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 Study to Assess Safety of Canagliflozin and Metformin Hydrochloride Combination Given as a Supplement to Diet and Exercise to Improve Blood Sugar Level in Indian Adult Participants With Diabetes (NCT04288778), a na phase 4 study. The primary outcome is Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04288778 |
| Phase | Phase 4 |
| Condition | Diabetes Mellitus |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 276 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Johnson & Johnson Private Limited |
| Results posted | Yes |
2. Clinical Question
The registry record describes a study of canagliflozin plus metformin hydrochloride immediate-release fixed-dose combination as an adjunct to diet and exercise in Indian adults with type 2 diabetes. Its primary question concerns safety: what percentage of participants experienced treatment-emergent adverse events or treatment-emergent serious adverse events during the period from Baseline (Day 1) up to 24 weeks?
Population
Indian adult participants with type 2 diabetes mellitus, for whom treatment with both canagliflozin and metformin was appropriate. The safety analysis set included participants who had taken at least 1 dose of study treatment.
Intervention
Canagliflozin plus metformin hydrochloride immediate-release fixed-dose combination, posted as oral tablets at 50 mg + 500 mg or 50 mg + 1000 mg, alongside diet and exercise.
Comparator
There was no separate comparator group. The registry describes a single-group study and records allocation as not applicable.
Primary question
What percentage of participants had treatment-emergent adverse events or treatment-emergent serious adverse events from Baseline (Day 1) up to 24 weeks?
This is a descriptive safety question rather than a comparative question about whether the combination changes risk relative to another treatment. An adverse event was defined as an untoward medical occurrence after study drug exposure, without requiring a causal relationship to the drug. Seriousness was defined using specified outcomes and circumstances, including death, life-threatening events, inpatient hospitalization or its prolongation, persistent or significant disability or incapacity, congenital anomaly or birth defect, and suspected transmission of an infectious agent through a medicinal product.
The registry also lists percent change from baseline in HbA1c at Weeks 12 and 24 as a secondary outcome. Results for that outcome are not reported in the registry record. The posted primary safety results therefore address event occurrence, not the degree of glycemic change or a comparison with another care strategy.
3. Trial Design
The registry identifies this as a prospective, multicentric, open-label, single-arm, Phase 4 study. It lists the study status as completed, with a start date of 2020-11-25 and a primary completion date of 2022-07-26. The listed enrollment is 276. The study evaluated canagliflozin plus metformin hydrochloride immediate-release fixed-dose combination as an adjunct to diet and exercise in Indian adults with type 2 diabetes mellitus when treatment with both medicines was appropriate.
Participants received one of two listed tablet strengths: 50 mg + 500 mg or 50 mg + 1000 mg. The registry does not report how participants were assigned between these strengths, how dose selection was made, or how many participants received each strength. It records allocation as not applicable and describes one treatment group, rather than a randomized comparison. There is consequently no concurrent control group in the registry design against which to compare adverse events or changes in glycemic measures.
Open-label means the study was not masked. The registry does not report additional details about who knew the treatment assignment or whether outcome assessment involved independent review. The multicentric description indicates participation across multiple centers, but the number or locations of centers are not reported in the registry record.
The primary endpoint concerns treatment-emergent adverse events and serious adverse events from Baseline (Day 1) up to 24 weeks. The safety analysis set was defined as all participants who had taken at least 1 dose of study treatment. The registry lists percent change from baseline in HbA1c at Weeks 12 and 24 as a secondary outcome, but results for this measure are not reported in the registry record.
Further detail about the planned statistical design is not reported in the registry record. This includes the rationale for the listed enrollment, any prespecified interim analyses, and the statistical analysis plan. The study's single-arm design supports description of events observed among treated participants, but does not establish how those outcomes would compare with outcomes under another treatment or no study treatment.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Canagliflozin + Metformin Hydrochloride FDC |
|---|---|
| STARTED | 276 |
| Treated | 274 |
| COMPLETED | 265 |
| NOT COMPLETED | 11 |
Reasons for not completing this period:
| Reason | Canagliflozin + Metformin Hydrochloride FDC |
|---|---|
| Withdrawal by Subject | 2 |
| Adverse Event | 5 |
| Non-Compliance With Study Drug | 1 |
| Other | 1 |
| Started but not treated | 2 |
Analysis population for the primary outcome, as defined in the registry: Safety analysis set included all participants who had taken at least 1 dose of study treatment.
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: Safety analysis set included all participants who had taken at least 1 dose of study treatment.
| Characteristic | Unit | Canagliflozin + Metformin Hydrochloride FDC |
|---|---|---|
| Participants analysed | 274 | |
| Age, Continuous | years | 52.1 (SD 8.34) |
| Sex: Female, Male: Female | Participants | 106 |
| Sex: Female, Male: Male | Participants | 168 |
| Race/Ethnicity, Customized: Indian | Participants | 274 |
| Region of Enrollment: India | Participants | 274 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs), measured over Baseline (Day 1) up to 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with treatment-emergent adverse events and treatment-emergent serious adverse events from Baseline (Day 1) up to 24 weeks. A treatment-emergent event was defined as an event that started on or after the study medication start date and time. The endpoint separates events that meet the registry's seriousness criteria from adverse events that do not meet those criteria.
An adverse event was defined as an untoward medical occurrence in someone who received study drug, whether or not a causal relationship to the drug was considered possible. This definition is deliberately broader than a suspected drug reaction: an event can be counted even when its cause is uncertain or unrelated. Seriousness is based on specified consequences or circumstances, such as death, life-threatening events, inpatient hospitalization or its prolongation, persistent or significant disability or incapacity, congenital anomaly or birth defect, or suspected transmission of an infectious agent through a medicinal product.
Reporting the percentage of participants with events is useful for describing how commonly events occurred in the safety population during the stated observation period. Separating serious events from other events also distinguishes events meeting the defined seriousness criteria. These measures do not, by themselves, determine whether the study medication caused an event, how severe every non-serious event was, or whether event frequency differs from another treatment.
The registry's stated safety population includes participants who took at least 1 dose of study treatment. The primary outcome's event percentages are not reproduced in the registry entries, while the adverse-event record lists affected counts and selected serious-event terms. The registry also lists HbA1c change as a secondary outcome, but its results are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety record lists 3 participants affected by serious adverse events among 274 at risk in the canagliflozin plus metformin fixed-dose combination group. It lists 114 affected by other adverse events among 274 at risk, and 0 deaths. These are descriptions of events recorded in the treated group during the study's safety observation period; they are not comparative estimates because the study had no separate control group.
The registry lists urinary tract infection at 0.7%, COVID-19 at 0.4%, diabetic ketoacidosis at 0.4%, and prostatomegaly at 0.4% among the top serious-event terms. These values describe selected terms in the posted record. They should not be treated as an exhaustive list of all events, nor do the percentages establish that treatment caused the events. The registry definition of an adverse event explicitly does not require a causal relationship to study drug.
The primary endpoint is framed as a percentage of participants with treatment-emergent events, but the registry entries available for interpretation include the affected counts rather than an overall primary-endpoint percentage. No confidence interval, hypothesis test, or adjusted estimate for the safety endpoint is reported in the registry record. As a result, the precision of an overall event percentage cannot be assessed from these details, and no statistical comparison with another group is possible.
The study's open-label, single-arm design matters when interpreting any observed event frequency. Without a comparator, the record cannot show whether the event frequency was higher or lower than it would have been under another treatment or in a similar population not receiving this combination. Events may also reflect participants' underlying health, other exposures, or circumstances during follow-up; the registry event definition does not separate these possible causes.
The listed enrollment is 276, while the safety analysis set is defined by having taken at least 1 dose and the serious and other event figures list 274 at risk. These entries describe different registry fields or analysis details; the record does not explain their relationship. It is therefore not appropriate to infer reasons for the difference or to treat it as evidence of withdrawal or missing follow-up.
The registry lists percent change from baseline in HbA1c at Weeks 12 and 24 as a secondary outcome, but no result is reported in the registry record. The safety information consequently does not establish a change in glycemic control. The posted figures are best read as a description of reported safety events among treated participants, within the stated follow-up and definitions, rather than as evidence of a causal effect or comparative safety advantage.
9. Statistical Methods Explained
The primary outcome uses a proportion: the number of participants meeting an event definition in relation to the participants considered at risk in the safety analysis. In general, a proportion describes how often an outcome was observed in a defined group during a stated period. Here, the registry defines the safety analysis set as participants who took at least 1 dose of study treatment, and the primary timeframe as Baseline (Day 1) up to 24 weeks. The reported event counts should be interpreted in that context rather than as measures of incidence over an unspecified period.
What does treatment-emergent mean?
In general, a treatment-emergent definition uses timing to identify events that begin after treatment starts. It does not by itself establish causation. The registry defines treatment-emergent adverse events as events that started on or after the study medication start date and time. That timing rule helps distinguish newly starting events from events that began earlier, but it cannot determine whether a newly occurring event resulted from the medication.
The registry defines an adverse event broadly as an untoward medical occurrence in a participant who received study drug, regardless of the possibility of a causal relationship. This is a common safety-tracking approach: it collects events for review without requiring investigators to conclude at the outset that a medicine caused them. The event record is therefore a count of occurrences meeting the specified definition, not a list of confirmed drug reactions.
How is seriousness different from severity?
In general, seriousness and severity are different concepts. Seriousness is classified by defined outcomes or consequences, while severity describes the intensity of an event. The registry's serious-event definition includes death, a life-threatening event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, and suspected transmission of an infectious agent through a medicinal product. The registry entries do not report a severity grading scale for non-serious events. A non-serious event is not necessarily mild, and a serious event category should not be read as a complete description of symptom intensity.
The primary endpoint includes percentages of participants with treatment-emergent adverse events and treatment-emergent serious adverse events. A participant-level percentage is not interchangeable with a count of event episodes: a participant can potentially experience more than one event. The registry entries list affected counts, but do not explain whether repeated events of the same kind were handled in any particular way in the analysis. No episode-level event totals or detailed coding rules are reported in the registry record.
What can a confidence interval tell readers?
In general, a confidence interval expresses the uncertainty around an estimate under a specified statistical method. A narrower interval indicates greater precision under that method, while a wider interval indicates more uncertainty. An interval can also help readers judge which values remain compatible with the observed data. It does not remove possible bias, establish causation, or resolve limitations of the study design.
No confidence interval for the primary safety endpoint is reported in the registry record. Without such an interval or another measure of uncertainty, the precision of an overall event percentage cannot be evaluated from the registry entries. The available affected counts remain useful descriptively, but readers should not infer that a small or zero count proves an event is impossible or that the observed frequency is precisely estimated.
Why does a single-arm design constrain inference?
In general, a comparator provides a reference for interpreting an outcome. In a single-arm study, observed events occur in the treated group, but there is no concurrent group to show what would have occurred under a different treatment strategy during the same study conditions. Differences from an external expectation can reflect differences in population, event collection, follow-up, or other circumstances, as well as treatment. The registry records allocation as not applicable and the model as single group, so comparative treatment estimates are not available.
The open-label design means masking was absent. In general, knowledge of treatment can influence event reporting, care-seeking, or assessment, although the direction and extent of any such influence cannot be determined from the design label alone. The registry does not report whether outcome assessment was independently adjudicated or whether procedures were used to reduce reporting or assessment bias.
The record's sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not describe the single-arm study's own design or its observed safety analysis. A sample-size illustration is a planning exercise, not observed power and not evidence that the trial was designed to detect a particular safety difference. The registry does not report the study's own sample-size justification or statistical plan.
More generally, over-dispersion arises when variation in observed counts exceeds what a chosen statistical model expects. It can make standard errors too small and uncertainty look less than it is if a model fails to account for that extra variation. This is a general concept, not a method reported for this study. The registry entries do not identify a count model, an over-dispersion adjustment, or a regression analysis. No such method should be attributed to the study based on the available record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary safety endpoint and a secondary outcome of percent change from baseline in HbA1c at Weeks 12 and 24. Results for the HbA1c outcome are not reported in the registry record. The registry entries do not describe a hierarchy for testing endpoints, an adjustment for multiple comparisons, or how the analysis handled repeated measures across the listed weeks. Those procedures are not reported in the registry record, so no claim can be made that multiplicity was or was not controlled in a particular way.
Multiplicity is a general statistical concern when several outcomes, time points, or subgroup analyses are examined. Looking across many estimates can increase the chance that at least one appears unusual by chance. Prespecified testing rules or adjustments can address that concern, but the registry record does not provide enough information to identify any such rules for this study. The list of selected serious-event terms is descriptive and does not, on its own, indicate formal hypothesis testing.
The safety analysis population included participants who had taken at least 1 dose of study treatment. The registry also lists enrollment as 276 and the adverse-event records list 274 at risk. The registry entries do not explain how these entries relate, how missing safety information was handled, or whether all eligible participants had complete event follow-up through the stated timeframe.
In general, missing outcomes can affect an estimate if participants without recorded outcomes differ from those with recorded outcomes. The direction of any such effect depends on why information is missing and on the outcomes among those not observed. The registry record does not report a missing-data method, an imputation approach, or a sensitivity analysis for missing safety observations. It also does not report a separate analysis population for the HbA1c outcome. These omissions limit assessment of how analysis choices might affect reported results.
The record does not report interim analyses, a prespecified statistical analysis plan, or procedures for controlling multiplicity. These are not assumptions that can be filled in from a Phase 4 label or from the endpoint list.
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 |
|---|---|---|---|
| Canagliflozin + Metformin Hydrochloride FDC | 3 | 274 | 1.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Canagliflozin + Metformin Hydrochloride FDC | 0 of 274 |
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 |
|---|---|
| Canagliflozin + Metformin Hydrochloride FDC | 114 of 274 |
Most frequent serious adverse event terms
| Event term | Organ system | Canagliflozin + Metformin Hydrochloride FDC |
|---|---|---|
| Urinary Tract Infection | Infections and infestations | 2 of 274 |
| COVID-19 | Infections and infestations | 1 of 274 |
| Diabetic Ketoacidosis | Metabolism and nutrition disorders | 1 of 274 |
| Prostatomegaly | Reproductive system and breast disorders | 1 of 274 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Canagliflozin + Metformin Hydrochloride FDC |
|---|---|---|
| Pyrexia | General disorders | 13 of 274 |
| Dyslipidaemia | Metabolism and nutrition disorders | 13 of 274 |
| Genital Infection | Infections and infestations | 9 of 274 |
| Hypoglycaemia | Metabolism and nutrition disorders | 9 of 274 |
| Urinary Tract Infection | Infections and infestations | 7 of 274 |
| Asthenia | General disorders | 5 of 274 |
| COVID-19 | Infections and infestations | 5 of 274 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 5 of 274 |
| Pain in Extremity | Musculoskeletal and connective tissue disorders | 5 of 274 |
| Proteinuria | Renal and urinary disorders | 5 of 274 |
Serious events with the highest arm-level rate: urinary tract infection (0.7%), covid-19 (0.4%), diabetic ketoacidosis (0.4%), prostatomegaly (0.4%).
The safety record lists 3 participants affected by serious adverse events among 274 at risk, 114 affected by other adverse events among 274 at risk, and 0 deaths. These are registry counts for the canagliflozin plus metformin hydrochloride fixed-dose combination group. The registry entries do not give an overall percentage for either adverse-event category, so no percentage should be inferred by recalculating from the counts.
The selected serious-event terms are urinary tract infection at 0.7%, COVID-19 at 0.4%, diabetic ketoacidosis at 0.4%, and prostatomegaly at 0.4%. These are the terms and percentages listed in the record; they do not indicate that every serious event is represented by those terms or that events were caused by treatment. The registry's adverse-event definition includes events regardless of whether a causal relationship was considered possible.
Seriousness is based on specified outcomes and circumstances, not necessarily on symptom intensity. The record's count of other adverse events should not be read as meaning those events were all mild. Nor does a zero count for deaths establish that a risk is absent; it states that no deaths are listed in this record for the group and observation period. The single-arm design supplies no concurrent reference group for judging whether these counts differ from another treatment strategy.
12. What the Result Does, and Does Not, Mean
The posted results describe safety events recorded among participants receiving canagliflozin plus metformin hydrochloride immediate-release fixed-dose combination in this open-label, single-arm study. They include counts for serious and other adverse events, a death count, and selected serious-event terms with percentages. The information is specific to the registry's event definitions, safety population, and timeframe from Baseline (Day 1) up to 24 weeks.
These results do not establish that the combination caused any listed event. The registry defines adverse events without regard to the possibility of causal relationship, and there is no separate comparator group. The observed events may be associated with treatment, the underlying condition, other exposures, or other circumstances; the posted record cannot distinguish those explanations. Likewise, the absence of a recorded death does not prove that death or other serious events cannot occur.
The study also does not provide a randomized comparison of safety against another medicine, placebo, or usual care. The single-group design can describe events in the treated participants, but cannot isolate a treatment effect by comparing outcomes across study groups. The open-label design and unreported details about event assessment further constrain interpretation of the event record.
The record lists percent change from baseline in HbA1c at Weeks 12 and 24 as a secondary outcome, but results for it are not reported in the registry record. The safety figures therefore do not establish how glycemic control changed. They also do not answer whether one of the listed tablet strengths was associated with a different event pattern, because strength-specific group results are not reported.
In general, the most appropriate reading is descriptive: the record documents events observed in the study population according to its definitions. The reported figures do not provide a causal estimate, a comparison with other care, or a complete account of uncertainty around the overall safety percentages. The findings should be interpreted within the listed population and follow-up rather than generalized automatically to other settings or treatment conditions.
13. Why This Trial Matters Statistically
This study is statistically informative as a description of safety reporting for a fixed-dose combination in Indian adults with type 2 diabetes. A clearly defined safety population and an explicit observation period help readers understand which participants and events the endpoint is intended to cover. The distinction between serious and other adverse events also makes the outcome categories easier to interpret.
The record illustrates why design and endpoint must be considered together. A single-arm study can document events after treatment exposure, but it cannot directly estimate how event frequency compares with another treatment. Counts can be clinically relevant as descriptions of what was recorded, yet they do not answer a comparative question without a reference group. The adverse-event definition also allows events to be captured without presuming that treatment caused them, which is important for distinguishing surveillance from causal attribution.
The registry's selected serious-event terms and participant counts show how safety information can be presented in more than one form. Counts communicate the number of affected participants listed, while percentages attached to selected terms describe the listed terms as presented in the record. These summaries do not replace a fuller account of event definitions, timing, repeated events, and uncertainty. The absence of confidence intervals or a reported statistical analysis plan makes precision and analytic choices difficult to assess.
The registry also shows the importance of separating primary safety questions from secondary outcome questions. HbA1c change is listed as a secondary outcome at Weeks 12 and 24, but those results are not reported in the registry record. Safety findings should not be treated as evidence about that unreported glycemic outcome.
For statistical readers, the central lesson is that a completed study and a listed enrollment do not by themselves guarantee that every planned analysis or result is available. The design supports a bounded description of reported safety events, while missing comparative and analytic details limit what can be inferred beyond that description.
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 main limitation for interpretation is the single-arm design. With no concurrent comparator, the record cannot estimate a relative safety difference or distinguish treatment-associated events from events that would have occurred under another care strategy. The study is also open-label, and the registry does not report whether adverse events were independently adjudicated or how reporting was standardized across centers.
The primary endpoint is described as a percentage of participants with treatment-emergent adverse events and serious adverse events, but the overall percentages are not included in the registry entries. The registry provides affected counts and selected serious-event terms, but no confidence intervals or other uncertainty measures for the primary outcome are reported. The selected terms should not be assumed to represent every serious event.
The listed enrollment is 276, whereas the adverse-event group reports 274 at risk. The safety population is defined as participants who took at least 1 dose. The registry does not explain the relationship between these figures, so reasons for the difference cannot be inferred. Follow-up completeness, handling of missing safety observations, and any sensitivity analyses are not reported in the registry record.
Although two tablet strengths are listed, the registry entries do not report how participants received each strength or provide strength-specific safety results. The number and locations of participating centers are also not reported. The record lists HbA1c change at Weeks 12 and 24 as a secondary outcome, but does not report its results.
Finally, the registry does not report the study's sample-size justification, interim analyses, statistical analysis plan, or multiplicity procedures. The planning illustration assumptions associated with the posted material are not the study's own design parameters. These gaps limit evaluation of the intended inferential analyses and the precision of the reported safety findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Assess Safety of Canagliflozin and Metformin Hydrochloride Combination Given as a Supplement to Diet and Exercise to Improve Blood Sugar Level in Indian Adult Participants With Diabetes — NCT04288778.
- Registry record last updated 2025-03-30; status last verified 2025-03.
- Results first posted 2023-08-18.
- 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
The registry record identifies NCT04288778 as a completed, prospective, multicentric, open-label, single-arm, Phase 4 study sponsored by Johnson & Johnson Private Limited. It lists enrollment as 276, a start date of 2020-11-25, and a primary completion date of 2022-07-26. The study evaluated canagliflozin plus metformin hydrochloride immediate-release fixed-dose combination alongside diet and exercise in Indian adults with type 2 diabetes mellitus.
The primary outcome was the percentage of participants with treatment-emergent adverse events and serious adverse events from Baseline (Day 1) up to 24 weeks. The safety population included participants who had taken at least 1 dose of study treatment. The adverse-event record lists 3 affected by serious events and 114 affected by other events among 274 at risk, with 0 deaths. Selected serious-event terms and percentages are listed in the safety record.
Percent change from baseline in HbA1c at Weeks 12 and 24 is listed as a secondary outcome, but its results are not reported in the registry record. No concurrent comparator is described, and further details about the statistical plan, missing-data handling, and uncertainty estimates are not reported in the registry record.