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 of Abemaciclib in Participants With Cancer That is Advanced or Has Spread to Another Part(s) of the Body (NCT02688088), a non-randomized phase 1 study. The primary outcome is Pharmacokinetics: Maximum Concentration (Cmax) of Caffeine.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02688088 |
| Phase | Phase 1 |
| Condition | Neoplasm Metastasis |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 48 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled participants with cancer that was advanced or had spread to another part of the body. The registry lists Neoplasm Metastasis as a condition and an enrollment of 48. The primary-endpoint population is narrower: participants who received at least one dose of study drug and had evaluable pharmacokinetic data. The number meeting that endpoint-population definition is not reported in the registry record.
Intervention
The study assessed abemaciclib and a drug cocktail containing caffeine, warfarin, dextromethorphan, and midazolam. In the cocktail-only period, participants received a single oral dose. In the combination period, the cocktail was administered alongside abemaciclib. The registry describes subsequent periods of abemaciclib treatment and an optional safety extension.
Comparator
The registry describes a fixed sequence of study periods rather than randomized parallel groups. The cocktail-only assessment in Period 1 is therefore a within-study reference for the combination assessment in Period 2, not a separately randomized control group. No masking was used. The record does not report a randomized allocation process or a conventional like-for-like control comparison.
Primary question
The primary endpoint was caffeine maximum concentration, measured after the cocktail alone and after the cocktail was given with abemaciclib. The pharmacokinetic question is whether caffeine’s peak concentration differed between those dosing conditions. The registry record identifies the endpoint and its assessment times, but the actual concentration estimates and comparison results are not reported in the registry record. The endpoint concerns drug exposure, not a clinical benefit outcome.
3. Trial Design
This was a Phase 1, non-randomized, single-group study with no masking. Its official title describes an investigation of how multiple doses of abemaciclib affect the pharmacokinetics of substrates for CYP1A2, CYP2C9, CYP2D6, and CYP3A. The tested cocktail contained caffeine, warfarin, dextromethorphan, and midazolam. The brief summary calls it a drug interaction study and describes screening, four study periods in a fixed sequence, an optional safety extension, and safety follow-up.
The first period used a single oral cocktail dose: 100 mg caffeine, 10 mg warfarin, 30 mg dextromethorphan, and 0.2 mg midazolam. In Period 2, participants received 200 mg abemaciclib orally every 12 hours on Days 1 - 12, with the cocktail administered on Day 8. Period 3 continued 200 mg abemaciclib every 12 hours on Days 13 to 28, with the possibility of continuing until discontinuation criteria were met. Period 4 and the safety extension also describe 200 mg abemaciclib every 12 hours, with continuation subject to discontinuation criteria.
The registry lists enrollment of 48 and status as completed. The recorded start date is 2016-03-08 and the primary completion date is 2018-02-04. These dates and the enrollment figure describe the registry record; the number of participants completing each period or contributing to each analysis is not reported in the registry record.
Because treatment sequence was not randomized, the periods should not be interpreted as independent randomized arms. Differences between period measurements could reflect the dosing condition as well as other changes over time or in the participants contributing data. The record does not report details of a statistical plan, sample-size justification, interim analyses, or adjustment for period effects.
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.
Single Dose Drug Cocktail - Period 1
| Stage | Drug Cocktail - Period 1 | 200 mg Abemaciclib + Drug Cocktail - Period 2 | 200 mg Abemaciclib - Period 3 | 200 mg Abemaciclib Period - 4 | Abemaciclib Safety Extension Period |
|---|---|---|---|---|---|
| STARTED | 44 | 0 | 0 | 0 | 0 |
| Received One Dose of Drug Cocktail | 44 | 0 | 0 | 0 | 0 |
| COMPLETED | 44 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
Abemaciclib + Drug Cocktail - Period 2
| Stage | Drug Cocktail - Period 1 | 200 mg Abemaciclib + Drug Cocktail - Period 2 | 200 mg Abemaciclib - Period 3 | 200 mg Abemaciclib Period - 4 | Abemaciclib Safety Extension Period |
|---|---|---|---|---|---|
| STARTED | 0 | 44 | 0 | 0 | 0 |
| Received at Least One Dose of Study Drug | 0 | 42 | 0 | 0 | 0 |
| COMPLETED | 0 | 37 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 7 | 0 | 0 | 0 |
Reasons for not completing this period:
| Reason | Drug Cocktail - Period 1 | 200 mg Abemaciclib + Drug Cocktail - Period 2 | 200 mg Abemaciclib - Period 3 | 200 mg Abemaciclib Period - 4 | Abemaciclib Safety Extension Period |
|---|---|---|---|---|---|
| Adverse Event | 0 | 1 | 0 | 0 | 0 |
| Death | 0 | 1 | 0 | 0 | 0 |
| Withdrawal by Subject | 0 | 3 | 0 | 0 | 0 |
| Physician Decision | 0 | 2 | 0 | 0 | 0 |
Abemaciclib Days 13 to 28 - Period 3
| Stage | Drug Cocktail - Period 1 | 200 mg Abemaciclib + Drug Cocktail - Period 2 | 200 mg Abemaciclib - Period 3 | 200 mg Abemaciclib Period - 4 | Abemaciclib Safety Extension Period |
|---|---|---|---|---|---|
| STARTED | 0 | 0 | 37 | 0 | 0 |
| Received at Least One Dose of Study Drug | 0 | 0 | 36 | 0 | 0 |
| COMPLETED | 0 | 0 | 29 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 8 | 0 | 0 |
Reasons for not completing this period:
| Reason | Drug Cocktail - Period 1 | 200 mg Abemaciclib + Drug Cocktail - Period 2 | 200 mg Abemaciclib - Period 3 | 200 mg Abemaciclib Period - 4 | Abemaciclib Safety Extension Period |
|---|---|---|---|---|---|
| Physician Decision | 0 | 0 | 7 | 0 | 0 |
| Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
Abemaciclib Days 1 to 28 - Period 4
| Stage | Drug Cocktail - Period 1 | 200 mg Abemaciclib + Drug Cocktail - Period 2 | 200 mg Abemaciclib - Period 3 | 200 mg Abemaciclib Period - 4 | Abemaciclib Safety Extension Period |
|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 29 | 0 |
| COMPLETED | 0 | 0 | 0 | 21 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 8 | 0 |
Reasons for not completing this period:
| Reason | Drug Cocktail - Period 1 | 200 mg Abemaciclib + Drug Cocktail - Period 2 | 200 mg Abemaciclib - Period 3 | 200 mg Abemaciclib Period - 4 | Abemaciclib Safety Extension Period |
|---|---|---|---|---|---|
| Physician Decision | 0 | 0 | 0 | 7 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of study drug and had evaluable PK data.
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: All participants who received at least one dose of drug cocktail.
| Characteristic | Unit | Overall |
|---|---|---|
| Participants analysed | 44 | |
| Age, Continuous | years | 60.1 (SD 11.0) |
| Sex: Female, Male: Female | Participants | 20 |
| Sex: Female, Male: Male | Participants | 24 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 41 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 40 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| Region of Enrollment: United States | Participants | 44 |
6. Primary Endpoint
The registry lists the primary outcome as Pharmacokinetics: Maximum Concentration (Cmax) of Caffeine, measured over Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours (hr) Postdose.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | nanograms per milliliter (ng/mL) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the pharmacokinetic maximum concentration, or Cmax, of caffeine. Cmax is the highest measured concentration of a drug in blood over the assessment schedule. It is used in pharmacokinetic studies because it describes peak exposure after a dose. It does not by itself describe the full concentration-time profile, total exposure, clinical effect, or safety.
Concentrations were assessed after the single cocktail dose in Period 1 and after the cocktail was given with abemaciclib in Period 2. The registry lists predose and postdose assessments at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours on Days 1 and 8. The endpoint is summarized as a geometric mean with geometric coefficient of variation, and its unit is nanograms per milliliter (ng/mL).
A geometric mean is a way to summarize positive measurements when values are better understood on a multiplicative scale. The geometric coefficient of variation describes relative spread around that summary. These summaries can be useful for pharmacokinetic measurements, which may vary proportionally rather than by a fixed additive amount. The registry record does not report the Cmax estimates, their variability, or a numerical comparison between periods. The magnitude and precision of any difference therefore cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study’s stated primary question concerns caffeine Cmax after the drug cocktail alone compared with caffeine Cmax after the cocktail was given with abemaciclib. Although the registry gives the endpoint definition, unit, summary measure, and assessment schedule, it does not report the endpoint values or the result of the comparison. Consequently, the direction, magnitude, and precision of any pharmacokinetic change are not reported in the registry record.
That absence matters for interpretation. A difference estimate would indicate the observed contrast between the two dosing conditions; a confidence interval, if reported, would convey the range of values compatible with the data under the analysis assumptions. Neither the estimate nor its uncertainty is reported in the registry record. A p-value and the statistical procedure used for the primary comparison are also not reported. It is therefore not possible to assess statistical evidence for a change, distinguish a precise estimate from an uncertain one, or determine whether the result met a prespecified criterion.
The fixed sequence also limits what a contrast between periods can establish. Period 1 and Period 2 are not randomized groups. The comparison is relevant to the stated drug-interaction question, but a period contrast may be influenced by changes over time and by which participants have evaluable measurements in each period. The registry describes the sequence but does not report a statistical method for handling period effects, within-participant correlation, or incomplete measurements.
The record does include safety counts by study-period category. These describe reported events among the participants at risk for each listed category, but the groups have different denominators and occur at different stages of the sequence. They should not be read as randomized comparative estimates. Counts of affected participants do not establish that an event was caused by a study drug. The record’s listed serious-event terms are accompanied by 5.6% values, but the denominator and category context for those terms are not made clear in the available record.
Thus, the registry supports a description of the study question, dosing sequence, endpoint, and reported safety counts. It does not support a numerical conclusion about the primary pharmacokinetic result. The lack of a posted estimate is not evidence that the two conditions were alike, nor does it establish that they differed. Any interpretation beyond the study design and recorded counts would require results and analysis details not reported in the registry record.
9. Statistical Methods Explained
What the endpoint summarizes. Cmax is a summary of the highest concentration measured after dosing. In this study, the registry defines caffeine Cmax as the primary pharmacokinetic endpoint and specifies a geometric mean with geometric coefficient of variation. In general, a geometric mean summarizes positive values using their multiplicative relationships. It is often useful when measurements are right-skewed or when proportional changes are more meaningful than absolute changes. The geometric coefficient of variation conveys relative variability, rather than variability in the original measurement units. These are general statistical explanations; the registry does not describe the detailed calculation used for the reported endpoint, and it does not report an endpoint result.
Why samples are taken at multiple times. Concentration measurements at multiple postdose times trace how drug levels change over the assessment window. The highest observed measurement in that schedule contributes to Cmax. The listed schedule runs from predose through 48 hours after the dose, with measurements at the specified intermediate times. In general, the observed maximum depends on the sampling schedule: a peak occurring between scheduled measurements may not be measured directly. The record does not report whether any measurements were missing, how missing concentration values were handled, or whether any estimation method was used for an unobserved peak.
Interpreting a comparison across periods. The question compares a cocktail-only period with a period in which the cocktail was administered alongside abemaciclib. Because the study is non-randomized and uses a fixed sequence, the comparison is not a randomized treatment contrast. In general, repeated measurements from the same participant can be correlated, and measurements taken in different periods can also reflect time-related changes. An analysis may need to account for those features. The registry record does not report whether the primary comparison used paired measurements, a model for repeated observations, covariate adjustment, or another method. No statistical plan or model specification is reported.
Precision and statistical evidence. A point estimate gives the center of an estimated contrast, while a confidence interval describes uncertainty around that estimate under the model and assumptions used. A narrower interval generally indicates greater precision than a wider interval. A p-value, when reported, summarizes how compatible the observed data are with a specified null hypothesis under an analysis model; it is not a measure of clinical importance. General interpretation of these quantities depends on the design, analysis, and assumptions. The registry does not report a primary contrast estimate, confidence interval, p-value, or the method used to calculate uncertainty. Statistical significance and precision therefore cannot be evaluated from the record.
Multiplicity. The registry lists 14 outcome measures and 8 analyses. When many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase if each is tested separately. General approaches to multiplicity include prespecifying a primary comparison, adjusting significance thresholds, or treating secondary analyses as exploratory. The record identifies a primary endpoint, but it does not report a multiplicity strategy or the statistical plan. The count of listed outcomes alone does not establish whether or how multiplicity was addressed.
Planning illustrations. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The record says time-to-event illustrations use a total event count, while other illustrations use participants per arm. These are planning assumptions, not evidence about the study’s actual design: the trial itself was non-randomized and single-group. In general, sample-size calculations based on an observed effect can illustrate the sample size associated with a chosen target and assumptions; they do not measure the probability that a completed study detected an effect. Such illustrations are not observed power. Numerical planning outputs and an observed primary effect are not reported in the registry record, so no sample-size result or planning adequacy can be assessed.
Over-dispersion and variability. General statistical models sometimes assume that the variation in observations follows a specified distribution. Over-dispersion means the observed variability is greater than that assumption allows; standard errors can then be too small if the extra variability is ignored. The registry record does not identify an over-dispersion assessment or report a model for the primary endpoint. This concept is relevant as a general consideration, not as a claim that over-dispersion occurred in this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 14 outcome measures and 8 analyses, but the statistical plan is not reported in the registry record. It does not state how the primary endpoint was tested, whether secondary outcomes were considered confirmatory or exploratory, or whether any adjustment for multiple outcomes or comparisons was made. Listing a primary endpoint helps identify the main question, but does not by itself show how multiplicity was handled. Without the analysis plan and results, the impact of multiple testing cannot be assessed.
Missing-data methods are also not reported in the registry record. The primary population is described as participants who received at least one dose of study drug and had evaluable pharmacokinetic data. The number meeting that definition, the number with missing concentration measurements, the reasons for missingness, and any rules for excluding or imputing observations are not reported. These details matter because an analysis based only on evaluable observations can differ from one that accounts for all enrolled participants, particularly if missingness is related to treatment, tolerability, or measured concentrations. The record does not allow those possibilities to be assessed.
The registry also does not report whether the primary analysis used all available paired measurements, how participants with incomplete period data were handled, or whether protocol deviations affected analysis inclusion. The brief summary describes safety follow-up and an optional extension, but does not establish which participants were included in each endpoint analysis. The reported enrollment of 48 should therefore not be treated as the primary endpoint sample size. Analysis-population counts and the handling of missing data 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 |
|---|---|---|---|
| Drug Cocktail - Period 1 | 1 | 44 | 2.3% |
| 200 mg Abemaciclib - Period 2 | 3 | 42 | 7.1% |
| 200 mg Abemaciclib + Drug Cocktail - Period 2 | 2 | 35 | 5.7% |
| 200 mg Abemaciclib - Periods 3 and 4 | 6 | 28 | 21.4% |
| Abemaciclib Safety Extension Period | 2 | 18 | 11.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Drug Cocktail - Period 1 | 1 of 44 |
| 200 mg Abemaciclib - Period 2 | 0 of 42 |
| 200 mg Abemaciclib + Drug Cocktail - Period 2 | 0 of 35 |
| 200 mg Abemaciclib - Periods 3 and 4 | 0 of 28 |
| Abemaciclib Safety Extension Period | 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 |
|---|---|
| Drug Cocktail - Period 1 | 22 of 44 |
| 200 mg Abemaciclib - Period 2 | 33 of 42 |
| 200 mg Abemaciclib + Drug Cocktail - Period 2 | 26 of 35 |
| 200 mg Abemaciclib - Periods 3 and 4 | 25 of 28 |
| Abemaciclib Safety Extension Period | 16 of 18 |
Most frequent serious adverse event terms
| Event term | Organ system | Drug Cocktail - Period 1 | 200 mg Abemaciclib - Period 2 | 200 mg Abemaciclib + Drug Cocktail - Period 2 | 200 mg Abemaciclib - Periods 3 and 4 | Abemaciclib Safety Extension Period |
|---|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 0 of 44 | 1 of 42 | 1 of 35 | 0 of 28 | 0 of 18 |
| Diarrhoea | Gastrointestinal disorders | 0 of 44 | 0 of 42 | 1 of 35 | 1 of 28 | 0 of 18 |
| Ascites | Gastrointestinal disorders | 0 of 44 | 1 of 42 | 0 of 35 | 0 of 28 | 0 of 18 |
| Colitis | Gastrointestinal disorders | 0 of 44 | 0 of 42 | 0 of 35 | 0 of 28 | 1 of 18 |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | 0 of 44 | 0 of 42 | 0 of 35 | 1 of 28 | 0 of 18 |
| Oesophagitis | Gastrointestinal disorders | 0 of 44 | 0 of 42 | 0 of 35 | 0 of 28 | 1 of 18 |
| Pancreatitis | Gastrointestinal disorders | 0 of 44 | 0 of 42 | 0 of 35 | 0 of 28 | 1 of 18 |
| Medical device complication | General disorders | 0 of 44 | 1 of 42 | 0 of 35 | 0 of 28 | 0 of 18 |
| Cholangitis | Hepatobiliary disorders | 0 of 44 | 1 of 42 | 0 of 35 | 0 of 28 | 0 of 18 |
| Clostridium difficile colitis | Infections and infestations | 0 of 44 | 0 of 42 | 0 of 35 | 0 of 28 | 1 of 18 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Drug Cocktail - Period 1 | 200 mg Abemaciclib - Period 2 | 200 mg Abemaciclib + Drug Cocktail - Period 2 | 200 mg Abemaciclib - Periods 3 and 4 | Abemaciclib Safety Extension Period |
|---|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 1 of 44 | 18 of 42 | 11 of 35 | 12 of 28 | 2 of 18 |
| Nausea | Gastrointestinal disorders | 5 of 44 | 8 of 42 | 6 of 35 | 7 of 28 | 4 of 18 |
| Vomiting | Gastrointestinal disorders | 2 of 44 | 8 of 42 | 5 of 35 | 7 of 28 | 4 of 18 |
| Fatigue | General disorders | 1 of 44 | 6 of 42 | 6 of 35 | 5 of 28 | 3 of 18 |
| Decreased appetite | Metabolism and nutrition disorders | 1 of 44 | 3 of 42 | 4 of 35 | 6 of 28 | 5 of 18 |
| Abdominal pain | Gastrointestinal disorders | 2 of 44 | 6 of 42 | 2 of 35 | 2 of 28 | 3 of 18 |
| Constipation | Gastrointestinal disorders | 2 of 44 | 3 of 42 | 4 of 35 | 1 of 28 | 3 of 18 |
| Hypokalaemia | Metabolism and nutrition disorders | 0 of 44 | 5 of 42 | 0 of 35 | 5 of 28 | 3 of 18 |
| International normalised ratio increased | Investigations | 7 of 44 | 2 of 42 | 3 of 35 | 0 of 28 | 0 of 18 |
| Anaemia | Blood and lymphatic system disorders | 0 of 44 | 1 of 42 | 2 of 35 | 6 of 28 | 2 of 18 |
Serious events with the highest arm-level rate: colitis (5.6%), oesophagitis (5.6%), pancreatitis (5.6%), clostridium difficile colitis (5.6%), diverticulitis (5.6%).
The registry reports serious adverse events and other adverse events separately for each listed study-period category. The serious-event counts are 1 of 44 at risk in Drug Cocktail - Period 1, 3 of 42 in 200 mg Abemaciclib - Period 2, 2 of 35 in 200 mg Abemaciclib + Drug Cocktail - Period 2, 6 of 28 in 200 mg Abemaciclib - Periods 3 and 4, and 2 of 18 in the Abemaciclib Safety Extension Period. The listed deaths are 1, 0, 0, 0, and 0, respectively. These are counts by registry category, not randomized comparisons.
The other-adverse-event counts are 22 of 44, 33 of 42, 26 of 35, 25 of 28, and 16 of 18, respectively. The registry lists Colitis, Oesophagitis, Pancreatitis, Clostridium difficile colitis, Diverticulitis, and Dyspnoea among the top serious-event terms, each with a reported value of 5.6%. The record does not make the denominator and category context for those term values clear.
These counts describe participants recorded as affected, not the total number of event episodes or the risk attributable to a particular drug. The denominators vary across periods, and the categories occur in a fixed sequence with different exposure periods. The record does not report a like-for-like safety comparison or establish that any event or death was caused by study treatment.
12. What the Result Does, and Does Not, Mean
This study addresses a pharmacokinetic question: whether caffeine’s maximum concentration differed when the drug cocktail was administered with abemaciclib compared with when the cocktail was administered alone. That question is distinct from whether a treatment improves a cancer outcome. The primary endpoint is a concentration measure, not a measure of tumor response, survival, or quality of life.
The registry supplies the design, dosing sequence, endpoint definition, measurement schedule, and some safety counts. It does not report the caffeine Cmax estimates or the statistical comparison. The primary result’s direction and size, along with its precision, are therefore not available in the registry record. The absence of a posted result should not be interpreted as evidence of no difference, evidence of a difference, or evidence that a clinically important threshold was or was not crossed.
Even with a reported pharmacokinetic contrast, interpretation would require its uncertainty and analysis context. A measured concentration difference is not automatically a clinical effect. Its importance depends on the relevant exposure-response evidence and clinical context, neither of which is established by the endpoint definition alone. No such inference can be made from the available record.
The safety counts are similarly descriptive. They show affected-participant counts in period-specific categories, but the non-randomized sequential design and changing denominators limit direct comparisons. The counts do not establish causation. The registry record does not provide enough detail to determine whether the listed serious-event term percentages apply to a particular period or population.
The most defensible reading is therefore narrow: this was a completed Phase 1 drug-interaction study in participants with advanced or metastatic cancer, designed to assess pharmacokinetics and safety across a specified dosing sequence. Its central numerical pharmacokinetic findings and statistical analysis are not reported in the registry record. No conclusion about the size or certainty of a caffeine exposure change can be drawn from the endpoint description alone.
13. Why This Trial Matters Statistically
This trial illustrates why design details matter when interpreting pharmacokinetic studies. The scientific question is a comparison between two dosing conditions, but the study uses a non-randomized, fixed sequence rather than randomized groups. That structure can be appropriate for an interaction investigation, while still requiring care in distinguishing a condition contrast from a randomized treatment effect. The registry does not report the statistical method used to make that distinction.
The endpoint also shows the difference between defining a measurement and reporting a result. Caffeine Cmax is specified with its unit, summary form, assessment schedule, and endpoint population. Those details make the intended measurement understandable. Without the actual estimate and its uncertainty, however, readers cannot judge the magnitude or precision of the observed contrast. A well-defined endpoint is not a substitute for a posted outcome result.
The design highlights the importance of analysis populations and completeness. Enrollment is listed as 48, while the primary endpoint requires participants to have received study drug and to have evaluable pharmacokinetic data. The count contributing to that endpoint is not reported in the registry record. That distinction matters because the enrollment total and the analyzed endpoint population need not be the same.
Finally, safety summaries across sequential periods show why denominators and exposure context are essential. Period-specific counts are useful descriptive information, but they are not automatically comparable across periods. A statistical interpretation needs to account for who was at risk, when events were collected, and how the study sequence shaped exposure. The registry record gives some counts but does not provide all of that context or a comparative safety analysis.
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 primary limitation for interpreting efficacy-like statistical evidence is that the registry record does not report the primary pharmacokinetic results. It gives no Cmax estimate, between-condition contrast, confidence interval, p-value, or analysis model. The size, direction, and precision of the caffeine comparison cannot therefore be evaluated.
The non-randomized, single-group design and fixed treatment sequence limit causal interpretation of differences between periods. The cocktail-only and combination assessments are not randomized parallel groups. The record does not report how period effects, within-participant correlation, or differences in who contributed data across periods were handled. No masking was used.
The endpoint population is defined by receipt of at least one dose and evaluable pharmacokinetic data, but the number included and the completeness of those data are not reported in the registry record. Missing-data rules, exclusions, protocol deviations, and analysis-population counts are also not reported. The registry does not report the statistical plan, sample-size justification, interim analyses, or a multiplicity strategy.
Safety interpretation has additional limits. The numbers at risk vary by period category, and the categories occur at different stages of the sequence. The record does not report exposure-adjusted event rates or a randomized safety comparison. It also does not make the denominator and period context for the 5.6% serious-event term values clear. The listed death count does not establish cause.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Abemaciclib in Participants With Cancer That is Advanced or Has Spread to Another Part(s) of the Body — NCT02688088.
- Registry record last updated 2022-10-18; status last verified 2022-04-01.
- Results first posted 2022-10-18.
- 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
NCT02688088 is a completed Phase 1, non-randomized, single-group study sponsored by Eli Lilly and Company. The registry lists enrollment of 48 and a study population of participants with advanced or metastatic cancer. Its purpose was to assess how abemaciclib affected the pharmacokinetics of a cocktail containing caffeine, warfarin, dextromethorphan, and midazolam.
The primary endpoint was caffeine maximum concentration, summarized as a geometric mean with geometric coefficient of variation. The study used a fixed sequence that included cocktail-only and cocktail-with-abemaciclib assessments, followed by abemaciclib periods and an optional safety extension. The registry reports period-specific adverse-event counts and deaths.
The primary pharmacokinetic estimates, statistical comparison, uncertainty measures, and analysis details are not reported in the registry record. The available information supports description of the intended question and study structure, but not a numerical conclusion about the caffeine concentration result.