Twelve Month Safety and Efficacy Study of CVT-301 In Parkinson's Disease Patients With OFF Episodes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Twelve Month Safety and Efficacy Study of CVT-301 In Parkinson's Disease Patients With OFF Episodes (NCT02242487), a non-randomized phase 3 study. The primary outcome is Pulmonary Safety of CVT-301 Change From Baseline for FEV1..

2. Clinical Question

3. Trial Design

This was a phase 3, multicenter, 12-month study of two inhaled dose levels of CVT-301 in patients with Parkinson’s disease and motor response fluctuations. Its stated purpose was to characterize pulmonary safety and assess the treatment over time. The registry lists a parallel-group model and enrollment of 325. The two groups are described as low-dose and high-dose CVT-301, with capsules used for OFF episodes up to 5 times per day for 12 months.

The treatment description says that all patients received active treatment and were blinded to dose level. However, the registry lists masking as NONE and allocation as NON RANDOMIZED. The primary-outcome description says 325 patients were randomized, while also stating that 13 did not receive study drug and 312 were included in the Safety Population. These entries are internally inconsistent: the record does not resolve how allocation was conducted or how its stated masking relates to dose-level blinding. Accordingly, the group listings should not be interpreted as a randomized controlled comparison.

The study was completed. Its primary outcome was change from baseline in FEV1 at 52 weeks, reported as a mean with standard deviation and measured in liters. The listed secondary outcomes were the count of patients achieving resolution of an OFF state to an ON state within 60 minutes and change from baseline in OFF time. The registry lists 5 outcome measures but no posted analyses. It does not report a protocol-level sample-size justification or a statistical analysis plan. The study description says it served as an extension for some eligible participants from earlier CVT-301 studies and could also include eligible participants who had completed other studies or were CVT-301 naïve.

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: Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.

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: Baseline Characteristics of 312 is based on the Safety Population of 325 participants randomized less 13 who were randomized and Not Dosed.

6. Primary Endpoint

The registry lists the primary outcome as Pulmonary Safety of CVT-301 Change From Baseline for FEV1., measured over Change from baseline at 52 weeks.

The primary endpoint is change from baseline in forced expiratory volume in one second, or FEV1, at 52 weeks. FEV1 is measured by spirometry and expressed in liters. A change score describes how the measurement at the specified follow-up differs from the participant’s baseline measurement. The registry says the outcome was to characterize pulmonary safety by treatment group and treatment visit.

FEV1 is used in this context because it is a measurable pulmonary function outcome that can be assessed repeatedly during a study of an inhaled treatment. Reporting change from baseline focuses attention on the direction and size of change over the follow-up period, rather than only on the final measurement. A group mean summarizes the average observed change, while a standard deviation describes variation among participants’ changes. Neither summary alone shows the full distribution or establishes the cause of any change.

The record defines baseline differently according to study-entry history: for some patients it is the last non-missing assessment before the first CVT-301 dose in CVT-301-004; for the rest, it is the last non-missing assessment before the first CVT-301-004E dose. The primary outcome is specified at 52 weeks. The posted record does not give the numerical mean changes, standard deviations, group estimates, confidence intervals, or statistical test results. Therefore the endpoint’s observed magnitude, variability, and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a change in FEV1 measured in liters. The registry specifies the mean and standard deviation as the summary measures. A mean describes the average change in a group; the standard deviation describes how spread out individual changes are around that average. These summaries answer different questions. A small standard deviation does not necessarily imply a small mean change, and a mean alone does not show how individual participants’ results were distributed.

What does a change-from-baseline outcome represent?

A change score compares each participant’s follow-up measurement with that participant’s baseline measurement, then summarizes those changes. This can make the baseline definition consequential. The record defines baseline as the last non-missing assessment before the first dose in CVT-301-004 for one group of patients, and before the first dose in CVT-301-004E for the rest. The registry does not further explain how these two study-entry histories were handled in the analysis, whether baseline differences were adjusted for, or how incomplete paired measurements were treated. Those details are not reported in the registry record.

The primary endpoint is specified at 52 weeks, while the description also refers to treatment visits. The record does not provide the visit-level analysis method, model specification, or an account of how repeated measurements were handled. In general, repeated-measures methods can use information from more than one visit and account for the association between measurements from the same participant. The appropriateness of a particular method depends on the data and assumptions; the method used in this study is not reported in the registry record.

Why do uncertainty estimates matter?

An estimate such as a group mean is an estimate of an underlying average, not an exact value known without uncertainty. A confidence interval expresses a range of values that are reasonably compatible with the data under a stated method and its assumptions. Narrower intervals generally indicate greater precision, while wider intervals indicate less precision. The registry does not post confidence intervals for the primary endpoint, so readers cannot assess its inferential precision from the record.

A p-value, when reported, describes how unusual the data would be under a specified null hypothesis and statistical model. It does not measure the size or clinical importance of an effect, and it does not establish causation. No p-value or test result for the primary outcome is posted. The record also does not describe a prespecified testing hierarchy or provide an analysis plan.

Why does allocation matter?

Random allocation, when properly implemented, can balance measured and unmeasured baseline characteristics on average across groups. In a nonrandomized comparison, group membership may be related to participant characteristics, prior study participation, or other factors that also relate to outcomes. This creates the possibility of confounding. Statistical adjustment can sometimes address measured differences, but it cannot guarantee removal of unmeasured confounding. The registry classifies allocation as NON RANDOMIZED, so a low-dose versus high-dose difference should not be interpreted as a causal dose effect solely from these group listings.

The record also contains a conflicting statement that 325 patients were randomized. It does not explain this discrepancy. Masking is listed as NONE, while the study description says patients were blinded to dose level. The record does not clarify who knew each patient’s dose assignment or how the stated blinding was implemented. These reporting inconsistencies should be kept distinct from the observed outcome data.

How should the planning illustrations be understood?

Planning calculations based on an observed effect are illustrative, not evidence that the study had a particular probability of detecting an effect. The stated assumptions for such calculations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the stated quantity is the total number of events; for other outcomes, it is participants per arm. These assumptions do not establish the trial’s original design rationale. The record does not report its own sample-size justification, and no posted primary effect estimate is available in the registry record to interpret as an observed treatment effect.

General statistical caution: when outcomes are more variable than a simple model assumes, over-dispersion can make standard errors too small if it is ignored. That can make intervals appear too narrow and tests overly optimistic. The registry does not report whether over-dispersion was relevant or assessed for any outcome in this study. Likewise, no analysis of the primary endpoint, uncertainty interval, missing-data method, or model diagnostics is described. Consequently, the statistical methods used for the posted analyses are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 5 outcome measures, including the primary FEV1 change outcome and secondary outcomes concerning OFF-to-ON resolution within 60 minutes and change from baseline in OFF time. It does not report a multiplicity strategy: there is no stated hierarchy, adjustment procedure, or explanation of how the risk of false-positive findings across outcomes was handled. The registry lists 0 analyses, so no inferential results are available to evaluate across endpoints. Whether interim analyses were planned or performed is not reported in the registry record.

The record describes a Safety Population of 312 patients who received at least 1 dose of study drug. It states that 13 of the 325 patients described as randomized did not receive study drug. The allocation entry, however, is NON RANDOMIZED, leaving an unresolved inconsistency in the account of participant assignment. The record does not state whether the primary endpoint used the Safety Population or another analysis population, beyond describing the Safety Population in the primary outcome entry.

The primary outcome definition uses a last non-missing baseline assessment, but the record does not explain how missing follow-up FEV1 measurements were handled. It does not report whether participants with missing outcome data were excluded, whether values were imputed, or whether sensitivity analyses examined assumptions about missingness. The handling of participants who stopped treatment or missed visits is also not reported in the registry record. These omissions matter because the observed group summaries can depend on which participants contribute data and on how missing measurements are addressed.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: osteoarthritis (2.0%), hip fracture (1.3%), angina pectoris (1.3%), dyspnoea (1.3%), radius fracture (0.7%).

The posted safety entries list 153 patients at risk in the CVT-301 Low Dose group and 159 in the CVT-301 High Dose group. Serious adverse events are listed for 22 and 13 patients, respectively; deaths are listed as 0 in each group. Other adverse events are listed for 81 and 69 patients, respectively. The record also lists selected serious adverse event terms, including osteoarthritis at 2.0%, hip fracture at 1.3%, angina pectoris at 1.3%, dyspnoea at 1.3%, radius fracture at 0.7%, and concussion at 0.7%.

These entries are counts and listed percentages in the registry record, not estimates from a randomized comparison. They do not show whether events were judged related to treatment, their timing, duration, severity beyond the serious classification, or the uncertainty around group differences. The record does not report an adjusted comparison or statistical test for these safety entries. Because allocation is listed as NON RANDOMIZED, differences in counts should not be read as causal evidence about dose. Zero deaths listed in each group describes the registry entry, not a general conclusion about risk.

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

The registry record documents a 12-month study of low-dose and high-dose CVT-301 in people with Parkinson’s disease and OFF episodes. It identifies change from baseline in FEV1 at 52 weeks as the primary outcome and describes the study’s intended pulmonary safety assessment. It also records that 312 patients received at least 1 dose and were included in the Safety Population, with selected adverse-event counts for each dose group.

What the record does not provide is the numerical result for the primary FEV1 endpoint. The group means and standard deviations, an estimate of the difference between groups, confidence intervals, and test results are not reported. As a result, the posted record cannot establish the direction, magnitude, or precision of the pulmonary function changes. It also cannot show whether the two dose groups differed on the primary endpoint.

The design information further limits conclusions. Allocation is labeled NON RANDOMIZED, even though the outcome description says 325 patients were randomized. The record does not resolve that inconsistency. It says dose level was blinded to patients but lists masking as NONE. Without clarification of allocation and masking, a direct causal interpretation of differences between the listed groups is not justified by the registry information.

The adverse-event entries give descriptive counts, not a complete evaluation of comparative safety. They do not supply inferential estimates or explain event attribution, and the record does not describe adjustment for differences between groups. Similarly, the presence of secondary outcomes in the registry does not tell readers their numerical results; those results are not reported in the registry record.

These limitations do not imply that no analyses were conducted or that the primary outcome was unchanged. They mean that the registry record does not include the information needed to determine the observed primary outcome or its uncertainty. The evidence that can be described from the record is therefore limited to its design and population statements, endpoint definition, and posted safety entries.

13. Why This Trial Matters Statistically

This study raises a useful statistical distinction between asking a safety question and having enough posted results to answer it quantitatively. FEV1 is specified as a continuous pulmonary measure, and the registry identifies a 52-week change from baseline as the primary endpoint. Yet the record does not include the mean changes or their variability. Without those estimates, even a clearly defined endpoint cannot convey the observed magnitude or precision.

The record also illustrates why design labels need to be reconciled before interpreting group comparisons. The allocation entry says NON RANDOMIZED, while the primary-outcome population description says 325 patients were randomized. The treatment description says patients were blinded to dose level, whereas masking is recorded as NONE. These are not minor wording details: allocation and masking affect how confidently differences can be attributed to treatment assignment and how outcomes might be influenced by expectations or other factors.

The safety listings show that descriptive event counts can be reported without a comparative statistical analysis. Counts can be informative as a record of what was observed, but they do not, by themselves, indicate whether an apparent group difference is reliable or attributable to dose. The absence of confidence intervals or tests also means the precision of those comparisons cannot be assessed.

Finally, a completed study and a defined set of outcomes do not ensure that the registry contains a complete statistical account. The record lists 5 outcome measures and 0 analyses. It does not describe its sample-size justification, missing-data approach, multiplicity handling, or primary analysis method. For biostatisticians and clinical researchers, this makes the record a case in separating what the study was designed to assess from what the posted results allow readers to conclude.

14. 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.

A central limitation is that the registry record does not report numerical results for the primary FEV1 endpoint. Without group estimates, variability, or uncertainty intervals, the endpoint cannot be interpreted quantitatively. The record’s statement that 312 patients entered the Safety Population does not establish how many contributed usable measurements at 52 weeks.

Design reporting is internally inconsistent. Allocation is classified as NON RANDOMIZED, but the primary-outcome description says 325 patients were randomized. Masking is listed as NONE, while the study description states patients were blinded to dose level. The record does not explain these differences. Therefore, the stated dose groups cannot be assumed to represent comparable randomized arms, and the degree of blinding cannot be determined from the registry alone.

The baseline definition differs according to whether patients were entering from CVT-301-004 or CVT-301-004E. The record does not describe whether prior study history was accounted for in the analysis or whether baseline differences between participants were adjusted. It also does not specify the model used for the endpoint, handling of repeated measurements, missing-data methods, or sensitivity analyses.

The registry lists 5 outcomes but does not report how multiplicity was handled or which analyses were conducted; it lists 0 analyses. The protocol-level sample-size justification, interim analyses, and statistical analysis plan are not reported in the registry record. Safety entries are descriptive, with no posted adjusted comparisons or uncertainty estimates. Finally, the available record does not state how adverse-event relatedness was assessed or provide further context for event timing and follow-up.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Twelve Month Safety and Efficacy Study of CVT-301 In Parkinson's Disease Patients With OFF Episodes — NCT02242487.
• Registry record last updated 2019-08-14; status last verified 2019-07.
• Results first posted 2019-07-30.
• 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.

18. Record Summary

This completed phase 3 study evaluated two dose levels of inhaled CVT-301 over 12 months in patients with idiopathic Parkinson’s disease and OFF episodes. Its primary outcome was mean change from baseline in FEV1 at 52 weeks, measured in liters and summarized with standard deviations. The record describes a Safety Population of 312 patients who received at least 1 dose, out of 325 described as randomized.

Allocation is classified as NON RANDOMIZED, conflicting with the statement that patients were randomized. Masking is listed as NONE, although the study description says patients were blinded to dose level. The record lists selected adverse-event counts and 5 outcome measures, but 0 analyses. Numerical results for the primary outcome, inferential comparisons, missing-data methods, multiplicity procedures, and the statistical analysis plan are not reported in the registry record. These gaps prevent quantitative interpretation of the primary pulmonary endpoint and limit causal interpretation of differences between dose groups.