Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to assess safety of canagliflozin + metformin hydrochloride immediate Release (IR) fixed-dose combination.
Interventions
DRUGCanagliflozin + Metformin hydrochloride (Fixed Dose Combination)
Participants will receive canagliflozin + metformin hydrochloride IR fixed-dose combination, 50 milligram (mg) + 500 mg or 50 mg + 1000 mg, will be provided as tablets for oral administration. The study Treatment duration will be of 24 weeks.
Sponsors
Johnson & Johnson Private Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participant willing to adhere to diet and exercise regimen as recommended by the investigator * Type 2 diabetes mellitus (T2DM) with inadequate glycemic control on diet and exercise, who in investigator's opinion are eligible to receive study drug as per prescribing information along with standard care for management of T2DM * Women must be postmenopausal, defined as greater than (\>) 45 years of age with amenorrhea for at least 18 months, or \> 45 years of age with amenorrhea for at least 6 months and less than (\<) 18 months and a serum follicle stimulating hormone (FSH) level \> 40 International Units Per Liter (IU/L), or surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal occlusion), or otherwise be incapable of pregnancy, or sexually active and practicing a highly effective method of birth control, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, tubal ligation, intrauterine device, double-barrier method (example, condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization, and consistent with local regulations regarding use of birth control methods for participant participating in clinical studies, for the duration of their participation in the study, or not sexually active * Women of childbearing potential, regardless of age must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening and negative UPT at baseline (predose, Day 1) * Treatment naive participants or participants on stable antihyperglycemic agent (AHA) therapy (for at least 12 weeks before screening) and have a screening visit Glycosylated Haemoglobin (HbA1c) of greater than or equal to (\>=) 7.0 percent (%) and less than or equal to (\<=) 10.0 %
Exclusion criteria
* History of liver or renal insufficiency (estimated creatinine clearance below 45 milliliter per minute \[mL/min\]); significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances * Known allergies, hypersensitivity, or intolerance to Canagliflozin, Metformin or Canagliflozin + metformin hydrochloride immediate release (IR) Fixed Dose combination (FDC) or its excipients * Use of any other sodium glucose cotransporter 2 (SGLT2) inhibitor within 12 weeks before the screening visit * If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 30 days after last dose of study medication; or intending to donate ova during such time period * History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Baseline (Day 1) up to 24 weeks | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product. TEAEs were defined as events that started on or after the study medication start date and time. |
| Percentage of Participants With Unexpected Adverse Events (AEs) | Baseline (Day 1) up to 24 weeks | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An adverse event was considered unexpected if the nature or severity was not consistent with the applicable product reference safety information. |
| Percentage of Participants With Adverse Drug Reactions (ADRs) | Baseline (Day 1) up to 24 weeks | ADRs were defined as the treatment related TEAEs. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAEs were defined as events that started on or after the study medication start date and time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 | Baseline, Weeks 12 and 24 | Percent change from baseline in HbA1c at Weeks 12 and 24 was reported. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Canagliflozin + Metformin Hydrochloride FDC Participants received either (canagliflozin 50 milligram \[mg\] + metformin hydrochloride 500 mg) or (canagliflozin 50 mg + metformin hydrochloride 1000 mg) immediate release (IR) fixed-dose combination (FDC) tablets twice daily (BD) up to Week 24. | 274 |
| Total | 274 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Non-Compliance With Study Drug | 1 |
| Overall Study | Other | 1 |
| Overall Study | Started but not treated | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Canagliflozin + Metformin Hydrochloride FDC |
|---|---|
| Age, Continuous | 52.1 years STANDARD_DEVIATION 8.34 |
| Race/Ethnicity, Customized Indian | 274 Participants |
| Region of Enrollment India | 274 Participants |
| Sex: Female, Male Female | 106 Participants |
| Sex: Female, Male Male | 168 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 274 |
| other Total, other adverse events | 114 / 274 |
| serious Total, serious adverse events | 3 / 274 |
Outcome results
Primary
Percentage of Participants With Adverse Drug Reactions (ADRs)
ADRs were defined as the treatment related TEAEs. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAEs were defined as events that started on or after the study medication start date and time.
Time frame: Baseline (Day 1) up to 24 weeks
Population: Safety analysis set included all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canagliflozin + Metformin Hydrochloride FDC | Percentage of Participants With Adverse Drug Reactions (ADRs) | 10.6 Percentage of participants |
Primary
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product. TEAEs were defined as events that started on or after the study medication start date and time.
Time frame: Baseline (Day 1) up to 24 weeks
Population: Safety analysis set included all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canagliflozin + Metformin Hydrochloride FDC | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 41.6 Percentage of participants |
| Canagliflozin + Metformin Hydrochloride FDC | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 1.1 Percentage of participants |
Primary
Percentage of Participants With Unexpected Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An adverse event was considered unexpected if the nature or severity was not consistent with the applicable product reference safety information.
Time frame: Baseline (Day 1) up to 24 weeks
Population: Safety analysis set included all participants who had taken at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canagliflozin + Metformin Hydrochloride FDC | Percentage of Participants With Unexpected Adverse Events (AEs) | 0 Percentage of participants |
Secondary
Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24
Percent change from baseline in HbA1c at Weeks 12 and 24 was reported.
Time frame: Baseline, Weeks 12 and 24
Population: Efficacy analysis set included all participants who had taken at least 1 dose of study treatment and had both baseline and at least 1 post-baseline efficacy assessment. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure and 'n' (number analyzed) represents number of participants evaluable at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canagliflozin + Metformin Hydrochloride FDC | Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 | Percent change at Week 12 | -0.918 Percent change | Standard Deviation 1.1348 |
| Canagliflozin + Metformin Hydrochloride FDC | Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 | Percent change at Week 24 | -0.926 Percent change | Standard Deviation 1.3054 |