PRAX-944-105
15 evidence topics · 2 sources
Objective
Safety and clinical pharmacology
Location and study date
Location and conduct dates
Study design
Open-label and randomized parts
| Study component | Reported design |
|---|---|
| Part A | “open-label” |
| Part B | “randomized, double-blind, placebo-controlled” |
| Part B allocation | “3:1” |
Eligibility criteria
Healthy adult population
| Criterion | Reported requirement |
|---|---|
| Population | “healthy participants” |
| Age range | “18–55 years” |
Treatment
Fixed-dose titration
| Treatment component | Reported value |
|---|---|
| Part A dose sequence | “5, 10, and 20 mg” |
| Part A treatment duration | “12 days” |
| Initial Part B dose | “20 mg” |
| Subsequent Part B dose | “40 mg” |
| Later Part B doses | “60, 80, 100, and 120 mg” |
| Part B assessment days at later dose levels | “10, 17, 24, and 31” |
Study outcomes
Rationale for using NREM Sigma-Power as a pharmacodynamic endpoint
Summary
NREM sigma-power was investigated as a pharmacodynamic measure of central T-type calcium-channel blockade. The study compared human changes in this signal with preclinical findings at exposures associated with tremor reduction. This is target-engagement evidence in healthy participants, not direct evidence that a specified sigma-power reduction produces a clinically meaningful benefit in essential tremor.
Frequency range used for sigma-power measurement
| Measurement | Reported frequency range |
|---|---|
| Absolute NREM sigma-power | “11 and 15 Hz” |
Statistical analysis description
Number of participants (Planned and analyzed)
Description of analysis sets
Summary
The Part B pharmacodynamic analysis used natural-log-transformed NREM sigma-power values. The repeated-measures model included timepoint, treatment, their interaction, and baseline value, with an unstructured covariance pattern. Treatment-to-placebo ratios were obtained by exponentiating the estimated between-group differences. The published analysis table included ten PRAX-944 participants and four placebo participants.
Results
Participant disposition
Full participant flow and reasons for exclusions from pharmacodynamic analysis
No evidence found.
Baseline characteristics
No evidence found.
Efficacy results
Pharmacodynamic response in healthy participants
Part B NREM sigma-power ratios versus placebo
| Assessment | Treatment-to-placebo difference ratio and 95% CI | Probability value |
|---|---|---|
| Day 10, 60 mg | “0.550 (0.353, 0.859)” | “0.0132” |
| Day 17, 80 mg | “0.498 (0.257, 0.965)” | “0.0407” |
| Day 24, 100 mg | “0.482 (0.335, 0.695)” | “0.0011” |
| Day 31, 120 mg | “0.507 (0.314, 0.819)” | “0.0098” |
Clinical efficacy in essential tremor
Not applicable.
Health-related quality of life and patient-reported outcomes
Not applicable.
Safety results
Study limitations
Summary
The study enrolled healthy adults rather than participants with essential tremor. Part A included eight participants; Part B allocated twelve to PRAX-944 and four to placebo, with ten active-treatment participants represented in the reported pharmacodynamic analysis. The treatment periods and small placebo population limit safety precision. NREM sigma-power is a target-engagement measure rather than a patient-centered clinical outcome, so these results do not establish essential tremor efficacy, a clinically meaningful response threshold, or long-term tolerability.