A Study To Assess the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor (ET): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study To Assess the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor (ET) (NCT05122650), a randomized phase 2 study. The primary outcome is Change From Baseline to Week 12 on the TETRAS Composite Outcome Score as Summarized by Each Dose of JZP385 and Placebo.

2. Clinical Question

3. Trial Design

The registry describes a Phase 2b, 12-week, double-blind, placebo-controlled, randomized, parallel-group, multicenter study of JZP385 in adults with moderate to severe essential tremor. The phase field identifies the study as Phase 2. The study is listed as completed, with enrollment of 420 participants. The registry dates are 2021-12-06 for study start and 2024-05-30 for primary completion.

Participants were assigned to placebo or one of three JZP385 dose groups. The active-dose groups used gradual dose increases: all began at 5 mg/day from Day 1 through Day 7; the 10 mg group began 10 mg/day on Day 8; the 20 mg group increased to 10 mg/day from Day 8 through Day 14 and to 20 mg/day starting on Day 15; and the 30 mg group increased to 10 mg/day from Day 8 through Day 14, 20 mg/day from Day 15 through Day 21, and 30 mg/day starting on Day 22. Placebo was given from Day 1.

Double-blinding means participants and relevant study personnel were masked to assigned treatment, as recorded by the registry. The record does not report which individuals were masked or the procedures used to maintain masking. It also does not report the allocation ratio or the original sample-size justification. The registry enrollment figure is not the same as the number contributing to each posted outcome: the primary-outcome summaries include 94 participants for placebo, 79 for 10 mg, 82 for 20 mg, and 78 for 30 mg.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The primary outcome was assessed in participants in the Intent to Treat (ITT) analysis population set that completed the baseline and week 12 TETRAS assessment.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to Week 12 on the TETRAS Composite Outcome Score as Summarized by Each Dose of JZP385 and Placebo, measured over Change from baseline to week 12.

The primary endpoint is change from baseline to week 12 in the TETRAS composite outcome score. It adds 14 modified items: items 1 through 11 of the TETRAS activities-of-daily-living subscale and items 6 and 7 of the TETRAS performance subscale. The activities-of-daily-living subscale is patient-rated with a trained interviewer and covers the impact of tremor on daily functioning, including eating, drinking, dressing, and fine motor skills. The performance scale is a clinical rating of tremor in the head, face, voice, limbs, and trunk; the selected items assess upper-limb tremor during drawing and handwriting.

Each item ranges from 0 to 3, and the summed composite score ranges from 0 to 42. Higher scores represent more severe essential tremor. The endpoint is therefore intended to capture changes across daily activities and selected performance tasks, rather than relying on a single symptom or task. A negative change indicates a decrease in the score from baseline. By comparing the mean change in each dose group with the mean change under placebo, the analysis describes the relative size and uncertainty of the observed changes.

The registry states that the primary outcome was assessed in the Intent to Treat analysis population set that completed baseline and week 12 TETRAS assessments. The exact operational definition of that population and the handling of participants without both assessments are not reported in the registry record.

7. Results Posted in the Registry

• 10 Milligram (mg) JZP385: mean -5.80 versus -6.30 on control; difference 0.50 (95% CI -1.47 to 2.47), standardized effect d = 0.08; z-test p = 0.618.
• 20 mg JZP385: mean -6.70 versus -6.30 on control; difference -0.40 (95% CI -2.35 to 1.55), standardized effect d = -0.06; z-test p = 0.687.
• 30 mg JZP385: mean -7.50 versus -6.30 on control; difference -1.20 (95% CI -3.25 to 0.85), standardized effect d = -0.18; z-test p = 0.252.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants Who Improved (≥ 1-Point Improvement) From Baseline to Week 12 on the Clinical Global Impression- Severity Scale (CGI-S)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • 10 Milligram (mg) JZP385: 49.5% (52/105) versus 50.0% (52/104) on control; risk difference -0.5 percentage points (95% CI -14.0 to 13.1), risk ratio 0.99 (0.75–1.30); unadjusted two-proportion z-test p = 0.945.
  • 20 mg JZP385: 55.8% (58/104) versus 50.0% (52/104) on control; risk difference 5.8 percentage points (95% CI -7.8 to 19.3), risk ratio 1.12 (0.86–1.44); unadjusted two-proportion z-test p = 0.405.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 10 Milligram (mg) JZP385 and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 20 mg JZP385 and the control. The interval gives the range of effects that remain compatible with the data.

Proportion of Participants Reported as Much Improved on the Clinical Global Impression of Change (CGI-C) at Week 12

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • 10 Milligram (mg) JZP385: 22.8% (18/79) versus 23.4% (22/94) on control; risk difference -0.6 percentage points (95% CI -13.2 to 12.0), risk ratio 0.97 (0.56–1.68); unadjusted two-proportion z-test p = 0.923.
  • 20 mg JZP385: 23.2% (19/82) versus 23.4% (22/94) on control; risk difference -0.2 percentage points (95% CI -12.7 to 12.3), risk ratio 0.99 (0.58–1.69); unadjusted two-proportion z-test p = 0.971.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 10 Milligram (mg) JZP385 and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 20 mg JZP385 and the control. The interval gives the range of effects that remain compatible with the data.

Proportion of Participants Reported as Much Improved on the Patient Global Impression of Change (PGI-C) at Week 12

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • 10 Milligram (mg) JZP385: 13.9% (11/79) versus 17.0% (16/94) on control; risk difference -3.1 percentage points (95% CI -13.9 to 7.7), risk ratio 0.82 (0.40–1.66); unadjusted two-proportion z-test p = 0.576.
  • 20 mg JZP385: 24.4% (20/82) versus 17.0% (16/94) on control; risk difference 7.4 percentage points (95% CI -4.6 to 19.4), risk ratio 1.43 (0.80–2.58); unadjusted two-proportion z-test p = 0.227.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 10 Milligram (mg) JZP385 and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 20 mg JZP385 and the control. The interval gives the range of effects that remain compatible with the data.

The numerical secondary results cover participant-rated and clinician-rated global impressions at week 12, along with improvement on the Clinical Global Impression-Severity scale. The posted percentages or counts vary across the placebo and dose groups, but the corresponding unadjusted comparisons have confidence intervals that include no difference. Across these measures, the pattern is not uniformly aligned across doses or across the different types of assessment. The registry record also lists additional secondary outcome measures based on TETRAS subscales and the quality-of-life questionnaire; numerical results for those outcomes are not reported in the registry record.

These outcomes provide different perspectives from the primary TETRAS composite score. Global change measures capture an overall judgment of improvement, while the composite score combines selected daily-activity and performance items. Agreement across different measures can add context, but disagreement is also possible because the measures assess different constructs and use different scales. The secondary findings do not resolve the uncertainty in the primary comparison: the primary estimates are imprecise, and the secondary comparisons are unadjusted.

Unadjusted secondary results carry less weight as confirmatory evidence because multiple outcomes and group comparisons create multiple opportunities for chance findings. The registry record does not report a multiplicity strategy, a hierarchy of endpoints, or formal reported analyses for the secondary outcomes. Their estimates are best treated as exploratory descriptions of the posted data rather than as independent confirmation of a treatment effect. The results can help identify patterns for future evaluation, but they do not establish a consistent effect across outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants Who Improved (≥ 1-Point Improvement) From Baseline to Week 12 on the Clinical Global Impression- Severity Scale (CGI-S)
• Proportion of Participants Reported as Much Improved on the Clinical Global Impression of Change (CGI-C) at Week 12
• Proportion of Participants Reported as Much Improved on the Patient Global Impression of Change (PGI-C) at Week 12
• Change From Baseline to Week 12 on the TETRAS-ADL Subscale as Summarized by Each Dose of JZP385 and Placebo
• Change From Baseline to Week 12 on the TETRAS-PS Subscale as Summarized by Each Dose of JZP385 and Placebo
• Change From Baseline to Week 12 on the Upper Limb Score (Item 4) of the TETRAS-PS as Summarized by Each Dose of JZP385 and Placebo
• Change From Baseline to Week 12 on the TETRAS Total Score, as Summarized by Each Dose of JZP385 and Placebo.
• Change From Baseline to Week 12 on the Quality of Life in Essential Tremor Questionnaire (QUEST) as Summarized by Each Dose of JZP385 and Placebo

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: each participant’s TETRAS composite score can take values across a numerical scale, and the registry reports mean change and standard deviation by group. A mean is a measure of the group’s average change. The standard deviation describes how spread out participant-level changes are around that average. A larger standard deviation means more variability among the observed changes, not necessarily greater uncertainty about the mean by itself. The primary group standard deviations were 6.22 for placebo, 6.85 for 10 mg, 6.88 for 20 mg, and 7.31 for 30 mg.

What does a mean difference express?

The mean difference compares the average change in a JZP385 group with the average change in placebo. The posted estimates are 0.5 for 10 mg, -0.4 for 20 mg, and -1.2 for 30 mg. In this comparison, a negative difference means the active-dose group’s average score change was more negative than placebo’s; a positive difference means it was less negative. The sign is an arithmetic description of relative change, not a judgment about clinical importance. The registry does not report a threshold for a clinically meaningful difference on this composite score.

The between-group estimates and confidence intervals in the comparison summaries are recalculated, unadjusted comparisons based on the posted group means, standard deviations, and participant counts. They are not reported sponsor analyses. A confidence interval gives a range of values reasonably compatible with the observed data under the assumptions of the calculation. Its width reflects uncertainty: all else equal, more variability or fewer observations tends to make an estimate less precise. These confidence intervals are not adjusted for the set of dose comparisons or outcomes.

How should p-values be understood?

A p-value describes how unusual the observed data, or data more extreme, would be under a specified null model. For the primary comparisons, the recalculated unadjusted p-values are 0.618, 0.687, and 0.252. They do not measure the probability that the null hypothesis is true, the probability that a result will replicate, or the size or importance of an effect. Nor do they substitute for considering the estimate and its confidence interval. The registry does not report a prespecified statistical analysis plan or a multiplicity adjustment, so the p-values should be interpreted as unadjusted descriptive results.

General statistical explanation: testing several doses or endpoints increases the opportunities to observe a small p-value by chance if each test is considered separately. Methods that account for multiple testing can change the interpretation of a collection of tests. Whether and how such a method was planned or used is not reported in the registry record. Consequently, the unadjusted values should not be treated as if they control the overall chance of a false-positive conclusion across all comparisons.

What does the standard deviation contribute?

General statistical explanation: standard deviation describes participant-to-participant spread, while the standard error describes the precision of an estimated mean. The comparison calculations use the reported group spreads and sample sizes. The posted mean difference is therefore not just a comparison of the two means in isolation; its uncertainty also depends on how variable the participant changes were and how many participants contributed. The registry record does not report individual participant data, so the recalculations cannot account for covariates, repeated measurements, or other adjustments that might appear in a prespecified model.

The record lists no reported analyses for the primary comparison. It reports means and standard deviations for the primary outcome and sample counts by group, but does not describe a model, covariate adjustment, assumptions checking, or handling of departures from model assumptions. These details are not reported in the registry record. The recalculated comparisons should therefore be understood as simple unadjusted comparisons, not as reconstructions of an unknown sponsor model.

Why does the outcome population matter?

The primary outcome population is described as the Intent to Treat population set that completed both baseline and week 12 TETRAS assessments. In common statistical usage, an intention-to-treat analysis generally aims to retain participants according to randomized assignment, but the registry’s specific wording also requires completed assessments for this outcome. It does not state whether missing week 12 values were imputed, whether participants with incomplete assessments were excluded, or how deviations from assigned treatment were handled. Those details matter because missing outcome data can affect the group means and the reliability of comparisons.

General statistical explanation: if outcome availability is related to treatment assignment, participant characteristics, or the unobserved outcome itself, an analysis restricted to observed assessments can differ from an analysis of all randomized participants. This does not show that such bias occurred in this trial; the registry record does not provide the information needed to assess it.

The sample-size figures are planning illustrations based on fractions of the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They do not reproduce the original trial’s design calculation, whose assumptions are not reported in the registry record. They address hypothetical future planning under stated assumptions, not the statistical power of the completed trial.

11. Confidence Intervals and Precision

The primary confidence intervals are broad relative to their point estimates and each crosses zero. For 10 mg, the mean-difference estimate is 0.5, with a confidence interval from -1.465 to 2.465. For 20 mg, the estimate is -0.4, with an interval from -2.349 to 1.549. For 30 mg, the estimate is -1.2, with an interval from -3.253 to 0.853. These ranges include both differences favoring a greater decrease in the score with JZP385 and differences favoring placebo, because a lower score change is more negative.

A confidence interval is not a range that contains the true value with certainty. In general statistical terms, it is a measure of uncertainty generated by a method that would cover the underlying value at its stated confidence level over repeated use under the method’s assumptions. The registry does not report sponsor confidence intervals for the primary comparisons; these are unadjusted recalculations from posted summary statistics. Their interpretation relies on the simple comparison assumptions and does not incorporate any adjustment for multiple comparisons.

The group standard deviations show appreciable variation in observed score changes, while the outcome counts are 94 for placebo and 79, 82, and 78 in the respective JZP385 groups. Both variability and sample size affect precision. The intervals do not rule out meaningful differences in either direction, but the registry does not define a threshold for clinical importance, so the range cannot be classified as excluding or demonstrating a clinically important effect. Precision is limited for distinguishing modest differences, and the point estimates alone should not be treated as definitive evidence of a dose pattern.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size planning figures are participants per arm for 80% power or participants per arm for 90% power; these comparisons are not time-to-event outcomes, so the figures are not total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The original trial’s own sample-size assumptions and justification are not reported in the registry record.

The 80% power column describes the number of participants per arm that the planning calculation estimates would be needed to detect the specified effect with 80% power under those assumptions. The 90% power column gives the corresponding number for 90% power. Power is the chance of detecting an effect of the assumed size under the model if that effect is present; it is not a guarantee that a study will find a difference. The displayed values are planning illustrations, not observed power for the completed trial.

Rows based on 100%, 75%, and 50% of the observed effect show how the planning estimate changes when the assumed effect is made smaller. Smaller effects generally require more participants to distinguish them from random variation at the same power and significance level. These calculations use the observed effect as a reference, but an observed estimate may be imprecise and may not represent the effect in a future study. The figures therefore illustrate the consequences of the stated assumptions rather than prescribe a design or validate the size of the original study.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.500; pooled standard deviation σ = 6.515.
2. n = 2 × (1.96 + 0.842)² × 6.515² / 0.500² = 2,665.1, rounded up to 2,666 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.5                      # observed difference in means
sigma <- 6.51492941352075                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(5122650)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2,666 (80% power), 3,568 (90% power)
 75% of observed effect: n per arm = 4,738 (80% power), 6,343 (90% power)
 50% of observed effect: n per arm = 10,661 (80% power), 14,272 (90% power)
power.t.test: 2666.1 
Simulated power at n = 2,666 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and multiple secondary outcomes, including several comparisons of JZP385 doses with placebo. It does not report a statistical analysis plan, a testing hierarchy, or a method for controlling multiplicity. The unadjusted comparisons therefore do not account for the fact that several doses and outcomes are being considered together. This limits the strength of conclusions drawn from any single unadjusted p-value, particularly for secondary endpoints.

The primary outcome population is described as the Intent to Treat population set that completed baseline and week 12 assessments. That wording identifies the participants contributing to the primary endpoint but does not fully describe how randomized participants with incomplete measurements were handled. Missing-data procedures, imputation methods, sensitivity analyses, and reasons for missing endpoint assessments are not reported in the registry record. The handling of missing data for the secondary endpoints is also not reported in the registry record.

The registry enrollment is 420, whereas the primary outcome summaries have smaller arm-specific counts. This difference is not by itself evidence of a particular reason for non-inclusion: the record does not provide a full accounting of the randomized participants, withdrawals, exclusions, or outcome availability in the primary analysis population. It also does not report whether analyses were adjusted for baseline values or other participant characteristics.

Interim analyses, stopping rules, and the prespecified significance threshold for the trial’s own primary analysis are not reported in the registry record. The planning illustration specifies a two-sided significance level of 0.05, but that is an assumption used for those calculations and should not be taken as the trial’s original analysis plan. Without the missing details, readers cannot establish whether the posted summaries represent the planned primary analysis or assess how analytic decisions may have affected the results.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: coronary artery disease (1.0%), abscess limb (1.0%), pneumonia (1.0%), fall (1.0%), foot fracture (1.0%).

The registry reports serious adverse events by group, with each group’s at-risk count and the number affected. There were 3 serious adverse events among 104 participants in the placebo group, 3 among 104 in the 10 mg JZP385 group, 4 among 103 in the 20 mg group, and 4 among 105 in the 30 mg group. These are counts, not estimates of comparative risk adjusted for exposure time or other factors. The registry lists no deaths in the JZP385 groups and 1 death in the placebo group.

The record also lists serious-event terms, each at 1.0%: coronary artery disease, abscess limb, pneumonia, fall, foot fracture, and chest pain. The listed terms should be read as event categories in the registry, not as evidence that treatment caused an event. The record does not report a statistical comparison of serious adverse events across groups or enough detail to infer differences in risk from these counts.

For other adverse events, the affected counts are 20 of 104 for placebo, 35 of 104 for 10 mg, 35 of 103 for 20 mg, and 46 of 105 for 30 mg. These are distinct from the serious-event counts. Adverse-event summaries describe reported events during the study; they do not, on their own, establish causality or characterize an individual participant’s risk.

16. What the Result Does, and Does Not, Mean

The primary outcome summaries show decreases in the mean TETRAS composite score from baseline in all four groups. The active-dose group means were not all lower than the placebo mean, and the between-group estimates are modest relative to their uncertainty. Each primary confidence interval includes zero, so the posted comparisons do not clearly distinguish the dose groups from placebo on the basis of these unadjusted summaries. They also do not rule out differences in either direction.

This interpretation is about the observed score changes and their precision, not a medical recommendation. The registry data do not support a simple conclusion that every dose produced a larger decrease than placebo, nor do the summaries establish that no difference exists. The estimates are compatible with a range of possible between-group effects. The record does not report a threshold defining how large a change on the composite scale would be clinically important, so statistical estimates cannot be translated directly into a judgment about practical importance.

The secondary outcome summaries offer context but do not supply a definitive resolution. They involve different perspectives on tremor and improvement, and the displayed comparisons are unadjusted. The lack of reported multiplicity procedures and the absence of numerical results for several listed outcomes further limit how strongly the secondary results can support a broad claim.

Safety counts should likewise be interpreted descriptively. The recorded serious adverse events and deaths provide a summary of what was reported in each group, but they are not adjusted comparisons and cannot establish cause. Taken together, the record supports a careful reading of group-level outcome and safety summaries, with substantial uncertainty about comparative effects. It does not provide the full analysis plan, missing-data methods, or enough detail to reconstruct the trial’s complete inferential analysis.

17. Why This Trial Matters Statistically

This study is statistically informative because it compares three active dose groups with a concurrent placebo group in a randomized, double-blind, parallel-group design. The primary outcome combines activity-of-daily-living and selected performance assessments, while the secondary outcomes include global judgments and other tremor-related measures. The design therefore allows the registry to report several complementary descriptions of outcomes over the 12-week study period.

The primary results also illustrate why estimates need to be considered together with their uncertainty. The group means show decreases from baseline, but the between-group confidence intervals extend across zero. A point estimate alone could make the 30 mg comparison look more distinct from placebo than the interval supports. Reading the estimate, interval, sample count, and analysis-population description together gives a more cautious account of what the posted data can distinguish.

The record is also useful for showing the limits of registry-level interpretation. It contains outcome summaries and adverse-event counts, but does not report a formal analysis plan, multiplicity procedure, missing-data handling, or the trial’s original sample-size justification. Those absences matter when readers assess whether the results answer a prespecified question and how much inferential weight to place on multiple comparisons. Planning illustrations based on observed effects can demonstrate how assumed effect size affects future sample requirements, but they do not replace a design rationale or resolve uncertainty in the completed trial.

For biostatisticians and clinical researchers, the central statistical lesson is that randomized design does not eliminate the need to examine outcome definitions, analysis populations, precision, and reporting completeness. The posted summaries are a starting point for interpretation, not a substitute for detailed methods and analysis reporting.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report the statistical model or adjustments used for the trial’s own primary analysis. The available primary comparisons are simple unadjusted recalculations from group summary statistics. They do not reproduce any unreported model and cannot account for participant-level covariates, repeated measurements, or other design features not described in the posted summaries.

The primary endpoint population is restricted to participants with baseline and week 12 TETRAS assessments, but the record does not explain how many randomized participants lacked those assessments or why. It does not describe missing-data handling or sensitivity analyses. Because the primary outcome counts are smaller than overall enrollment, the connection between enrollment, randomization, and endpoint availability cannot be fully assessed from the record.

The trial has several dose comparisons and multiple secondary outcomes, while adjustment for multiple testing is not reported. The secondary record includes numerical results for only some of the outcomes listed, and formal reported analyses are absent. This makes it difficult to judge whether the observed patterns were prespecified, how outcomes were prioritized, or whether findings were intended to be confirmatory.

The registry reports group means and standard deviations but not individual participant data. It also does not report a threshold for clinical importance on the composite score or describe how the trial’s own sample size was justified. The planning calculations based on observed effects are not a substitute for those missing design details. Finally, safety counts are descriptive; detailed exposure-adjusted comparisons or causal assessments are not reported in the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study To Assess the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor (ET) — NCT05122650.
• Registry record last updated 2025-07-24; status last verified 2025-07.
• Results first posted 2025-07-24.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT05122650 is a completed randomized, double-blind, placebo-controlled, parallel-group, multicenter study of JZP385 in adults with moderate to severe essential tremor. The official title describes it as a Phase 2b study lasting 12 weeks; the phase field lists Phase 2. Registry enrollment is 420, and the primary completion date is 2024-05-30.

The primary outcome is change from baseline to week 12 in the TETRAS composite score. Mean changes were -6.3 for placebo, -5.8 for 10 mg, -6.7 for 20 mg, and -7.5 for 30 mg. Recalculated unadjusted comparisons have confidence intervals that include zero. The registry also reports selected global-impression outcomes and adverse-event counts, but does not report a full statistical analysis plan, multiplicity procedure, or missing-data approach.