Table 4. Efficacy data of canagliflozin in phase III clinical trials.
| Trial registration number/study type | Design, duration (duration to primary end point/duration of extension phase) | Intervention | No. subjects per treatment arm (ITT) | Primary end point | Baseline HbA1c (%), mean±s.d. | Change in HbA1c from baseline (%), LS mean (SE) |
|---|---|---|---|---|---|---|
| Monotherapya | ||||||
| NCT01081834,50,51 main studyb monotherapy (90 centres) | PC, PG 52 wks (26 wks/26 wks) | Placebo | 192 | Δ BL to wk 26 in HbA1c | 7.97±0.955 | 0.14±0.065 |
| Canagliflozin 100mg | 195 | 8.06±0.959 | −0.77±0.065 | |||
| Canagliflozin 300mg | 197 | 8.01±0.988 | −1.03±0.064 | |||
| 52 wks extension period | Canagliflozin 100mg | 191 | Δ BL to wk 52 in HbA1c | 8.06±0.959 | −0.75±0.067 | |
| Canagliflozin 300mg | 194 | 8.01±0.988 | −1.04±0.067 | |||
| High glycaemic substudy monotherapy (40 centres) | PG 26 wks (26 wks/no extension) | Canagliflozin 100mg | 47 | Δ BL to wk 26 in HbA1c | 10.59±0.873 | −2.13±0.220 |
| Canagliflozin 300mg | 44 | 10.62±0.955 | −2.56±0.227 | |||
| Add-on to AHA monotherapya | ||||||
| NCT01106677b,52 add-on to metformin monotherapy (169 centres) | PC, AC, PG 52 wks (26 wks/26 wks) | Placebo | 183 | Δ BL to wk 26 in HbA1c | 7.96±0.896 | −0.17±0.060 |
| Canagliflozin 100mg | 368 | 7.94±0.879 | −0.79±0.044 | |||
| Canagliflozin 300mg | 367 | 7.95±0.931 | −0.94±0.044 | |||
| Sitagliptin 100mg | 366 | 7.92±0.875 | −0.82±0.044 | |||
| 52-wks extension period | Canagliflozin 100mg | 365 | Δ BL to wk 52 in HbA1c | 7.94±0.879 | −0.73±0.047 | |
| Canagliflozin 300mg | 360 | 7.95±0.931 | −0.88±0.047 | |||
| Sitagliptin 100mg | 354 | 7.92±0.875 | −0.73±0.047 | |||
| NCT00968812,30 add-on to metformin monotherapy (157 centres) | AC, PG 104 wks (52 wks/52 wks) | Canagliflozin 100mg | 483 | Δ BL to wk 52 in HbA1c | 7.78±0.787 | −0.82±0.039 |
| Canagliflozin 300mg | 485 | 7.79±0.779 | −0.93±0.039 | |||
| Glimepiride (titrated from 1–6 or 8mg) | 482 | 7.83±0.795 | −0.81±0.039 | |||
| Add-on to dual-combination AHA therapya | ||||||
| NCT01106625, add-on to metformin+sulphonylurea (85 centres) | PC, PG 52 (26 wks/26 wks) | Placebo | 156 | Δ BL to wk 26 in HbA1c | 8.12±0.896 | −0.13±0.075 |
| Canagliflozin 100mg | 157 | 8.13±0.926 | −0.85±0.075 | |||
| Canagliflozin 300mg | 156 | 8.13±0.942 | −1.06±0.076 | |||
| 52-wks extension period | Placebo | 150 | Δ BL to wk 52 in HbA1c | 8.12±0.896 | −0.01±0.077 | |
| Canagliflozin 100mg | 155 | 8.13±0.926 | −0.74±0.077 | |||
| Canagliflozin 300mg | 152 | 8.13±0.942 | −0.97±0.078 | |||
| NCT01106690,b add-on to metformin+pioglitazone (74 centres) | PC, PG 52 wks (26 wks/26 wks) | Placebo | 115 | Δ BL to wk 26 in HbA1c | 8.00±1.010 | −0.26±0.069 |
| Canagliflozin 100mg | 113 | 7.99±0.940 | −0.89±0.069 | |||
| Canagliflozin 300mg | 114 | 7.84±0.911 | −1.03±0.070 | |||
| NCT01137812,53 add-on to metformin+sulphonylurea (140 centres) | AC, PG 52 wks (52 wks/no extension) | Canagliflozin 300mg | 377 | Δ BL to wk 52 in HbA1c | 8.12±0.910 | −1.03±0.048 |
| Sitagliptin 100mg | 378 | 8.13±0.916 | −0.66±0.049 | |||
| Special population studiesa | ||||||
| NCT01106651,29 older adults (⩾55 to ⩽80 years of age) (90 centres) | PC, PG104 wks (26 wks/78 wks) | Placebo | 237 | Δ BL to wk 26 in HbA1c | 7.76±0.785 | −0.03±0.063 |
| Canagliflozin 100mg | 241 | 7.77±0.773 | −0.60±0.063 | |||
| Canagliflozin 300mg | 236 | 7.69±0.779 | −0.73±0.064 | |||
| NCT01064414,24 moderate renal impairment (eGFR ⩾30 to <50 ml–1 min–1 per 1.73 m2) (89 centres) | PC, PG 52 wks (26 wks/26 wks) | Placebo | 90 | Δ BL to wk 26 in HbA1c | 8.02±0.917 | −0.03±0.090 |
| Canagliflozin 100mg | 90 | 7.89±0.898 | −0.33±0.090 | |||
| Canagliflozin 300mg | 89 | 7.97±0.805 | −0.44±0.089 | |||
| 52-wks extension | Placebo | 87 | Δ BL to wk 52 in HbA1c | 8.02±0.917 | −0.07±0.104 | |
| Period | Canagliflozin 100mg | 89 | 7.88±0.886 | −0.19±0.104 | ||
| Canagliflozin 300mg | 89 | 7.97±0.805 | −0.33±0.103 | |||
| Cardiovascular assessment study with efficacy substudiesa | ||||||
| NCT01032629, cardiovascular study (369 centres) | PC, PG duration is event driven based on number of MACE events | Placebo | 1441c | Assessment of hazard ratio for MACE events | ||
| Canagliflozin 100mg | 1445c | |||||
| Canagliflozin 300mg | 1441c | |||||
| Insulin substudy (316 centres) | PC, PG 18 wks (18 wks/no extension) | Placebo | 565 | Δ BL to wk 18 in HbA1c | 8.20±0.837 | 0.01±0.032 |
| Canagliflozin 100 mg | 566 | 8.33±0.905 | −0.63±0.031 | |||
| Canagliflozin 300 mg | 587 | 8.27±0.894 | −0.72±0.030 | |||
| Sulphonylurea substudy (80 centres) | PC, PG 18 wks (18 wks/no extension) | Placebo | 45 | Δ BL to wk 18 in HbA1c | 8.49±1.130 | 0.04±0.146 |
| Canagliflozin 100mg | 42 | 8.29±0.831 | −0.70±0.145 | |||
| Canagliflozin 300 mg | 40 | 8.28±1.005 | −0.79±0.147 | |||
Abbreviations: Δ, change from; AC, active-controlled; AHA, anti-hyperglycaemic agent; BL, baseline; eGFR, estimated glomerular filtration rate; ITT, intent-to-treat population; LS, least-squares; MACE, major adverse cardiovascular events; No., number; PC, placebo-controlled; PG, parallel group; QD, once daily; SU, sulphonylurea; wk(s), week(s).
Source of information: European Public Assessment Report (EPAR) of canagliflozin26 if not otherwise indicated.
a
Double-blind and randomized.
b
Subjects assigned to placebo were switched to sitagliptin during the double-blind extension period.
c
Randomized and treated subjects (that is, safety analysis set).