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 Safety of Tobramycin Inhalation Powder (TIP) vs Tobramycin Solution for Inhalation in Patients With Cystic Fibrosis (NCT00388505), a randomized phase 3 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00388505 |
| Phase | Phase 3 |
| Condition | Cystic Fibrosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 517 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Participants with cystic fibrosis were enrolled in the trial. The primary outcome description identifies the analysis population as the All Randomized Safety population. The registry does not give further eligibility criteria in the record summarized for this analysis.
Intervention
The intervention was tobramycin inhalation powder (TIP), delivered using the T-326 inhaler. Participants received four 28 mg capsules twice daily for 28 days, followed by 28 days off therapy. This pattern constituted a cycle, and the registry describes a total of three cycles.
Comparator
The comparator was tobramycin solution for inhalation (TOBI), delivered using a nebulizer. Participants received one 300 mg ampoule in 5 mL twice daily for 28 days, followed by 28 days off therapy, for a total of three cycles.
Primary question
The primary endpoint was the number of participants with treatment-emergent adverse events over 25 weeks. The registry describes the study as comparing safety, but it does not post a single reduced comparison for this endpoint. The available record therefore does not establish an inferential answer to whether the arms differ on the primary endpoint.
In statistical terms, the comparison concerns participant-level safety events during the recorded timeframe. A participant-level endpoint counts people meeting an event definition rather than the total number of event episodes. The record also lists serious adverse event counts and other adverse event counts by arm, along with selected serious-event terms. Those summaries provide safety context, but they do not by themselves constitute a complete analysis of the primary endpoint.
The question is limited to the trial’s stated comparison and the information registered for it. It does not extend to a general judgment about the medicines, to safety beyond the recorded timeframe, or to outcomes not described in the registry record.
3. Trial Design
The trial was randomized, open-label, parallel-group and Phase 3. Its official title describes it as a multicentre trial comparing the safety of tobramycin inhalation powder with tobramycin solution for inhalation in people with cystic fibrosis. The registry lists an enrollment of 517. The study status is completed.
Random allocation means treatment assignment was intended to be determined by a random process, rather than chosen solely by a participant or clinician. The registry record does not report the randomization sequence method, allocation concealment procedure, or allocation ratio. These details cannot be inferred from the word “randomized.”
The trial was open-label, with masking listed as none. Participants and study personnel therefore were not recorded as masked to treatment assignment. This matters when interpreting outcomes that involve reporting, clinical judgment, or decisions about additional care: knowledge of the assigned delivery method could influence assessment or reporting. The registry does not say whether any particular outcome assessment was independently masked.
The assigned treatments differed in both formulation and delivery. TIP used capsules and an inhaler; TOBI used an ampoule and a nebulizer. Both regimens were described as twice daily for 28 days followed by 28 days off therapy, repeated for a total of three cycles. The record gives the dose and delivery details for each arm, but does not provide adherence summaries or information about treatment received after discontinuation.
The primary endpoint timeframe was 25 weeks. The registry lists the study start as 2006-02 and primary completion as 2009-03. These dates describe the registered study record; they do not provide participant-level follow-up duration or explain the timing of individual events. The registry does not report additional details about site count, recruitment procedures, or the statistical plan.
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 | Tobramycin Inhalation Powder (TIP) | Tobramycin Solution for Inhalation (TOBI) |
|---|---|---|
| STARTED | 308 | 209 |
| COMPLETED | 225 | 171 |
| NOT COMPLETED | 83 | 38 |
Reasons for not completing this period:
| Reason | Tobramycin Inhalation Powder (TIP) | Tobramycin Solution for Inhalation (TOBI) |
|---|---|---|
| Adverse Event or Death | 43 | 17 |
| Withdrawal by Subject | 24 | 9 |
| Lost to Follow-up | 5 | 3 |
| Inappropriate Enrollment | 0 | 1 |
| Administrative Reason | 1 | 0 |
| Protocol Violation | 6 | 5 |
| Unable to classify | 4 | 3 |
Analysis population for the primary outcome, as defined in the registry: All Randomized Safety population.
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 | Tobramycin Inhalation Powder (TIP) | Tobramycin Solution for Inhalation (TOBI) | Total |
|---|---|---|---|---|
| Participants analysed | 308 | 209 | 517 | |
| Age Continuous | years | 25.9 (SD 11.36) | 25.2 (SD 10.20) | 25.6 (SD 10.90) |
| Age, Customized: ≥6 to <13 years | participants | 28 | 18 | 46 |
| Age, Customized: ≥13 to <20 years | participants | 66 | 48 | 114 |
| Age, Customized: ≥20 years | participants | 214 | 143 | 357 |
| Sex: Female, Male: Female | Participants | 137 | 94 | 231 |
| Sex: Female, Male: Male | Participants | 171 | 115 | 286 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events, measured over 25 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with treatment-emergent adverse events during 25 weeks. The registry defines an adverse event as an unfavorable or unintended sign, symptom, or disease occurring in temporal association with study medication, whether or not it is considered caused by that medication. This definition captures events observed during treatment without requiring a causal judgment.
The registry separately defines a serious adverse event by consequences such as death, a life-threatening event, inpatient hospitalization or prolonged hospitalization, persistent or significant disability, a congenital anomaly or defect, or a significant medical event that may jeopardize the participant or require intervention to prevent one of those outcomes. Seriousness is therefore based on specified consequences, not simply on how often an event occurs.
A participant-count endpoint is useful for describing how many people experienced at least one qualifying event. It differs from a count of all event episodes, because one participant may experience more than one event. The registry identifies the endpoint unit as participants, but does not post a single arm-to-arm primary comparison reduced from its categories or time points.
The record names the All Randomized Safety population for this endpoint. That population label indicates the intended safety analysis population, but the registry does not provide additional rules for inclusion, follow-up, or handling of missing safety observations. Those details are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports serious adverse event figures of 85 participants at risk and 85 affected in the TIP arm, and 209 participants at risk and 61 affected in the TOBI arm. For other adverse events, it reports 308 at risk and 241 affected for TIP, and 209 at risk and 148 affected for TOBI. These are posted counts, not a complete statistical comparison. The record does not provide an adjusted estimate, confidence interval, or significance test for the primary endpoint.
The primary outcome is described as having several categories or time points and is not reduced to one comparison. Consequently, the available counts should not be read as a definitive estimate of a treatment effect on the registered primary endpoint. The record does not state how the listed adverse-event categories relate to each other for the endpoint, or whether participants can appear in more than one category. No total across categories should be inferred.
The registry also lists selected serious adverse-event terms with percentages: Lung disorder, 19.5%; Haemoptysis, 2.6%; Cough, 2.4%; Bronchitis, 1.9%; Dyspnoea, 1.9%; and Sputum increased, 1.6%. The record does not specify the denominator or arm attribution for these percentages in the information available. They should therefore be read as listed event terms and percentages, not as a direct comparison between arms.
Several ingredients needed for a more complete interpretation are not reported in the registry record: uncertainty intervals, a prespecified statistical test for the primary endpoint, the treatment-effect measure, and the handling of missing observations. Without those, the counts do not show how precise an arm difference may be or whether any observed difference is compatible with chance variation under a stated model.
General statistical context: event counts describe what was observed, while an inferential comparison estimates how compatible the observed data are with a specified no-difference model and quantifies uncertainty. A confidence interval expresses a range of effect values compatible with the data and analysis assumptions; it is not a guarantee that the true value lies in that interval. No such interval is posted for this primary endpoint.
The registry record lists zero analyses. That absence limits what can be concluded from the posted record: there is no recorded primary-effect estimate or formal test to interpret. The counts remain descriptive safety information. They do not by themselves establish a causal difference, equivalence, or absence of a difference between the treatments.
9. Statistical Methods Explained
What does randomization contribute?
Randomization is a design method intended to make treatment assignment independent of participants’ measured and unmeasured characteristics on average. It supports a fair comparison by reducing systematic differences in assignment. It does not ensure that the groups are identical, and it does not replace analysis of the outcomes. The registry says the study was randomized but does not describe the sequence-generation or allocation-concealment methods. Those implementation details are not reported in the registry record.
The parallel-group design means participants were assigned to a treatment arm rather than described as crossing between the two regimens. The record names the arms and gives their administration schedules. It does not report whether participants switched treatments, how treatment discontinuations were handled, or what exposure participants received after discontinuation.
Why does open-label status matter?
General statistical context: masking can reduce the chance that knowledge of assignment changes treatment, reporting, or outcome assessment. In an open-label trial, participants and study staff know the assigned treatment. For a safety endpoint that includes reported symptoms and clinical events, that knowledge may affect how events are noticed, reported, categorized, or followed. This is a potential source of measurement differences, not proof that such differences occurred. The registry does not report blinded adjudication of adverse events.
The formulations also differ in delivery method: TIP was taken with an inhaler and TOBI with a nebulizer. This trial therefore compares the registered treatment regimens as a whole, not formulation while holding every aspect of delivery constant. The registry does not report analyses that separate the effect of the drug formulation from the effect of delivery method.
What does a participant count represent?
The primary endpoint is expressed as the number of participants with treatment-emergent adverse events. This is a participant-level summary: it concerns whether a person experienced a qualifying event, not how many episodes that person had. Such a summary can be useful for comparing the proportion of participants affected, but a count alone does not provide that proportion, an effect estimate, or its uncertainty. No new proportions or comparisons can be derived from the record without choosing a definition and analysis that the registry does not post.
The record separately gives counts for serious and other adverse events, with at-risk and affected values by arm. The listed values describe those categories as registered; they should not be added together because the record does not establish that the categories are mutually exclusive. Nor does it say whether an individual can contribute to more than one event term. The primary endpoint’s note says it has several categories or time points and was not reduced to one comparison.
What can a confidence interval or test add?
General statistical context: an estimate describes the size and direction of an association under a chosen analysis. A confidence interval adds information about precision: a narrower interval generally indicates less statistical uncertainty than a wider interval, conditional on the model and data. A hypothesis test summarizes how compatible the data are with a specified null hypothesis under its assumptions. Neither a confidence interval nor a p-value establishes causation on its own, and neither substitutes for judging the clinical context.
No confidence interval, test statistic, p-value, or treatment-effect estimate for the primary endpoint is reported in the registry record. As a result, statistical significance and precision cannot be assessed from the primary endpoint record. The registry also does not report a statistical model or adjustment variables for this outcome.
How should planning illustrations be read?
General statistical context: a sample-size calculation asks how many participants a future study might need under stated assumptions about the effect to detect, variability or event frequency, significance level, allocation, and analysis. Such a calculation is a planning exercise. It is not an estimate of the power achieved by a completed trial and does not establish whether its findings are reliable.
The registry’s stated planning illustration uses the observed effect as its basis, a two-sided significance level of 0.05, equal allocation, and a normal approximation; the target effect is a stated fraction of the observed effect. These are assumptions for an illustration, not the trial’s documented original design rationale. The record does not report a sample-size justification or establish that these assumptions were used to design the trial. Any planning values should therefore be understood as hypothetical planning outputs, not observed power or evidence of efficacy.
General statistical context: binary outcomes are often analyzed with methods for event counts or probabilities, while repeated observations, time-to-event outcomes, and clustered observations may call for other methods. Over-dispersion occurs when observed variation exceeds what a simple model assumes; ignoring it can make uncertainty estimates too small. These are general considerations only. The registry does not report that over-dispersion was assessed or that a particular model was used for this endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies the primary safety endpoint and lists secondary outcomes covering serum tobramycin concentrations, auditory acuity, relative change in percent predicted FEV1, treatment satisfaction, sputum density, minimum inhibitory concentration, antibiotic usage, and hospitalization due to respiratory events. It lists nine outcome measures in total. When a study examines multiple outcomes, multiple time points, or multiple categories, the chance of at least one apparently notable result can increase if many tests are performed. General statistical practice may address this through a prespecified testing hierarchy or adjustment, but the registry does not report a multiplicity strategy.
The primary outcome is explicitly not reduced to one comparison because it has several categories or time points. The registry record does not report which comparison was designated as the principal statistical contrast, how repeated measurements were handled, or whether any adjustment for multiple testing was planned or applied. It also lists zero analyses, so no registered inferential results are available to assess.
The primary population is named as the All Randomized Safety population. The record does not report detailed analysis-population rules, how participants with incomplete follow-up were treated, how missing event information was handled, or whether sensitivity analyses were conducted. It does not describe imputation, censoring rules, or exclusions from the safety analysis. Each of these items is not reported in the registry record.
These omissions do not prove that no methods were used in the trial; they mean that the registry record does not document them. Without the analysis rules and results, readers cannot assess how multiplicity, incomplete data, or deviations from assigned treatment affected the primary comparison.
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 |
|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | 85 | 308 | 27.6% |
| Tobramycin Solution for Inhalation (TOBI) | 61 | 209 | 29.2% |
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 |
|---|---|
| Tobramycin Inhalation Powder (TIP) | 241 of 308 |
| Tobramycin Solution for Inhalation (TOBI) | 148 of 209 |
Most frequent serious adverse event terms
| Event term | Organ system | Tobramycin Inhalation Powder (TIP) | Tobramycin Solution for Inhalation (TOBI) |
|---|---|---|---|
| Lung disorder | Respiratory, thoracic and mediastinal disorders | 60 of 308 | 39 of 209 |
| Cough | Respiratory, thoracic and mediastinal disorders | 7 of 308 | 5 of 209 |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | 8 of 308 | 4 of 209 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 5 of 308 | 4 of 209 |
| Bronchitis | Infections and infestations | 6 of 308 | 1 of 209 |
| Pulmonary function test decreased | Investigations | 4 of 308 | 3 of 209 |
| Sputum increased | Respiratory, thoracic and mediastinal disorders | 5 of 308 | 1 of 209 |
| Cystic fibrosis lung | Congenital, familial and genetic disorders | 2 of 308 | 2 of 209 |
| Lower respiratory tract infection | Infections and infestations | 2 of 308 | 2 of 209 |
| Pneumonia | Infections and infestations | 2 of 308 | 2 of 209 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tobramycin Inhalation Powder (TIP) | Tobramycin Solution for Inhalation (TOBI) |
|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | 145 of 308 | 63 of 209 |
| Lung disorder | Respiratory, thoracic and mediastinal disorders | 57 of 308 | 33 of 209 |
| Sputum increased | Respiratory, thoracic and mediastinal disorders | 49 of 308 | 35 of 209 |
| Pyrexia | General disorders | 47 of 308 | 25 of 209 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 44 of 308 | 22 of 209 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 43 of 308 | 22 of 209 |
| Headache | Nervous system disorders | 34 of 308 | 25 of 209 |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | 35 of 308 | 23 of 209 |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | 42 of 308 | 8 of 209 |
| Nausea | Gastrointestinal disorders | 23 of 308 | 19 of 209 |
Serious events with the highest arm-level rate: lung disorder (19.5%), haemoptysis (2.6%), cough (2.4%), bronchitis (1.9%), dyspnoea (1.9%).
The registry reports serious adverse event counts by arm: 85 affected participants among 308 at risk for TIP, and 61 affected participants among 209 at risk for TOBI. It also gives other adverse event counts: 241 affected among 308 at risk for TIP, and 148 affected among 209 at risk for TOBI. These figures should be read as the registered counts for their respective categories, not combined into a single total or treated as the primary endpoint comparison.
The record lists serious-event terms and percentages for Lung disorder (19.5%), Haemoptysis (2.6%), Cough (2.4%), Bronchitis (1.9%), Dyspnoea (1.9%), and Sputum increased (1.6%). The available information does not specify their denominator or identify an arm for each percentage. The percentages therefore cannot be used to compare the arms. Death figures are not reported in the registry record.
General statistical context: raw counts depend on the number of people observed and on the event definition. A count alone does not quantify uncertainty, account for follow-up differences, or establish that treatment caused an event. The registry does not provide a formal comparative safety estimate or its confidence interval for these summaries.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized, open-label, parallel-group Phase 3 trial of TIP and TOBI in people with cystic fibrosis. It provides treatment schedules, a primary safety endpoint, the endpoint timeframe, and adverse-event counts by arm. It also lists selected serious-event terms and percentages. These details allow a reader to understand the type of safety outcome being tracked and the descriptive information registered.
The posted counts do not provide a complete statistical comparison of the primary endpoint. There is no single reduced primary comparison, no posted effect estimate, no uncertainty interval, and no test result. Without those items, the record cannot show the precision of an arm difference or support a conclusion about whether an observed difference is compatible with chance variation under a specified analysis.
The serious-event percentages also have limits: the registry record does not state their denominator or arm attribution in the information available. They should not be interpreted as arm-specific risks. Similarly, counts for serious and other adverse events should not be added, because overlap is not described.
General statistical context: a non-significant test, if one were reported, would not by itself prove equivalence; equivalence requires a prespecified margin and an analysis designed to assess it. A lack of a posted test is not evidence that the arms are the same. Here, the registry does not report a primary inferential comparison, so neither equivalence nor a treatment difference can be established from the available record.
The registered information also does not determine whether a particular event was caused by treatment. The adverse-event definition includes events temporally associated with medication regardless of whether a causal relationship is established. A safety count is therefore a description of observed events under the registry’s definitions, not a causal judgment.
The appropriate interpretation is bounded: these are descriptive registered safety summaries from a trial with the stated design and timeframe. They do not provide a complete answer about comparative safety, do not address outcomes beyond those listed, and do not replace a fuller analysis with methods, uncertainty estimates, and documented handling of missing data.
13. Why This Trial Matters Statistically
This trial illustrates a common challenge in clinical-trial interpretation: a clearly named endpoint and arm-level counts do not necessarily amount to a complete statistical result. The primary endpoint is the number of participants with treatment-emergent adverse events, but the registry notes multiple categories or time points and does not reduce them to one comparison. Without a stated contrast and inferential estimate, the descriptive counts cannot answer the primary comparative question on their own.
The open-label design also matters for how safety outcomes are understood. General statistical context: outcomes based partly on participant reports and clinical assessments may be sensitive to awareness of treatment assignment. That concern does not establish that outcome measurement was biased in this trial, but it makes documentation of event definitions, assessment procedures, and adjudication particularly useful. The registry provides an adverse-event definition but does not report blinded adjudication.
The arms differ not only in formulation but also in delivery device. A comparison of the registered regimens therefore reflects those treatment packages together. Statistical interpretation should not attribute any possible difference solely to the powder or solution formulation when the administration methods also differ.
The record further demonstrates why denominators and uncertainty matter. Serious-event counts are listed by arm, but selected event-term percentages are not accompanied by an arm attribution or denominator in the record summarized for this analysis. A percentage without a clear reference population cannot be used as a direct arm-to-arm contrast. Likewise, counts without confidence intervals do not show how precisely the underlying comparison is estimated.
More broadly, the record offers an opportunity to distinguish design information from analysis information. Randomization and a safety population describe important aspects of the trial, while a statistical analysis plan, missing-data rules, multiplicity handling, and comparative estimates are needed to understand how the primary question was evaluated. The registry record does not report those analysis details.
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 principal limitation for interpretation is that the registry does not provide a single analysis of the primary endpoint. It identifies several categories or time points, but does not post a reduced comparison, effect estimate, confidence interval, or significance test. The record lists zero analyses, leaving the primary comparative result unavailable in the registry record.
The adverse-event summaries are incomplete for some comparisons. Serious and other event counts are listed by arm, but the record does not state whether categories overlap or how the counts relate to the primary endpoint’s multiple categories or time points. The selected serious-event percentages are not accompanied by a denominator or arm attribution in the information available. Death figures are not reported in the registry record.
The registry does not report the randomization method, allocation concealment, statistical model, multiplicity procedure, missing-data method, or detailed analysis-population rules. It names the All Randomized Safety population, but does not explain how incomplete follow-up or deviations from treatment assignment were handled. The open-label design is stated, while blinded event adjudication is not reported.
The treatment arms also differ in delivery method as well as formulation. Results from the registered comparison would therefore concern the regimens as administered, not an isolated formulation effect. The record does not provide adherence information, participant-level follow-up, or enough detail to assess exposure differences.
These are limitations of the information reported in the registry record. They do not establish that the trial lacked additional analyses or procedures; those details are simply not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety of Tobramycin Inhalation Powder (TIP) vs Tobramycin Solution for Inhalation in Patients With Cystic Fibrosis — NCT00388505.
- Registry record last updated 2012-07-24; status last verified 2012-06.
- Results first posted 2012-07-24.
- 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
The registry record describes NCT00388505, a completed, randomized, open-label, parallel-group Phase 3 trial in cystic fibrosis. It compares tobramycin inhalation powder delivered by inhaler with tobramycin solution for inhalation delivered by nebulizer. Both regimens are described as twice daily for 28 days followed by 28 days off therapy, for a total of three cycles.
The primary endpoint is the number of participants with treatment-emergent adverse events over 25 weeks, in the All Randomized Safety population. The record reports serious and other adverse-event counts by arm and selected serious-event terms and percentages. It does not provide a single reduced primary comparison, inferential estimate, confidence interval, or test result.
The registry lists nine outcome measures and zero analyses. Methods for multiplicity, missing data, and detailed analysis-population handling are not reported in the registry record. The posted safety summaries are descriptive and do not establish a comparative treatment effect.