A Two Part Study (306A/306B) to Assess Droxidopa in Treatment of NOH in Patients With Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Two Part Study (306A/306B) to Assess Droxidopa in Treatment of NOH in Patients With Parkinson's Disease (NCT01176240), a randomized phase 3 study. The primary outcome is 306A Efficacy: Change in Orthostatic Hypotension Questionnaire Score (OHQ).

2. Clinical Question

3. Trial Design

The registry identifies this as a phase 3, randomized, parallel-group, placebo-controlled study with quadruple masking. It describes a two-part study, 306A/306B, assessing droxidopa in patients with Parkinson’s disease and NOH. The sponsor was Chelsea Therapeutics, and the study status is completed. The registry records a start in 2010-06 and primary completion in 2012-10.

The study description outlines screening, dose finding, an 8 week treatment period, and follow-up, with a maximum duration of approximately 14 weeks. It also says that an extension study was available when considered appropriate by the study doctor. The exact allocation procedures, masking roles, and detailed conduct of the extension are not reported in the registry record.

The registry lists enrollment of 225. The study description says that a sufficient number of patients would be screened to allow approximately 211 randomized patients. Those figures describe enrollment and the stated target, respectively; the actual randomized count across the study is not reported in the registry record. The primary endpoint results are for 306A and include 24 participants in the droxidopa arm and 27 in the placebo arm. The 306B secondary results have different arm counts, reflecting that they concern a different study part and outcome time points.

The primary outcome was change in the OHQ composite score from baseline to end of study, with the timeframe described as baseline and Week 8. The posted primary endpoint analysis used last observation carried forward (LOCF) for patients without an end-of-study visit. Further details about analysis populations, allocation concealment, and the trial’s original sample-size rationale are not reported in the registry record.

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.

Before assignment: Post-randomization, up to 2 weeks dose titration followed by 8 wks at optimal dose. The first 51 patients enrolled in the study were analyzed as a separate group in an interim analysis (Study 306A). The final 171 patients remained blinded until the end of the study and analyzed as a separate study (Study 306B).

Study 306A

Reasons for not completing this period:

Study 306B

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: LOCF was used to impute values for patients who did not have an end of study visit.

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: The population only includes those patients who were randomized and took at least one dose of study drug (n=222). The first 51 patients enrolled in the study were analyzed as a separate group in an interim analysis (Study 306A). The final 171 patients remained blinded until the end of the study and analyzed as a separate study (Study 306B).

6. Primary Endpoint

The registry lists the primary outcome as 306A Efficacy: Change in Orthostatic Hypotension Questionnaire Score (OHQ), measured over Baseline, Week 8.

The primary endpoint was the change in the Orthostatic Hypotension Questionnaire (OHQ) composite score from baseline to the end of study in 306A. The OHQ combines two patient-reported subscales: the Orthostatic Hypotension Symptom Assessment Scale (OHSA) and the Orthostatic Hypotension Daily Activities Scale (OHDAS). OHSA covers symptoms, while OHDAS captures the impact of NOH on standing and walking activities. Each item asks about the past week and uses a Likert scale from 0 to 10, with 10 representing the most severe rating.

The composite is used to bring symptom burden and activity impact into a single outcome measure. This makes it possible to compare average change between randomized groups, while retaining the limitation that a mean can conceal variation between individual participants. The registry defines negative change as improvement from baseline. That direction is important when interpreting the arm means: a more negative value indicates a larger average improvement on this scale, not worsening.

The primary endpoint description calls the endpoint a relative mean change, while the posted arm results are presented as mean changes in units on a scale. The endpoint is patient-reported and therefore reflects participants’ experiences, rather than a direct measurement of blood pressure. The registry also lists blood pressure and additional symptom measures as secondary outcomes. The clinical importance threshold for a change in OHQ is not reported in the registry record.

7. Results Posted in the Registry

• Droxidopa: mean -2.20 versus -2.10 on control; difference -0.10 (95% CI -1.45 to 1.25), standardized effect d = -0.04; z-test p = 0.885.

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.

306B Efficacy: Change in OHSA Item 1 From Baseline to Week 2 (Visit 5)

• 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:
  • Droxidopa: mean -1.90 versus -1.60 on control; difference -0.30 (95% CI -1.26 to 0.66), standardized effect d = -0.10; z-test p = 0.539.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Droxidopa and the control. The interval gives the range of effects that remain compatible with the data.

306B Efficacy: Change in OHSA Item 1 From Baseline to Week 4 (Visit 6)

• 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:
  • Droxidopa: mean -2.00 versus -1.50 on control; difference -0.50 (95% CI -1.47 to 0.47), standardized effect d = -0.17; z-test p = 0.312.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Droxidopa and the control. The interval gives the range of effects that remain compatible with the data.

306B Efficacy: Change in Systolic Blood Pressure (SBP) Measurements Post Standing From Baseline to Week 1

• 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:
  • Droxidopa: mean 6.40 versus 0.70 on control; difference 5.70 (95% CI -0.63 to 12.03), standardized effect d = 0.29; z-test p = 0.078.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Droxidopa and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering symptom ratings, standing systolic blood pressure, falls, and the broader OHQ. The posted 306B summaries include symptom and blood pressure outcomes at selected time points. Across those available summaries, the symptom mean changes are more negative in the droxidopa groups, while the standing systolic blood pressure change is more positive. The recalculated uncertainty intervals for these comparisons include zero. Taken together, the directions are not a uniform signal across measurement types, and the estimates remain uncertain.

These outcomes relate to the primary result by examining particular symptoms, a blood pressure response, and additional aspects of NOH burden. They do not replace the primary 306A OHQ composite comparison. Differences in study part, outcome definition, scale, and assessment time mean that results should not be treated as though they were repeated measurements of one identical endpoint.

The registry lists 10 outcome measures and reports six posted secondary outcomes, with four analyses reported. A complete multiplicity plan is not reported in the registry record. When many outcomes or time points are examined, the chance of finding an apparently notable result by chance can increase. Unadjusted secondary p-values therefore carry less weight than a prespecified primary analysis unless the analysis plan explains how the family of comparisons was handled. The registry reports a Wilcoxon (Mann-Whitney) p-value for one secondary outcome; the analysis method for the other listed secondary results is not consistently reported. The record does not report enough detail to determine which secondary findings were prespecified for formal inference or how missing secondary measurements were handled.

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

• 306B Efficacy: Change in OHSA Item 1 From Baseline to Week 2 (Visit 5)
• 306B Efficacy: Change in OHSA Item 1 From Baseline to Week 4 (Visit 6)
• 306B Efficacy: Change in Systolic Blood Pressure (SBP) Measurements Post Standing From Baseline to Week 1
• 306B Efficacy: Change in OHSA Item 1 From Baseline to Week 8 (Visit 7)
• 306B Efficacy: Rate of Patient Reported Falls
• 306B Efficacy: Change in Orthostatic Hypotension Questionnaire Score (OHQ)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: it is measured on a numeric scale, and the registry reports a mean and standard deviation for each group. A mean gives the group’s average change, while the standard deviation describes how dispersed participant values are around that average. These summaries are useful for describing the data, but they do not show the full distribution or how individual participants’ outcomes varied.

What does the recalculated mean difference represent?

The recalculated mean difference compares the droxidopa mean change with the placebo mean change, with the contrast expressed as droxidopa relative to placebo. A negative difference on this endpoint points toward a more negative average change in the droxidopa group. Since the registry says negative change represents improvement, the direction can be interpreted as a greater average improvement in that group. The estimated difference is -0.1 units. This is a simple unadjusted recalculation from the posted group summaries, not the registry’s ANCOVA result.

An unadjusted comparison uses the observed group summaries without accounting for covariates in a model. In general, an adjusted analysis can account for specified participant characteristics or baseline measures, potentially changing the estimate and its uncertainty. The registry names ANCOVA for its reported primary analysis, but the model details and adjusted estimate are not reported in the registry record. The recalculation should therefore be treated as a transparent descriptive comparison, not as a reconstruction of the sponsor’s model.

How should the p-values be read?

A p-value describes how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The recalculated unadjusted p-value is 0.885, while the registry reports p = 0.978 for its ANCOVA analysis. The difference between those values is consistent with the analyses being different; it is not a reason to select whichever value appears more favorable. The ANCOVA result is the registry’s reported analysis, while the recalculation is an unadjusted comparison based on summary statistics.

In general, a confidence interval presents a range of effect estimates compatible with the data and the method used to construct it. Its width reflects precision: wider intervals permit a broader range of possible effects. Whether an interval excludes a null difference can inform statistical interpretation, but does not alone establish clinical importance. The recalculated interval includes zero, meaning it is compatible with no between-group difference as well as differences in either direction. No adjusted confidence interval for the ANCOVA result is reported in the registry record.

What role does variability play?

The group standard deviations describe substantial variation in individual change scores relative to the small observed difference between group means. In general, greater outcome variability makes it harder to estimate a group contrast precisely, unless balanced by more information or a different analysis structure. For count outcomes, over-dispersion means that the observed variability exceeds what a simple model assumes; it can make standard errors too small if ignored. The outcomes are continuous scores or blood pressure measurements, so over-dispersion is not the specific concern for these mean comparisons. The registry’s detailed distributional diagnostics are not reported in the registry record.

The primary endpoint description states that LOCF was used for patients without an end-of-study visit. LOCF carries a participant’s last observed value forward to stand in for a later missing value. In general, this approach can be biased if outcomes change after the last observation, and it can understate uncertainty because the substituted value is treated as if it were known. How many participants had values imputed, why visits were missing, and whether other missing-data analyses were performed are not reported in the registry record.

The registry reports a continuous outcome as mean and standard deviation, and the recalculation uses a mean difference. That approach summarizes average change but may not capture all features of a skewed or otherwise unusual distribution. A nonparametric Wilcoxon (Mann-Whitney) method is reported for one secondary outcome; this method compares the rank distributions of observations rather than directly testing a difference in means. A p-value from that test should not be interpreted as if it were a mean-difference estimate.

These methods answer different questions and rely on different assumptions. The primary ANCOVA result, the unadjusted mean-difference recalculation, and the secondary Wilcoxon analysis should each be interpreted according to their own analysis method. Details needed to evaluate all model assumptions, covariate choices, and analysis populations are not reported in the registry record.

11. Confidence Intervals and Precision

The recalculated primary mean difference is -0.1 units, with a confidence interval from -1.455 to 1.255. The interval spans zero and extends in both directions. It is therefore compatible with a range of possible group differences, including a larger average improvement with droxidopa, a larger average improvement with placebo, or little difference. The interval’s width indicates that the point estimate alone should not be read as a precise estimate of the between-group contrast.

Precision is distinct from the direction of the point estimate. The droxidopa mean change is slightly more negative than the placebo mean change, but the interval indicates substantial uncertainty about the size and direction of the contrast. It does not support a claim that the groups are equivalent: showing equivalence would require a prespecified margin and an analysis designed for that question, neither of which is reported in the registry record.

The confidence interval is a recalculated, unadjusted interval based on posted summary statistics. The registry’s ANCOVA analysis reports a p-value but does not report its effect estimate or confidence interval. Consequently, the interval should not be attributed to the ANCOVA model or used as though it were its adjusted result. A clinically meaningful difference threshold is also not reported in the registry record, so the interval cannot be classified against such a threshold.

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 planning figures are illustrative participant counts per arm for the continuous outcomes in this study, not total event counts. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect. The original trial’s own design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the specified effect, under those assumptions, if that effect were the true effect. The 90% power column uses a higher target chance of detection and therefore gives a larger required count under the same planning setup. These are planning interpretations, not guarantees about the outcome of a future study.

Rows planning for 100%, 75%, or 50% of the observed effect illustrate how the assumed effect size changes the required sample. Smaller effects need more participants to distinguish them from random variation with the same target power and significance level. When the observed effect is very small, the illustrative counts can become very large; that does not mean the trial enrolled those numbers or that the observed estimate is a reliable forecast of a future effect.

This is not observed power. It is a planning calculation based on the observed effect and stated assumptions, not a measure of how likely the completed trial was to detect its actual effect. The planning values should not be mistaken for the registry’s original target or for evidence that the completed study was adequately or inadequately powered.

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 = -0.100; pooled standard deviation σ = 2.467.
2. n = 2 × (1.96 + 0.842)² × 2.467² / -0.100² = 9,551.1, rounded up to 9,552 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 <- -0.1                      # observed difference in means
sigma <- 2.46665683028008                     # 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(1176240)
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 = 9,552 (80% power), 12,787 (90% power)
 75% of observed effect: n per arm = 16,980 (80% power), 22,732 (90% power)
 50% of observed effect: n per arm = 38,205 (80% power), 51,146 (90% power)
power.t.test: 9552.1 
Simulated power at n = 9,552 per arm: 0.802 (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. Analyses Reported by the Sponsor

The registry reports an ANCOVA analysis for the primary endpoint, with p = 0.978. The adjusted estimate, confidence interval, covariate details, and analysis population for that model are not reported in the registry record. The recalculated comparison instead uses the posted arm means and standard deviations to form an unadjusted mean difference of -0.1 units, with a confidence interval from -1.455 to 1.255 and an unadjusted p-value of 0.885.

These are not duplicate versions of one analysis. ANCOVA can adjust for model terms that the summary-statistic recalculation does not include, and its result cannot be recreated from the posted group summaries alone. The recalculation is useful for showing the basic contrast and its uncertainty, but it does not supersede or reproduce the sponsor’s reported model. Both results indicate that the posted record does not provide a precise separation between the groups, while the sponsor’s analysis remains the official reported analysis for the primary endpoint.

The record indicates no discrepancy flag for this comparison. Even so, the different methods and incomplete model reporting limit direct numerical comparison of the two p-values. The missing adjusted estimate and confidence interval prevent a fuller assessment of the magnitude and precision of the ANCOVA result.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, time points, or statistical comparisons are examined. In general, the more comparisons made, the greater the chance that at least one result will appear notable by chance even if there is no underlying effect. The registry lists 10 outcome measures, including several secondary endpoints, and reports four analyses. A correction, hierarchy, or other strategy for controlling multiplicity is not reported in the registry record. Accordingly, secondary results should be treated as exploratory unless a prespecified inferential plan can be established from information not present in the registry record.

The primary endpoint description does report one missing-data method: LOCF was used for patients without an end-of-study visit. LOCF substitutes a participant’s last recorded value for the missing end-of-study value. The number of participants affected, reasons for missing visits, and sensitivity analyses are not reported in the registry record. Those details matter because a missing-value method can influence the estimated group means and their uncertainty, particularly if the likelihood or pattern of missingness differs between groups.

The analysis populations used for the primary ANCOVA and secondary analyses are not reported in the registry record. It is therefore unclear from the posted information whether all randomized participants were included in each analysis, how protocol deviations were addressed, or how participants with incomplete data were handled beyond the stated LOCF approach. The original sample-size justification, interim analyses, and full statistical analysis plan are also not reported in the registry record. These omissions limit assessment of prespecification, the risk of selective emphasis, and the robustness of the reported inferences.

16. Safety Results

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

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: syncope (1.9%), viral infection (0.9%), asthenia (0.9%), fibula fracture (0.9%), abdominal pain upper (0.9%).

The registry reports serious adverse events affecting 5 of 114 participants at risk in the droxidopa group and 4 of 108 participants at risk in the placebo group. It also lists other affected participants as 54 of 114 and 52 of 108, respectively. These are reported counts, not a causal comparison. The record’s serious-event terms include syncope at 1.9%, with viral infection, asthenia, fibula fracture, upper abdominal pain, and faecaloma each listed at 0.9%. The listed percentages are presented as registry terms and should not be assigned to a particular treatment group unless the record explicitly does so.

Adverse-event counts describe events recorded during the study; they do not by themselves establish that the study drug caused an event. The registry does not provide a detailed account of event timing, severity beyond the serious-event designation, or the method used to judge relatedness in the information available for these results. Death counts are not reported in the registry record. The observed counts should be interpreted in the context of the study’s size and duration, rather than as a complete characterization of safety.

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

The posted primary results show similar average OHQ changes in the two groups, with a recalculated mean difference close to zero and an interval that includes differences in either direction. The registry’s own ANCOVA analysis reports p = 0.978, but its adjusted estimate and confidence interval are not reported in the registry record. Together, these results do not demonstrate a clear between-group difference in the primary endpoint in the posted record.

That interpretation is not the same as proving that droxidopa and placebo have identical effects. An absence of clear evidence for a difference can reflect a small true difference, imprecision, or both. The recalculated interval is broad enough to permit a range of effects, and the record does not report an equivalence margin or a clinical threshold for interpreting the OHQ difference. The data therefore do not establish equivalence or resolve whether any possible difference would matter to patients.

The endpoint captures reported symptoms and daily activity impact, while some secondary outcomes concern specific symptoms or blood pressure. These measures address related but distinct aspects of NOH. Their results should be interpreted with attention to their separate scales, time points, and analysis methods, as well as the unreported multiplicity plan and analysis populations.

The findings apply to the participants and study conditions represented in the registry record. They do not establish how results would generalize to populations or settings not described in the record. The statistical findings alone are not medical advice and do not determine an individual treatment decision. They describe the posted group-level evidence and its uncertainty.

18. Why This Trial Matters Statistically

This study illustrates why an estimated difference should be read together with its uncertainty. The two primary group means are close, but the recalculated interval is wide enough to allow differences on either side of zero. Looking only at the point estimate would understate uncertainty; looking only at a p-value would conceal the range of effects compatible with the data.

It also illustrates why the analysis method matters. The registry reports ANCOVA for the primary endpoint, whereas the summary-statistic recalculation is unadjusted. The p-values differ, and the adjusted estimate is not available in the registry record. A transparent re-calculation can help readers understand the basic contrast, but it cannot substitute for a model whose details and estimate are not posted.

The study has multiple secondary outcomes and time points, but the approach to multiplicity is not reported in the registry record. This makes it important to distinguish the primary endpoint from secondary patterns and to avoid treating an isolated result as decisive. The missing-data approach is also relevant: LOCF is reported for the primary endpoint, but the extent of missingness and sensitivity of results to that choice are not reported.

Finally, illustrative sample-size calculations based on an observed effect are not evidence of the original design rationale or of observed power. Keeping these distinctions clear helps separate what the registry reports, what can be recalculated from posted summaries, and what remains unknown.

19. 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’s posted primary analysis does not include the ANCOVA effect estimate or confidence interval, and its model details are not reported. This limits assessment of the magnitude and precision of the sponsor-reported result and prevents direct reconstruction from the available summaries. The recalculated interval is unadjusted and should not be treated as the adjusted primary result.

LOCF is reported for participants without an end-of-study visit, but the number affected, reasons for missingness, and sensitivity analyses are not reported in the registry record. The primary and secondary analysis populations are also not reported. These gaps make it difficult to judge how missing outcomes and exclusions may have influenced the estimates.

The registry describes a two-part study, while the primary endpoint is from 306A and the posted secondary outcomes include measures from 306B. The populations and sample counts differ across those results, so the secondary findings should not be assumed to be direct replications of the primary analysis. The number randomized by study part and the complete participant flow are not reported in the registry record.

The clinical importance threshold for OHQ change, the original sample-size justification, and the strategy for handling multiple outcomes are not reported in the registry record. The study’s completion status and enrollment are recorded, but these registry entries do not resolve those methodological uncertainties. The safety information includes event counts and selected serious-event terms, but detailed event-level context and death counts are not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Two Part Study (306A/306B) to Assess Droxidopa in Treatment of NOH in Patients With Parkinson's Disease — NCT01176240.
• Registry record last updated 2014-05-20; status last verified 2014-04.
• Results first posted 2014-05-20.
• 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.

23. Record Summary

This completed phase 3 study compared droxidopa with placebo in patients with Parkinson’s disease and symptomatic NOH. It was randomized, parallel-group, and quadruple-masked. The primary endpoint for 306A was change in OHQ composite score from baseline to end of study, with negative change defined as improvement.

The primary arm means were -2.2 for droxidopa and -2.1 for placebo. The recalculated unadjusted mean difference was -0.1 units, with a confidence interval from -1.455 to 1.255. The registry reports an ANCOVA p-value of 0.978, but not its adjusted estimate or confidence interval. Secondary results cover symptoms and blood pressure, with uncertain between-group estimates. The registry reports LOCF for missing primary end-of-study values; further details on missingness, multiplicity, and analysis populations are not reported in the registry record.