Safety and Efficacy Study of Vigabatrin to Treat Methamphetamine Dependence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of Vigabatrin to Treat Methamphetamine Dependence (NCT00730522), a randomized phase 2 study. The primary outcome is The Proportion of Subjects in Each Treatment Group Who Are Amphetamine Abstinent During the Last 2 Weeks of the Treatment Phase (Weeks 11 and 12)..

2. Clinical Question

The registry’s brief objective describes the desired outcome as being methamphetamine-free during the last 2 weeks of treatment. The primary outcome title uses the phrase “amphetamine abstinent,” while the condition and study objective concern methamphetamine dependence. The registry record does not provide a more detailed definition of abstinence, such as the specific testing or assessment rule used to classify a participant.

The posted counts are 4 of 28 participants in the Vigabatrin group and 2 of 27 in the Placebo group. The comparison therefore concerns the proportion meeting the recorded abstinence outcome, rather than the number of negative urine tests or the number of weeks of methamphetamine use. Those measures appear among the secondary outcomes, but the registry record does not post their results.

The clinical question is about a between-group difference in a binary outcome at the end of treatment. The counts describe what was recorded in this trial; by themselves, they do not establish a precise or conclusive treatment effect. The reported interval estimates are wide, and the reported unadjusted p-value is 0.413.

3. Trial Design

This was a Phase II randomized, parallel-group study sponsored by Catalyst Pharmaceuticals, Inc. The registry record lists quadruple masking. Participants were assigned to CPP-109 vigabatrin tablets or matching placebo tablets. Enrollment was 55, with 28 participants listed in the Vigabatrin group and 27 in the Placebo group.

The study concerned methamphetamine dependence. Its stated objective was to demonstrate that a larger proportion of vigabatrin-treated participants than placebo-treated participants would be methamphetamine-free during the last 2 weeks of the Treatment Phase. The primary outcome title describes participants as amphetamine-abstinent during Weeks 11 and 12. This wording difference is present in the registry record; a fuller operational definition is not reported in the registry record.

The record lists a study start of 2008-07 and primary completion of 2009-06. The overall study status is TERMINATED. The reason for termination is not reported in the registry record, so the status alone does not explain why the study ended or whether termination affected the planned analyses.

The primary outcome is a count of participants meeting a binary abstinence classification in each treatment group. The posted counts are 4 in the Vigabatrin group and 2 in the Placebo group. Two secondary outcomes are named: the number of methamphetamine-negative urines during the Treatment Phase and the number of methamphetamine-use weeks during the Treatment Phase. The registry record does not post results for those secondary outcomes.

Although the study is described as randomized and masked, details such as the randomization procedure, allocation concealment, masking assessment, eligibility criteria, treatment schedule, and follow-up procedures are not reported in the registry record. The registry record also does not report the trial’s original statistical analysis plan or its sample-size justification.

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

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: Study terminated early due to failed trial in another category of substance dependence, very limited data summary performed and therefore most data not available, or not collected. What is available has been entered.

6. Primary Endpoint

The registry lists the primary outcome as The Proportion of Subjects in Each Treatment Group Who Are Amphetamine Abstinent During the Last 2 Weeks of the Treatment Phase (Weeks 11 and 12)., measured over Weeks 11-12.

The primary endpoint counts participants in each treatment group who were classified as amphetamine-abstinent during the last 2 weeks of the Treatment Phase, identified as Weeks 11 and 12. It is a binary participant-level outcome: each participant either met the recorded classification or did not. The outcome title gives the unit as participants, and the posted values are counts rather than percentages.

The stated study objective describes this endpoint as being methamphetamine-free in the final 2 weeks of treatment. A final-period abstinence outcome focuses on whether participants met the abstinence classification at the end of the treatment period. It is distinct from measures that count negative urine results across treatment or count weeks of use. Those measures are named as secondary outcomes, but their results are not posted in the registry record.

Binary outcomes are often used when a study question concerns the proportion of participants who reach a clearly specified state. A between-group comparison can then describe the difference in proportions, while also representing uncertainty around that difference. Interpretation depends on how the outcome was defined and assessed. In this case, the registry record does not report the detailed classification rule, assessment schedule beyond Weeks 11–12, or handling of missing assessments.

The posted primary counts are 4 participants in the Vigabatrin group and 2 in the Placebo group. They describe the recorded outcome in the groups; they do not, on their own, resolve how precisely the underlying group difference is estimated.

7. Results Posted in the Registry

• Vigabatrin: 14.3% (4/28) versus 7.4% (2/27) on control; risk difference 6.9 percentage points (95% CI -9.4 to 23.2), risk ratio 1.93 (0.38–9.68); unadjusted two-proportion z-test p = 0.413.

8. Statistical Interpretation

9. Statistical Methods Explained

A randomized parallel-group study compares outcomes among participants assigned to different groups. Random allocation is intended to make the groups comparable on average at the start of a trial, although it cannot guarantee balance in a small study. Masking is intended to reduce the influence of treatment knowledge on care, assessment, or reporting. The registry record describes this study as randomized, parallel, and quadruple-masked, but does not report procedural details about allocation or masking.

What does a risk difference describe?

A risk difference subtracts the outcome proportion in one group from the outcome proportion in the other. In this comparison, the direction is Vigabatrin relative to Placebo. The posted proportions are 0.143 and 0.074, and the reported risk difference is 0.069. The risk difference is an absolute measure: it describes the separation between group proportions on the probability scale. It is not a relative increase and should not be paraphrased as one.

The risk difference is useful when the question concerns how far apart the outcome probabilities are in the groups. Its interpretation depends on the outcome definition and the population being compared. Here, the endpoint is a participant count for abstinence during Weeks 11–12. The registry record does not specify the detailed rule by which participants were classified or how participants without an assessment were treated.

How do relative risk and odds ratio differ?

The relative risk compares the outcome probability in one group with the probability in another. The odds ratio compares the odds, where odds are the probability of the event divided by the probability of no event. These relative measures use different scales from the risk difference and from each other. The record reports a relative risk of 1.929 and an odds ratio of 2.083. The associated confidence intervals are broad: 0.384 to 9.677 for the relative risk, and 0.349 to 12.45 for the odds ratio. Such ranges indicate that the point estimates alone do not convey the uncertainty of the comparison.

What does the p-value tell a reader?

The unadjusted p-value is 0.413. In general, a p-value describes how compatible the observed data, or data more extreme under a specified test, are with a null hypothesis under the test’s assumptions. It is not the probability that the null hypothesis is true, and it does not measure the probability that a finding will reproduce. It also does not measure effect size. The registry record does not report the full test specification or a detailed statistical analysis plan, so the p-value should be read as the posted unadjusted result rather than as a complete account of the analysis.

Confidence intervals add information that a single p-value does not: they display a range of estimates consistent with the data under a particular interval method. The risk-difference interval, -0.094 to 0.232, includes no difference and extends in both directions. The relative-risk and odds-ratio intervals are also wide. Taken together, the posted estimates show uncertainty about both the direction and size of the group difference.

Why does a small event count matter?

When only a few participants meet a binary endpoint, each observed outcome can have a substantial influence on the estimated group proportions. Estimates based on few events are commonly less precise than estimates based on more information. This general statistical point helps explain why an estimate can look different from no difference while its interval remains broad. It does not justify assuming what additional data would have shown.

For outcomes measured as counts, the choice of model may also matter. General statistical methods for count outcomes can account for variation that exceeds what a simple count model expects; this is called over-dispersion. Such modeling is relevant only if the outcome and analysis support it. The registry record names secondary count-related outcomes but does not post their results, model details, or analysis methods. There is therefore no basis in the registry record for claiming that a particular count model or over-dispersion adjustment was used.

What can be inferred from the posted analysis?

The posted primary counts support a descriptive comparison of the two groups and the reported unadjusted effect estimates. They do not establish the analysis population, whether all randomized participants were included, or how missing outcomes were handled. The record lists 55 participants enrolled and group sizes of 28 and 27 for the primary outcome, but does not explain participant flow or whether the outcome denominators reflect the full randomized groups. The randomized design is relevant context, but the available record does not provide enough analysis detail to assess all potential sources of bias.

10. Confidence Intervals and Precision

Precision concerns how tightly an estimate is determined by the data. A confidence interval presents a range around an estimate that reflects sampling uncertainty under the method used. It is not a guarantee that the true effect lies in the interval, and its interpretation depends on the statistical method and assumptions.

For the risk difference, the reported estimate is 0.069 and its confidence interval is -0.094 to 0.232. This interval is wide relative to the point estimate and includes zero, which represents no difference on the risk-difference scale. The range includes possible differences in either direction, so the estimate does not precisely determine whether the underlying group difference favors one group or the other.

The relative risk is 1.929, with a confidence interval from 0.384 to 9.677. The odds ratio is 2.083, with a confidence interval from 0.349 to 12.45. Each interval spans values below and above the no-difference value for its measure. The point estimates are therefore not precise enough to settle the direction or size of the relative contrast.

The small number of participants meeting the primary outcome is relevant to this imprecision. The registry record reports 4 participants in the Vigabatrin group and 2 in the Placebo group. With relatively few recorded outcomes, uncertainty can remain substantial even when the point estimates differ. The confidence intervals communicate that uncertainty more directly than the point estimates alone.

The interval method is not reported in detail in the registry record. These intervals should therefore be interpreted as the posted estimates, without assuming a particular adjustment or analysis population beyond what the record states.

11. 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 planning figures describe hypothetical trial sizes based on the observed risk difference, not the trial’s original design. They are stated as participants per arm, not as a combined total and not as total events. The calculation assumptions listed in the registry record 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 a stated fraction of the observed effect.

For planning for 100% of the observed effect, the figures are 320 participants per arm for 80% power and 428 participants per arm for 90% power. For planning for 75% of the observed effect, they are 530 participants per arm for 80% power and 708 participants per arm for 90% power. For planning for 50% of the observed effect, they are 1,100 participants per arm for 80% power and 1,472 participants per arm for 90% power.

In plain terms, the 80% power column gives the planned number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions. The 90% power column gives the corresponding planning number for a design with a 90% chance. Higher planned power requires more participants under the same assumptions. Smaller effects also require more participants to detect, which is why the planning numbers rise as the assumed fraction of the observed effect becomes smaller.

These values are planning illustrations based on the observed effect, not observed power and not evidence about what the trial was originally designed to detect. The registry record does not report the original sample-size justification or design assumptions.

12. 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 = 0.074; treatment proportion p₁ = 0.143; average p̄ = 0.108.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4398 = 0.8619.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4371 = 0.3679.
4. n = (0.8619 + 0.3679)² / (0.0688)² = 319.7, rounded up to 320 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 <- 0.0740740740740741                          # control proportion
p1 <- 0.142857142857143                          # 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(730522)
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 = 320 (80% power), 428 (90% power)
 75% of observed effect: n per arm = 530 (80% power), 708 (90% power)
 50% of observed effect: n per arm = 1,100 (80% power), 1,472 (90% power)
power.prop.test: 319.7 
Simulated power at n = 320 per arm: 0.811 (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.

13. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, comparisons, or analyses. In general, making many statistical tests can increase the chance of at least one apparently noteworthy result unless the analysis plan accounts for that possibility. The registry record names the primary abstinence outcome and two secondary outcomes: the number of methamphetamine-negative urines during the Treatment Phase and the number of methamphetamine-use weeks during the Treatment Phase.

The registry record posts a primary comparison but does not post results for the named secondary outcomes. It does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a prespecified strategy for interpreting multiple tests. Those details are not reported in the registry record, so it is not possible to determine whether multiplicity was addressed in the trial’s planned analysis.

The record also does not describe missing-data procedures. It does not state how participants with incomplete treatment-period assessments were classified for the primary endpoint, whether missing observations were imputed, or whether sensitivity analyses were conducted. The displayed group counts and outcome counts do not by themselves answer those questions.

The analysis population is likewise not reported in the registry record. The record identifies 55 enrolled participants and lists 28 in the Vigabatrin outcome group and 27 in the Placebo outcome group, but it does not explicitly say whether the analysis followed an intention-to-treat approach, included all randomized participants, or used another population definition. The randomization procedure and participant flow are not detailed.

These omissions matter because outcome definitions, missingness, and analysis populations can affect the interpretation of a treatment-group comparison. They do not show that the analysis was inappropriate; they mean that the registry record does not contain enough information to assess these aspects of the statistical plan.

14. 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: hernia obstructive (3.6%), fracture (3.6%).

The registry record lists serious adverse events for 2 of 28 participants in the Vigabatrin group and 0 of 27 in the Placebo group. It reports zero deaths in each group. These are participant counts, and they describe the serious adverse event totals recorded for the groups; they do not establish whether an event was caused by treatment.

The record also lists “Hernia obstructive” and “fracture” among the top serious-event terms, each reported as 3.6%. The record does not provide enough detail alongside those terms to interpret their timing, relatedness, duration, or distribution across treatment groups. A serious adverse event is not necessarily the same as an adverse event judged treatment-related, and the registry record does not report that judgment for these entries.

Other adverse events are listed for 24 of 28 participants in the Vigabatrin group and 23 of 27 in the Placebo group. Those totals are broader than the serious-event counts and should not be combined with them. The record does not provide event-level details or a complete safety analysis in the information. These counts are descriptive and should not be used alone to draw conclusions about comparative safety.

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

The posted primary results describe a randomized comparison of vigabatrin with matching placebo in participants with methamphetamine dependence. The primary endpoint concerned the number of participants classified as amphetamine-abstinent during Weeks 11–12. The observed counts were 4 of 28 in the Vigabatrin group and 2 of 27 in the Placebo group, and the reported risk difference was 0.069.

The confidence interval for that risk difference, -0.094 to 0.232, is broad and spans no difference. The relative-risk and odds-ratio intervals are also wide and span their respective no-difference values. The unadjusted p-value is 0.413. These statistics indicate that the posted data do not estimate the between-group difference precisely. The numerically higher observed proportion in the Vigabatrin group should not be treated as proof of a true difference.

The findings also do not establish that the groups were equivalent. A lack of a precise distinction is not the same as evidence that any difference is absent or negligible. The intervals include a range of possible effects in both directions, and the available counts are limited.

The registry record does not report results for the two named secondary outcomes, detailed missing-data methods, analysis-population definitions, or the original statistical plan. It also lists the study as TERMINATED without reporting the reason. These gaps constrain interpretation of the posted outcome and make it difficult to evaluate the full conduct and analysis of the trial.

The results should therefore be read as a record of the observed primary counts and their uncertain comparison, not as a definitive statement about treatment efficacy or as medical guidance. The trial’s posted data alone do not resolve the clinical question with precision.

16. Why This Trial Matters Statistically

This trial illustrates why an observed difference and a statistically precise estimate are not the same thing. The primary outcome counts are higher in the Vigabatrin group than in the Placebo group, but the reported risk-difference interval extends from a negative value to a positive value. The relative-risk and odds-ratio intervals are also broad. A reader who focuses only on the point estimates could miss how uncertain the comparison remains.

It also demonstrates the importance of specifying an endpoint clearly. The objective describes being methamphetamine-free, while the primary outcome title uses “amphetamine abstinent.” The registry record does not provide the operational definition used to classify participants. Statistical interpretation depends on knowing exactly what was measured, how it was assessed, and how incomplete observations were handled.

The record’s missing analysis details are instructive as well. The study lists secondary outcomes but does not post their results, and it does not report the analysis population, missing-data approach, multiplicity strategy, or original sample-size justification. Without those details, readers cannot fully assess whether the displayed primary comparison reflects the planned analysis or how other outcomes were interpreted.

Finally, planning calculations based on an observed effect should be distinguished from a trial’s original design and from the uncertainty in the result. The planning illustrations show how required participant counts change with the effect assumed and desired power, but they do not recover what the original investigators planned. Keeping these distinctions clear is central to sound statistical reading of small clinical trials.

17. 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 leaves several trial-specific questions unanswered. It does not report the detailed definition of the primary abstinence classification, despite describing the objective as methamphetamine-free and titling the outcome as amphetamine-abstinent. The outcome timeframe is Weeks 11–12, but assessment procedures and the treatment schedule are not described in detail.

The record does not explain the reason for the TERMINATED status. It also does not provide a participant flow account, the number screened or randomized, or reasons for any exclusions or missing assessments. Although the enrolled total and primary outcome group counts are listed, the analysis population and missing-data handling are not reported in the registry record.

The registry record names two secondary outcomes but does not post their results. It does not report a full statistical analysis plan, multiplicity procedures, the method used to calculate confidence intervals, or the original sample-size justification. The planning illustrations are based on the observed effect and should not be mistaken for the trial’s original design assumptions.

For safety, the record lists group counts and selected serious-event terms but does not provide enough detail to assess event timing, treatment relatedness, or the full pattern of events. The posted serious adverse event counts are descriptive, not causal evidence.

These reporting gaps limit independent assessment of the trial’s conduct and analysis. They do not establish that a particular procedure was or was not performed; those details are simply not reported in the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of Vigabatrin to Treat Methamphetamine Dependence — NCT00730522.
• Registry record last updated 2020-12-09; status last verified 2020-10.
• Results first posted 2020-12-09.
• 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.

21. Record Summary

NCT00730522 is a randomized, quadruple-masked, parallel-group Phase II study sponsored by Catalyst Pharmaceuticals, Inc. It compared CPP-109 vigabatrin tablets with matching placebo in participants with methamphetamine dependence. The registry record lists enrollment of 55 and study status as TERMINATED.

The primary outcome concerned participants classified as amphetamine-abstinent during Weeks 11–12. The posted counts are 4 of 28 in the Vigabatrin group and 2 of 27 in the Placebo group. The risk difference is 0.069, with a confidence interval from -0.094 to 0.232; the unadjusted p-value is 0.413. These estimates are imprecise.

Two secondary outcomes are named, but their results are not posted. The reason for termination, original sample-size justification, analysis population, and missing-data methods are not reported in the registry record.