improvements were observed in each of the 12 items of the Meno-D, with the largest reductions observed in measures of low energy, sexual interest, sleep disturbance, irritability and anxiety. At Day 28, two weeks following discontinuation of treatment, frequency of moderate-to-severe hot flashes and Meno-D total score trended toward baseline.
Daily treatment of PRAX-114 in Part B of the Phase 2a study showed a rapid and marked decrease in mood symptoms throughout the 14-day treatment period. Treatment with PRAX-114 resulted in mean decreases from baseline at Day 15 of 47% in the HAM-D total score, 65% in the HAM-A total score and 40% in the total score of the Symptoms of Depression Questionnaire (SDQ)2, a patient reported outcome of depression severity. At Day 28, two weeks following discontinuation of treatment, HAM-D, HAM-A and SDQ total scores trended toward baseline.
Figure 1: Rapid and marked decrease in menopausal and mood symptoms, as measured by frequency of moderate-to-severe hot flashes per day, the Meno-D total score, the Hamilton Depression Rating Scale (HAM-D) total score, the Hamilton Anxiety Rating Scale (HAM-A) total score and SDQ total score
  Baseline Mean (SD) Day 15 CFB Mean (SD) [%] Day 28* Follow-up CFB Mean (SD) [%]Mod-Severe Hot Flashes 3.2 (0.43) -1.9 (1.23) [-60%] -0.9 (2.19) [-23%]Meno-D 25.3 (5.85) -18.4 (5.27) [-68%] -10.2 (5.63) [-37%]HAM-D 25.3 (2.16) -12.0 (8.09) [-47%] -8.2 (6.69) [-31%]HAM-A 24.8 (4.31) -16.2 (5.22) [-65%] -8.4 (8.14) [-32%]SDQ 166.2 (14.72) -67.6 (25.64) [-40%] -53.0 (32.58) [-31%]Change from baseline (CFB) columns present mean, standard deviation (SD) and % change from baseline values*Day 28 assessment performed two-weeks following discontinuation of treatmentSafety Results
Daily treatment with 60mg of PRAX-114 suspension formulation in Part B of the Phase 2a study was well tolerated, with no change in the overall safety profile. One Part B participant discontinued treatment due to adverse events (AEs) of moderate daytime sedation and mild feeling abnormal. There have been no prior reports of daytime sedation in the PRAX-114 Phase 1 and Phase 2 studies, which includes 185 participants. All AEs were mild to moderate in severity. There were no serious adverse events (SAEs).
In the Phase 2a study overall, PRAX-114 suspension formulation was well tolerated in 52 participants with major depressive disorder (MDD) or PMD. The most common AEs were headache, somnolence, dizziness, fatigue and feeling abnormal. The majority of AEs were mild, and there were no SAEs.
Figure 2: Treatment emergent adverse events reported in ≥10% of participants across all parts of the PRAX-114 Phase 2a study (Parts A, B and C)
  45 mg* 60 mg 80 mg* OverallPreferred Term (N=13) (N=32) (N=7) (N=52)Any TEAE 9 (69.2%) 31 (96.9%) 7 (100.0%) 47 (90.4%)Headache 7 (53.8%) 12 (37.5%) 3 (42.9%) 22 (42.3%)Somnolence 2 (15.4%) 12 (37.5%) 3 (42.9%) 17 (32.7%)Dizziness 0 (0.0%) 5 (15.6%) 4 (57.1%) 9 (17.3%)Fatigue 3 (23.1%) 2 (6.3%) 1 (14.3%) 6 (11.5%)Feeling abnormal 1 (7.7%) 4 (12.5%) 1 (14.3%) 6 (11.5%)Nausea 0 (0.0%) 5 (15.6%) 1 (14.3%) 6 (11.5%)*Includes participants from Part A onlyIn Part A, PRAX-114 was administered at daytime of Day 1, nighttime of Days 2-14About the PRAX-114 Phase 2a Study for Depression
The PRAX-114 Phase 2a study for depression included three open-label parts to assess the safety and efficacy of PRAX-114 suspension formulation in patients with moderate to severe MDD or PMD. Part A of the open-label trial included 14-days of treatment and was designed to evaluate the timing and magnitude of the antidepressant effects of PRAX-114 across a range of doses (45 mg, 60 mg, 80 mg) in patients with MDD. Part B of the Phase 2a study was an open-label, proof-of-concept assessment of a single daily dose of PRAX-114 60 mg suspension formulation administered for 14-days in an outpatient setting to women with PMD. The objectives of the study were to examine safety and efficacy of PRAX-114 in PMD, a population of women with symptoms of menopause, including vasomotor symptoms (hot flashes), insomnia and sexual dysfunction, and mood symptoms, including depression and anxiety. Part C was intended to evaluate the safety of 28-day outpatient dosing of PRAX-114 and the efficacy profile from Day 15 to Day 28 in patients with MDD.