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 The Effect of Antacids on the Pharmacokinetics (PK) of Raltegravir in Human Immunodeficiency Virus (HIV)-Infected Participants (MK-0518-824) (NCT02473367), a na phase 1 study. The primary outcome is Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hrs (AUC 0-24hr) of Raltegravir Following Once Daily Administration of Raltegravir.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02473367 |
| Phase | Phase 1 |
| Condition | HIV Infection |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
The study asked whether taking metal-cation-containing antacids at specified times in relation to once-daily raltegravir was associated with changes in raltegravir exposure. Its focus was pharmacokinetics, not a comparison of HIV treatment outcomes. The primary measure was the area under the plasma concentration-time curve from time 0 to 24 hours after raltegravir administration.
Population
HIV-infected participants already taking raltegravir as part of a stable treatment regimen. The primary endpoint population is described as per-protocol: participants whose protocol compliance was considered sufficient for the data to reflect the treatment effects under the scientific model.
Intervention
Participants received once-daily raltegravir 1200 mg, alone and in periods involving TUMS or Leader Antacid. The described schedules included antacid use concomitantly with raltegravir or 12 hours later.
Comparator
Raltegravir alone in Period 1 served as a within-study reference for periods involving antacids. The registry describes a single-group sequence, not a randomized comparison between separate groups.
Primary question
How did raltegravir exposure over the 24-hour sampling interval differ across the described antacid schedules, as assessed by the area under the plasma concentration-time curve?
The posted record does not give the numerical endpoint estimates or confidence intervals, so the size and precision of any exposure differences cannot be assessed from the registry record.
3. Trial Design
This was a completed Phase 1, single-group study with an enrollment of 20 participants. The registry lists allocation as not applicable and masking as none. Its design followed participants through a sequence of treatment periods rather than assigning separate randomized groups to different antacid schedules.
Participants began taking raltegravir 1200 mg once daily five days before Period 1. In Period 1, they received raltegravir alone. In Period 2, they received raltegravir with three tablets of TUMS Ultra Strength 1000 taken orally at the same time. In Period 3, they received raltegravir and, 12 hours later, 20 mL of Leader Antacid Maximum Strength taken orally. In Period 4, they received raltegravir and, 12 hours later, three tablets of TUMS US 1000 taken orally. Between periods, the wait was a maximum of 7 days, and participants continued once-daily raltegravir.
Blood sampling for the primary endpoint extended from predose through 24 hours after dosing, with collection times specified in the record. The endpoint population was per-protocol. The record does not report how many participants contributed evaluable data to each endpoint analysis or whether any participants failed to complete the sequence.
Because the treatment periods occurred in sequence within a single group, the design does not provide a randomized, concurrent control comparison. Period order, changes over time, and other sequence-related influences cannot be separated from treatment conditions by treating the periods as if they were independent trial arms. The registry record does not report a protocol justification for the sequence or additional design details addressing those possibilities.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Starting five days prior to Period 1 participants were treated with 1200 mg raltegravir (MK-0518), once daily for five days.
Period 1
| Stage | Four Period Fixed Sequence |
|---|---|
| STARTED | 20 |
| COMPLETED | 20 |
| NOT COMPLETED | 0 |
Wait 1
| Stage | Four Period Fixed Sequence |
|---|---|
| STARTED | 20 |
| COMPLETED | 19 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Four Period Fixed Sequence |
|---|---|
| Withdrawal by Subject | 1 |
Period 2
| Stage | Four Period Fixed Sequence |
|---|---|
| STARTED | 19 |
| COMPLETED | 19 |
| NOT COMPLETED | 0 |
Wait 2
| Stage | Four Period Fixed Sequence |
|---|---|
| STARTED | 19 |
| COMPLETED | 19 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Per-Protocol: Participants who complied with the protocol sufficiently to ensure that generated data would reflect the effects of treatment, according to the underlying scientific model.
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 | All Enrolled Participants |
|---|---|---|
| Participants analysed | 20 | |
| Age, Continuous | Years | 49.8 (SD 9.8) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 18 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hrs (AUC 0-24hr) of Raltegravir Following Once Daily Administration of Raltegravir, measured over Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | hr*µM |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was the area under the plasma concentration-time curve from time 0 to 24 hours for raltegravir following once-daily administration. The unit was hr*µM. An area-under-the-curve measure combines the concentration readings across the sampling interval and represents drug exposure over that period. It is a continuous pharmacokinetic measure, not a direct measure of symptoms, disease progression, or treatment benefit.
Concentration samples were collected at predose and at the specified post-dose times through 24 hours. The record states that natural log-transformed values were used in an analysis of variance model to derive geometric least-squares means. This approach is used for concentration and exposure measures that are analyzed on a multiplicative scale: transforming values can make model assumptions more suitable, while reporting geometric means returns the estimate to the original scale.
The registry record does not report the numerical least-squares means, the confidence intervals, or the comparisons for the primary endpoint. Therefore, the direction, magnitude, and precision of any differences in exposure across the periods are not available in the record. The endpoint is useful for describing pharmacokinetic differences under the studied schedules, but by itself it does not establish a clinical consequence.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a focused pharmacokinetic question: whether raltegravir exposure differed when participants took metal-cation-containing antacids according to the study’s schedules. It also gives the primary endpoint definition and says that natural log-transformed values were analyzed using an analysis of variance model to derive geometric least-squares means. However, numerical results for that endpoint are not reported in the registry record. Without estimates and confidence intervals, the extent and precision of any exposure differences cannot be described.
The single-group sequence matters when interpreting the comparison. Each period took place within the same study sequence, and the registry does not describe randomized allocation to separate antacid and control groups. Period 1 provides a raltegravir-alone reference within that sequence, but it is not a concurrent randomized control group. Any contrast between periods should therefore be understood in light of the design, rather than as a randomized between-group effect.
A confidence interval, in general, expresses the uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, but precision is not the same as clinical importance. Since no primary endpoint confidence intervals or estimates are reported, neither precision nor the scale of an exposure difference can be judged from the registry record.
The record describes a per-protocol population for the primary endpoint. This means the stated analysis concerns participants considered sufficiently compliant with the protocol, but the registry does not give the number included in each period’s endpoint analysis or the criteria applied to individual participants. The enrollment count alone should not be treated as the number contributing to every analysis.
The posted safety information gives counts of participants with serious events and other events for each period. These are descriptive period-specific counts, not randomized comparative estimates. The at-risk counts differ across periods, and the record does not supply a statistical comparison of safety outcomes. Death counts are not reported in the registry record.
The record also lists serious-event terms with percentages, but does not provide additional context linking those terms to timing, recurrence, or treatment attribution. These listings cannot resolve the primary pharmacokinetic question. Overall, the registry supports describing the study’s question, sequence, endpoint, and analysis approach; it does not support stating how much exposure changed or drawing a conclusion about clinical consequences.
9. Statistical Methods Explained
The methods described for the primary endpoint combine repeated concentration measurements with a model-based summary. The endpoint, area under the plasma concentration-time curve from time 0 to 24 hours, represents exposure across the sampling window rather than a concentration at a single time. Measurements were scheduled from predose through 24 hours after dosing. The registry record does not report the concentration values themselves or the numerical endpoint estimates.
Why use an area-under-the-curve measure?
Drug concentrations can rise and fall over time after a dose. A single measurement captures only one point on that profile, while an area-under-the-curve measure incorporates the sampled profile over an interval. In pharmacokinetic studies, this can summarize overall exposure during the specified period. It does not, by itself, indicate whether an exposure difference has a clinical effect. Interpreting clinical importance requires evidence beyond the endpoint definition, and such conclusions are not reported in the registry record.
Why analyze natural log-transformed values?
The record says that analysis of variance was performed on natural log-transformed values. A logarithmic transformation changes the scale of the measurements before modeling. For positive exposure measures, it can make multiplicative patterns easier to model and may help the data better meet model assumptions. When estimates are converted back to the original scale, the result is expressed as a geometric least-squares mean. A geometric mean is not the same summary as an ordinary arithmetic mean; it reflects averaging on the log scale and returning to the measurement scale.
Least-squares means are model-based estimates. They summarize the expected outcome under the fitted model, accounting for the terms included in that model. The registry identifies an analysis of variance model but does not report the full model specification, its terms, diagnostics, or the exact contrasts used. No additional modeling details should be inferred from the brief description.
What does a confidence interval communicate?
The primary endpoint is described as a least-squares mean with a 95% confidence interval. In general, a confidence interval gives a range of values compatible with the data and the statistical model at the stated confidence level. It communicates uncertainty around an estimate; it is not a guarantee that the true value lies within a particular interval. A confidence interval can also help distinguish a precise estimate from one with substantial uncertainty. The numerical estimates and intervals are not reported in the registry record, so this uncertainty cannot be evaluated for the endpoint.
For comparisons between schedules, an estimate and its interval would be needed to describe the direction, scale, and precision of a contrast. The record does not report those results. It is therefore not possible to characterize an antacid schedule as associated with a specific amount of change in exposure, or to compare the precision of the scheduled conditions.
Why does the sequence affect interpretation?
The model is applied to observations collected during sequential periods in a single group. A within-participant sequence can make each participant their own reference, but period order is not randomized according to the registry record. When conditions occur in an established order, treatment condition and period can be entangled unless the analysis and design account for relevant effects. The registry does not report whether period, sequence, or carryover terms were included in the analysis, nor does it report a washout rationale. The stated maximum wait between periods and continued raltegravir dosing are part of the design description, but do not establish how possible sequence effects were handled statistically.
Over-dispersion is a general issue for some outcome models when observed variability exceeds what the assumed model expects. It is not a stated feature of this continuous pharmacokinetic analysis, and the record does not report a finding of over-dispersion. The relevant general point is that model assumptions and variability affect the reliability of standard errors and confidence intervals; the registry’s brief methods description does not provide diagnostics to assess these assumptions.
The record includes planning illustrations based on an observed effect, with assumptions described for significance level, allocation, and normal approximation. Such illustrations are planning calculations, not observed power, and they do not replace the primary endpoint estimates or their uncertainty. The registry does not report the trial’s own sample-size justification. The displayed planning assumptions cannot establish what design rationale was used for enrollment.
In sum, the registry gives a high-level description of the endpoint and model, but not enough detail to reproduce the analysis or assess its assumptions. Numerical results, full model terms, diagnostics, and the contrasts of interest are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures and nine analyses, but it does not report a multiplicity strategy for interpreting the analyses collectively. Multiplicity arises when several outcomes, time points, treatment contrasts, or statistical tests are considered. Testing many questions can increase the chance of observing a nominally notable result by chance. Statistical approaches can address that issue, but the appropriate approach depends on which outcomes and comparisons were prespecified and how they relate to the main question. Those details are not reported in the registry record.
The primary endpoint description gives the sampling times, the per-protocol population, and the general model approach. It does not state whether there was a hierarchy of endpoints or contrasts, whether any adjustment was planned, or how secondary analyses were to be interpreted. An adjustment method or analysis hierarchy is not reported in the registry record.
Missing-data handling is also not described. The registry record does not report how missing concentration samples, incomplete period data, protocol deviations, or withdrawals were handled in the endpoint analysis. It does not provide the number of participants with evaluable data for each period or explain whether participants were excluded from particular analyses.
The endpoint population is identified as per-protocol, with a general description of sufficient compliance. The record does not report participant-level inclusion criteria or an intention-to-treat analysis population for the primary endpoint. Thus, the impact of exclusions or incomplete observations cannot be assessed from the registry record.
The record’s brief analysis statement should not be taken as a complete statistical analysis plan. Details on interim analyses, missing-data assumptions, sensitivity analyses, and prespecified handling of multiple comparisons 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 |
|---|---|---|---|
| Period 1: Raltegravir Only | 0 | 20 | 0.0% |
| Period 2: Raltegravir + TUMS Concomitantly | 1 | 19 | 5.3% |
| Period 3: Raltegravir + 12 Hrs Leader Antacid | 0 | 19 | 0.0% |
| Period 4: Raltegravir + 12 Hrs TUMS | 1 | 19 | 5.3% |
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 |
|---|---|
| Period 1: Raltegravir Only | 9 of 20 |
| Period 2: Raltegravir + TUMS Concomitantly | 4 of 19 |
| Period 3: Raltegravir + 12 Hrs Leader Antacid | 5 of 19 |
| Period 4: Raltegravir + 12 Hrs TUMS | 5 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | Period 1: Raltegravir Only | Period 2: Raltegravir + TUMS Concomitantly | Period 3: Raltegravir + 12 Hrs Leader Antacid | Period 4: Raltegravir + 12 Hrs TUMS |
|---|---|---|---|---|---|
| Chest pain | General disorders | 0 of 20 | 0 of 19 | 0 of 19 | 1 of 19 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 20 | 0 of 19 | 0 of 19 | 1 of 19 |
| Rash | Skin and subcutaneous tissue disorders | 0 of 20 | 1 of 19 | 0 of 19 | 0 of 19 |
| Orthostatic hypotension | Vascular disorders | 0 of 20 | 0 of 19 | 0 of 19 | 1 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Period 1: Raltegravir Only | Period 2: Raltegravir + TUMS Concomitantly | Period 3: Raltegravir + 12 Hrs Leader Antacid | Period 4: Raltegravir + 12 Hrs TUMS |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | 3 of 20 | 2 of 19 | 1 of 19 | 2 of 19 |
| Diarrhoea | Gastrointestinal disorders | 1 of 20 | 1 of 19 | 2 of 19 | 0 of 19 |
| Headache | Nervous system disorders | 3 of 20 | 1 of 19 | 0 of 19 | 0 of 19 |
| Thrombocytopenia | Blood and lymphatic system disorders | 1 of 20 | 0 of 19 | 0 of 19 | 0 of 19 |
| Constipation | Gastrointestinal disorders | 1 of 20 | 0 of 19 | 0 of 19 | 0 of 19 |
| Dyspepsia | Gastrointestinal disorders | 0 of 20 | 0 of 19 | 1 of 19 | 0 of 19 |
| Vomiting | Gastrointestinal disorders | 0 of 20 | 0 of 19 | 1 of 19 | 0 of 19 |
| Non-cardiac chest pain | General disorders | 0 of 20 | 0 of 19 | 0 of 19 | 1 of 19 |
| Urinary tract infection | Infections and infestations | 0 of 20 | 0 of 19 | 0 of 19 | 1 of 19 |
| Hepatic enzyme increased | Investigations | 0 of 20 | 1 of 19 | 0 of 19 | 0 of 19 |
Serious events with the highest arm-level rate: chest pain (5.3%), dyspnoea (5.3%), rash (5.3%), orthostatic hypotension (5.3%).
The safety figures are presented by treatment period. In Period 1, 20 participants were at risk for serious events and 0 were affected; 20 were at risk for other events and 9 were affected. In Period 2, 19 were at risk for serious events and 1 was affected; 19 were at risk for other events and 4 were affected. In Period 3, 19 were at risk for serious events and 0 were affected; 19 were at risk for other events and 5 were affected. In Period 4, 19 were at risk for serious events and 1 was affected; 19 were at risk for other events and 5 were affected.
These are descriptive counts for sequential periods, not results from a randomized comparison. The number at risk is not the same in every period, and the registry does not report a statistical comparison, event-level timing, recurrence, or attribution to a particular treatment. The figures should not be interpreted as estimates of comparative risk.
The registry also lists Chest pain, Dyspnoea, Rash, and Orthostatic hypotension among the serious-event terms, each with 5.3%. Additional context for these percentages is not reported in the registry record. Death counts are not reported in the registry record. These safety listings do not provide the missing numerical results for the pharmacokinetic endpoint.
12. What the Result Does, and Does Not, Mean
This study is designed to describe raltegravir pharmacokinetics under specified dosing schedules, including schedules involving TUMS and Leader Antacid. Its primary endpoint is a measure of exposure over the interval from time 0 to 24 hours. The registry also describes the sampling schedule and an analysis based on natural log-transformed values and an analysis of variance model.
The record does not report the primary endpoint estimates, confidence intervals, or numerical contrasts between periods. Consequently, it is not possible to state from the registry record whether exposure was higher or lower under a particular schedule, how large any difference was, or how precisely it was estimated. The design description alone is not a result.
Even if a numerical pharmacokinetic contrast were available, it would describe exposure under the studied conditions. An exposure measure is not itself a measure of clinical benefit or harm. The registry record does not report evidence that would establish clinical consequences of a pharmacokinetic difference, and no treatment recommendation follows from the design description.
The sequence also limits how comparisons can be interpreted. Participants moved through periods in a single group, rather than being assigned to randomized concurrent groups. The raltegravir-alone period is a reference condition within that sequence, not a randomized external control. The record does not report whether or how potential period or carryover effects were modeled.
The safety counts are likewise descriptive. They do not establish comparative safety, particularly without a randomized group comparison, detailed event context, or statistical analysis. The completed status and enrollment do not fill in the absent outcome estimates. In short, the registry provides a study question and methods description, but its posted results do not support a numerical conclusion about exposure differences or their clinical meaning.
13. Why This Trial Matters Statistically
The study illustrates a common statistical distinction in clinical research: a clear question and a well-defined endpoint do not, on their own, establish what the results were. Here, the pharmacokinetic question is explicit, and the record describes sampling over a full post-dose interval and a model-based approach to summarizing exposure. Yet the numerical endpoint results are not reported in the registry record. Without estimates and uncertainty intervals, the central quantitative question remains unanswered by the posted record.
It also highlights why study structure matters. A single-group sequence can provide repeated measurements under different conditions, but the periods are not randomized concurrent arms. Interpreting within-sequence contrasts requires attention to order and possible period-related influences. The registry describes the sequence but does not report enough analysis detail to determine how these issues were addressed.
The record further shows why pharmacokinetic endpoints should be kept distinct from clinical outcomes. Area under the concentration-time curve is useful for describing drug exposure, but it does not directly quantify patient-centered outcomes. A statistical difference in exposure, if reported, would require separate interpretation before making claims about clinical consequences.
Finally, safety counts, primary endpoint estimates, and planning calculations answer different questions. Period-specific adverse-event counts are descriptive; planning illustrations are not observed power; and neither substitutes for endpoint results. Keeping these roles separate helps readers avoid treating design information as evidence of an effect. In this record, precision and magnitude of the primary pharmacokinetic results cannot be assessed because the numerical results are not reported.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most direct limitation for interpretation is that the registry record does not report numerical results for the primary pharmacokinetic endpoint. Least-squares means, confidence intervals, and contrasts among periods are absent, preventing assessment of effect size, direction, and precision.
The study used a single-group sequential design with no masking. The registry identifies allocation as not applicable, so the periods should not be treated as randomized arms. Period order and treatment condition occur together in the stated sequence; the record does not describe whether period or carryover effects were examined or how they were handled.
The record gives an enrollment of 20 and describes the primary population as per-protocol, but does not report the number of evaluable participants in each period or the handling of incomplete data. That leaves uncertainty about the analyzed sample and the potential influence of exclusions or missing concentration measurements.
The statistical description is brief. Although it identifies a natural log transformation and analysis of variance, the model terms, diagnostics, exact contrasts, and multiplicity approach are not reported in the registry record. The sample-size justification for the trial is also not reported; planning illustrations based on observed effects do not establish the original design rationale.
Safety information is reported as period-specific counts and serious-event terms, without a comparative analysis or detailed event context. Death counts and the relationship of listed terms to treatment are not reported in the registry record. These limitations constrain interpretation of both the pharmacokinetic question and the safety listings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Effect of Antacids on the Pharmacokinetics (PK) of Raltegravir in Human Immunodeficiency Virus (HIV)-Infected Participants (MK-0518-824) — NCT02473367.
- Registry record last updated 2018-08-27; status last verified 2018-07.
- Results first posted 2016-09-01.
- 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
NCT02473367 is a completed Phase 1, single-group pharmacokinetic study with an enrollment of 20 HIV-infected participants. Participants followed a sequence involving once-daily raltegravir alone and raltegravir with TUMS or Leader Antacid, taken concomitantly or 12 hours later. The primary endpoint was raltegravir area under the plasma concentration-time curve from time 0 to 24 hours.
The registry describes analysis of natural log-transformed values using an analysis of variance model to derive geometric least-squares means, with a 95% confidence interval specified for the endpoint. Numerical primary endpoint results and interval estimates are not reported in the registry record. Period-specific adverse-event counts are posted, but they are descriptive and are not reported as randomized comparisons. The record does not provide enough outcome detail to quantify pharmacokinetic differences or their clinical implications.