Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Canagliflozin
JNJ 28431754 · 27 trials · 11 indications
Change from baseline in KCCQ-TSS was reported. KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ-TSS was average of domains- symptom frequency and symptom burden, and transformed to a single score which ranged from 0 (worst) to 100 (the best possible status), where the higher score reflected better health status.
Change from baseline in HbA1c at Week 26 was analyzed using a pattern mixture model with multiple imputation. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAE was defined as the AEs occurring after first administration of double blind study intervention up to 30 days post last dose of study intervention.
Primary composite endpoint is the composite of DoSC, ESKD, and renal or CV death. DoSC: from baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: as initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an estimated glomerular filtration rate (eGFR) value of less than (\<)15 milliliters per minute per 1.73 square meter (mL/min/1.73 m\^2) (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who had reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in blinded fashion. Event rate estimated based on time to first occurrence of primary composite endpoint are presented.
The change in the value of glycated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) from baseline at Week 26 was compared between the different treatment groups.
The table below shows the least-squares (LS) mean change in HbA1c from baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change.
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.
MACE, defined as a composite of CV death, non-fatal MI, and nonfatal stroke. Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of MACE are presented.
The percent change from baseline in body weight at Week 26 was analysed.
Clinical response at Weeks 18 was assessed by the percentage of participants with Hemoglobin A1c (HbA1c) reduction greater than or equal to 0.4 % and had no increase in body weight.
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
The table below shows the mean percent change in body weight from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the least-squares mean percent change.
The table below shows the mean change in HbA1c from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.
Plasma concentrations of canagliflozin are used to evaluate how long canagliflozin stays in the body.
Baseline is defined as up to 3 days predose (Week -1)
Treatment-related adverse events are adverse events with onset during the treatment phase.
Baseline is defined as up to 3 days predose (Week -1)
Baseline is defined as up to 3 days predose (Week -1)
Baseline is defined as up to 3 days predose (Week -1)
Baseline is defined as up to 3 days predose (Week -1)
Baseline is defined as up to 3 days predose (Week -1)
Baseline is defined as up to 3 days predose (Week -1)
Baseline is defined as up to 3 days predose (Week -1)
Baseline is defined as up to 3 days predose (Week -1)
| Arm | Type | Description |
|---|---|---|
| Canagliflozin 100 mg | EXPERIMENTAL | Participants will be administered 100 milligram (mg) immediate-release, over-encapsulated tablets (as a capsule) orally once daily for 12 weeks. |
| Placebo | PLACEBO_COMPARATOR | Participants will be administered matching placebo capsules orally once daily for 12 weeks. |
| Single-blind run-in Period: Placebo | EXPERIMENTAL | Participants will receive 1 placebo tablet matching canagliflozin 100 milligram (mg) once-daily during the 2-week single-blind placebo run-in period. |
| Double-blind Treatment Phase: Canagliflozin or Placebo | EXPERIMENTAL | Canagliflozin 100 mg/matching placebo once-daily during first 12 weeks. At Week 13, participants who have glycated hemoglobin (HbA1c) of greater than or equal to (\>=)7.0 percent (%), estimated glomerular filtration rate (eGFR) \>=60 milliliter/minute/1.73 meter square (mL/min/1.73 m\^2) will be re-randomized to either remain on canagliflozin 100 mg/matching placebo or up-titrate to canagliflozin 300 mg/matching placebo till Week 52. |
| Canagliflozin 300 mg | EXPERIMENTAL | Participants will receive one 300 mg canagliflozin capsule before the morning meal and one matching placebo capsule with the evening meal plus placebo tablets with the evening meal (to match the metformin XR tablets administered in other treatment arms) for 26 weeks. |
| Metformin XR | EXPERIMENTAL | Participants will receive metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal, plus one placebo capsule before the morning meal and one placebo capsule with the evening meal (to match the canagliflozin capsules administered in other treatment arms) for 26 weeks. |
| Canagliflozin 100 mg + Metformin XR | EXPERIMENTAL | Participants will receive one 100 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks. |
| Canagliflozin 300 mg + Metformin XR | EXPERIMENTAL | Participants will receive one 300 mg canagliflozin capsule with the evening meal and one matching placebo capsule before the morning meal plus metformin XR tablets (in doses titrated over 9 weeks) once daily with the evening meal for 26 weeks. |
| Canagliflozin 100mg | EXPERIMENTAL | Each participant will receive 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea. |
| Canagliflozin 300mg | EXPERIMENTAL | Each participant will receive 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea. |
| Sitagliptin 100 mg | ACTIVE_COMPARATOR | Each patient will receive 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea |
| Placebo/Sitagliptin | OTHER | Each patient will receive matching placebo once daily for 26 weeks with stable doses of metformin and pioglitazone. At Week 26, patients will be switched from placebo to 100 mg of sitagliptin once daily with stable doses of metformin and pioglitazone until Week 52. |
| Canagliflozin (JNJ-28431754) 100 mg | EXPERIMENTAL | Each patient will receive canagliflozin (JNJ-28431754) 100 mg once daily on background standard of care for diabetes once daily for the duration of the study |
| Canagliflozin (JNJ-28431754) 300 mg | EXPERIMENTAL | Each patient will receive canagliflozin (JNJ-28431754) 300 mg once daily on background standard of care for diabetes once daily for the duration of the study |
| Glimepiride | ACTIVE_COMPARATOR | Each patient will receive glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks. |
| Canagliflozin + Phentermine | EXPERIMENTAL | 300 mg capsule of Canagliflozin along with 15 mg capsule of Phentermine, taken once daily, orally for 26 weeks. |
| Canagliflozin + Placebo (Phentermine) | EXPERIMENTAL | 300 mg capsule of Canagliflozin along with matching placebo to Phentermine, taken once daily, orally for 26 weeks. |
| Phentermine + Placebo (Canagliflozin) | EXPERIMENTAL | 15 mg capsule of Phentermine along with matching placebo to Canagliflozin, taken once daily, orally for 26 weeks. |
| Canagliflozin 50 mg bid | EXPERIMENTAL | Each patient will receive 50 mg canagliflozin twice daily for 18 weeks. |
| Canagliflozin 150 mg bid | EXPERIMENTAL | Each patient will receive 150 mg canagliflozin twice daily for 18 weeks |
| Canagliflozin 50 mg | EXPERIMENTAL | Each patient will receive 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. |
| Canagliflozin 50 mg daily | EXPERIMENTAL | Each patient will receive 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). |
| Canagliflozin 100 mg daily | EXPERIMENTAL | Each patient will receive 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). |
| Canagliflozin 200 mg daily | EXPERIMENTAL | Each patient will receive 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). |
| Canagliflozin 300 mg daily | EXPERIMENTAL | Each patient will receive 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo capsule once daily (in the evening). |
| Canagliflozin 300 mg twice daily | EXPERIMENTAL | Each patient will receive 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks. |
| Sitagliptin 100 mg daily | ACTIVE_COMPARATOR | Each patient will receive 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). |
| Canagliflozin (JNJ-28431754) | EXPERIMENTAL | Each patient will receive canagliflozin 100 mg once daily during the first 4 weeks of the 25 weeks double-blind period, then the dose may be increased to 300 mg once daily, till the end of the period. |
| Canagliflozin (Dose Group 1) | EXPERIMENTAL | Participants will receive 100 mg (as 1 x 100-mg tablet) of canagliflozin daily for 14 days. |
| Canagliflozin (Dose Group 2) | EXPERIMENTAL | Participants will be enrolled into Dose Group 2 to receive either 50 mg (as 1 x 50-mg tablet) or 300 mg (as 1 x 300-mg tablet) of canagliflozin daily for 14 days. |
| Canagliflozin | EXPERIMENTAL | - |
| 001 | PLACEBO_COMPARATOR | Placebo Treatment A: Form=capsule route=oral administration. Capsule is taken once daily on Day 1 and Day 2 in 1 of 4 treatment periods. |
| 002 | EXPERIMENTAL | Canagliflozin 300mg/Placebo Treatment B: Type=1 unit=mg number=300 form=capsule route=oral use. Capsule is taken once on Day 1 in 1 of 4 treatment periods. Form=capsule route=oral administration. Capsule is taken once on Day 2 in 1 of 4 treatment periods. |
| 003 | EXPERIMENTAL | Canagliflozin 300mg Treatment C: Type=1 unit=mg number=300 form=capsule route=oral use. Capsule is taken once daily on Day 1 and Day 2 in 1 of 4 treatment periods. |
| 004 | EXPERIMENTAL | Canagliflozin 300mg/Canagliflozin 150mg Treatment D: Type=1 unit=mg number=300 form=capsule route=oral use. Capsule is taken once on Day 1 in 1 of 4 treatment periods. Type=1 unit=mg number=150 form=capsule route=oral use. Capsule is taken once on Day 2 in 1 of 4 treatment periods. |
| Part 1: no Intervention | NO_INTERVENTION | In Part 1 of the study, patients will not receive any study drug. |
| Part 2: canagliflozin | EXPERIMENTAL | In Part 2 of the study, patients will receive canagliflozin once daily on Days 1 through 8. |
| Cohort 1 | EXPERIMENTAL | JNJ-28431754 30 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts. |
| Cohort 2 | EXPERIMENTAL | JNJ-28431754 100 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts. |
| Cohort 3 | EXPERIMENTAL | JNJ-28431754 300 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts. |
| Cohort 4 | EXPERIMENTAL | JNJ-28431754 600 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts. |
| Cohort 5 | EXPERIMENTAL | JNJ-28431754 at 30 mg/day, 100 mg/day, or 300 mg/day or placebo (the dose level to be determined from the prior cohort of patients tested and considered to be well tolerated). |
| Name | Type | Description |
|---|---|---|
| Canagliflozin 100 mg | DRUG | Participants will receive 100 mg immediate-release, over-encapsulated tablets (as a capsule) orally once daily. |
| Placebo | DRUG | Participants will receive matching placebo capsules orally once daily. |
| Canagliflozin 300 mg | DRUG | Canagliflozin 300 mg tablet will be administered orally once-daily. |
| Canagliflozin | DRUG | One 100 mg over-encapsulated tablet orally once daily |
| Metformin XR | DRUG | One 500 mg tablet (Day 1 up to week 1); two 500 mg tablets (Week 1 up to Week 3); three 500 mg tablets (Week 3 to Week 6); four 500 mg tablets (Week 6 to Week 9). Tablets will be administered with the evening meal. |
| Canagliflozin 100mg | DRUG | Type=1, unit=mg, number=100, form=capsule, route=oral use. One capsule once daily for up to 18 weeks after completing a single-blind placebo run-in period (1 placebo capsule once daily for up to 2 weeks). |
| Canagliflozin 300mg | DRUG | Type=1, unit=mg, number=300, form=capsule, route=oral use. One capsule once daily for up to 18 weeks after completing a single-blind placebo run-in period (1 placebo capsule once daily for up to 2 weeks). |
| Metformin | DRUG | The participant's stable dose of background therapy of metformin should be continued throughout the study. |
| Sulphonylurea | DRUG | The participant's stable dose of background therapy of metformin plus sulphonylurea should be continued throughout the study. |
| Sitagliptin 100 mg | DRUG | One 100 mg capsule once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea |
| Antihyperglycemic agent(s) | DRUG | Stable doses of antihyperglycemic agents (sulfonylurea agent, thiazolidinediones, dipeptidyl peptidase 4 \[DPP-4\] inhibitors, metformin, insulin \[all types\]) and their combinations (sulfonylurea agent and insulin \[all types\], metformin and insulin \[all types\], metformin and sulfonylurea, alpha glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 \[DPP-4\]) are used as per protocol specifications. |
| Sitagliptin | DRUG | One 100 mg over-encapsulated tablet orally once daily beginning at Week 26 until Week 52 with stable doses of metformin and pioglitazone. |
| Pioglitazone | DRUG | The patient's stable dose of pioglitazone background therapy should be continued throughout the study. |
| Sulphonylruea | DRUG | The patient's stable dose of background sulphonylurea therapy should be continued throughout the study. |
| Metformin immediate release | DRUG | The patient's stable dose of metformin immediate release background therapy should be continued throughout the study. |
| Canagliflozin (JNJ-28431754) 100 mg | DRUG | One 100 mg capsule taken orally (by mouth) once daily |
| Canagliflozin (JNJ-28431754) 300 mg | DRUG | One 300 mg capsule taken orally (by mouth) once daily |
| Glimepiride | DRUG | Glimepiride will be given orally (by mouth), as over-encapsulated tablets, starting at a dose of 1mg once daily and increasing to a maximum of 6 mg or 8 mg once daily for 104 weeks. |
| Canagliflozin (JNJ-28431754) | DRUG | Canagliflozin (JNJ-28431754) will be given orally as over-encapsulated tablets, at a dose of 100 mg or 300 mg once daily for 104 weeks. |
| Phentermine | DRUG | 15 mg capsule, taken once daily, orally for 26 weeks. |
| Matching Placebo to Canagliflozin | DRUG | Placebo capsules look like canagliflozin but do not contain any active drug, taken once daily, orally for 26 weeks. |
| Matching Placebo to Phentermine | DRUG | Placebo capsules look like phentermine but do not contain any active drug, taken once daily, orally for 26 weeks. |
| Canagliflozin 50 mg | DRUG | One canagliflozin 50-mg capsule taken orally twice daily with a meal for 18 weeks |
| Canagliflozin 150 mg | DRUG | 1 canagliflozin 150-mg capsule taken orally twice daily with a meal for 18 weeks |
| Canagliflozin, 100 mg | DRUG | One 100 mg capsule taken orally (by mouth) once daily |
| Canagliflozin, 300 mg | DRUG | One 300 mg capsule taken orally (by mouth) once daily |
| Canagliflozin 300mg/Placebo | DRUG | Treatment B: Type=1, unit=mg, number=300, form=capsule, route=oral use. Capsule is taken once on Day 1 in 1 of 4 treatment periods. Form=capsule, route=oral administration. Capsule is taken once on Day 2 in 1 of 4 treatment periods. |
| Canagliflozin 300mg/Canagliflozin 150mg | DRUG | Treatment D: Type=1, unit=mg, number=300, form=capsule, route=oral use. Capsule is taken once on Day 1 in 1 of 4 treatment periods. Type=1, unit=mg, number=150, form=capsule, route=oral use. Capsule is taken once on Day 2 in 1 of 4 treatment periods. |
| JNJ 28431754 300 mg/placebo | DRUG | one 300-mg capsule of JNJ-28431754 or placebo twice-daily for 4 weeks |
| JNJ 28431754 100 mg/placebo | DRUG | one 100-mg capsule of JNJ-28431754 or placebo once-daily for 4 weeks |
| JNJ 28431754 | DRUG | A liquid suspension of 30 mg, 100 mg, 300 mg of JNJ-28431754 taken once (or twice) daily or 600 mg taken once daily will be administered by study personnel directly into the patient's mouth using an oral liquid dispenser for 14 days (Day 1 and Days 3 through 16). |
Inclusion Criteria: \- Have clinically stable symptomatic heart failure (HF) (heart failure with reduced ejection fraction \[HFrEF\] and heart failure with preserved ejection fraction \[HFpEF\]): (A) For HFrEF: (a) ejection fraction (EF) less than or equal to (\<=) 40 percent (%) and (b) a primary ...
JNJ 28431754 is an investigational small molecule developed by Johnson & Johnson for the treatment of type 2 diabetes mellitus. It has been studied in Phase 1 clinical trials evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with type 2 diabetes. It is not an approved therapy.
JNJ 28431754 is being studied for the treatment of type 2 diabetes mellitus. Its clinical program has focused on assessing safety, tolerability, pharmacokinetics, and pharmacodynamics in adult patients with the condition. The drug remains investigational and has not been established as a marketed treatment for type 2 diabetes.
JNJ 28431754 is developed by Johnson & Johnson, which trades on the New York Stock Exchange under the ticker JNJ. The company sponsored the Phase 1 studies conducted in patients with type 2 diabetes mellitus.
JNJ 28431754 is in Phase 1 development. Both of its recorded clinical trials are Phase 1 studies, and both have been completed. The drug is investigational and has not been approved by the FDA for any indication.
JNJ 28431754 has been evaluated in two completed Phase 1 trials: NCT01177163, which enrolled 29 patients with type 2 diabetes in the United States, and NCT00963768, which enrolled 116 patients across the United States, Germany, and South Korea. Both studies assessed safety, tolerability, pharmacokinetics, and pharmacodynamics.
Both Phase 1 trials of JNJ 28431754 were randomized, double-blind, and controlled studies in adults with type 2 diabetes mellitus. NCT01177163 enrolled 29 participants aged 18 years and older, while NCT00963768 enrolled 116 participants aged 25 years and older. Neither trial used biomarker-based patient selection.