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 A Study to Investigate the Effect of RO7049389 on the Pharmacokinetics of Pitavastatin in Healthy Volunteers (NCT03717064), a non-randomized phase 1 study. The primary outcome is Period 1: Maximum Plasma Concentration (Cmax) of Pitavastatin.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03717064 |
| Phase | Phase 1 |
| Condition | Healthy Volunteers |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 18 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Healthy volunteers enrolled in the study. The registry record lists an enrollment of 18. The volunteers were studied to characterize a drug interaction, not to assess clinical benefit in people being treated for a condition.
Intervention
RO7049389 was given in Period 2 on Days 1–6. Participants also received a single dose of pitavastatin on Day 4 of that period. The record describes the study as open-label and fixed sequence.
Comparator
In Period 1, participants received a single dose of pitavastatin on Day 1, followed by a wash-out period of at least 7 and up to 21 days. This within-study sequence supplies a pitavastatin-only period for comparison with pitavastatin given during RO7049389 exposure. It is not a randomized, parallel-group control comparison.
Primary question
The listed primary outcome is the maximum plasma concentration (Cmax) of pitavastatin in Period 1. The study’s stated purpose is to characterize the interaction between RO7049389 and pitavastatin, but a numerical primary-outcome result and a direct statistical comparison are not reported in the registry record.
The sequence makes each participant’s Period 1 and Period 2 observations potentially relevant to understanding changes in drug exposure across conditions. However, the primary outcome entry specifically identifies Period 1 Cmax, rather than a stated contrast between Period 1 and Period 2. The registry record does not report a primary analysis estimate, confidence interval, or test result that would quantify an interaction. It also does not state a clinical benefit objective; its brief summary explicitly describes the aim as characterizing an interaction in healthy volunteers.
3. Trial Design
The registry record describes NCT03717064 as a completed Phase 1 study sponsored by Hoffmann-La Roche. It is an open-label, fixed-sequence, two-period study in healthy volunteers. Enrollment is listed as 18. The recorded start date is 2018-11-07 and the primary completion date is 2018-12-17. The total study duration for each participant is described as approximately 12 weeks.
In Period 1, participants received one dose of pitavastatin on Day 1. This was followed by a wash-out period lasting at least 7 and up to 21 days. In Period 2, participants received RO7049389 on Days 1–6 and a single dose of pitavastatin on Day 4. Thus, the sequence places pitavastatin exposure both outside and during RO7049389 administration. The design can support a within-participant pharmacokinetic comparison in principle, but the registry entry does not give a reported estimate for such a comparison.
The study was nonrandomized, unmasked, and classified as a single-group study. Periods in a fixed sequence are not equivalent to randomized parallel groups: treatment order is not assigned by randomization, and there is no like-for-like concurrent control arm identified in the record. The registry also records 21 outcome measures and zero analyses. Those counts describe what is listed in the registry; they do not establish which analyses were conducted outside the record or what results were obtained.
The stated purpose was to characterize the interaction between RO7049389 and pitavastatin in healthy volunteers. The record says there was no intended clinical benefit. It does not report a sample-size justification, details of an interim analysis, or a full statistical analysis plan. These omissions limit what can be concluded about how the study was planned to estimate effects or handle uncertainty.
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: This study had two periods. Period 1: Participants received a single dose of pitavastatin, followed by a washout period of 7-21 days. Period 2: Participants received a single dose of pitavastatin along with a twice-daily dose of RO7049389.
Period 1
| Stage | Pitavastatin/RO7049389 |
|---|---|
| STARTED | 18 |
| COMPLETED | 18 |
| NOT COMPLETED | 0 |
Period 2
| Stage | Pitavastatin/RO7049389 |
|---|---|
| STARTED | 18 |
| COMPLETED | 17 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Pitavastatin/RO7049389 |
|---|---|
| Adverse Event | 1 |
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 | Pitavastatin/RO7049389 |
|---|---|---|
| Participants analysed | 18 | |
| Age, Continuous | Years | 39.2 (SD 14.5) |
| Sex: Female, Male: Female | Participants | 7 |
| Sex: Female, Male: Male | Participants | 11 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 8 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 10 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 5 |
| Race (NIH/OMB): White | Participants | 13 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Period 1: Maximum Plasma Concentration (Cmax) of Pitavastatin, measured over Period 1 Day 1.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | ng/mL |
| Endpoint classification | not reduced to a single comparison |
The listed primary endpoint is Period 1 maximum plasma concentration (Cmax) of pitavastatin, measured in ng/mL, with a timeframe of Period 1 Day 1. Cmax is the highest measured concentration of a drug in plasma during the relevant sampling period. In pharmacokinetic research, it describes the peak level observed after dosing and can be useful when characterizing how drug exposure changes under different conditions.
The registry specifies that this endpoint is summarized as a geometric mean and that dispersion is expressed as a geometric coefficient of variation. A geometric mean is often used for concentration data because such measurements can be positively skewed: a smaller number of high values can pull an arithmetic mean upward. The geometric coefficient of variation describes relative variability on a multiplicative scale. These are summary choices, not evidence by themselves that an effect occurred.
The endpoint entry identifies the Period 1 measurement, when pitavastatin was given without the recorded Period 2 RO7049389 dosing. The study’s overall purpose concerns an interaction, but the registry does not report a numerical Period 1 result or a numerical contrast between periods for this primary endpoint. It also does not provide sampling schedules, the number of measurements contributing to Cmax, or a confidence interval. Consequently, the endpoint’s definition can be described, but its observed magnitude and precision cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the clinical pharmacology question and the dosing sequence, but it does not include numerical results for the primary endpoint. No Period 1 geometric mean for pitavastatin Cmax, geometric coefficient of variation, confidence interval, or test result is reported in the record. There is therefore no posted primary estimate to interpret for magnitude or precision. The endpoint name and its units describe what was intended to be measured; they do not reveal the observed concentration.
The study’s broader purpose was to characterize the interaction between RO7049389 and pitavastatin. The dosing schedule creates a period in which pitavastatin was administered with RO7049389 and a prior period in which pitavastatin was given without it. But an interaction estimate requires an outcome contrast defined and analyzed across those conditions. The registry does not report such a contrast for the primary endpoint. It would be inappropriate to infer an interaction’s direction or size from the study objective or dosing schedule alone.
The primary endpoint is specifically listed as Period 1 Cmax. That description should not be silently reinterpreted as a treatment effect or as a comparison with Period 2. The record also lists secondary pharmacokinetic outcomes, including outcomes for RO7049389 and pitavastatin lactone, but does not provide numerical results for them in the information recorded. Their presence in the outcome list does not establish what those outcomes showed.
Design features also shape interpretation. This was a nonrandomized, open-label, single-group, fixed-sequence study, not a randomized comparison between separate treatment arms. The same participants were scheduled to move through both periods, so any analysis comparing periods would need to account for paired observations and for the order in which the periods occurred. The registry record does not report whether or how such an analysis was performed. Potential period effects, changes over time, or other influences on measurements cannot be evaluated from the listed design and outcome definitions alone.
The record lists 18 enrolled participants and reports no serious adverse events in the study group, alongside 7 in the other adverse-event category. Those safety entries are descriptive and do not supply the missing pharmacokinetic result. The record does not report event details, timing, exposure-specific attribution, or a comparative safety analysis.
Overall, the registry record supports a description of the question, sequence, endpoint definition, and limited safety counts. It does not provide enough result information to quantify the primary outcome, its uncertainty, or the drug interaction. No conclusion about the direction, size, or clinical meaning of a pharmacokinetic effect can be drawn from the recorded endpoint definition alone.
9. Statistical Methods Explained
Pharmacokinetic studies examine how drug concentrations change over time after administration. Cmax is the highest measured plasma concentration in the sampling interval. It captures peak exposure, while area-under-the-curve measures describe exposure accumulated across time. These measures answer related but different questions: one concerns the peak, and the other concerns total exposure over a specified interval. This general distinction explains why the registry lists several pharmacokinetic outcomes.
Why use a geometric mean?
Concentration measurements often have a right-skewed distribution: many observations may be relatively low while some are much higher. A geometric mean is based on logarithmic values and is a common way to summarize positive, multiplicative data. It gives a central summary suited to ratios and fold-changes. The registry specifies a geometric mean for the primary Cmax endpoint, but it does not report the resulting estimate.
The geometric coefficient of variation describes spread relative to the geometric mean, rather than expressing spread in the original measurement units. It can help readers understand how variable individual concentration measurements are around a multiplicative center. The registry identifies this as the dispersion measure but does not report its value. Therefore, the record does not allow assessment of the observed variability.
What would a period comparison represent?
In general, a comparison of pitavastatin exposure between periods could be expressed as a within-participant contrast. Because observations from the same person are related, an analysis would ordinarily need to account for that pairing rather than treating all period observations as independent. The fixed sequence is important: Period 1 always precedes Period 2 in the described schedule, and the study was not randomized. A period contrast could therefore reflect the intended co-administration condition as well as effects related to sequence or time. The registry record does not state the model or method used to analyze any period contrast.
A confidence interval, when reported, gives a range of values compatible with the data and the analysis assumptions. It conveys uncertainty about an estimate; it is not a guarantee that the true value falls inside the interval. A narrow interval indicates greater precision than a wide interval, conditional on the method and assumptions. No confidence interval for the primary endpoint or an interaction contrast is reported in the registry record, so precision cannot be assessed.
What does a significance level mean?
In general, a significance level sets a threshold for how surprising data must be under a specified null hypothesis before a result is labelled statistically significant. The planning assumptions associated with sample-size illustrations specify a two-sided significance level of 0.05 and a normal approximation. Those assumptions describe the illustrations, not necessarily the trial’s own design or analysis. The trial’s statistical plan and any test results are not reported in the registry record.
The planning assumptions also describe equal allocation between two arms and an effect to detect as a stated fraction of an observed effect. The actual study is listed as a nonrandomized single-group, fixed-sequence study, not a two-arm randomized comparison. Planning illustrations under those assumptions should therefore be read as hypothetical planning scenarios rather than as a description of the enrolled design. They are not observed power, and their assumptions do not establish that the trial had a particular probability of detecting an effect.
Why can over-dispersion matter?
In general, over-dispersion occurs when observed variation is greater than a statistical model expects. If a model assumes less variability than is present, standard errors may be too small and confidence intervals may be too narrow. A suitable analysis may need to account for extra variability, but the appropriate approach depends on the outcome and model. The registry does not report a model, a variance assessment, or any adjustment for over-dispersion. This general concern cannot be used to infer that over-dispersion occurred in this study.
There are also distinctions among a defined endpoint, a statistical analysis, and a reported result. The endpoint definition specifies the quantity to measure. An analysis plan specifies how measurements will be summarized or compared. Results show the estimate and its uncertainty. The registry lists the primary endpoint and its summary type, but the numerical result and analysis method are not reported. The record’s count of zero analyses means no analyses are listed in that entry; it should not be taken as proof that no analysis was conducted elsewhere.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 21 outcome measures, including the primary Period 1 pitavastatin Cmax endpoint and secondary measures related to adverse events, RO7049389 exposure, and pitavastatin lactone. When multiple outcomes are evaluated, the chance of at least one apparently unusual result can increase if each is tested separately without accounting for the number of questions. Statistical methods can address multiplicity, but the method depends on the planned inferential priorities and testing structure.
A multiplicity strategy, including whether outcomes were grouped into a hierarchy or adjusted as a family, is not reported in the registry record. The record also lists zero analyses, so it does not give test results or show which outcomes were included in any inferential analysis. No conclusion about statistical significance across the outcome set can be made from the outcome list alone.
Missing-data handling is also not reported in the registry record. The entry does not describe how missing concentration measurements, incomplete periods, or withdrawals would be treated, nor does it give the number of participants contributing to each endpoint. A planned enrollment figure is not necessarily the same as the analysis population for a particular measurement. The registry does not identify an intention-to-treat, per-protocol, pharmacokinetic, or safety analysis population by name.
The record gives a fixed dosing sequence and an enrollment of 18, but those details do not establish how many observations were available for each endpoint or whether all participants completed both periods. No assumptions about imputation, exclusions, or sensitivity analyses should be made without a report. These omissions make it impossible to assess how missingness or multiple outcome testing may have influenced any estimate.
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 |
|---|---|---|---|
| Pitavastatin/RO7049389 | 0 | 18 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pitavastatin/RO7049389 | 0 of 18 |
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 |
|---|---|
| Pitavastatin/RO7049389 | 7 of 18 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pitavastatin/RO7049389 |
|---|---|---|
| Headache | Nervous system disorders | 3 of 18 |
| Nausea | Gastrointestinal disorders | 2 of 18 |
| Dizziness | Nervous system disorders | 2 of 18 |
| Hypoaesthesia oral | Gastrointestinal disorders | 1 of 18 |
| Vomiting | Gastrointestinal disorders | 1 of 18 |
| Fatigue | General disorders | 1 of 18 |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 1 of 18 |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 1 of 18 |
The registry records one study group titled Pitavastatin/RO7049389. It reports 18 participants at risk for serious adverse events and 0 affected by serious adverse events. For the other adverse-event category, it reports 18 at risk and 7 affected. The record lists no serious adverse-event terms.
These are descriptive registry counts, not a comparison between randomized treatment groups. The study used a fixed sequence in which participants received pitavastatin in Period 1 and RO7049389 with pitavastatin in Period 2. The group-level record does not separate events by period, exposure, or suspected cause. It therefore does not establish which treatment, if any, was associated with a particular event.
A recorded count of 0 serious adverse events means none are listed for this group in the registry entry; it does not establish that an event was impossible or that the study can rule out uncommon harms. The record does not provide the event descriptions, severity details for the other category, timing, or a comparative safety analysis. The count of 7 should not be treated as a rate or as a treatment effect without the relevant definitions and analysis.
12. What the Result Does, and Does Not, Mean
This study addresses a pharmacokinetic question: how RO7049389 and pitavastatin are characterized when administered in the sequence described for healthy volunteers. The registry’s stated purpose is to investigate their interaction. The design and listed outcome measures help define the question, but they do not answer it without reported measurements and analyses.
The primary endpoint is Period 1 pitavastatin Cmax. Its definition tells readers that peak plasma concentration was the intended primary measurement in that period. The registry does not report its numerical value, its geometric coefficient of variation, or a confidence interval. It also does not report a primary statistical comparison between Period 1 and Period 2. As a result, the available record cannot quantify an interaction or indicate how precisely one was estimated.
The listed secondary outcomes expand the range of pharmacokinetic and safety questions addressed by the protocol, but outcome names are not results. No values or analysis results for these outcomes are reported in the registry record. The listed safety counts show 0 serious adverse events and 7 in the other adverse-event category for the recorded group, but event details and exposure-specific attribution are absent.
The study is described as Phase 1, open-label, nonrandomized, and single-group, with a fixed order of periods. This is useful context for interpreting the design, but it is not a randomized comparison of separate groups. Any period-based inference would require an analysis that accounts for the repeated measurements and the fixed order; the method and estimates are not reported.
The record does not establish whether an observed pharmacokinetic change was present, how large it might have been, or whether it was clinically important. It also does not support conclusions about treatment effects in patients: participants were healthy volunteers, and the stated purpose was interaction characterization rather than clinical benefit. The appropriate reading is therefore narrow: the registry documents a completed interaction study and its planned measurement framework, while leaving the numerical pharmacokinetic findings and their uncertainty unreported.
13. Why This Trial Matters Statistically
Drug-interaction studies are designed to examine whether exposure to one drug changes when another drug is also administered. That question is distinct from whether either drug improves a clinical outcome. Here, the registry describes a pharmacokinetic study in healthy volunteers and explicitly notes that clinical benefit was not intended. Keeping those aims separate helps prevent a concentration endpoint from being mistaken for evidence about patient benefit.
The fixed sequence is statistically important. It enables measurements under more than one dosing condition in the same study, but it is not randomized, and the order is not varied across participants. A period comparison, if performed, would need to consider the paired nature of the measurements and the possibility that changes over time or sequence could matter. The registry does not describe the analysis used to address these issues.
Clear reporting of estimates and uncertainty is central to pharmacokinetic interpretation. A geometric mean can summarize a concentration outcome, while its dispersion and confidence interval help readers judge variability and precision. The endpoint definition identifies a geometric mean and geometric coefficient of variation, but their numerical values are not reported in the registry record. The interaction question is thus visible, but its quantitative answer is not.
The listed outcome set also illustrates why statistical planning matters. Multiple pharmacokinetic and safety measures can raise questions about which comparisons are primary and how multiplicity is handled. The registry does not report a multiplicity plan or analysis results. Similarly, planning illustrations based on two equal arms do not describe this actual single-group, fixed-sequence design; such illustrations are not observed power.
For biostatisticians and clinical researchers, this record underscores the difference between registration metadata and a complete results report. Knowing the population, sequence, endpoint, and safety counts is valuable, yet interpretation also requires outcome estimates, uncertainty, analysis methods, and clear populations. Without those items, conclusions must remain limited to the study structure and what the registry explicitly records.
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 limitation for interpreting the pharmacokinetic question is that numerical primary results are not reported in the registry record. The record gives the primary endpoint definition and summary approach but not the geometric mean, geometric coefficient of variation, confidence interval, or a test result. It therefore does not permit assessment of effect size or precision.
The endpoint is specified as Period 1 Cmax, while the stated study purpose is to characterize an interaction across dosing conditions. A numerical comparison between periods is not reported for this primary endpoint. The record also does not explain how the primary endpoint relates analytically to the broader interaction question.
The nonrandomized, open-label, single-group, fixed-sequence design has no like-for-like randomized control group. Period order is fixed, so any within-participant difference could potentially be entangled with period or sequence effects. The registry does not report an analysis method or details that would allow these issues to be evaluated.
Further limitations are the absence of a reported statistical analysis plan, sample-size justification, multiplicity strategy, missing-data approach, and endpoint-specific analysis populations. The registry lists 21 outcome measures and zero analyses, but does not give numerical results for the outcomes. Safety reporting is also limited to group-level counts, with no event details or period-specific attribution. These reporting gaps do not show that analyses or documentation were absent elsewhere; they mean those details are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Investigate the Effect of RO7049389 on the Pharmacokinetics of Pitavastatin in Healthy Volunteers — NCT03717064.
- Registry record last updated 2020-01-10; status last verified 2019-12.
- Results first posted 2020-01-10.
- 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
NCT03717064 is a completed Phase 1, open-label, nonrandomized, single-group, fixed-sequence study sponsored by Hoffmann-La Roche. It enrolled 18 healthy volunteers and was intended to characterize the interaction between RO7049389 and pitavastatin, without an intended clinical benefit.
Participants received pitavastatin in Period 1, followed by a wash-out of at least 7 and up to 21 days. In Period 2, RO7049389 was administered on Days 1–6, with a single pitavastatin dose on Day 4. The listed primary endpoint is Period 1 pitavastatin Cmax, summarized by geometric mean with geometric coefficient of variation.
The registry reports 0 serious adverse events and 7 affected in the other adverse-event category. Numerical primary and secondary pharmacokinetic results, analysis methods, and uncertainty estimates are not reported in the registry record.