This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Trial to Evaluate the Safety, Tolerability, and Efficacy of MK-8457 in Participants With Rheumatoid Arthritis (MK-8457-010) (NCT01651936), a randomized phase 2 study. The primary outcome is Change From Baseline in Disease Activity Score (DAS28) as Measured by C-Reactive Protein (CRP) at Week 12.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01651936 |
| Phase | Phase 2 |
| Condition | Rheumatoid Arthritis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 56 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants had active rheumatoid arthritis and an inadequate response or intolerance to anti-TNF-α therapy. The primary outcome population was narrower: randomized Base Study participants who received at least one dose of study drug and had both Baseline and Week 12 DAS28-CRP measurements. The registry reports enrollment of 56, but does not report the number meeting that primary-outcome definition by treatment group beyond the posted outcome counts.
Intervention
The intervention was MK-8457 100 mg taken orally twice daily with methotrexate at the stable dose received at study enrollment. The Base Study was described as lasting up to 24 weeks. A Safety Extension was also described for participants receiving MK-8457, with a planned duration of up to 76 weeks.
Comparator
The comparator was dose-match placebo taken orally twice daily, also with methotrexate at the stable dose received at enrollment. The primary contrast is between the Base Study MK-8457 and Base Study placebo groups. The registry describes randomization, double masking, and a parallel-group design.
Primary question
The stated primary hypothesis was that MK-8457 plus methotrexate would be superior to placebo plus methotrexate on change in DAS28-CRP after 12 weeks of treatment. DAS28-CRP combines joint counts, C-reactive protein, and the patient's global assessment of disease activity. The posted estimate is a difference in least squares means with a 95% confidence interval and p-value. This gives an estimate of the contrast and its uncertainty; it does not by itself establish that the treatment caused a particular outcome for an individual participant.
3. Trial Design
The registry describes a Phase IIa, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. It was intended to assess the safety, tolerability, and efficacy of MK-8457 in participants with active rheumatoid arthritis and inadequate response or intolerance to anti-TNF-α therapy. The sponsor was Merck Sharp & Dohme LLC. The registry lists the trial as terminated. The reason for termination is not reported in the registry record.
The Base Study compared MK-8457 100 mg twice daily plus stable-dose methotrexate with dose-match placebo twice daily plus stable-dose methotrexate. The Base Study was to last up to 24 weeks. The record also describes a Safety Extension for participants receiving MK-8457, planned to last up to 76 weeks. The listed primary endpoint was assessed at Week 12, and the listed secondary outcomes included measures at Week 12 and Week 24.
Enrollment was 56. The primary outcome analysis included participants who were randomized, received at least one dose, and had both Baseline and Week 12 DAS28-CRP measurements. The posted primary outcome counts are 13 for MK-8457 and 18 for placebo. The registry does not report why participants were not included in that outcome population or provide a full account of missing measurements. The recorded start date was 2012-08-29, and the primary completion date was 2013-10-08. The randomization method, allocation concealment procedures, site count, and detailed conduct of the trial are not reported in the registry record.
The registry gives a primary hypothesis but does not report a sample-size justification, a detailed statistical analysis plan, or whether interim analyses were conducted. The trial's termination status should be distinguished from those missing details: the registry does not state why the study ended or whether the termination affected its planned analyses.
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.
Base Study
| Stage | Base Study: MK-8457 | Base Study: Placebo | Extension Study: MK-8457 |
|---|---|---|---|
| STARTED | 30 | 26 | 0 |
| COMPLETED | 3 | 1 | 0 |
| NOT COMPLETED | 27 | 25 | 0 |
Reasons for not completing this period:
| Reason | Base Study: MK-8457 | Base Study: Placebo | Extension Study: MK-8457 |
|---|---|---|---|
| Adverse Event | 3 | 0 | 0 |
| Withdrawal by Subject | 1 | 1 | 0 |
| Early Escape | 2 | 8 | 0 |
| Study terminated by sponsor | 21 | 16 | 0 |
Extension Study
| Stage | Base Study: MK-8457 | Base Study: Placebo | Extension Study: MK-8457 |
|---|---|---|---|
| STARTED | 0 | 0 | 14 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 14 |
Reasons for not completing this period:
| Reason | Base Study: MK-8457 | Base Study: Placebo | Extension Study: MK-8457 |
|---|---|---|---|
| Lack of Efficacy | 0 | 0 | 1 |
| Study terminated by sponsor | 0 | 0 | 13 |
Analysis population for the primary outcome, as defined in the registry: Randomized participants in the Base Study who received at least one dose of study drug and had both Baseline and Week 12 DAS28-CRP measurements
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 randomized participants
| Characteristic | Unit | Base Study: MK-8457 | Base Study: Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 30 | 26 | 56 | |
| Age, Continuous | Years | 57.8 (SD 12.7) | 59.3 (SD 10.8) | 58.5 (SD 11.8) |
| Age, Customized: <65 years | Participants | 21 | 20 | 41 |
| Age, Customized: ≥65 years | Participants | 9 | 6 | 15 |
| Sex: Female, Male: Female | Participants | 22 | 21 | 43 |
| Sex: Female, Male: Male | Participants | 8 | 5 | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Disease Activity Score (DAS28) as Measured by C-Reactive Protein (CRP) at Week 12, measured over Baseline and Week 12.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from Baseline in DAS28-CRP at Week 12, expressed in units on a scale. DAS28-CRP is a continuous index combining tender-joint count across 28 joints, swollen-joint count across 28 joints, C-reactive protein, and the patient's global assessment of disease activity on a visual analog scale. The registry describes the score as ranging from 0 to 10, with higher values indicating greater rheumatoid arthritis disease activity. It notes that a decrease in C-reactive protein indicates improvement.
A composite measure can represent several aspects of disease activity in a single outcome, rather than treating each component as the primary question. Change from Baseline focuses the comparison on how the score shifted during the treatment period. Because higher DAS28-CRP represents greater activity, a decrease is directionally consistent with improvement in the score. The endpoint is continuous, so the analysis reports group-level least squares means and a contrast between those means, rather than the proportion of participants crossing a response threshold.
The registry reports least squares mean changes of -1.83 for MK-8457 and -1.31 for placebo. The sponsor-reported difference in least squares means is -0.52, with a 95% confidence interval from -1.54 to 0.50. These estimates describe the posted analysis population and do not imply that every participant experienced the group average change. The definition of the primary analysis population requires a Week 12 measurement, so the result does not directly describe participants without the measurements needed for inclusion.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
In the primary outcome population, the posted least squares mean change in DAS28-CRP was -1.83 for MK-8457 and -1.31 for placebo. Since higher DAS28-CRP indicates greater disease activity, negative changes indicate decreases in the score. The treatment contrast, expressed as the difference in least squares means, was -0.52. Its 95% confidence interval ranged from -1.54 to 0.50, and the reported p-value was 0.308.
The point estimate favors a larger decrease in the MK-8457 group, but the confidence interval includes zero. In statistical terms, the posted estimate is compatible with a range of possible contrasts that includes no difference and values on either side of no difference. The interval is also wide enough that the point estimate alone should not be read as a precise estimate of the size of a treatment-group difference. The p-value does not establish that there is no difference; it describes how compatible the observed data are with a specified null model under the analysis assumptions.
The outcome counts are 13 for MK-8457 and 18 for placebo in the primary analysis. These are the participants meeting the registry's stated outcome-population requirements, not the overall enrollment. The endpoint uses available Baseline and Week 12 DAS28-CRP measurements, and the registry does not describe the handling of participants lacking either measurement. That limits assessment of how missing outcome data may affect the result.
The posted evidence therefore does not give a precise or conclusive estimate of the primary contrast. It does show a numerically greater average decrease in the MK-8457 group, while the uncertainty includes no difference. This is a description of the registry analysis, not a claim about the treatment's effects beyond the participants, endpoint, and analysis reported.
The primary hypothesis concerned superiority after 12 weeks. The registry reports the model-based contrast and uncertainty, but does not report the detailed prespecified analysis plan or sample-size rationale. The trial is listed as terminated, with no reason given in the registry record. Neither the termination status nor the point estimate explains why the observed result occurred. Interpretation should remain tied to the reported endpoint, analysis population, and uncertainty, without treating the study as proof of benefit or lack of benefit.
9. Statistical Methods Explained
The primary endpoint is continuous: each participant's DAS28-CRP is a score, and the registry reports change in that score between Baseline and Week 12. For a continuous endpoint, a group mean summarizes the central tendency of observed changes. The registry reports least squares means, which are model-based group estimates rather than necessarily simple arithmetic averages. The details of covariates and model specification beyond the method name are not reported in the registry record.
What does the primary contrast estimate?
The reported difference in least squares means is -0.52 for MK-8457 compared with placebo. It expresses the estimated separation between the groups on the change-from-Baseline scale. A negative contrast indicates a more negative estimated change in the MK-8457 group than in the placebo group. Because higher DAS28-CRP indicates greater disease activity, that direction corresponds to a larger average decrease in the score. The contrast is an estimate for groups, not a statement that each participant changed by that amount.
How should the confidence interval be read?
The 95% confidence interval runs from -1.54 to 0.50. In general, a confidence interval conveys the precision of an estimate under the statistical model and its assumptions. A wider interval indicates greater uncertainty about the size and direction of the contrast. Here, the interval includes zero, so the registry result is compatible with no group difference as well as with contrasts in either direction. The confidence interval should be considered alongside the point estimate, rather than using the point estimate alone.
What does the p-value add?
The reported p-value is 0.308. In general, a p-value measures how unusual data at least as inconsistent with a null hypothesis would be if that null hypothesis and the analysis assumptions were true. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of a result. The registry's primary analysis reports a non-small p-value alongside an interval that includes zero. Those features are consistent with uncertainty about the contrast; they do not establish equivalence or prove that there is no treatment-group difference.
Why does the analysis population matter?
The primary endpoint population consisted of randomized Base Study participants who received at least one dose and had both Baseline and Week 12 measurements. This definition excludes participants who did not meet any one of those conditions. The record does not report a detailed account of missing measurements, reasons for exclusion, or sensitivity analyses. In general, missing outcome data can affect an estimate when the likelihood of having a measurement is related to treatment or outcome. Without information about the missingness and its handling, the robustness of the primary estimate cannot be fully assessed from the registry record.
What does the analysis method mean?
The sponsor reports Constrained Longitudinal Data Analysis and a difference in least squares means. In general, longitudinal analysis models repeated measurements over time, while a constrained approach applies a specified condition to the modeled group profiles, often at Baseline. The exact constraints, covariance structure, and other model details are not reported in the registry record, so the label alone does not allow independent verification of every modeling choice. A model-based result can use information across repeated measurements, but the posted outcome population still requires the listed Baseline and Week 12 measurements.
General statistical considerations also include the distinction between an estimate and its precision. The contrast gives the estimated direction and size of the group separation; the confidence interval describes uncertainty around it, conditional on the model and data. Neither quantity by itself captures all possible sources of bias, such as missing outcomes or departures from the intended conduct of a trial. Randomization and masking are design features listed in the record, but details needed to assess their implementation are not reported.
The registry lists secondary binary outcomes as percentages achieving ACR response thresholds. Such outcomes summarize whether participants crossed a defined response threshold, rather than their continuous DAS28-CRP change. Their estimates can be less precise when event counts are limited. General comparison methods for binary outcomes may report differences in percentages or related measures; for the Week 12 ACR comparisons, the sponsor reports Cochran-Mantel-Haenszel differences in percentages. The registry does not give enough detail to reconstruct all model specifications or any adjustment for multiple secondary comparisons.
Planning calculations based on an observed effect are not observed power and are not the trial's own sample-size justification. The planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set to a stated fraction of the observed effect. Such calculations illustrate how an assumed effect size relates to a planning sample size under those assumptions. They cannot establish what the study was originally designed to detect; the trial's own sample-size justification is not reported in the registry record.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Constrained Longitudinal Data Analysis | Difference in least squares means -0.52 | -1.54 to 0.50 | 0.308 |
For the primary endpoint, the registry reports the sponsor's Constrained Longitudinal Data Analysis: a difference in least squares means of -0.52, with a 95% confidence interval from -1.54 to 0.50 and p=0.308. No separate recalculated primary contrast is posted in the registry data described for this analysis. The interpretation should therefore center on the reported model-based result, while recognizing that the available registry description does not give the full model specification.
For Week 12 ACR20 and ACR50, the sponsor reports Cochran-Mantel-Haenszel differences in percentages. The separately calculated unadjusted comparisons use the posted group counts and proportions, and should be understood as simple recalculations rather than replacements for the sponsor's analysis. For ACR20, the recalculated unadjusted p-value is 0.983, compared with the sponsor-reported p-value of 0.91. For ACR50, the recalculated unadjusted p-value is 0.39, compared with the sponsor-reported p-value of 0.468. The methods differ, so modest variation in estimates or p-values can arise without implying an error.
The recalculated intervals for both binary outcomes include zero for the risk difference. The registry reports no discrepancy flag for these comparisons, but their unadjusted nature remains important. The sponsor's reported analyses and the recalculated summaries answer closely related, not necessarily identical, statistical questions. A recalculation from aggregate counts cannot reproduce an analysis that may use additional design or stratification information not present in those counts.
11. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary endpoint and lists secondary outcomes, but does not report a multiplicity procedure, a testing hierarchy, or a statistical analysis plan describing how the family of comparisons was handled. This matters because repeated testing across outcomes can increase the chance of apparently notable results arising by chance. Without a reported adjustment or prespecified hierarchy, secondary p-values should be treated as nominal and interpreted cautiously. The registry record does not establish whether any adjustment was used outside the information posted.
The primary analysis population required randomization, at least one dose of study drug, and both Baseline and Week 12 DAS28-CRP measurements. This is the population to which the primary estimate applies. The registry does not report the number or reasons for participants lacking the required measurements, nor does it describe imputation, a missing-data model, or sensitivity analyses. In general, missingness can affect estimates if the availability of outcome data is associated with treatment assignment, disease status, or the outcome itself. The posted population definition alone does not show whether that concern arose or how it was addressed.
The record also does not report whether the primary analysis followed an intention-to-treat principle, how protocol deviations were handled, or whether other analysis populations were considered. These details should not be inferred from the stated eligibility conditions for the outcome analysis. The registry's trial status is terminated, but neither the reason for termination nor its relationship to missing outcome data or analysis decisions is reported.
The registry reports no sample-size justification, interim-analysis plan, or detailed account of stopping decisions. Consequently, it is not possible to assess from the record whether the study was planned around a particular target difference or whether interim monitoring influenced the final analysis. Planning illustrations based on observed effects do not fill that gap: they are conditional calculations and are not evidence of the trial's original design or its observed power.
12. 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 |
|---|---|---|---|
| Base Study: MK-8457 | 5 | 30 | 16.7% |
| Base Study: Placebo | 0 | 26 | 0.0% |
| Extension Study: MK-8457 | 2 | 14 | 14.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Base Study: MK-8457 | 10 of 30 |
| Base Study: Placebo | 2 of 26 |
| Extension Study: MK-8457 | 6 of 14 |
Most frequent serious adverse event terms
| Event term | Organ system | Base Study: MK-8457 | Base Study: Placebo | Extension Study: MK-8457 |
|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | 1 of 30 | 0 of 26 | 0 of 14 |
| Enterocolitis | Gastrointestinal disorders | 1 of 30 | 0 of 26 | 0 of 14 |
| Bronchitis | Infections and infestations | 1 of 30 | 0 of 26 | 0 of 14 |
| Lung infection | Infections and infestations | 0 of 30 | 0 of 26 | 1 of 14 |
| Hip fracture | Injury, poisoning and procedural complications | 1 of 30 | 0 of 26 | 0 of 14 |
| Humerus fracture | Injury, poisoning and procedural complications | 0 of 30 | 0 of 26 | 1 of 14 |
| White blood cell count decreased | Investigations | 1 of 30 | 0 of 26 | 0 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Base Study: MK-8457 | Base Study: Placebo | Extension Study: MK-8457 |
|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 5 of 30 | 1 of 26 | 2 of 14 |
| Blood pressure increased | Investigations | 1 of 30 | 1 of 26 | 1 of 14 |
| Iron deficiency anaemia | Blood and lymphatic system disorders | 2 of 30 | 0 of 26 | 0 of 14 |
| Abdominal pain | Gastrointestinal disorders | 2 of 30 | 0 of 26 | 0 of 14 |
| Abdominal pain upper | Gastrointestinal disorders | 2 of 30 | 0 of 26 | 0 of 14 |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | 2 of 30 | 0 of 26 | 0 of 14 |
| Atrioventricular block first degree | Cardiac disorders | 0 of 30 | 0 of 26 | 1 of 14 |
| Dyspepsia | Gastrointestinal disorders | 0 of 30 | 0 of 26 | 1 of 14 |
| Toothache | Gastrointestinal disorders | 0 of 30 | 0 of 26 | 1 of 14 |
| Contusion | Injury, poisoning and procedural complications | 0 of 30 | 0 of 26 | 1 of 14 |
Serious events with the highest arm-level rate: lung infection (7.1%), humerus fracture (7.1%), lymphadenopathy (3.3%), enterocolitis (3.3%), bronchitis (3.3%).
For serious adverse events in the Base Study, the registry lists 5 affected participants among 30 at risk in the MK-8457 group and 0 among 26 at risk in the placebo group. In the Extension Study, it lists 2 affected participants among 14 at risk. These are group-specific counts; they should not be added together because the record does not establish whether participants appear in more than one study period. Deaths are not reported in the registry record.
The registry also lists serious adverse event terms, including lung infection and humerus fracture at 7.1% each, and lymphadenopathy, enterocolitis, bronchitis, and hip fracture at 3.3% each. These entries describe reported event terms, not necessarily a complete account of all safety outcomes or their causes. The record does not provide event timing, exposure-adjusted rates, or enough detail to determine whether an event was considered related to study treatment.
Serious adverse event counts are descriptive. Differences in counts do not by themselves establish a causal relationship, and absence of a reported event is not proof that risk is absent. The registry's termination status and the reason for it are not linked to these safety figures in the posted record.
13. What the Result Does, and Does Not, Mean
The primary result describes a model-based comparison of Week 12 DAS28-CRP change among the participants included in the registry's primary outcome population. The estimated contrast was -0.52, but the 95% confidence interval ranged from -1.54 to 0.50 and the reported p-value was 0.308. The estimate points toward a larger decrease in the MK-8457 group, while the interval includes no difference and a range of possible effects in either direction. The result is therefore uncertain rather than a precise demonstration of a group difference.
This does not mean that the treatments are equivalent. Establishing equivalence or non-inferiority requires a design and analysis with prespecified margins and an appropriate interpretation of the confidence interval; such details are not reported in the registry record. Nor does the result prove that there is no effect. It indicates that the posted analysis does not estimate the primary contrast precisely enough to rule out a range of possibilities.
The result also does not establish what would happen for an individual participant. Group averages and response percentages describe distributions of outcomes, not guaranteed personal outcomes. The primary outcome population required observed Baseline and Week 12 measurements, and the registry does not report the handling or reasons for missing measurements. The trial's terminated status is recorded, but its reason and implications are not reported.
Safety counts provide a separate descriptive view and should not be treated as proof of causation. The record does not provide a complete causal assessment or full context for each reported event. Overall, the registry supports a cautious description of the observed estimates and their uncertainty, not a medical recommendation or a definitive claim that MK-8457 does or does not work.
14. Why This Trial Matters Statistically
This trial illustrates why a point estimate should not be separated from its uncertainty. The primary contrast is numerically in the direction of a larger decrease in DAS28-CRP with MK-8457, but its confidence interval includes zero and extends to values favoring either group. A statistical reading that reports only the point estimate would overstate what the data establish; a reading that treats the p-value as proof of no effect would also overstate the evidence.
It also illustrates how endpoint definitions shape interpretation. DAS28-CRP is a continuous composite combining joint counts, an inflammatory marker, and a patient global assessment. The ACR outcomes use response thresholds and produce percentages. These are related clinical measures, but they do not answer identical questions, and their estimates should not be expected to match exactly.
The primary analysis population is another important part of the result. The registry requires participants to have received at least one dose and to have both Baseline and Week 12 measurements. Without a fuller account of missing outcomes and analysis choices, readers cannot fully judge how representative that population is of all randomized participants. The registry's termination status, without a reported reason, is relevant context but cannot be used to infer the cause of the posted result.
Finally, the record demonstrates the limits of registry-level evidence. It provides estimates, intervals, p-values, and safety counts, but does not report several details needed for a complete audit, including the sample-size rationale, multiplicity strategy, and full model specification. Transparent interpretation depends not only on the numerical result but also on understanding which participants and analyses generated it.
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 registry does not report the reason the trial was terminated. It also does not report whether termination affected recruitment, follow-up, or the planned analysis. The enrollment entry is 56, while the primary outcome analysis population is defined by treatment exposure and availability of both Baseline and Week 12 measurements. The reasons that some enrolled participants are not represented in those primary outcome counts are not reported in the registry record.
The statistical description is incomplete for independent reproduction. The record names Constrained Longitudinal Data Analysis but does not give the full model specification, covariates, covariance structure, or other implementation details. It does not report a sample-size justification, a detailed prespecified analysis plan, interim analyses, multiplicity handling, or sensitivity analyses. These omissions limit assessment of model assumptions and the robustness of the primary result.
The posted secondary results cover only some of the listed outcomes. Results for the listed Week 24 measures and other outcomes are not reported in the registry record. This makes it difficult to assess consistency across time points and endpoint types. The Week 12 binary results also have uncertainty, and simple recalculations from aggregate counts cannot reproduce every feature of the sponsor's analysis.
Safety reporting is likewise limited in the registry summary. The record gives group counts and selected serious adverse event terms but does not report deaths, event timing, exposure-adjusted rates, or a complete assessment of treatment relatedness. The extension results are a separate study period and should not be combined with Base Study counts without participant-level information. These limitations do not invalidate the posted observations, but they constrain the conclusions that can be drawn from them.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Trial to Evaluate the Safety, Tolerability, and Efficacy of MK-8457 in Participants With Rheumatoid Arthritis (MK-8457-010) — NCT01651936.
- Registry record last updated 2021-07-30; status last verified 2021-07.
- Results first posted 2017-02-23.
- 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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19. Record Summary
The registry describes a randomized, double-blind, placebo-controlled, parallel-group Phase IIa trial of MK-8457 100 mg twice daily plus methotrexate versus placebo plus methotrexate in active rheumatoid arthritis after inadequate response or intolerance to anti-TNF-α therapy. Enrollment was 56, and the trial is listed as terminated. Its reason for termination is not reported in the registry record.
The primary endpoint was change in DAS28-CRP from Baseline to Week 12. The sponsor-reported difference in least squares means was -0.52, with a 95% confidence interval from -1.54 to 0.50 and p=0.308. The interval includes zero, leaving uncertainty about the direction and size of the contrast. The registry also posts Week 12 ACR20 and ACR50 results and selected safety counts. The sample-size rationale, multiplicity approach, detailed model specification, and handling of missing data are not reported in the registry record.