Minocycline Pharmacokinetics (ACUMIN): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Minocycline Pharmacokinetics (ACUMIN) (NCT03369951), a na phase 4 study. The primary outcome is Calculated Exposure Measures for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24).

2. Clinical Question

3. Trial Design

ACUMIN is a Phase IV, open-label, multicenter pharmacokinetic study of a single intravenous minocycline infusion in critically ill adults. The registry lists the study as completed, with a start date of 2018-03-28 and primary completion on 2019-07-20. The sponsor is the National Institute of Allergy and Infectious Diseases (NIAID). The registry records enrollment of 58 participants.

The study had one group, Minocin® IV, described as receiving 200 mg of minocycline hydrochloride by intravenous infusion over approximately 60 minutes. The arm description lists n=50. The study summary states that up to 67 participants would be enrolled to obtain 50 evaluable ICU patients. The registry does not explain the relationship between the overall enrollment of 58 and the arm description of 50; these figures refer to different registry entries and should not be treated as interchangeable counts.

Participants were expected to contribute seven pharmacokinetic samples: one before dosing and six after dosing, collected at designated times over approximately 48 hours following the start of infusion. The primary outcome timeframe identifies pre-dose, immediately after infusion termination at approximately 1 hour, and 4, 12, and 24 hours post dose. The study summary describes an approximately 16-month study duration and approximately 2 days of participation for each subject, with conduct planned at approximately 13 clinical sites.

Because allocation is listed as not applicable and the model is single-group, there is no like-for-like control arm. Open-label status means masking was not used. The study is designed to characterize exposure and explore covariates, not to estimate a randomized treatment contrast.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.

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 subjects enrolled and receiving study product are included in the baseline analysis population description.

6. Primary Endpoint

The registry lists the primary outcome as Calculated Exposure Measures for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24), measured over Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose.

The primary endpoint is total AUC0-24, the area under the plasma minocycline concentration–time curve from 0 to 24 hours after a dose. It is expressed in mg·hr/L and summarized as a mean with a standard deviation. AUC combines concentration and time into a measure of overall drug exposure during the specified interval. It is used in pharmacokinetic research because it describes exposure across a period rather than relying on a single concentration measurement.

The registry says that dosing histories and individual post-hoc pharmacokinetic parameters were used to generate total concentration–time profiles. AUC0-24 was calculated by numerical integration using data from 0 to 24 hours post dose. Although sampling was described over approximately 48 hours, this primary measure concerns the first 24 hours. The stated timeframe includes pre-dose, the end of infusion at approximately 1 hour, and 4, 12, and 24 hours post dose.

The registry gives the endpoint definition, units, summary measure, and pharmacokinetic analysis population, but a numerical mean and standard deviation for AUC0-24 are not reported in the registry record. Consequently, the size and precision of the observed average exposure cannot be assessed from the posted endpoint information. AUC is a pharmacokinetic measure; by itself, it does not establish a clinical benefit or compare minocycline with another treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The central statistical idea in ACUMIN is the description of a continuous pharmacokinetic measure. A continuous outcome can take values along a numerical scale; here, AUC0-24 is expressed in mg·hr/L. The registry specifies a mean as the summary measure and standard deviation as the measure of dispersion. A mean describes the average in the analyzed population, while a standard deviation describes how much individual observations vary around that average. These summaries answer different questions: the mean is about the center of the observed values, while the standard deviation is about their spread.

What does AUC represent?

As a general statistical and pharmacokinetic explanation, area under a concentration–time curve represents accumulated exposure across a defined time interval. Concentrations measured at selected times are used to represent the changing profile over time, and numerical integration approximates the area beneath that profile. The registry states that the AUC0-24 calculation used numerical integration from 0 to 24 hours, drawing on concentration–time profiles generated from dosing histories and individual post-hoc pharmacokinetic parameters. It does not report the numerical AUC result in the registry record.

The sampling schedule matters because the curve between observed samples must be represented to calculate an area. The study description identifies one pre-dose sample and six post-dose samples over approximately 48 hours. The primary timeframe separately lists pre-dose, the end of infusion at approximately 1 hour, and 4, 12, and 24 hours post dose. The registry’s definition says the integration interval for the primary outcome is 0 to 24 hours, so later sampling described in the study summary does not change the interval named by AUC0-24.

How should a mean and standard deviation be read?

In general, a mean and standard deviation describe the observed distribution but do not, alone, show the precision of the estimated population mean. Precision is often conveyed using a confidence interval, which gives a range of values compatible with the data under the assumptions of the analysis. The primary outcome information in the registry identifies a mean and standard deviation but does not report a confidence interval or numerical estimates. No interval can therefore be interpreted from the registry record.

Pharmacokinetic observations can vary substantially between patients. In general, variability may reflect differences in clinical characteristics, dosing histories, measurement timing, or other factors. The study’s stated objective to assess patient-level and clinical covariates is relevant because those characteristics may be associated with differences in pharmacokinetic properties. The registry does not specify which covariates were assessed, how they were modeled, or what associations were found; these details are not reported in the registry record.

What does a single-group design permit?

A single-group study can describe outcomes observed after participants receive the study intervention. It does not create a randomized comparator, and an observed value cannot be interpreted as a treatment difference versus an untreated or alternative-treatment group. The registry lists allocation as not applicable and masking as none. The study is therefore suited to descriptive pharmacokinetic characterization as stated in its objectives, rather than a controlled estimate of a comparative treatment effect.

The absence of masking does not alter the mathematical definition of AUC, but it is part of the design context in which measurements and other study procedures were conducted. The registry does not state whether any particular protections or checks were used to address possible measurement or assessment biases. Those details are not reported in the registry record.

How should the planning illustrations be understood?

The study information characterizes sample-size calculations as planning illustrations computed from an observed effect, not as the original design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. The registry’s sample-size description also distinguishes total events for time-to-event outcomes from participants per arm for other outcomes.

These assumptions describe hypothetical planning calculations. They do not change ACUMIN’s single-group design into a two-arm trial and do not imply that participants were randomized between two arms. A sample-size illustration based on an observed effect is not observed power, and it is not evidence that the study had a particular probability of detecting a true effect. No specific planning values or original sample-size justification are reported in the registry record.

More generally, a complete interpretation of a continuous outcome would consider the analysis population, the estimate and its uncertainty, the distribution of individual values, and any missing observations. In ACUMIN, the registry defines the pharmacokinetic population by infusion completion, specimen processing, and availability of a quantifiable concentration. It does not report the numerical primary estimate, a confidence interval, the individual-level distribution, or detailed missing-data procedures. Those omissions limit statistical interpretation of the primary endpoint.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Minocin® IV")
n   <- c(55)
m   <- c(24.3)
sp  <- c(7.88)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Minocin® IV  55  24.300  7.880  22.170  26.430

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures and 0 analyses. The primary measure is total AUC0-24, but other outcome details and any inferential analyses are not reported in the registry record. The record does not state whether a multiplicity strategy was used, whether any outcomes were designated as secondary or exploratory for statistical testing, or whether adjustments were planned for testing multiple outcomes or covariates. Without those details, it is not possible to assess how the study handled the increased chance of false-positive findings that can arise when many hypotheses are tested.

Missing-data procedures are also not reported in the registry record. The stated pharmacokinetic population requires receipt of the full infusion, at least one specimen processed according to the study procedures, and at least one such sample with a quantifiable minocycline concentration available for analysis. This defines who can contribute to the pharmacokinetic analysis, but it does not explain how participants with incomplete sampling, unquantifiable concentrations, or other missing measurements were handled.

The registry records enrollment of 58 and describes an arm of n=50, while the summary describes a goal of 50 evaluable patients. The record does not reconcile these counts or give the final number included in the primary endpoint analysis. It also does not report whether analyses used any alternative populations or sensitivity analyses. These gaps matter because the analyzed population and handling of incomplete observations can affect the interpretation of a mean pharmacokinetic outcome.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: cardio-respiratory arrest (1.8%).

The serious adverse-event listing reports 57 participants at risk and 1 participant affected in the Minocin® IV group. It also lists 1 death. Cardio-Respiratory Arrest is identified as the top serious term at 1.8%. These are descriptive registry entries for a single-group study; they do not show a comparison with another treatment group.

The listing does not establish whether the reported event or death was caused by minocycline. The registry information in this record does not provide a causal assessment, event-level timing, or details that would clarify the relationship between the death and the serious-event term. The death count should therefore be read as a separately listed safety figure, not as proof of a particular cause.

The other adverse-event category is recorded as 0 participants at risk and 0 affected. That entry should be interpreted as the registry’s recorded category, not as evidence that no non-serious events occurred in the study. The safety figures are limited to what is entered in the registry and cannot establish comparative risk or provide a complete clinical safety assessment.

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

ACUMIN addresses a pharmacokinetic question: it was designed to characterize minocycline exposure after a single infusion in critically ill adults with known or suspected Gram-negative infection. The registry defines the primary exposure measure as total AUC0-24 and specifies the population intended for its analysis. These details clarify what the primary endpoint represents and how participants qualified for that analysis.

The numerical result for the primary endpoint is not reported in the registry record. Therefore, the posted information does not permit a reader to state the observed average AUC0-24, its variability, or its precision. The study’s stated objectives also include assessment of patient-level and clinical covariates, but the covariate findings and modeling details are not reported in the registry record.

The single-group, open-label design supports descriptive reporting of observations after minocycline administration. It does not provide a randomized comparison, and it cannot establish how exposure or safety would differ under another treatment. The reported serious-event count and death count should likewise be interpreted descriptively; they do not by themselves establish a causal relationship with the infusion.

In general, pharmacokinetic exposure is one component of understanding how a drug behaves in a population. An exposure measure alone is not a clinical outcome, and this registry information does not establish a clinical treatment effect. The study is best understood according to its stated focus on pharmacokinetics and related covariates, while recognizing that the registry record does not report the numerical primary result needed to assess the observed exposure estimate.

14. Why This Trial Matters Statistically

Pharmacokinetic studies address how drug concentrations change over time and how those patterns vary among people. That question is especially pertinent to a study population described as critically ill, because the trial’s stated objective is to characterize population-level minocycline pharmacokinetics and assess patient-level and clinical covariates associated with pharmacokinetic properties. The endpoint, AUC0-24, condenses a concentration–time profile into an exposure measure over a defined interval.

Statistically, the study also illustrates why analysis populations need an explicit definition. Enrollment is not necessarily the same as inclusion in a pharmacokinetic analysis: the registry requires full infusion, specimen processing, and at least one quantifiable concentration. The record’s enrollment of 58, arm listing of n=50, and target of 50 evaluable patients are not reconciled, making it important to distinguish the different counts rather than assume they describe the same group.

The design is also consequential for interpretation. A single group can characterize observed exposure in the analyzed participants, but there is no randomized comparator for estimating a treatment contrast. The serious adverse-event and death entries are descriptive in the absence of a control group and cannot establish causality.

Finally, the registry demonstrates the difference between an endpoint definition and a reportable result. It specifies the AUC measure and its summary method, but the numerical mean and standard deviation are not reported in the registry record. Without those estimates, readers cannot assess the magnitude or precision of average exposure. The stated planning illustrations should be kept separate from trial design and observed power, particularly because the trial itself is a single-group study.

15. 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 statistical interpretation is that the numerical primary AUC0-24 result is not reported in the registry record. Although the measure is defined as a mean with a standard deviation, neither estimate is available in the information, and no confidence interval is reported. The size, variability, and precision of the observed exposure therefore cannot be evaluated.

The registry records 58 participants enrolled, lists n=50 in the single arm description, and describes a goal of 50 evaluable patients. It does not reconcile these counts or report the final number in the primary pharmacokinetic analysis. The analysis population criteria are stated, but the number meeting those criteria is not reported in the registry record.

The study is open-label and single-group, with no concurrent comparator. Its results cannot provide a randomized estimate of differences from another treatment, and the safety entries cannot establish causal attribution. The record also does not report detailed missing-data procedures, the number or pattern of incomplete samples, the covariates actually analyzed, the specific statistical model, or multiplicity handling. These details are not reported in the registry record.

Lastly, the sample-size information is characterized as planning illustrations based on an observed effect rather than the study’s own design justification. The stated hypothetical assumptions involve equal allocation between two arms, which does not match the single-group design. No specific planning estimates are reported in the registry record, and these illustrations should not be taken as observed power.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Minocycline Pharmacokinetics (ACUMIN) — NCT03369951.
• Registry record last updated 2020-12-03; status last verified 2017-12-04.
• Results first posted 2020-08-27.
• 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.

19. Record Summary

ACUMIN (NCT03369951) is a completed Phase IV, open-label, single-group pharmacokinetic study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The registry records enrollment of 58 participants and describes a single Minocin® IV arm receiving a 200 mg infusion over approximately 60 minutes.

The primary endpoint is mean total minocycline AUC0-24 in mg·hr/L, with standard deviation as the dispersion measure. The registry defines the pharmacokinetic population and describes numerical integration of concentration–time data to calculate the endpoint. The numerical primary result is not reported in the registry record.

The serious adverse-event listing records 1 affected participant among 57 at risk, 1 death, and Cardio-Respiratory Arrest as the top serious term at 1.8%. With no comparator, these entries are descriptive and do not establish causation.