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 Evaluation of Safety, Tolerability, and Antiviral Activity of Chlorcyclizine HCl in Patients With Chronic Hepatitis C (NCT02118012), a randomized phase 1, phase 2 study. The primary outcome is Change in Serum HCV RNA Viral Titer From Baseline to 28 Days.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02118012 |
| Phase | Phase 1, Phase 2 |
| Condition | Chronic Hepatitis C |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | 2 |
| Lead sponsor | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
| Results posted | Yes |
2. Clinical Question
Population
Adults with chronic hepatitis C were eligible if they had never been treated for the infection or had relapsed after prior treatment. The registry record does not report further details about the enrolled participants’ characteristics or how many had each treatment history.
Intervention
One group received chlorcyclizine HCl with ribavirin. The study description says participants took the study drug twice daily for 28 days, and the combination group also took ribavirin twice daily during that period.
Comparator
The comparison group received chlorcyclizine HCl alone, described as twice-daily dosing for 28 days. The trial was randomized, parallel-group, and unmasked; participants and study personnel were not masked to assignment according to the registry record.
Primary question
The primary endpoint asks how serum HCV RNA viral titer changed from baseline to 28 days in each group. The registry reports group medians and inter-quartile ranges. It does not report a formal estimate or test of the difference between groups, so the posted group summaries do not by themselves establish whether the treatment strategies differed statistically.
3. Trial Design
This was a randomized, parallel-group phase 1/phase 2 trial of chlorcyclizine HCl, given either alone or with ribavirin, in patients with chronic hepatitis C. The registry lists an enrollment of 24 and a completed status. The start date and primary completion date are both listed as 2014-03-20. The registry record does not explain those date entries or provide further details about the timing of recruitment and follow-up.
The two groups were chlorcyclizine HCl alone and chlorcyclizine HCl with ribavirin. The study description says each regimen was taken twice daily for 28 days. Participants were assigned randomly, but the trial had no masking. The brief description also outlines inpatient monitoring while starting study drug, clinic visits during the treatment period, and follow-up visits after treatment stopped. Details such as the timing and completion of those follow-up visits are not reported in the registry record.
The primary outcome was change in serum HCV RNA viral titer from baseline to 28 days. It is reported as a median with inter-quartile range, in log IU/ml. The posted outcome counts are 12 for the combination group and 10 for the chlorcyclizine-only group. These counts do not match the enrollment figure, and the registry record does not reconcile the difference or describe the analysis population used for the primary outcome.
The record lists two secondary outcome titles: change in ALT levels from baseline to 28 days and maximum chlorcyclizine HCl during weeks 1-4. It also lists four outcome measures overall. Further outcome details, including results for those secondary outcomes, are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Chlorcyclizine and RBV | Chlorcyclizine HCl Only |
|---|---|---|
| STARTED | 12 | 12 |
| Day 5 | 12 | 11 |
| Day 14 | 12 | 10 |
| COMPLETED | 12 | 10 |
| NOT COMPLETED | 0 | 2 |
Reasons for not completing this period:
| Reason | Chlorcyclizine and RBV | Chlorcyclizine HCl Only |
|---|---|---|
| Adverse Event | 0 | 1 |
| Physician Decision | 0 | 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 | Chlorcyclizine and RBV | Chlorcyclizine HCl Only | Total |
|---|---|---|---|---|
| Participants analysed | 12 | 12 | 24 | |
| Age, Continuous | years | 56 (47 to 60) | 57 (54 to 61) | 56 (50 to 60) |
| Sex: Female, Male: Female | Participants | 6 | 5 | 11 |
| Sex: Female, Male: Male | Participants | 6 | 7 | 13 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 4 | 1 | 5 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 4 | 5 |
| Race (NIH/OMB): White | Participants | 7 | 7 | 14 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| HCV Genotype: 1A | Participants | 7 | 4 | 11 |
| HCV Genotype: 1B | Participants | 3 | 4 | 7 |
| HCV Genotype: 2 | Participants | 0 | 1 | 1 |
| HCV Genotype: 3 | Participants | 1 | 2 | 3 |
| HCV Genotype: 4 | Participants | 0 | 1 | 1 |
| HCV Genotype: 6 | Participants | 1 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Serum HCV RNA Viral Titer From Baseline to 28 Days, measured over Baseline and 28 days.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | log IU/ml |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in serum HCV RNA viral titer from baseline to 28 days, measured in log IU/ml. HCV RNA is a measure of the amount of hepatitis C virus genetic material in serum. A change over time describes how the measured viral titer at follow-up compares with its baseline value. Because the measurement is on a logarithmic scale, the endpoint expresses change in log units rather than a direct count of viral particles.
Viral titer is used in a trial of antiviral activity because it provides a laboratory measure of viral burden over the treatment period. In general, a negative change indicates that the measured titer is lower at follow-up than at baseline, while a positive change indicates a higher measured titer. This endpoint describes a laboratory outcome over the stated period; it is not, by itself, a measure of symptoms, long-term disease course, or patient experience.
The registry identifies the summary statistic as the median and the measure of dispersion as the inter-quartile range. The combination group has a reported median change of -0.46, with listed bounds of -0.83 to -0.04. The chlorcyclizine-only group has a median change of -0.11, with listed bounds of -0.21 to 0.21. Those are group summaries, not a direct between-group treatment-effect estimate. A formal comparison and its uncertainty are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For the combination group, the median change in serum HCV RNA viral titer from baseline to 28 days is -0.46 log IU/ml, and the reported inter-quartile range is -0.83 to -0.04. For the chlorcyclizine-only group, the median change is -0.11 log IU/ml, with an inter-quartile range of -0.21 to 0.21. Negative values indicate a lower measured titer at 28 days relative to baseline; the positive upper bound in the chlorcyclizine-only group indicates that at least part of the middle half of its reported distribution extends above zero.
The group medians describe the center of the observed changes in each group. The inter-quartile range describes the spread of the middle half of those observations, rather than the precision of a treatment-effect estimate. The reported ranges overlap. Overlap or non-overlap of inter-quartile ranges is not a formal test of a difference between groups, and the summaries cannot be used to determine statistical significance.
The registry reports 12 observations for the combination group and 10 for the chlorcyclizine-only group for this endpoint. It does not state why the recorded group counts differ or how missing outcome values, if any, were handled. The enrollment figure is 24, but the record does not explain how enrollment relates to the endpoint counts. This makes it important to distinguish the stated enrollment from the group counts attached to the primary outcome.
No p-value, confidence interval for a between-group contrast, adjusted analysis, or individual-level result is reported for the primary endpoint. The record lists zero analyses. Consequently, the posted figures support a descriptive account of the two group distributions, not a claim that one regimen produced a greater change than the other. A direct comparison would need an estimate of the difference between groups and its uncertainty, along with information about the analysis population and methods.
Random allocation is intended, in general, to make assigned groups comparable on average, but it does not guarantee balance in a particular trial. The record does not report baseline characteristics that would allow readers to assess the groups’ comparability, nor does it describe an adjustment for baseline differences. The unmasked design is also relevant when interpreting outcomes that may be affected by knowledge of assignment. The primary endpoint is a laboratory measure, but details of laboratory procedures and outcome assessment are not reported in the registry record.
The figures should therefore be read as short-term, group-level summaries for this trial. They do not establish a causal difference between the treatment strategies, and they do not address outcomes beyond the stated 28-day endpoint. The registry’s posted result is informative about the observed distributions, while leaving comparative inference and longer-term interpretation unresolved.
9. Statistical Methods Explained
What does a median summarize?
The median is the center of a distribution when observations are ordered from lowest to highest. It is less influenced by unusually high or low observations than the arithmetic mean. In general, it can be a useful summary when data are skewed or when a typical value is more informative than an average. The trial record identifies the primary outcome summary as a median, but does not describe the distribution of individual participant changes.
What does the inter-quartile range show?
The inter-quartile range spans the middle half of observed values, from the first quartile to the third quartile. It conveys variability among observations; it is not a confidence interval for the median or for a difference between groups. In this trial, the registry reports the primary endpoint’s dispersion as an inter-quartile range. The listed bounds are -0.83 to -0.04 for chlorcyclizine with ribavirin and -0.21 to 0.21 for chlorcyclizine alone.
In general, measures of spread and measures of precision answer different questions. Spread describes how varied participants’ results are. Precision describes how uncertain an estimated quantity is, such as a group median or a between-group contrast. A confidence interval is a commonly used way to express uncertainty in an estimate, under a statistical model and its assumptions. The registry record does not report a confidence interval for the treatment-group contrast.
Why report a change from baseline?
A change score compares a follow-up measurement with the participant’s baseline measurement. This focuses the endpoint on movement during the treatment period rather than the follow-up value alone. Here, the specified comparison is baseline to 28 days. The endpoint is expressed in log IU/ml, so its values represent changes on a logarithmic measurement scale. In general, change scores can be affected by baseline values, measurement variability, and the way missing follow-up measurements are handled. The registry record does not report a baseline-adjusted model or a missing-data method.
What does randomization contribute?
Random assignment is designed to reduce systematic differences between treatment groups at the point of assignment. In general, it supports causal comparisons when assignment is followed as planned and outcomes are collected and analyzed appropriately. Randomization does not ensure that groups have identical characteristics, especially in a small study. The registry says allocation was randomized, but does not report the randomization procedure, concealment of assignment, baseline characteristics, or a detailed analysis plan.
The trial used a parallel design: participants were assigned to one treatment group rather than receiving both regimens in sequence. It was unmasked, meaning assignment was not concealed from participants and study personnel. General concerns with an unmasked design include effects of treatment knowledge on participant behavior, clinical management, or outcome assessment. The primary endpoint is a laboratory measure, but the record does not report whether laboratory personnel were masked or how the assay was conducted.
What can be inferred from the posted group summaries?
The medians and inter-quartile ranges describe each group separately. They do not estimate the between-group contrast, account for baseline differences, or provide a test of a null hypothesis. A formal comparative analysis could use a method suited to the endpoint distribution and trial design, but the statistical method actually used is not reported in the registry record. The record lists zero analyses, so there is no posted analysis result to explain beyond the descriptive outcome entries.
General statistical interpretation also requires attention to the analysis population. An intention-to-treat analysis usually compares participants according to randomized assignment, while other analysis populations may impose additional criteria. The record does not say which population was used for this endpoint. The primary-outcome group counts are 12 and 10, and the reason for those counts is not stated.
How should planning illustrations be understood?
Any sample-size illustrations associated with the posted results are planning calculations based on the observed effect, not results of a prospective design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustrated effect is a stated fraction of the observed effect. Such calculations ask how many participants per arm might be needed under those assumptions to detect an effect of the chosen size.
These illustrations do not show the trial’s observed power. Observed power is not a substitute for an estimate and its uncertainty, and a calculation based on an observed effect can be unstable when the effect estimate is imprecise. The registry record does not report a prospective sample-size justification or its assumptions. The record also does not report interim analyses or a detailed statistical analysis plan, so none should be inferred from the planning assumptions.
In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. If present and ignored, it can make standard errors too small and inferences too certain. The registry does not report an over-dispersion assessment, and the available group summaries are not enough to assess that issue. As a result, the central statistical reading remains descriptive: the endpoint summaries indicate the distribution of observed changes within each group, while comparative uncertainty is not reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures overall, with one primary outcome and two named secondary outcomes: change in ALT levels from baseline to 28 days and maximum chlorcyclizine HCl during weeks 1-4. Results for those secondary outcomes are not reported in the registry record. The remaining outcome details and any hierarchy among outcomes are also not reported.
When a study evaluates multiple outcomes or performs multiple statistical tests, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures can control that risk, or a prespecified hierarchy can identify which results are confirmatory and which are exploratory. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a statistical analysis plan. It is therefore not possible to determine how multiplicity was addressed.
Missing-data handling and analysis populations are not reported in the registry record. For the primary endpoint, the posted group counts are 12 and 10; the enrollment figure is 24. The record does not explain the difference between those counts, state whether there were missing endpoint observations, or describe any imputation or sensitivity analysis. The safety record lists 12 participants at risk in each group, which also differs from the posted primary-outcome count for the chlorcyclizine-only group. The record does not reconcile these figures.
These omissions limit interpretation of the observed summaries. Without a stated analysis population and missing-data approach, readers cannot tell how participants without a recorded endpoint were treated or whether the analyzed groups correspond exactly to randomized assignment. The record also does not report interim analyses or stopping rules. None can be assumed from the outcome summaries or planning illustrations.
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 |
|---|---|---|---|
| Chlorcyclizine and RBV | 0 | 12 | 0.0% |
| Chlorcyclizine HCl Only | 0 | 12 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Chlorcyclizine and RBV | 0 of 12 |
| Chlorcyclizine HCl Only | 0 of 12 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Chlorcyclizine and RBV | 9 of 12 |
| Chlorcyclizine HCl Only | 10 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Chlorcyclizine and RBV | Chlorcyclizine HCl Only |
|---|---|---|---|
| Dry Mouth | Gastrointestinal disorders | 9 of 12 | 10 of 12 |
| Drowsiness | General disorders | 6 of 12 | 5 of 12 |
| Nervousness | Nervous system disorders | 6 of 12 | 2 of 12 |
| Inability to concentrate | Psychiatric disorders | 4 of 12 | 3 of 12 |
| Light Headedness | General disorders | 2 of 12 | 4 of 12 |
| Numbness or Tingling | Nervous system disorders | 2 of 12 | 3 of 12 |
| Fatigue | General disorders | 3 of 12 | 2 of 12 |
| Headaches | Nervous system disorders | 2 of 12 | 2 of 12 |
| Difficulty Urinating | Renal and urinary disorders | 2 of 12 | 1 of 12 |
| Nausea | Gastrointestinal disorders | 1 of 12 | 0 of 12 |
The registry’s serious adverse event entries list 0 affected participants among 12 at risk in the chlorcyclizine-and-ribavirin group, and 0 among 12 at risk in the chlorcyclizine-only group. Deaths are also listed as 0 in each group. These are the serious-event and death counts recorded in the safety summary; they do not establish that no other safety events occurred.
The separate entry for other adverse events lists 9 affected participants among 12 at risk in the combination group and 10 among 12 at risk in the chlorcyclizine-only group. The record does not give event-level terms for these other events in the posted summary. It is therefore not possible to describe their types, severity, timing, or relation to treatment from these counts alone.
Counts at risk are the denominators attached to the safety summary. They should not be assumed to match the primary endpoint analysis population: the primary outcome lists 12 and 10 observations, while the safety summary lists 12 at risk in each group. The registry record does not explain this difference. A zero count in a study’s safety record is a description of the recorded events in that trial, not proof that an event cannot occur or a definitive comparison of safety between regimens.
12. What the Result Does, and Does Not, Mean
The posted primary results describe short-term changes in serum HCV RNA viral titer in two randomized groups. The median change was -0.46 log IU/ml for chlorcyclizine with ribavirin and -0.11 log IU/ml for chlorcyclizine alone. The corresponding inter-quartile ranges were -0.83 to -0.04 and -0.21 to 0.21. These values characterize the observed group distributions from baseline to 28 days.
The figures do not provide a direct estimate of the difference between treatment groups. No comparative confidence interval or p-value is reported, and the registry lists zero analyses. Thus, the posted summaries do not establish whether the regimens differed statistically. They also do not establish what would happen outside the observed study participants or beyond the 28-day endpoint.
The trial record describes random assignment, which is a design feature intended to support comparisons between groups. However, the record does not report baseline characteristics, details of the randomization procedure, the primary analysis method, or the analysis population. The absence of those details limits assessment of how the study was conducted and how the reported summaries should be interpreted. The difference between the endpoint counts and the safety counts is not explained.
The result is not a measure of long-term viral response, symptoms, liver outcomes, or quality of life. Those outcomes are not reported as the primary endpoint. The record names ALT change and maximum chlorcyclizine HCl as secondary outcomes but does not provide their results. Safety counts are also limited: serious adverse events and deaths are listed as zero in each group, while the registry gives counts for other adverse events without event-level details in the posted summary.
Accordingly, the defensible conclusion is descriptive. The registry reports the median and spread of short-term viral-titer changes for each regimen, alongside limited safety counts. It does not report enough inferential detail to establish comparative efficacy or safety, and the results should not be treated as a definitive estimate of longer-term outcomes.
13. Why This Trial Matters Statistically
This trial is statistically interesting because it sets out a randomized comparison of chlorcyclizine HCl alone with chlorcyclizine HCl combined with ribavirin, while reporting a continuous laboratory endpoint as medians and inter-quartile ranges. That choice communicates the center and spread of the observed changes without assuming that an average adequately describes each group. It also highlights a distinction central to clinical-trial interpretation: separate group summaries are not the same as an estimated treatment contrast.
The registry states that allocation was randomized, but the trial was unmasked. Those design features affect how results are read. Randomization is intended to support fair comparisons, while lack of masking can matter for outcomes and study conduct. The endpoint is laboratory-based, but details about laboratory assessment and masking are not reported. The record also does not provide baseline characteristics or the comparative statistical analysis needed to assess the size and precision of a between-group effect.
The outcome counts and safety denominators illustrate why clear reporting of analysis populations matters. The primary endpoint lists 12 observations in one group and 10 in the other, while the safety record lists 12 at risk in each group. The reason for this difference is not reported. These counts cannot be reconciled from the registry record alone, and they should not be treated as interchangeable.
Finally, the record makes visible the limits of interpreting planning calculations alongside trial results. The stated sample-size illustrations use assumptions and observed-effect fractions, but they are planning illustrations rather than observed power. Without a reported prospective justification or inferential analysis, readers should distinguish the descriptive evidence from design calculations and avoid treating the latter as confirmation of a treatment effect.
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 registry record does not report a formal between-group estimate for the primary endpoint, a confidence interval, a p-value, or a detailed statistical analysis plan. The outcome summaries therefore permit description of each group, but not a direct assessment of the magnitude or precision of a treatment contrast. The statistical methods used to produce the posted summaries are not described beyond identifying the median and inter-quartile range.
The primary outcome counts are 12 for the combination group and 10 for the chlorcyclizine-only group, while the stated enrollment is 24. The safety groups each list 12 at risk. The record does not explain these differences or identify the analysis populations. It also does not report whether endpoint data were missing, how any missing data were handled, or whether sensitivity analyses were performed.
Baseline characteristics, details of random sequence generation and allocation concealment, and laboratory measurement procedures are not reported. The trial was unmasked, and the record does not state whether outcome assessors or laboratory personnel were masked. These omissions limit assessment of group comparability and possible influences on outcome measurement.
The outcome record lists two secondary endpoints but does not report their results, and it does not explain how multiple outcomes were handled. No interim-analysis plan or stopping rules are reported. The primary endpoint covers baseline to 28 days; longer-term viral, clinical, and patient-reported outcomes are not reported in the record. Safety reporting includes counts for serious events, deaths, and other adverse events, but the posted summary does not provide terms for the other events. These trial-specific reporting gaps restrict what can be concluded from the registry entries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluation of Safety, Tolerability, and Antiviral Activity of Chlorcyclizine HCl in Patients With Chronic Hepatitis C — NCT02118012.
- Registry record last updated 2020-06-09; status last verified 2019-09-17.
- Results first posted 2020-06-09.
- 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
NCT02118012 is a completed randomized, unmasked, parallel-group phase 1/phase 2 trial in chronic hepatitis C. It compared chlorcyclizine HCl alone with chlorcyclizine HCl and ribavirin. The registry lists an enrollment of 24, and the study description states that treatment was taken twice daily for 28 days.
The primary endpoint was change in serum HCV RNA viral titer from baseline to 28 days, reported as a median and inter-quartile range. The median change was -0.46 log IU/ml for the combination group and -0.11 log IU/ml for chlorcyclizine alone. The record does not report a formal between-group analysis. Safety entries list zero serious adverse events and zero deaths in each group, with other adverse events recorded for 9 and 10 participants, respectively.
The registry does not report the primary analysis method, missing-data approach, analysis populations, multiplicity handling, or a reconciliation of outcome and safety counts. Results for the named secondary outcomes are not reported in the registry record.