Phase II Pharmacokinetics Study of CAM2038: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Pharmacokinetics Study of CAM2038 (NCT02710526), a randomized phase 2 study. The primary outcome is AUCss(Area Under the Plasma Concentration-time Curve During a 7-day Dosing Interval at Steady State) for Each Injection Site, i.e., Buttock (Reference), Abdomen, Thigh and Back of Upper Arm for the Evaluable Pharmacokinetic (PKEVAL) Population.

2. Clinical Question

The clinical question is pharmacokinetic: it concerns plasma exposure after subcutaneous administration, not a clinical outcome such as pain relief or opioid-use outcomes. Comparing injection sites can describe whether the observed exposure summaries vary by site under the studied weekly regimen. The registry identifies the buttock as the reference site, but a reference label by itself does not establish a statistical comparison or show whether differences are meaningful.

The study also included monthly dosing groups, but the stated primary endpoint is specific to the weekly regimen and the four injection sites. The registry record does not report a primary endpoint comparison between weekly and monthly dosing groups. The results therefore should be read as descriptive exposure summaries for the endpoint and population specified, not as evidence about comparative clinical effects.

3. Trial Design

This was a Phase II, open-label, partially randomized, parallel-group, multi-site study. It assessed pharmacokinetics after repeated subcutaneous administration of CAM2038, a long-acting buprenorphine depot, using weekly and monthly regimens. The registry lists an enrollment of 66 and records the study as completed. The recorded start was 2015-02, and primary completion was 2017-05-17.

The weekly group received 32 mg CAM2038 at multiple injection sites. The monthly groups received 128 mg CAM2038 by injection in the buttocks, or 24 mg sublingual BPN for the first 7 days followed by 160 mg CAM2038 by monthly injection in the buttocks starting on Day 8. Although allocation is recorded as randomized, the study is described as partially randomized. The registry record does not report further details about which assignments were randomized or how assignment was implemented.

Masking is recorded as none. In an open-label study, treatment assignment is not masked, which describes the study setup but does not by itself determine the reliability of a laboratory-based pharmacokinetic measurement. The primary endpoint focused on the weekly regimen and compared exposure summaries across injection sites, with the buttock as reference. The PKEVAL population required sufficient pharmacokinetic data from all four randomized injection sites to derive the parameters of interest.

The brief study description says the aim was to evaluate steady-state pharmacokinetics of buprenorphine and norbuprenorphine following repeated administrations. The registry’s stated primary endpoint is specifically buprenorphine AUCss. The registry record does not report the protocol’s full randomization procedures, a sample-size justification, an interim-analysis plan, or a detailed statistical analysis 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.

Treatment Phase

Safety Extension

Analysis population for the primary outcome, as defined in the registry: Evaluable Pharmacokinetic (PKEVAL) Population consisted of all subjects who had sufficient PK data for all 4 randomized injection sites to derive PK parameters of interest.

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.

6. Primary Endpoint

The registry lists the primary outcome as AUCss(Area Under the Plasma Concentration-time Curve During a 7-day Dosing Interval at Steady State) for Each Injection Site, i.e., Buttock (Reference), Abdomen, Thigh and Back of Upper Arm for the Evaluable Pharmacokinetic (PKEVAL) Population, measured over PK samples were collected at pre-dose and at 0.5, 1, 2, 4, 6, 10, 24, 30, 48, 72, 96, 120 and 168 hours post-CAM2038 q1w for Doses/Weeks 4, 5, 6, and 7..

The primary endpoint was AUCss: the area under the plasma concentration-time curve during a 7-day dosing interval at steady state. It was assessed for buprenorphine at the buttock, abdomen, thigh, and back of the upper arm in the PKEVAL population. The unit is ng*h/mL, and the registry reports geometric means with geometric coefficients of variation.

AUC represents cumulative drug exposure over the specified interval. At steady state, measurements are intended to describe exposure under a repeated dosing regimen rather than after an initial dose alone. For a weekly injection, measuring exposure across the 7-day interval characterizes the concentration profile over the dosing period. The registry lists pharmacokinetic sampling before dosing and at 0.5, 1, 2, 4, 6, 10, 24, 30, 48, 72, 96, 120, and 168 hours after CAM2038 q1w for Doses/Weeks 4, 5, 6, and 7.

AUC is used in pharmacokinetic research because it summarizes exposure over time rather than relying on a single concentration measurement. That makes it useful for describing exposure across the interval and comparing descriptive summaries across sites. It does not, by itself, measure a clinical benefit or establish the clinical importance of any exposure difference. The registry record does not provide inferential comparisons or confidence intervals for the site-specific summaries.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports the primary endpoint using geometric means and geometric coefficients of variation. These summaries are suited to describing positive measurements such as pharmacokinetic exposure, which can vary multiplicatively and may be right-skewed. The geometric mean is calculated on a logarithmic scale and then expressed on the original scale. It represents a central exposure level, but it should not be read as the arithmetic average.

The geometric coefficient of variation describes relative dispersion around a geometric mean. In general, a coefficient of variation expresses variability relative to the scale of the measurements, which can make dispersion easier to interpret when values differ in magnitude. It is not a measure of precision for the estimated mean. A confidence interval would address uncertainty around an estimate; the registry record does not report confidence intervals for these site-specific primary summaries.

AUC is an integrated measure of concentration over time. In general, integration uses concentration measurements across an interval to summarize cumulative exposure, rather than treating an isolated measurement as representative of the entire interval. The registry lists multiple sampling times after the weekly injection and defines the endpoint over a 7-day interval at steady state. The resulting endpoint is expressed in ng*h/mL.

What does the evaluable population represent?

The PKEVAL population consisted of subjects with sufficient pharmacokinetic data for all four randomized injection sites to derive the parameters of interest. This definition links inclusion in the primary pharmacokinetic analysis to data completeness across the sites. It does not mean that every enrolled subject necessarily contributed to every reported estimate. The registry reports site-specific sample sizes of 21.0 for the buttock, abdomen, and thigh, and 20.0 for the upper arm.

In general, an analysis population defined by evaluable measurements can differ from an enrolled population because some participants may not have the required data. The record does not explain the reasons for the reported sample-size variation, identify individual missing measurements, or state whether missing values were imputed. No missing-data method is reported in the registry record.

What can be inferred from the reported summaries?

Descriptive statistics characterize the observed data; they do not, on their own, test a hypothesis about a difference. The geometric means give a central summary by injection site, while the geometric coefficients of variation describe relative spread. To assess uncertainty in a site comparison, an analysis would generally need an estimate of the contrast and its uncertainty, such as a confidence interval, or a clearly reported hypothesis test. Those results are not reported in the registry record.

The primary pharmacokinetic population required data from all four randomized injection sites. This makes the site-specific summaries relevant to the population meeting that data requirement, but it does not establish that the estimates apply to every enrolled subject or to populations outside the study. The record does not describe any adjustment for baseline characteristics or other covariates.

Why might an analysis account for over-dispersion?

In general, over-dispersion means that observed variability exceeds what a statistical model expects. If a model underestimates variability, its standard errors may be too small and confidence intervals too narrow. The appropriateness of any over-dispersion adjustment depends on the outcome and model. The registry record does not report a model for the primary endpoint or an over-dispersion assessment, so no such method can be attributed to this analysis.

The registry records randomized allocation, no masking, and a parallel model, while describing the study as partially randomized. These design descriptions do not reveal the analysis method used for the primary endpoint. The record does not report how randomization was implemented, whether the site observations were analyzed as paired data, or how any within-subject correlation was handled. Those details matter because measurements across multiple sites in the same subject may be statistically related.

The registry lists 22 outcome measures and one posted secondary outcome, concerning participants with adverse events for both weekly and monthly CAM2038. It records zero analyses. Accordingly, the posted information supports description of the primary site-specific summaries and safety counts, but not a reconstruction of unreported inferential procedures. General principles about model choice or uncertainty should not be mistaken for methods documented for this trial.

10. Multiplicity, Missing Data and Analysis Populations

The study considered multiple injection sites for the primary pharmacokinetic endpoint, and the registry lists 22 outcome measures. When multiple outcomes or comparisons are assessed, the chance of obtaining at least one apparently unusual result can increase if each is tested independently. In general, multiplicity procedures can address that issue by controlling error rates or by defining a testing hierarchy. The registry record does not report whether a multiplicity adjustment, hierarchy, or other strategy was planned or used.

The primary results posted are descriptive geometric means and geometric coefficients of variation. The registry records zero analyses and does not report p-values, confidence intervals, or adjusted comparisons for the injection sites. Therefore, there is no documented inferential analysis from which to assess how multiplicity was handled. The absence of a reported method should not be interpreted as evidence that a particular adjustment was or was not performed outside the registry record.

The PKEVAL population required sufficient pharmacokinetic data for all four randomized injection sites. This criterion indicates that data completeness was relevant to inclusion in the primary analysis. The record does not give reasons for the site-specific sample-size variation, describe missing-data patterns, or report an imputation or sensitivity-analysis method. It is therefore not possible to assess from the registry whether missingness could have influenced the exposure summaries.

The registry record also does not report a detailed analysis plan defining populations for every outcome or explaining how protocol deviations were handled. The PKEVAL definition is available for the primary pharmacokinetic endpoint, but other analysis-population details are not reported in the registry record. These gaps limit evaluation of selective outcome reporting, the handling of incomplete data, and the robustness of any unposted analyses.

11. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event counts are zero affected participants in each listed group: 0 of 28 at risk in the 32 mg CAM2038 weekly group, 0 of 20 in the 128 mg CAM2038 monthly injection group, 0 of 17 in the 160 mg CAM2038 monthly injection group, and 0 of 18 in the 24 mg SL BPN group. The registry also reports zero deaths in each group. No serious adverse event terms are listed.

These are counts recorded during the study, with the group-specific at-risk figures as listed in the registry. A zero count means that no affected participants were recorded for that category in that group; it does not establish that the risk is absent. The counts alone also do not demonstrate that the groups have equivalent safety, since the registry provides no inferential safety comparison or confidence intervals.

The 24 mg SL BPN group is described as the initial sublingual regimen before monthly CAM2038 in the corresponding study arm. The safety record lists this group separately. The registry record does not provide further detail about how adverse events were attributed across treatment periods, their timing, or their duration. Serious adverse event counts should also be distinguished from other adverse events, which are a separate category in the registry.

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

The posted primary results describe buprenorphine exposure over a 7-day dosing interval at steady state for four injection sites in the evaluable pharmacokinetic population. The buttock, abdomen, thigh, and upper-arm geometric means are 700.0, 657.0, 613.0, and 591.0 ng*h/mL, respectively. The associated geometric coefficients of variation describe relative dispersion, not the precision of the estimates or a test of differences.

These summaries can inform a descriptive understanding of exposure under the studied weekly regimen. The registry identifies the buttock as the reference site, but does not report a formal contrast between it and the other sites. Without confidence intervals or inferential tests, the posted values do not establish that any observed separation is statistically reliable. They also do not show whether any difference is clinically important.

The endpoint measures pharmacokinetic exposure, not pain, opioid use, quality of life, or another clinical outcome. It therefore cannot be used by itself to conclude that one injection site or dosing schedule produces a better clinical result. The record’s broader study description mentions buprenorphine and norbuprenorphine pharmacokinetics, but the posted primary endpoint summaries are for buprenorphine AUCss.

The safety record reports no serious adverse events and no deaths in the listed groups. These counts describe the registry’s recorded events; they do not prove the absence of risk or establish safety equivalence. The record does not provide inferential safety comparisons or detailed event descriptions.

More broadly, the study was open-label and partially randomized, and the PKEVAL population required sufficient data for all four sites. The registry record does not report the reasons for site-specific sample-size variation, a detailed missing-data method, or a statistical analysis plan. The results are therefore best understood as descriptive registry summaries, with limits on conclusions about statistical uncertainty, generalizability, and clinical meaning.

13. Why This Trial Matters Statistically

Pharmacokinetic studies distinguish exposure from clinical outcomes. AUC summarizes concentration over a dosing interval and can describe how exposure varies by administration site. Reporting both a geometric mean and a geometric coefficient of variation offers information about the central exposure level and relative variability, rather than relying on a single concentration or a central estimate alone.

This study is statistically notable for assessing multiple injection sites under a weekly regimen and defining an evaluable population that required sufficient data across all four randomized sites. That design focus makes completeness across sites important to interpreting the reported summaries. The site-specific sample sizes show that the number contributing to the upper-arm estimate differs from the others, while the registry does not explain why.

The record also illustrates a distinction between descriptive results and inferential evidence. Numeric differences among geometric means can be observed, but without reported uncertainty estimates or formal comparisons, their statistical reliability cannot be determined from the posted primary results. This distinction is important when a reference site is named: a reference designation is not itself evidence of a tested difference.

Finally, the registry contains safety counts and multiple outcome measures, but records zero analyses and does not provide a detailed statistical plan. Readers can identify the recorded endpoint definitions and counts while recognizing that methods for missing data, multiplicity, and inferential testing are not documented. That separation between what is reported and what remains unreported is central to a careful statistical reading.

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 pharmacokinetic results are descriptive. The registry record does not report confidence intervals, p-values, or adjusted comparisons for the injection sites, so uncertainty around contrasts and statistical evidence of differences cannot be assessed from the posted summaries.

The PKEVAL population required sufficient data for all four randomized injection sites. This complete-data criterion may restrict the population represented by the primary estimates. The registry record does not explain the reasons for the site-specific sample-size variation, describe missing-data patterns, or report imputation or sensitivity analyses. It is not possible to determine how incomplete data affected the summaries.

The study is recorded as open-label and partially randomized. The registry record does not provide details about the randomization process, how the partially randomized assignments were determined, or whether the site measurements were analyzed as paired observations. It also does not report how within-subject correlation, if relevant to the analysis, was handled.

The record lists 22 outcome measures but does not report a multiplicity strategy or a detailed statistical analysis plan. It also records zero analyses. The primary endpoint is buprenorphine AUCss; the broader study description refers to buprenorphine and norbuprenorphine pharmacokinetics, but norbuprenorphine results are not included in the posted primary summaries.

Finally, the endpoint is pharmacokinetic rather than clinical, and the registry does not report inferential comparisons between weekly and monthly regimens. The safety counts do not include detailed event descriptions or comparative analyses. These limitations restrict conclusions about clinical relevance, comparative safety, and generalizability beyond the specified evaluable population.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase II Pharmacokinetics Study of CAM2038 — NCT02710526.
• Registry record last updated 2020-04-30; status last verified 2020-04.
• Results first posted 2020-04-30.
• 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.

18. Record Summary

NCT02710526 is a completed Phase II, open-label, partially randomized, parallel, multi-site study of CAM2038 in opioid-dependent subjects with chronic pain. The registry records enrollment of 66, a start of 2015-02, and primary completion on 2017-05-17. The study assessed weekly and monthly subcutaneous regimens.

The primary endpoint was steady-state buprenorphine AUC over a 7-day interval at the buttock, abdomen, thigh, and upper arm in the PKEVAL population. The posted summaries are geometric means and geometric coefficients of variation. The registry records 22 outcome measures, one secondary outcome, and zero analyses. It does not report inferential comparisons for the primary site summaries, a detailed statistical plan, or missing-data methods.

The safety record reports zero serious adverse events and zero deaths in each listed group. These are descriptive counts and do not establish absence of risk or equivalence between groups.