A Trial of Multiple-doses of Aripiprazole in Adults With Schizophrenia or Bipolar 1 Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial of Multiple-doses of Aripiprazole in Adults With Schizophrenia or Bipolar 1 Disorder (NCT04030143), a randomized phase 1, phase 2 study. The primary outcome is Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs).

2. Clinical Question

The trial also addressed pharmacokinetic questions: whether aripiprazole concentrations at the end of the dosing interval and exposure across the interval were similar between the injection schedules. The registry record lists outcomes for plasma concentrations, peak concentrations, time to peak, and exposure measures. Numerical results for these pharmacokinetic outcomes are not reported in the registry record.

The primary question is about safety events, not whether the schedules differ in symptom control. Secondary symptom-rating outcomes were also posted for some participants, but they do not replace the primary safety endpoint. The comparison concerns two active aripiprazole schedules; it does not compare aripiprazole with no treatment or with a different medicine.

3. Trial Design

This was a randomized, parallel-arm trial described as Phase 1b and Phase 2. It was open-label, with no masking. The registry record reports enrollment of 266 participants. The posted safety groups include 132 participants in the 2M LAI 960 mg arm and 134 in the IM Depot 400 mg arm.

Both groups received aripiprazole by injection over 32 weeks, but the schedules differed in dose, interval, and number of injections. The 2M LAI group received four injections of 960 mg every 56 days (± 2 days). The IM Depot group received eight injections of 400 mg every 28 days (± 2 days). The study therefore compares complete dosing schedules, rather than changing only the interval while holding all other features constant.

The stated purpose included assessing safety and tolerability and examining similarities in aripiprazole concentrations and exposure. The primary endpoint counted participants with one or more treatment-emergent adverse events from the first dose through the schedule-specific period after the last dose, up to approximately 11 months. The safety sample was defined as randomized participants who received at least one injection, regardless of protocol violation.

The registry record reports the trial as completed. It does not report the allocation procedure in greater detail, the original sample-size justification, or the planned statistical methods. Interim analyses are not reported in the registry record. The number enrolled is not necessarily the number contributing to every secondary outcome; the posted analyses use outcome-specific participant counts.

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: Safety sample included all randomized participants who received at least 1 dose of aripiprazole injection, regardless of any protocol violation.

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.

Population: Randomized sample consisted of all participants who were randomized.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs), measured over From first dose of study drug up to 56 days (2M LAI 960 mg) or 28 days (IM depot 400 mg) post last dose of study drug (up to approximately 11 months).

The primary endpoint is the number of participants with one or more treatment-emergent adverse events, or TEAEs. It is a participant-level count: each participant is counted as having the endpoint if at least one qualifying event occurs during the defined observation period. It does not indicate the total number of separate events, their duration, or their severity.

The registry definition covers an adverse event that starts after investigational product treatment begins. It also includes an event that continued from baseline when it was serious, related to the investigational product, or led to death, discontinuation, interruption, or dose reduction. An adverse event is defined as an untoward medical occurrence in a participant administered a medicinal product; a causal relationship with treatment is not required by that definition.

This endpoint is used to describe the proportion of participants experiencing at least one event, an important way of summarizing safety observations during exposure. The posted counts are 94 participants in the 2M LAI group and 95 in the IM Depot group. These counts alone do not establish whether an event was caused by treatment, and they do not summarize event seriousness or clinical importance. Serious adverse events and deaths are reported separately in the safety information.

The observation windows differed by schedule after the final dose: up to 56 days for 2M LAI and up to 28 days for IM Depot. That definition should be kept in mind when interpreting the groups’ safety counts.

7. Results Posted in the Registry

• Aripiprazole IM Depot 400 mg: Schizophrenia or Bipolar I Disorder: 70.9% (95/134) versus 71.2% (94/132) on control; risk difference -0.3 percentage points (95% CI -11.2 to 10.6), risk ratio 1.00 (0.85–1.16); unadjusted two-proportion z-test p = 0.955.

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.

Mean Change From Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Total Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Aripiprazole IM Depot 400 mg: Schizophrenia: mean -1.70 versus -2.60 on control; difference 0.90 (95% CI -2.13 to 3.93), standardized effect d = 0.09; z-test p = 0.560.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Aripiprazole IM Depot 400 mg: Schizophrenia and the control. The interval gives the range of effects that remain compatible with the data.

Mean Change From Baseline in Clinical Global Impression - Severity Scale (CGI-S) Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Aripiprazole IM Depot 400 mg: Schizophrenia: mean -0.10 versus -0.30 on control; difference 0.20 (95% CI 0.01 to 0.39), standardized effect d = 0.31; z-test p = 0.043.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Aripiprazole IM Depot 400 mg: Schizophrenia than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Mean Change From Baseline in Clinical Global Impression - Improvement Scale (CGI-I) Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Aripiprazole IM Depot 400 mg: Schizophrenia or Bipolar I Disorder: mean 3.50 versus 3.40 on control; difference 0.10 (95% CI -0.18 to 0.38), standardized effect d = 0.09; z-test p = 0.481.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Aripiprazole IM Depot 400 mg: Schizophrenia or Bipolar I Disorder and the control. The interval gives the range of effects that remain compatible with the data.

The secondary results cover distinct questions and populations. The registry lists pharmacokinetic measures, including peak concentration, time to peak, and exposure over specified dosing intervals, as well as symptom-rating measures. Numerical results for the pharmacokinetic outcomes are not reported in the registry record. Among the posted symptom outcomes, the direction and statistical pattern are not consistent across measures: two mean-difference intervals include zero, while one does not.

These outcomes complement the primary safety result but do not answer the same question. Symptom-rating scores describe clinical measures, while the primary endpoint counts participants with at least one TEAE. Pharmacokinetic measures concern concentration and exposure. A finding on one type of outcome does not by itself confirm or contradict a safety comparison on another type.

The secondary results carry less weight as confirmatory evidence because they are unadjusted and are among multiple outcomes. In general, repeated testing increases the chance of obtaining an apparently notable result by chance. The registry record does not report a prespecified testing hierarchy, multiplicity adjustment, or detailed analysis plan that would clarify how these outcomes were intended to be interpreted together. Outcome-specific participant counts also vary, and the registry record does not explain all differences in availability.

The overall pattern is therefore best described as mixed and exploratory in the absence of reported adjustment and analysis details. It does not establish a consistent advantage for either injection schedule across the secondary outcomes, and it does not convert the primary safety comparison into a claim of equivalence.

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

• Maximum Observed Plasma Concentration (Cmax) of Aripiprazole After First and Fourth Doses of Aripiprazole 2M LAI 960 mg
• Time to Reach the Maximum Plasma Concentration (Tmax) of Aripiprazole After First and Fourth Doses of Aripiprazole 2M LAI 960 mg
• AUC0-56 After the First Dose of Aripiprazole 2M LAI 960 mg
• Plasma Concentration of Aripiprazole 56 Days (C56) After the First Dose of Aripiprazole 2M LAI 960 mg
• AUC0-28 After the Fourth Dose of Aripiprazole 2M LAI 960 mg
• Area Under the Plasma Concentration-Time Curve From Time 29 to 56 Days (AUC29-56) After the Fourth Dose of Aripiprazole 2M LAI 960 mg
• Peak-to-Trough Percent Fluctuation (PTF%) After the Fourth Dose of Aripiprazole 2M LAI 960 mg
• Cmax of Aripiprazole After the First, Seventh, and Eighth Doses of Aripiprazole IM Depot 400 mg

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary at the participant level: each person either had one or more TEAEs during the defined period or did not. The posted arm counts are 94 of 132 and 95 of 134. The comparison is expressed as a risk difference, the estimated difference between the two groups’ event proportions. The reported estimate is -0.003. A negative value in this contrast indicates a slightly lower observed event proportion in the IM Depot group than in the 2M LAI group; the estimate is very close to zero.

What does the confidence interval contribute?

A confidence interval describes the range of values compatible with the observed data under the statistical procedure used. It gives a sense of precision as well as direction. For the primary risk difference, the interval extends across zero, so the posted data are compatible with either a lower or a higher event proportion in the IM Depot group. The interval is broad enough that the estimate should not be read as proof that the schedules have identical event rates. The registry record does not state the method used to construct this interval.

How should the p-value be read?

The unadjusted p-value for the primary comparison is 0.955. In general, a p-value measures how unusual data at least as discordant with a specified null model would be if that model were true. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The registry record does not report a complete analysis plan or indicate whether the posted comparison was a prespecified inferential test.

What do the secondary mean differences represent?

For the posted symptom-rating outcomes, the arm summaries are means and standard deviations. The comparison is a mean difference between the IM Depot and 2M LAI groups. A confidence interval for a mean difference describes uncertainty about the group contrast, not the range of individual participants’ scores. The PANSS and CGI-I intervals include zero, whereas the CGI-S interval lies on one side of zero. These interval patterns are descriptive of the posted contrasts; the secondary results are unadjusted.

In general, the standard deviation describes variation among participant scores, while the standard error describes uncertainty in an estimated mean. A standard deviation is not a confidence interval and does not mean that most individual observations fall within a fixed distance of the mean. The registry record gives standard deviations for the listed secondary outcomes but does not describe all assumptions behind the reported comparisons.

Why does multiplicity matter?

When several outcomes are examined, the chance of at least one apparently unusual result can increase even if there is no underlying difference on any outcome. This is the general multiplicity concern. The registry record lists many outcome measures, including safety and pharmacokinetic endpoints, and posts multiple secondary results. It does not report a multiplicity adjustment or a hierarchy for interpreting the secondary tests. Consequently, the unadjusted CGI-S p-value should not be treated as conclusive evidence of a broad treatment-schedule difference.

What is the role of the analysis population?

The safety population is defined as randomized participants who received at least one dose, regardless of protocol violation. This definition supports a description of events among exposed participants. It is not the same as an analysis of every randomized participant regardless of treatment received. The record does not report detailed missing-data methods, reasons for missing observations, or a full analysis population definition for each secondary endpoint. The posted sample sizes differ across outcomes, so each result pertains to the participants included in that particular summary.

In general, over-dispersion matters when count data vary more than a chosen probability model expects; it can make uncertainty estimates too narrow if ignored. The primary endpoint is a participant count with no dispersion estimate reported, rather than a repeated event count per person. No over-dispersion model or repeated-event analysis is reported in the registry record. The posted summary therefore addresses whether participants experienced any event, not how frequently events recurred.

11. Confidence Intervals and Precision

The primary estimate is precise enough to locate the observed contrast near zero, but its confidence interval spans values on either side of zero. That means the data do not determine the direction of a possible difference with confidence. The unadjusted p-value of 0.955 is consistent with the absence of a clear statistical separation in this comparison, but it does not show that the underlying event proportions are identical.

Precision is different from clinical importance. The record does not state a threshold for a difference in TEAEs that would be considered important, nor does it report an equivalence margin. Without such a threshold, the interval cannot be used to declare the schedules equivalent or to decide whether all values within it would be unimportant.

The secondary confidence intervals also have different patterns. The PANSS and CGI-I mean-difference intervals include zero, while the CGI-S interval does not. The registry record does not report multiplicity adjustment, so the apparent precision of an individual secondary interval should be considered in the context of the number of outcomes examined. The endpoint-specific sample sizes also vary, which affects how much information each estimate contains.

Confidence intervals address sampling uncertainty under a statistical model; they do not account automatically for limitations such as open-label treatment, incomplete outcome data, differences in follow-up windows, or unreported analysis choices. Those features are not resolved by a narrow or wide interval. The registry record does not report the interval-construction methods, so detailed assumptions behind the intervals cannot be assessed from the posted information.

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 figures are planning illustrations based on the observed effect, not the trial’s original design calculations. The registry record does not report the original sample-size justification or its assumptions. The illustrations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They use the stated fraction of the observed effect as the effect to detect.

For the binary primary endpoint and the continuous secondary outcomes, the figures are participants per arm. Thus, a value in a row is the number of participants planned in each group under that scenario, not the combined total. The 80% power column describes a planning target in which the assumed design would have an 80% chance of detecting the specified effect under the calculation’s assumptions. The 90% power column uses a higher chance of detecting that same effect, and therefore generally requires a larger planned sample.

Rows for 100%, 75%, and 50% of the observed effect illustrate how the requirement changes when planning around smaller effects. Smaller effects need more participants to distinguish them from random variation at the same significance level and power target. For example, the primary endpoint illustration gives 322,105 participants per arm for 80% power when planning for 100% of the observed effect, compared with 1,286,328 participants per arm when planning for 50% of the observed effect. These very large figures reflect the small observed risk difference used in the illustration; they are not enrollment goals for the completed trial.

This is not observed power. It is a prospective planning illustration, and the actual trial enrolled 266 participants. A planning calculation based on an observed effect does not tell whether a particular result is true, clinically important, or conclusive. The trial’s own planned effect size and design assumptions are not reported in the registry record.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.712; treatment proportion p₁ = 0.709; average p̄ = 0.711.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6414 = 1.2570.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6414 = 0.5398.
4. n = (1.2570 + 0.5398)² / (-0.0032)² = 322,104.0, rounded up to 322,105 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
p0 <- 0.712121212121212                          # control proportion
p1 <- 0.708955223880597                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4030143)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 322,105 (80% power), 431,206 (90% power)
 75% of observed effect: n per arm = 572,166 (80% power), 765,968 (90% power)
 50% of observed effect: n per arm = 1,286,328 (80% power), 1,722,028 (90% power)
power.prop.test: 322104 
Simulated power at n = 322,105 per arm: 0.798 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 broad collection of outcome measures, including a primary safety endpoint, pharmacokinetic measures, and symptom-rating outcomes. When many outcomes are analyzed, some may appear statistically notable by chance alone. This is the general reason that confirmatory studies often define a testing hierarchy or use a multiplicity adjustment. No such procedure is reported in the registry record, and no hierarchy for interpreting the secondary outcomes is reported.

The CGI-S comparison has an unadjusted p-value of 0.043, while the other posted symptom comparisons have different unadjusted results. Because the number and relationship of all statistical tests are not fully described, the individual p-values should not be treated as if they were the only tests conducted. The record does not report whether outcomes were selected for analysis before results were known, or whether any analyses were exploratory.

Missing-data handling is also not reported in the registry record. There is no detailed account of missing observations, reasons for missingness, imputation, or sensitivity analyses. The safety population is defined as randomized participants who received at least one dose, but the record does not provide a full account of how missing outcome information was handled within that population. For secondary outcomes, the participant counts are smaller than the safety group counts and differ by outcome. The reason for each difference is not reported in the registry record.

The record also does not report the original sample-size justification, interim analyses, or a complete statistical analysis plan. Without those details, it is difficult to assess which tests were planned as primary, how the investigators intended to manage multiple comparisons, or how incomplete data might affect the estimates. These omissions do not invalidate the posted summaries, but they limit the strength of conclusions that can be drawn from isolated secondary findings.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hallucination, auditory (1.5%), cardiac arrest (0.8%), cellulitis (0.8%), akathisia (0.8%), psychotic disorder (0.8%).

The serious adverse event figures are counts of participants in each arm: 6 in the 2M LAI group and 8 in the IM Depot group. Other adverse events were reported for 92 participants in each group. The registry record also reports 1 death in the 2M LAI group and 0 in the IM Depot group. These figures are descriptive, and no inferential comparison for serious events or deaths is reported in the registry record.

Serious adverse events and the primary TEAE endpoint are not interchangeable. The TEAE endpoint includes participants with any qualifying event, whether or not it was serious. The serious-event figures provide a separate view of events classified as serious, while the primary count does not distinguish severity. The record lists several serious-event terms with percentages, including auditory hallucination at 1.5% and cardiac arrest, cellulitis, akathisia, and psychotic disorder at 0.8% each. These listed terms do not provide a complete account of each participant’s clinical course.

The counts do not establish causality. The registry’s adverse-event definition does not require an event to be caused by treatment. Differences in exposure windows also matter: follow-up after the last dose was defined as 56 days for 2M LAI and 28 days for IM Depot. The posted figures should be read as recorded safety observations under those definitions.

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

The main result describes the proportion of exposed participants who had at least one TEAE during the defined observation period. The posted counts are close, and the risk-difference estimate is close to zero. Its confidence interval spans zero, so the observed data do not establish a clear direction of difference between the schedules for this endpoint.

That interpretation is narrower than saying that the schedules have identical safety profiles. The registry record does not report an equivalence margin or a non-inferiority framework, and the confidence interval allows differences in either direction. The result also does not show that events were caused by either schedule, predict an individual participant’s experience, or describe the nature and severity of all events through a single summary count.

The secondary clinical measures do not provide a uniform pattern across outcomes. One unadjusted comparison has an interval that does not include zero, while the other posted symptom comparisons have intervals that do. Given the number of outcomes and the absence of reported multiplicity procedures, these secondary results should be considered cautiously. The pharmacokinetic outcomes are part of the trial’s stated aims, but their numerical results are not reported in the registry record.

The trial compares two active dosing schedules in an open-label, randomized, parallel-arm design. It does not answer how either schedule compares with no treatment or another medicine. The posted information supports a description of the observed groups and the uncertainty around their comparisons; it does not establish a broad clinical benefit, a definitive equivalence, or a causal explanation for individual adverse events.

These are statistical interpretations of the registry record, not treatment recommendations. Clinical importance depends on context that is not captured by a p-value or a single count, including event type, severity, duration, and participant priorities. Those details are not fully represented in the primary endpoint summary.

17. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between comparing observed event proportions and demonstrating that two regimens are equivalent. The primary estimate is close to zero, but its interval crosses zero and the registry record does not report an equivalence margin. The result therefore illustrates why a small observed difference and a large p-value are not, by themselves, proof of sameness.

It also shows how endpoint definition shapes interpretation. Counting participants with any TEAE gives a direct safety summary, but it treats one event and multiple events alike at the participant level. Serious events, other adverse events, and deaths are reported separately, and each answers a different descriptive question. The schedule-specific follow-up windows should also remain visible when comparing the groups.

The study’s stated goals include pharmacokinetic similarity, but the registry record does not report numerical results for those outcomes. That gap matters because a trial can be designed to address several distinct questions, while the posted results may support interpretation of only some of them. The symptom-rating outcomes add context but do not substitute for the primary safety outcome.

Finally, the secondary findings highlight the importance of prespecification and multiplicity control. An unadjusted result among multiple outcomes deserves a different level of confidence than a single prespecified primary comparison. The registry record’s missing detail on analysis plans, missing data, and multiplicity limits how firmly the secondary results can be interpreted.

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 trial was open-label, so participants and study personnel were not masked to the assigned injection schedule. The registry record does not describe whether this could have affected event reporting or outcome assessment. The primary endpoint includes events that do not necessarily have a causal relationship with treatment, so the event counts alone cannot separate treatment-related events from other occurrences.

The two arms differed in dose, injection frequency, and number of injections. The comparison therefore concerns the full schedules rather than the isolated effect of injection interval. Follow-up after the final dose also differed by schedule, with 56 days for 2M LAI and 28 days for IM Depot. These features should be considered when interpreting between-group safety counts.

The primary endpoint counts participants with at least one TEAE, not the total number of events, recurrent events, or the clinical importance of each event. The serious-event and death counts are limited descriptive summaries, and inferential comparisons for these outcomes are not reported in the registry record.

For the secondary outcomes, participant counts vary, and missing-data handling is not reported. Numerical results for the pharmacokinetic outcomes are not reported in the registry record despite their place among the trial aims. The registry record also does not report the original sample-size rationale, interim analyses, complete statistical plan, or multiplicity procedures. These omissions limit assessment of precision, outcome selection, and the confirmatory status of secondary findings.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Trial of Multiple-doses of Aripiprazole in Adults With Schizophrenia or Bipolar 1 Disorder — NCT04030143.
• Registry record last updated 2023-11-18; status last verified 2023-10.
• Results first posted 2023-11-18.
• 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

NCT04030143 was a completed randomized, open-label, parallel-arm Phase 1b and Phase 2 trial in adults with schizophrenia or bipolar I disorder. It enrolled 266 participants and compared aripiprazole 2M LAI 960 mg with aripiprazole IM Depot 400 mg over 32 weeks.

The primary endpoint was the number of participants with one or more TEAEs. The posted counts were 94 of 132 in the 2M LAI arm and 95 of 134 in the IM Depot arm; the risk-difference estimate was -0.003, with an unadjusted p-value of 0.955. The confidence interval spans zero. Serious adverse events, other adverse events, and deaths are also reported descriptively.

Secondary outcomes include symptom-rating and pharmacokinetic measures. The posted symptom comparisons are mixed and unadjusted, while numerical pharmacokinetic results are not reported in the registry record. Details on the original sample-size justification, multiplicity, interim analyses, and missing-data methods are not reported in the registry record.