This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKAYCE™) - Extension Phase (NCT03905642), a na phase 2 study. The primary outcome is Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03905642 |
| Phase | Phase 2 |
| Condition | Cystic Fibrosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 49 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Insmed Incorporated |
| Results posted | Yes |
2. Clinical Question
Population
Participants with cystic fibrosis and chronic infections due to Pseudomonas aeruginosa were the population of interest. The registry reports an enrollment of 49. It does not report further eligibility details or the characteristics of participants who entered the extension phase.
Intervention
The study evaluated Arikayce™, also described as liposomal amikacin for inhalation. The reported cohort received 560 mg once daily, administered for six cycles over 18 months. The registry does not describe the timing or duration of each cycle in the information.
Comparator
There was no concurrent comparison group in the reported study design. The record describes a single-group study, with allocation listed as not applicable and no masking. Results therefore describe participants receiving Arikayce™; they do not provide a like-for-like comparison with another treatment or with no treatment.
Primary question
The primary outcome was the adverse-event profile among participants receiving the 560 mg once-daily dose over the stated treatment period. It was expressed as the number of participants with indicated adverse events. The registry also lists outcomes concerning lung function, sputum density, rescue therapy and the Cystic Fibrosis Questionnaire—Revised, but results for those outcomes are not reported in the registry record.
In plain terms, the study asks what adverse events were recorded during this treatment regimen in this enrolled group. It is not framed as a randomized test of whether Arikayce™ changes an outcome relative to a control. The extension-phase setting also means the record should not be read as a stand-alone comparison of treatment strategies. Further details about participants’ prior study experience and the rules for entering this phase are not reported in the registry record.
3. Trial Design
This is a completed Phase 2 study of liposomal amikacin for inhalation, listed under the title “Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKAYCE™) - Extension Phase.” Its official title describes a multidose safety and tolerability study in cystic fibrosis patients with chronic infections due to Pseudomonas aeruginosa. Insmed Incorporated is listed as the sponsor.
The design is single group, with no masking and allocation recorded as not applicable. The intervention arm is described as 560 mg Arikayce™. The registry reports 49 participants enrolled. This is not a randomized comparison, and the study does not include a concurrent control arm in the record. The observed group can therefore be summarized, but its outcomes cannot be separated from changes that might have occurred over time or from other influences using a control-group contrast.
The registry lists the study start as 2009-01-08 and primary completion as 2010-11-02; its status is completed. The primary outcome description concerns the number of participants with indicated adverse events while receiving 560 mg once daily for six cycles over 18 months. Listed secondary outcomes include FEV1 % Predicted, absolute change in sputum density, duration and time to antipseudomonal rescue therapy, and absolute change in the Cystic Fibrosis Questionnaire—Revised score. Although these outcomes are listed, their numerical results are not reported in the registry record.
The record does not report the protocol’s detailed eligibility criteria, the number of participants who completed treatment, or the analysis populations. It also does not report a statistical analysis plan, a sample-size justification, or details of any interim analyses. Those omissions matter when deciding how far to generalize a descriptive safety summary and when assessing whether all participants were evaluated in the same way.
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
| Stage | 560 mg Arikayce™ |
|---|---|
| STARTED | 49 |
| COMPLETED | 41 |
| NOT COMPLETED | 8 |
Reasons for not completing this period:
| Reason | 560 mg Arikayce™ |
|---|---|
| Withdrawal by Subject | 3 |
| Pregnancy | 1 |
| Adverse Event | 1 |
| Lack of Efficacy | 1 |
| Completed study but not 24 of 28 days | 2 |
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.
| Characteristic | Unit | 560 mg Arikayce™ |
|---|---|---|
| Participants analysed | 49 | |
| Age, Continuous | years | 17.4 (SD 6.22) |
| Sex: Female, Male: Female | Participants | 29 |
| Sex: Female, Male: Male | Participants | 20 |
| FEV1 % predicted | Percent % | 59.73 (SD 20.047) |
| P. aeruginosa density | Log10 CFU/mL | 6.289 (SD 2.8587) |
6. Primary Endpoint
The registry lists the primary outcome as Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months., measured over 18 Months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is an adverse-event profile for participants receiving 560 mg of Arikayce™ once daily for six cycles over 18 months. The registry describes the outcome as the number of participants with indicated adverse events and gives the unit as participants. This is a count-based, binary outcome: a participant is counted as having an event or not having that event, rather than the result being a continuous measurement such as a laboratory value.
Safety endpoints of this kind are used to describe the types of adverse events recorded and how many participants experienced them during the stated regimen. Counts can make it easier to see whether events were observed in a study group and which event categories appear in the record. They do not, by themselves, establish that treatment caused an event. In a single-group study, there is no concurrent control group to help distinguish events associated with treatment from events related to the underlying condition, other care, or the passage of time.
The registry gives aggregate serious and other adverse-event counts for the 560 mg group, but the detailed definition of the primary endpoint, event ascertainment procedures, and analysis rules are not reported in the registry record. Nor are numerical results for each of the primary outcome’s indicated adverse-event categories set out in the primary outcome description. The reported safety summaries should therefore be read as descriptive counts, not as a complete account of every endpoint detail or a causal comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The safety summary describes one group of 49 participants who received 560 mg Arikayce™. The registry reports 15 participants with serious adverse events and 29 participants with other adverse events; it reports zero deaths. These are counts within the treatment group. Because there is no concurrent comparator, they cannot show how many events would have occurred without the treatment or under a different treatment.
The listed serious adverse-event terms include “Cystic fibrosis lung” at 22.4%, followed by Endocarditis, Appendicitis, Bronchitis, Influenza and Endoscopy, each listed at 2.0%. These entries indicate which terms appear in the registry’s list and the percentages recorded there. The record does not provide the underlying participant counts for each listed term in the information, nor does it explain whether participants could contribute to more than one event category. The terms should not be added together or treated as mutually exclusive categories.
The primary outcome is intended to summarize adverse events over the stated dosing period, but the aggregate figures do not reveal when events began, how long they lasted, how severe they were, or whether they led to stopping treatment. Those details are not reported in the registry record. The information also does not establish whether all 49 enrolled participants received every cycle or were included in each safety summary.
For a single-group safety study, observed event counts are useful as a record of what was reported in the cohort. However, the precision of any estimate is limited by the group size and the absence of a comparison group. A confidence interval, if reported, would express statistical uncertainty around an estimate; no confidence intervals for these safety figures are reported in the registry record. Without those intervals and without detailed event-level results, the reader should avoid treating the listed percentages as precise estimates of event frequency beyond this study group.
The record also lists several secondary outcomes, but their numerical results are not reported in the registry record. No conclusions about changes in lung function, sputum density, rescue therapy, or questionnaire scores can be drawn from the adverse-event summary. Overall, the posted results support a descriptive account of reported safety events during the study regimen, not a comparative estimate of treatment effects or a definitive assessment of causation.
9. Statistical Methods Explained
The result tables and graphics on this page are generated from the registry’s posted results. The study design determines what those results can support: this record describes a single treatment group, not a randomized comparison. The methods discussion below explains general statistical ideas relevant to reading such results; it does not claim that any particular inferential method was used in this study.
What does a participant count represent?
The primary outcome is expressed as the number of participants with indicated adverse events. For an event category, this is a count of participants meeting the event definition, rather than a count of every episode or a measure of event duration. One participant might experience more than one event, and an individual event might be recorded under more than one term, depending on the study’s coding and reporting rules. Those rules are not reported in the registry record, so the categories should not be assumed to be exclusive.
Counts are straightforward to describe, but interpretation depends on the population included in the denominator. The registry’s adverse-event summary gives 49 participants at risk for the serious and other adverse-event summaries. The record does not report whether those participants all received the full regimen, whether any participants were excluded from safety follow-up, or how missing safety observations were handled. The denominator should consequently be understood as the one shown in the posted safety summary, not as evidence that every participant had identical exposure or follow-up.
Why does the lack of a comparator matter?
General statistical principle: a comparison group helps distinguish an outcome observed during treatment from the outcome that might have occurred under an alternative. In this study, only the Arikayce™ group is described. The observed counts can be reported for that group, but they cannot estimate a treatment-versus-control contrast. Events may relate to the underlying condition, other care, or unrelated circumstances; the study design does not provide a concurrent group to help evaluate those explanations.
Likewise, change over time cannot be attributed to treatment from a single-group summary alone. Even if a participant’s condition or an outcome measure changed during the study, the change could have other explanations. This is why the posted safety counts should be read descriptively and why the absence of a comparator is not repaired by applying a statistical test to the same single-group data.
How should uncertainty be understood?
General statistical principle: an estimate based on a sample is subject to sampling uncertainty. A confidence interval is a range calculated using a specified method that conveys uncertainty around an estimate; it is not a guarantee that the true value lies in that range, nor does it address biases caused by study design or incomplete reporting. The registry record does not report confidence intervals for the safety counts. The plots and tables can help display the observed results, but they cannot remove uncertainty that is not quantified in the record.
For event counts, the number observed is not the same as the underlying risk in every population or setting. The results describe this enrolled group and regimen. Generalization beyond that group requires caution, particularly because the registry record does not provide participant characteristics beyond the stated condition or detailed eligibility criteria.
What can the sample-size illustrations tell us?
The page includes a sample-size section whose calculations are described as planning illustrations based on the observed effect, not as the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event tables, the illustration gives a total number of events; other tables give participants per arm for 80% power or another displayed power target.
These are hypothetical planning calculations. They do not describe the actual single-group design, which has no randomized two-arm comparison, and they are not observed power. They cannot show that the study was adequately powered to detect or rule out an effect. The registry’s own sample-size justification is not reported in the registry record. The planning illustration should therefore be read only in light of its stated assumptions and not as evidence of the original design rationale.
What is known about the analysis plan?
The registry record identifies the primary safety outcome and lists secondary outcomes, but it does not report the statistical analysis plan, tests used, adjustment strategy, or rules for handling repeated events. It also does not report interim-analysis details. Without this information, the reader cannot verify from the record whether the posted summaries follow a prespecified approach or whether specific analyses were selected after examining the data. This limitation does not invalidate the descriptive counts; it limits what can be concluded about the analysis process and the precision or robustness of results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary adverse-event outcome and several secondary outcomes, including measures of lung function, sputum density, antipseudomonal rescue therapy, and questionnaire score. The numerical results for those secondary outcomes are not reported in the registry record. The record does not explain whether the outcomes were prespecified in a protocol, how multiple outcomes were handled, or whether any adjustment for multiple statistical tests was planned. Without those details, it is not possible to assess a multiplicity strategy or to know how the study’s conclusions were intended to account for testing more than one outcome.
Multiplicity matters in general because examining many outcomes or event categories can increase the chance that some findings appear notable by chance. This is a general statistical consideration, not a claim that a particular multiplicity problem occurred in this study. Since no inferential results or analysis plan are reported, the adverse-event terms should be treated as descriptive rather than as a set of statistically tested findings.
The registry record does not report how missing outcome data were handled, whether any participants discontinued, or which analysis populations were used. It also does not give the number of participants assessed at each time point for the listed secondary outcomes. Missingness can affect interpretation if participants with unavailable data differ from those with recorded data; the direction or size of any such effect cannot be assessed from the record. Details of outcome definitions, follow-up completeness, and analysis populations are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 560 mg Arikayce™ | 15 | 49 | 30.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 560 mg Arikayce™ | 0 of 49 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 560 mg Arikayce™ | 29 of 49 |
Most frequent serious adverse event terms
| Event term | Organ system | 560 mg Arikayce™ |
|---|---|---|
| Cystic fibrosis lung | Congenital, familial and genetic disorders | 11 of 49 |
| Endocarditis | Infections and infestations | 1 of 49 |
| Appendicitis | Infections and infestations | 1 of 49 |
| Bronchitis | Infections and infestations | 1 of 49 |
| Influenza | Infections and infestations | 1 of 49 |
| Endoscopy | Investigations | 1 of 49 |
| Drug abuse | Psychiatric disorders | 1 of 49 |
| Testicular appendage torsion | Reproductive system and breast disorders | 1 of 49 |
| Drug therapy | Surgical and medical procedures | 1 of 49 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 560 mg Arikayce™ |
|---|---|---|
| Cystic fibrosis lung | Congenital, familial and genetic disorders | 24 of 49 |
| Nasopharyngitis | Infections and infestations | 14 of 49 |
| Cough | Respiratory, thoracic and mediastinal disorders | 14 of 49 |
| Haemopytsis | Respiratory, thoracic and mediastinal disorders | 12 of 49 |
| Rhinitis | Infections and infestations | 11 of 49 |
| Productive cough | Respiratory, thoracic and mediastinal disorders | 11 of 49 |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | 7 of 49 |
| Influenza | Infections and infestations | 6 of 49 |
| Respiratory tract infection viral | Infections and infestations | 5 of 49 |
| Pharyngitis | Infections and infestations | 5 of 49 |
Serious events with the highest arm-level rate: cystic fibrosis lung (22.4%), endocarditis (2.0%), appendicitis (2.0%), bronchitis (2.0%), influenza (2.0%).
The registry reports 15 participants with serious adverse events among 49 at risk in the 560 mg Arikayce™ group. It reports 29 participants with other adverse events among 49 at risk, and zero deaths. These are group-level counts, not a comparison of event rates between treatments. The record does not provide a control group for context.
The serious-event terms listed include “Cystic fibrosis lung” at 22.4%, and Endocarditis, Appendicitis, Bronchitis, Influenza and Endoscopy at 2.0% each. The percentages are presented as registry entries; the record does not give enough detail to determine whether categories overlap or to reconstruct participant counts for every term. They should be read as reported labels, not as a partition of all serious events.
Serious adverse events are not necessarily caused by the study treatment. The registry’s aggregate summary does not report timing, duration, event-level severity, relatedness assessments, or the action taken in response. Those details are not reported in the registry record. The counts describe what was recorded in this cohort and should not be used alone to make a causal judgment or to estimate what would happen in another group.
12. What the Result Does, and Does Not, Mean
The posted results describe the adverse events reported in a single group receiving 560 mg Arikayce™ once daily for six cycles over 18 months. The registry reports 15 participants with serious adverse events, 29 with other adverse events, and zero deaths. It also lists several serious-event terms and their reported percentages. This is useful descriptive information about the cohort and treatment regimen recorded in this study.
It does not establish that Arikayce™ caused any particular adverse event. There is no concurrent control group, so the record cannot show whether the observed events were more or less common than they would have been under another treatment or no treatment. Nor does the summary show whether the regimen changes lung function, sputum density, rescue-therapy use, or questionnaire scores; results for those listed secondary outcomes are not reported in the registry record.
The counts also do not, on their own, characterize the timing or severity of each event, the completeness of follow-up, or the proportion of participants who completed the planned regimen. Those details are not reported in the registry record. The results should not be treated as a complete safety profile for all people with cystic fibrosis or as a precise estimate for settings beyond this study.
In statistical terms, the central contribution is a descriptive safety summary, not a randomized treatment-effect estimate. It can inform understanding of what was recorded in this cohort, while leaving important questions unanswered about causation, comparison, and generalizability. Further conclusions would require information that is not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically informative because it illustrates the difference between documenting events and estimating comparative effects. A single-group safety study can count events observed during a treatment regimen. That descriptive task is valuable, particularly when an outcome is intended to capture adverse events over an extended treatment period. But without a concurrent comparator, the design cannot isolate the treatment’s contribution to those events.
The distinction is important when reading a list of event counts or percentages. A number recorded in one cohort answers a question about that cohort; it does not automatically answer what would have happened under an alternative. The registry’s 49 participants and the reported serious and other adverse-event counts give a concrete description of the observed group, while leaving comparative risk unresolved.
The record also highlights the role of transparent reporting. Details such as event definitions, missing-data handling, analysis populations, and an analysis plan help readers understand how summaries were produced and what uncertainty remains. These details are not reported in the registry record. Without them, readers can still interpret the posted counts descriptively, but cannot fully assess the analysis procedures or the completeness of follow-up.
Finally, the sample-size illustrations on the page should not be mistaken for the trial’s design or for evidence of observed power. They use hypothetical two-arm assumptions, whereas the record describes a single-group study. Keeping planning calculations separate from actual study design helps prevent a common interpretive error: treating a modeled sample size as proof that a completed study could detect or exclude a particular effect.
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.
The most important design limitation is that the registry describes a single group with no concurrent control. Event counts therefore cannot be interpreted as a treatment-versus-control difference, and causal attribution is not supported by the design alone. The record also lists no masking, so it does not describe a masked assessment process.
The reported enrollment is 49, but the registry record does not report how many participants completed the planned regimen, how many contributed to each analysis, or how complete follow-up was. The handling of missing data and the specific analysis populations are not reported in the registry record. This makes it difficult to judge whether the adverse-event summaries include all enrolled participants on a consistent basis.
The serious-event summary includes aggregate counts and a list of terms, but the record does not report event timing, duration, severity details, relatedness assessments, or whether categories could overlap. The primary outcome description does not provide full operational definitions or event-collection procedures. These omissions limit interpretation of the event profile beyond its descriptive totals and listed terms.
The registry lists secondary outcomes, but their numerical results are not reported in the registry record. It also does not report a statistical analysis plan, a sample-size justification, interim-analysis details, or a multiplicity approach. Finally, participant characteristics and detailed eligibility criteria are not available in the information, limiting assessment of how well the results apply beyond this cohort.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKAYCE™) - Extension Phase — NCT03905642.
- Registry record last updated 2020-07-30; status last verified 2020-07.
- Results first posted 2019-05-14.
- 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.
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18. Record Summary
This completed Phase 2 extension study evaluated 560 mg Arikayce™ once daily in a single group of participants with cystic fibrosis and chronic Pseudomonas aeruginosa infections. The registry reports enrollment of 49, no masking, and no concurrent comparator. The primary outcome concerned the number of participants with indicated adverse events during six cycles over 18 months.
The safety summary reports 15 participants with serious adverse events, 29 with other adverse events, and zero deaths. The registry lists serious-event terms and associated percentages. The record also lists secondary outcomes involving lung function, sputum density, rescue therapy, and questionnaire scores, but their results are not reported in the registry record.
The results are descriptive. The single-group design cannot establish comparative effects or determine whether an event was caused by treatment. Details about the analysis plan, missing data, analysis populations, and sample-size justification are not reported in the registry record.