Table 2.
Dose–response relationship for mean 24-h intragastric pH >4 and >5 holding time ratio [HTR (%)] during the 24-h dosing interval and during the night-time period in healthy male subjects who received TAK-438 10–40 mg once daily at a fixed dose level for 7 consecutive days in Japanese and UK studies (Pharmacodynamic analysis set: Japan N = 60; UK N = 48)
| TAK-438 |
||||||
|---|---|---|---|---|---|---|
| Placebo | 10 mg | 15 mg | 20 mg | 30 mg | 40 mg | |
| Japanese study | ||||||
| n | 15 | 9 | 9 | 9 | 9 | 9 |
| 24-h pH >4 HTR (%) | ||||||
| Day 1 | 8.3 ± 4.0 | 38.4 ± 22.3 | 55.4 ± 13.2 | 63.3 ± 17.9 | 80.8 ± 14.0 | 85.3 ± 8.3 |
| Day 7 | 5.6 ± 3.5 | 63.3 ± 8.7 | 68.5 ± 16.1 | 83.4 ± 16.7 | 95.2 ± 10.1 | 100.0 ± 0.0 |
| 24-h pH >5 HTR (%) | ||||||
| Day 1 | 3.7 ± 2.4 | 25.1 ± 19.0 | 40.3 ± 16.8 | 53.5 ± 21.5 | 73.1 ± 16.1 | 78.3 ± 10.6 |
| Day 7 | 1.5 ± 1.5 | 52.6 ± 10.7 | 60.2 ± 16.8 | 73.2 ± 18.9 | 92.0 ± 12.5 | 98.6 ± 2.0 |
| Night-time pH >4 HTR (12–24 h post-dose) (%) | ||||||
| Day 1 | 3.0 ± 3.8 | 32.4 ± 18.7 | 50.5 ± 18.6 | 61.1 ± 29.3 | 78.1 ± 24.8 | 86.5 ± 15.5 |
| Day 7 | 2.0 ± 2.4 | 39.0 ± 13.1 | 48.8 ± 22.2 | 73.0 ± 26.5 | 90.4 ± 20.1 | 100 ± 0.1 |
| Night-time pH >5 HTR (12–24 h post-dose) (%) | ||||||
| Day 1 | 1.0 ± 1.6 | 18.6 ± 14.3 | 30.4 ± 19.2 | 47.9 ± 31.8 | 64.5 ± 29.3 | 73.6 ± 19.6 |
| Day 7 | 0.3 ± 0.6 | 27.1 ± 12.9 | 37.2 ± 19.4 | 55.9 ± 27.5 | 84.5 ± 24.2 | 97.2 ± 4.0 |
| UK study | ||||||
| n | 12 | 9 | 9 | 9 | 9 | |
| 24-h pH >4 HTR (%) | ||||||
| Day 1 | 6.2 ± 3.2 | 43.1 ± 21.2 | 62.7 ± 16.8 | 76.8 ± 9.9 | 85.6 ± 7.4 | |
| Day 4 | 10.5 ± 10.6 | 58.9 ± 20.9 | 82.9 ± 14.7 | 90.2 ± 9.2 | 94.0 ± 9.1 | |
| Day 7 | 6.5 ± 4.5 | 60.2 ± 19.1 | 85.2 ± 12.3 | 90.1 ± 7.9 | 93.2 ± 10.5 | |
| 24-h pH >5 HTR (%) | ||||||
| Day 1 | 2.6 ± 2.0 | 31.5 ± 20.8 | 49.2 ± 19.9 | 64.8 ± 15.4 | 73.1 ± 11.0 | |
| Day 4 | 6.7 ± 10.6 | 43.4 ± 18.5 | 75.3 ± 19.3 | 81.5 ± 11.6 | 88.6 ± 11.9 | |
| Day 7 | 3.2 ± 3.2 | 49.5 ± 15.8 | 78.6 ± 14.0 | 79.9 ± 13.7 | 85.0 ± 21.7 | |
| Night-time pH >4 HTR (20:00–08:00 hours) (%) | ||||||
| Day 1 | 2.1 ± 2.1 | 36.3 ± 21.2 | 57.3 ± 23.2 | 74.4 ± 17.3 | 87.7 ± 11.4 | |
| Day 4 | 2.8 ± 3.9 | 37.5 ± 19.2 | 73.8 ± 22.4 | 81.2 ± 18.2 | 91.0 ± 14.5 | |
| Day 7 | 4.8 ± 5.3 | 36.9 ± 16.4 | 75.4 ± 20.6 | 81.3 ± 15.2 | 90.4 ± 14.8 | |
| Night-time pH >5 HTR (20:00–08:00 hours) (%) | ||||||
| Day 1 | 1.1 ± 1.3 | 24.2 ± 20.8 | 37.8 ± 27.4 | 55.2 ± 24.5 | 65.6 ± 18.3 | |
| Day 4 | 1.0 ± 2.0 | 17.9 ± 10.8 | 61.6 ± 29.3 | 68.4 ± 21.2 | 84.1 ± 18.2 | |
| Day 7 | 2.2 ± 3.4 | 22.8 ± 10.9 | 66.9 ± 22.2 | 65.9 ± 26.5 | 77.5 ± 32.5 | |
All data are represented as mean ± s.d. HTR, holding time ratio; s.d., standard deviation.