PRAX-944-221

20 evidence topics · 4 sources

Objective

Clinical and pharmacokinetic evaluation

“evaluating efficacy, safety, tolerability, and pharmacokinetics of PRAX-944 in adults with essential tremor (ET).” (opens the source at this quote in a new tab)

Location and study date

Study locations and exact conduct dates

No evidence found.

Study design

Part A open-label design

“Part A: Open label” (opens the source at this quote in a new tab)

Part B lead-in and withdrawal periods

Design feature	Reported value
Open-label phase	“42-day”
Randomized-withdrawal phase	“14-day”
Withdrawal-phase masking and control	“randomized, double-blind, placebo-controlled”

Eligibility criteria

Adult population and background treatment

“adult patients (≥18 years) with ET.” (opens the source at this quote in a new tab)
“Eligible participants were receiving either no medications or 1 stable dose tremor medication, excluding primidone.” (opens the source at this quote in a new tab)

Treatment

Dose-escalation regimens

Treatment component	Reported regimen
Part A initial dose	“20 mg”
Part A subsequent dose	“40 mg”
Duration at each Part A dose	“7 days”
Highest Part B dose	“120 mg”

Study outcomes

Rationale for using TETRAS upper limb score as the primary endpoint

Primary outcomes by study part

Study part	Primary outcome
Part A	“upper limb tremor”
Part B	“safety and tolerability”

Reliability of head and upper-limb tremor assessments

“The inter- and intra-rater intraclass correlations for head and upper limb tremor ranged from 0.86 to 0.96” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Convenience-sample planning

“was not selected according to any statistical power calculation.” (opens the source at this quote in a new tab)

Planned sample size

Population	Planned participants
Each study part	“up to 12 participants”
Permitted expansion of Part B	“up to 24 participants”

Part A efficacy population

“Change from baseline in TETRAS score (N=6)” (opens the source at this quote in a new tab)

Description of analysis sets

Summary

The protocol defined the safety population by receipt of at least one dose. The full analysis population additionally required valid baseline and post-baseline TETRAS assessments. The pharmacokinetic population required at least one evaluable plasma concentration. Analyses were primarily descriptive and separated the study parts; the randomized portion of Part B was summarized by assigned continuation treatment. The sample size was selected for feasibility rather than a formal confirmatory power calculation.

Safety analysis population

“all participants who received at least 1 dose of study drug.” (opens the source at this quote in a new tab)

Results

Participant disposition

Part A disposition

Disposition	Reported participants
Received PRAX-944	“Seven”
Completed all study visits	“6”

Part B evaluable and completion populations

Population	Reported participants
Evaluable participants	“14”
Completed open-label and randomized-withdrawal phases	“Eleven”
Ulixacaltamide among completers	“6”
Placebo among completers	“5”

Baseline characteristics

Part A baseline severity and propranolol use

Characteristic	Reported value
Mean baseline TETRAS-UL score	“12.4”
Baseline TETRAS-UL range	“10-15”
Concomitant propranolol among efficacy participants	“Five (83%)”

Efficacy results

Part A upper-limb tremor change at Day 14

“TETRAS-UL decrease of 2.8 points from baseline on Day 14” (opens the source at this quote in a new tab)
“42% reduction in upper limb tremor amplitude” (opens the source at this quote in a new tab)

Part B instrument-measured tremor during randomized withdrawal

Outcome	Continued PRAX-944	Placebo
Kinesia One mean percentage change from Day 42	“3%”	“29%”

Health-related quality of life and patient-reported outcomes

Part B functional change during randomized withdrawal

Outcome	Continued PRAX-944	Placebo
Modified ADL mean percentage change from Day 42	“8%”	“139%”

Disease-specific quality-of-life questionnaire results

No evidence found.

Safety results

Part B dose completion and tolerability

Safety or exposure outcome	Reported value
Participants completing titration at the highest dose	“Eight of 11”
Highest dose	“120 mg”
Evaluable participants discontinuing because of TEAEs	“three of 14”
Discontinuation unrelated to study drug	“1”

Study limitations

Summary

Part A was open label, with seven treated participants and six completing all visits. Five of the six efficacy participants were receiving propranolol. Part B reported 14 evaluable participants and 11 completing the open-label and randomized-withdrawal phases. These small populations, the uncontrolled initial treatment periods, and the brief withdrawal comparison limit precision and generalizability. The protocol describes feasibility-based sampling and primarily descriptive analyses. The findings support dose and endpoint development but do not independently establish confirmatory efficacy or long-term safety.