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 Bioequivalence of a FDC Tablet of Linagliptin/Metformin (5mg/1000mg) Extended Release in Healthy Subjects (NCT02084082), a randomized phase 1 study. The primary outcome is Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02084082 |
| Phase | Phase 1 |
| Condition | Healthy |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 68 |
| Arms in the primary outcome | 4 |
| Lead sponsor | Boehringer Ingelheim |
| Results posted | Yes |
2. Clinical Question
Population
Healthy subjects who received study treatment and contributed at least one observation for at least one primary endpoint were included in the primary endpoint population, subject to the registry’s stated exclusion for important protocol violations affecting pharmacokinetic evaluation. The record describes separate fasted and fed populations. It does not report further demographic characteristics in the outcome description.
Intervention
The intervention was a fixed-dose combination tablet containing linagliptin and metformin extended release, with strengths of 5 mg and 1000 mg. The trial used single-dose treatment. The sequence descriptions indicate that some subjects received the fixed-dose tablet before the separate tablets, and others received the separate tablets before the fixed-dose tablet.
Comparator
The comparator was the free combination: separate linagliptin and metformin extended-release tablets. The comparison was made under both fasted and fed conditions. This is a formulation comparison of the same named medicines, not a comparison between an active treatment and no treatment.
Primary question
The primary question was whether linagliptin exposure, measured by plasma AUC from 0 to 72 hours, was similar after the fixed-dose combination and the separate tablets. The registry reports adjusted geometric mean ratios and 90% confidence intervals for the fasted and fed comparisons. The equivalence margins and the sponsor’s formal decision rule are not reported in the registry record, so the posted estimates should be read as pharmacokinetic comparisons rather than as a complete account of the protocol’s decision criteria.
3. Trial Design
This was a randomized, open-label, single-dose, two-way crossover trial in healthy subjects. In a crossover design, the same participant receives both formulations in a sequence, allowing a comparison that can account for stable differences between participants. The registry’s sequence descriptions identify fixed-dose combination first or separate tablets first, within both fasted and fed conditions. Details such as the interval between doses and the procedures used to manage possible carryover are not reported in the registry record.
The record lists an enrollment of 68 and identifies the trial as phase 1. It was sponsored by Boehringer Ingelheim, began in 2014-04, had primary completion in 2014-07, and is marked completed. The record identifies healthy subjects as the condition and describes the purpose as evaluating bioequivalence under fed and fasted conditions.
The posted primary endpoint population is described separately for the fasted and fed parts. It includes treated subjects with at least one observation for at least one primary endpoint, excluding those with important protocol violations regarding statistical evaluation of pharmacokinetic endpoints. The fasted arm summaries list 52 subjects in each formulation group; the fed summaries list 15 for the separate-tablet group and 14 for the fixed-dose group. These are outcome-specific counts and should not be taken as a complete explanation of participant flow. Reasons for the different counts are not reported in the registry record.
The record lists six outcome measures and 12 analyses, but the posted results in the primary outcome description are the linagliptin AUC0-72 comparisons. The two listed secondary outcomes concern linagliptin and metformin AUC0-inf. Results for other outcome measures are not reported in the registry record as usable two-arm comparisons.
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 Period 1 (4 Days)
| Stage | FDC 1000 Fast/ L+M 1000 Fast | L+M1000 Fast/ FDC1000 Fast | FDC1000 Fed/L+M1000 Fed | L+M1000 Fed/ FDC1000 Fed |
|---|---|---|---|---|
| STARTED | 26 | 26 | 8 | 8 |
| COMPLETED | 26 | 26 | 8 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Washout Period 1 (35 Days)
| Stage | FDC 1000 Fast/ L+M 1000 Fast | L+M1000 Fast/ FDC1000 Fast | FDC1000 Fed/L+M1000 Fed | L+M1000 Fed/ FDC1000 Fed |
|---|---|---|---|---|
| STARTED | 26 | 26 | 8 | 8 |
| COMPLETED | 26 | 26 | 7 | 6 |
| NOT COMPLETED | 0 | 0 | 1 | 2 |
Reasons for not completing this period:
| Reason | FDC 1000 Fast/ L+M 1000 Fast | L+M1000 Fast/ FDC1000 Fast | FDC1000 Fed/L+M1000 Fed | L+M1000 Fed/ FDC1000 Fed |
|---|---|---|---|---|
| Adverse Event | 0 | 0 | 1 | 1 |
| Withdrawal by Subject | 0 | 0 | 0 | 1 |
Treatment Period 2 (4 Days)
| Stage | FDC 1000 Fast/ L+M 1000 Fast | L+M1000 Fast/ FDC1000 Fast | FDC1000 Fed/L+M1000 Fed | L+M1000 Fed/ FDC1000 Fed |
|---|---|---|---|---|
| STARTED | 26 | 26 | 7 | 6 |
| COMPLETED | 26 | 26 | 7 | 6 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: PKS 1000 fast and PKS 1000 fed, included all treated subjects in Part 1 and Part 2, respectively, who provided at least 1 observation for at least 1 primary endpoint, without important protocol violations regarding the statistical evaluation of pharmacokinetic endpoints.
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: Treated set: All randomised subjects who received 1 dose of trial medication were included in the treated set.
| Characteristic | Unit | FDC 1000 Fast or L+M 1000 Fast | FDC 1000 Fed or L+M 1000 Fed | Total |
|---|---|---|---|---|
| Participants analysed | 52 | 16 | 68 | |
| Age, Continuous | years | 34.7 (SD 10.4) | 36.1 (SD 11.9) | 35.0 (SD 10.7) |
| Sex: Female, Male: Female | Participants | 29 | 10 | 39 |
| Sex: Female, Male: Male | Participants | 23 | 6 | 29 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72), measured over 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | nmol*h/L |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the area under the plasma concentration-time curve for linagliptin from 0 to 72 hours after administration, abbreviated AUC0-72. It summarizes drug exposure over the specified observation interval: it reflects both the concentration measured at sampling times and how those concentrations change over time. The registry states that blood samples were scheduled before administration and at multiple times through 72 hours afterward.
Pharmacokinetic exposure measures are used in formulation comparisons because they provide a quantitative way to assess whether a medicine reaches the circulation to a similar extent after different formulations. For this endpoint, the registry reports geometric means and geometric coefficients of variation. It clarifies that the values are adjusted geometric means and adjusted intra-individual gCVs. Geometric summaries are commonly used for pharmacokinetic measurements because such measurements may be asymmetric; this is a general statistical rationale, not an additional finding from this trial.
AUC0-72 is an exposure measure, not a direct measure of clinical benefit or harm. It also does not, by itself, describe every aspect of a concentration-time profile. The record lists AUC0-inf for both medicines as secondary outcomes, but the posted primary result concerns linagliptin AUC0-72. The unit is nmol*h/L.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For the fasted comparison, the posted adjusted geometric means are 286.6 for the separate tablets and 287.7 for the fixed-dose combination. The sponsor-reported adjusted geometric mean ratio is 100.37, with a 90% confidence interval from 96.562 to 104.326. The reported p-value is < 0.001. The geometric coefficient of variation is 11.8 in each group.
For the fed comparison, the posted geometric means are 234.1 for the separate tablets and 221.6 for the fixed-dose combination. The reported geometric mean ratio is 94.70, with a 90% confidence interval from 88.712 to 101.089. The reported p-value is < 0.001. The geometric coefficient of variation is 9.2 in each group. The fed estimates are based on smaller outcome-group counts than the fasted estimates, as reported in the registry.
A confidence interval describes the uncertainty around an estimated contrast under the analysis model. The intervals give a range of values compatible with the observed data and model assumptions; they are not a range containing a fixed proportion of individual participants’ values. Both estimates are near 100 on the ratio scale, but whether an interval meets a formal bioequivalence criterion depends on prespecified margins. Those margins are not reported in the registry record. Consequently, the reported estimates alone do not establish whether the sponsor’s formal criteria were satisfied.
The p-values should not be read in isolation as proof of equivalence. A p-value addresses a particular hypothesis under a specified statistical procedure. For an equivalence question, the margins and the analysis decision rule are essential to interpreting that test. The registry labels the analyses as non-inferiority or equivalence analyses but does not report the margins or explain precisely how the p-values relate to the decision rule. The ratio estimates and confidence intervals are therefore the most directly interpretable posted quantities, while the inferential conclusion remains incompletely documented.
The fasted and fed results should be read as condition-specific comparisons. They are not a pooled estimate, and the record does not report a formal test comparing the fed and fasted effects. The differences between the displayed group summaries cannot be used to infer a treatment effect across conditions. These are pharmacokinetic results from healthy subjects after single-dose administration, not clinical outcome results.
9. Statistical Methods Explained
The record describes an open-label randomized crossover study and reports analyses using ANOVA. The endpoint summaries are geometric means, and the comparisons are reported as ratios. These choices fit a common approach to pharmacokinetic data, but the registry does not provide enough detail to reconstruct the full statistical model, its terms, or all analysis decisions.
Why use a crossover comparison?
In a crossover study, participants receive both treatments in an assigned order. Comparing a participant’s responses under each formulation can reduce the influence of stable differences between people, such as differences in baseline pharmacokinetic characteristics. Randomization of order can help avoid systematic assignment of one sequence to participants with particular characteristics. These are general properties of crossover designs. The registry gives the treatment sequences but does not report the washout interval, period effects, sequence effects, or carryover assessments. Their handling in the sponsor’s model is not reported in the registry record.
What do geometric means and ratios convey?
A geometric mean summarizes positive measurements on a logarithmic scale and then expresses the summary on the original scale. A ratio expresses the relative level of exposure between formulations, rather than their absolute difference. A ratio of 100 on the percentage scale corresponds to equal estimates; values on either side indicate the direction of the estimated contrast. This is general interpretation. The registry reports adjusted geometric means and calls the fasted contrast an adjusted geometric means ratio. It calls the fed contrast a geometric mean ratio (net). The exact distinction implied by “net” is not explained in the registry record.
Geometric coefficients of variation describe relative variability on a multiplicative scale. They are not the same as standard deviations and do not describe the uncertainty in the treatment ratio. The primary endpoint description says these are adjusted intra-individual gCVs. In general, within-participant variability matters in crossover pharmacokinetic comparisons because the contrast is based on repeated measurements within participants. The record does not provide further details about how variability was estimated.
How should the confidence intervals be read?
The reported 90% confidence intervals accompany the sponsor’s ratios. In general, a confidence interval reflects both the observed data and the statistical model, and its width indicates the precision of the estimate under that model. A narrower interval indicates greater precision than a wider interval, all else equal. The intervals do not show the range of participant-level responses, nor do they account for uncertainty about whether the model assumptions are correct.
Bioequivalence is usually assessed by comparing a confidence interval with prespecified acceptance limits. The limits and the exact decision rule are not reported in the registry record. It would therefore be inappropriate to apply a threshold from another source or to infer the sponsor’s conclusion from the p-value alone. The registry identifies ANOVA and gives the ratio, interval, and p-value, but does not provide the ANOVA specification, transformations, model covariates, or treatment of period and sequence effects.
Why can variability and sample size matter?
General statistical principle: greater variability makes treatment contrasts less precise, while more observations can improve precision when the design and data quality are otherwise comparable. In crossover studies, within-participant variation is particularly relevant to the precision of the paired contrast. The record’s gCV summaries give a relative variability measure, but they do not replace the confidence intervals or reveal the full model inputs.
The record includes planning assumptions for sample-size illustrations elsewhere in the analysis: two-sided significance level 0.05, equal allocation, normal approximation, and effects defined as fractions of the observed effect. Such illustrations are planning exercises based on assumptions, not observed power and not evidence that the original trial was designed using those assumptions. The trial’s own sample-size justification is not reported in the registry record.
What remains unspecified?
The record does not report the equivalence margins, a complete statistical analysis plan, interim analyses, multiplicity adjustment, missing-data method, or detailed model specification. It does not state how observations below assay limits, if any, were handled. These omissions limit independent reproduction of the sponsor analysis and limit interpretation of the formal inferential claims. They do not change the numerical estimates posted, but they constrain what can be concluded from them.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| ANOVA | Adjusted Geometric Means ratio 100.37 | 96.562 to 104.326 | < 0.001 |
| ANOVA | Geometric mean ratio (net) 94.70 | 88.712 to 101.089 | < 0.001 |
The registry reports the sponsor’s ANOVA results directly: an adjusted geometric mean ratio of 100.37 with a 90% confidence interval of 96.562 to 104.326 for the fasted comparison, and a geometric mean ratio (net) of 94.70 with a 90% confidence interval of 88.712 to 101.089 for the fed comparison. The associated p-values are < 0.001 and < 0.001, respectively.
The arm-level geometric means are descriptive summaries, whereas the sponsor’s ratios come from the reported ANOVA analysis. In a crossover design, a ratio calculated only from displayed group summaries would not necessarily reproduce an adjusted model estimate. No discrepancy between a recalculation and the sponsor’s analysis is identified in the registry record, and the sponsor’s reported analysis is the relevant inferential result. The registry does not provide sufficient model detail to independently reproduce the ANOVA estimates or determine how the p-values implement the equivalence decision rule. The formal margins are not reported in the registry record, so the reported analysis cannot be fully evaluated against its stated decision criteria.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists six outcome measures and 12 analyses. It identifies linagliptin AUC0-72 as the primary outcome and lists linagliptin AUC0-inf and metformin AUC0-inf as secondary outcomes. The posted primary result includes separate fasted and fed comparisons. This means the record contains more than one outcome and more than one analysis, but it does not describe how the sponsor managed the possibility of false-positive findings across them.
Multiplicity refers generally to the increased chance of obtaining at least one apparently notable result when several hypotheses are examined. A prespecified testing hierarchy or adjustment can address this issue, depending on the aims and design. Whether any such procedure was specified or applied is not reported in the registry record. The listed p-values should therefore be interpreted in light of the individual reported analyses, not assumed to have a multiplicity adjustment.
The primary endpoint population includes treated subjects with at least one observation for at least one primary endpoint and excludes subjects with important protocol violations regarding pharmacokinetic statistical evaluation. The record does not report a full participant-flow account, reasons for the different outcome-group counts, or whether all randomized subjects are represented in each analysis. It also does not report how missing observations were handled, whether any values were imputed, or how incomplete concentration-time profiles affected AUC estimation.
These details matter because missing pharmacokinetic samples can affect exposure summaries and because analysis-population choices can influence the estimate. The record’s population description gives some eligibility information, but it does not establish that all randomized participants contributed to every outcome. A detailed statistical analysis plan, sample-size justification, interim-analysis information, missing-data procedures, and multiplicity strategy are not reported in the registry record.
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 |
|---|---|---|---|
| L+M 1000 Fasted | 0 | 52 | 0.0% |
| FDC 1000 Fasted | 0 | 52 | 0.0% |
| L+M 1000 Fed | 2 | 15 | 13.3% |
| FDC 1000 Fed | 0 | 14 | 0.0% |
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 |
|---|---|
| L+M 1000 Fasted | 4 of 52 |
| FDC 1000 Fasted | 9 of 52 |
| L+M 1000 Fed | 4 of 15 |
| FDC 1000 Fed | 4 of 14 |
Most frequent serious adverse event terms
| Event term | Organ system | L+M 1000 Fasted | FDC 1000 Fasted | L+M 1000 Fed | FDC 1000 Fed |
|---|---|---|---|---|---|
| Acetabulum fracture | Injury, poisoning and procedural complications | 0 of 52 | 0 of 52 | 1 of 15 | 0 of 14 |
| Bone contusion | Injury, poisoning and procedural complications | 0 of 52 | 0 of 52 | 1 of 15 | 0 of 14 |
| Concussion | Injury, poisoning and procedural complications | 0 of 52 | 0 of 52 | 1 of 15 | 0 of 14 |
| Fall | Injury, poisoning and procedural complications | 0 of 52 | 0 of 52 | 1 of 15 | 0 of 14 |
| Muscle contusion | Injury, poisoning and procedural complications | 0 of 52 | 0 of 52 | 1 of 15 | 0 of 14 |
| Pelvic fracture | Injury, poisoning and procedural complications | 0 of 52 | 0 of 52 | 1 of 15 | 0 of 14 |
| Road traffic accident | Injury, poisoning and procedural complications | 0 of 52 | 0 of 52 | 1 of 15 | 0 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | L+M 1000 Fasted | FDC 1000 Fasted | L+M 1000 Fed | FDC 1000 Fed |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | 3 of 52 | 5 of 52 | 2 of 15 | 0 of 14 |
| Diarrhoea | Gastrointestinal disorders | 1 of 52 | 4 of 52 | 0 of 15 | 1 of 14 |
| Rhinitis | Infections and infestations | 0 of 52 | 2 of 52 | 0 of 15 | 1 of 14 |
| Dizziness | Nervous system disorders | 0 of 52 | 2 of 52 | 1 of 15 | 0 of 14 |
| Vertigo | Ear and labyrinth disorders | 0 of 52 | 0 of 52 | 1 of 15 | 0 of 14 |
| Abdominal discomfort | Gastrointestinal disorders | 0 of 52 | 0 of 52 | 1 of 15 | 0 of 14 |
| Fatigue | General disorders | 0 of 52 | 0 of 52 | 0 of 15 | 1 of 14 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 52 | 0 of 52 | 0 of 15 | 1 of 14 |
| Rash | Skin and subcutaneous tissue disorders | 0 of 52 | 0 of 52 | 0 of 15 | 1 of 14 |
Serious events with the highest arm-level rate: acetabulum fracture (6.7%), bone contusion (6.7%), concussion (6.7%), fall (6.7%), muscle contusion (6.7%).
The registry reports serious adverse events by treatment group. In the fasted groups, no serious adverse events are listed for either the separate tablets or the fixed-dose combination. In the fed groups, 2 of 15 are listed for the separate tablets and 0 of 14 for the fixed-dose combination. These are group-specific counts in the registry, not adjusted comparisons, and they should not be treated as estimates of comparative safety.
The record also lists other adverse events affecting 4 of 52 in the fasted separate-tablet group, 9 of 52 in the fasted fixed-dose group, 4 of 15 in the fed separate-tablet group, and 4 of 14 in the fed fixed-dose group. The record does not provide enough detail to interpret these counts as treatment effects. Serious adverse event terms listed include acetabulum fracture, bone contusion, concussion, fall, muscle contusion, and pelvic fracture, each reported as 6.7%. The record does not clarify the relation of those terms to the treatment-group counts. Death counts are not reported in the registry record.
Because this was a single-dose study in healthy subjects and the reported groups are limited, these safety counts are descriptive. The registry does not provide a basis for drawing broad conclusions about risk or for comparing treatments clinically.
13. What the Result Does, and Does Not, Mean
The results describe how linagliptin exposure over 0 to 72 hours compared between a fixed-dose linagliptin/metformin extended-release tablet and the same medicines given as separate tablets. Separate estimates are posted for fasted and fed conditions. Their ratios and confidence intervals quantify the estimated relative exposure and its statistical precision under the sponsor’s reported analysis.
These results do not by themselves answer whether the formulations met the sponsor’s formal bioequivalence criterion, because the acceptance limits and full decision rule are not reported in the registry record. A ratio near 100 is not sufficient on its own: interpretation depends on the interval and the prespecified margin. The p-values also do not replace those criteria. The record labels the analyses as non-inferiority or equivalence analyses, but leaves important details of that inferential framework unstated.
The outcome is pharmacokinetic, not a clinical endpoint such as symptom change or disease control. The study involved healthy subjects and single-dose exposure. It does not establish the effects of repeated use, clinical outcomes, or safety in a patient population. Nor does the primary endpoint measure metformin exposure; metformin AUC0-inf is listed as a secondary outcome, but its results are not included in the primary comparison.
In general, a well-described bioequivalence analysis can support a formulation comparison for the specific products, conditions, and endpoints studied. The limits of this registry record are important: it does not provide the equivalence margins, complete model, missing-data procedures, or multiplicity strategy. The sound reading is therefore focused: the posted data give condition-specific estimates of linagliptin AUC0-72, with reported uncertainty, while the full basis for a formal equivalence conclusion is not reported in the registry record.
14. Why This Trial Matters Statistically
This trial illustrates why the distinction between descriptive summaries and model-based contrasts matters. The registry gives adjusted geometric means for each treatment condition and adjusted or net geometric mean ratios from ANOVA. A ratio is the inferential contrast of interest, while the arm summaries provide context. In a crossover study, the contrast depends on within-participant information and the model, so it is not necessarily recoverable from the displayed summaries alone.
It also illustrates the role of the confidence interval in a bioequivalence question. A point estimate near 100 does not settle the question. The interval must be interpreted relative to margins specified before analysis, and those margins are not reported in the registry record. The presence of a p-value does not fill that gap. Clear reporting of margins and the decision rule is necessary for readers to assess the formal conclusion.
Condition-specific estimates are useful because food status is part of the trial’s stated comparison. The posted fasted and fed analyses should remain distinct unless a justified combined analysis is reported. The record does not provide a formal comparison of these conditions or a pooled estimate.
Finally, the entry shows how registry results can communicate numerical estimates while leaving important analysis details unresolved. The sample-size illustrations use planning assumptions rather than reporting observed power, and the sample-size justification for the original study is not reported in the registry record. For biostatisticians and clinical researchers, this is a reminder to evaluate the estimand, analysis population, uncertainty, and decision rule together rather than treating any one number as a complete conclusion.
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 record provides only limited detail about the analysis. It reports ANOVA, ratios, confidence intervals, p-values, geometric means, and gCVs, but not the full model specification. The equivalence margins, statistical decision rule, treatment of period and sequence effects, and assessment of carryover are not reported in the registry record. These omissions prevent a complete independent assessment of the sponsor’s inferential procedure.
The outcome population is described in broad terms, but the record does not report a full account of participant flow or reasons for the different outcome-group counts under fed and fasted conditions. The missing-data method and handling of incomplete sampling profiles are not reported in the registry record. The effects of these choices on endpoint estimation therefore cannot be assessed from the posted information.
The registry lists multiple outcomes and analyses but does not report a multiplicity strategy. It also does not report the original sample-size justification or interim-analysis procedures. Sample-size planning illustrations based on observed effects are not a substitute for the trial’s design rationale and should not be interpreted as observed power.
There are also limits to the scope of the endpoint and population. The primary result concerns linagliptin AUC0-72 after single-dose administration in healthy subjects. The record lists secondary AUC0-inf outcomes, but their results are not reported as usable two-arm comparisons in the posted results. The design does not provide clinical outcome evidence, and its findings should not be generalized beyond the reported products, conditions, population, and endpoint without further evidence. Safety counts are descriptive, and the relation of the listed serious adverse event terms to the treatment groups is not explained in the registry record.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Bioequivalence of a FDC Tablet of Linagliptin/Metformin (5mg/1000mg) Extended Release in Healthy Subjects — NCT02084082.
- Registry record last updated 2016-08-04; status last verified 2015-08.
- Results first posted 2016-08-04.
- 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
NCT02084082 is a completed, randomized, open-label, single-dose, two-way crossover phase 1 trial sponsored by Boehringer Ingelheim. It compared a linagliptin/metformin extended-release fixed-dose tablet with separate linagliptin and metformin extended-release tablets in healthy subjects under fed and fasted conditions.
The primary endpoint was linagliptin plasma AUC0-72. The registry reports adjusted geometric means and sponsor ANOVA ratios with 90% confidence intervals for both conditions. The formal equivalence margins, full model specification, multiplicity approach, missing-data procedures, and original sample-size justification are not reported in the registry record. The results are pharmacokinetic estimates and do not by themselves establish clinical effects or a fully documented formal bioequivalence conclusion.