TABLE 3.
Simulation results (10,000 simulations) for TSF30 and TSFC10 in the classical tyramine challenge escalating to 800 mg of tyramine (n = 12 per treatment), and TSFC10 in the new design at different sample sizes per treatment, applied to placebo treatment (TSF = 1) and active treatments (TSF 2 and 4).
| Criterion | Classical design (n = 12) | New design (C max ≥ 10 ng/mL) | |||
|---|---|---|---|---|---|
| CFB BPP ≥30 mm Hg | C max ≥ 10 ng/mL | n = 12 | n = 16 | n = 20 | |
| Estimated TSF for placebo (TSF = 1) | 0.61 | 1.01 | 1.02 | 1.01 | 1.01 |
| Estimated TSF for selegiline (TSF = 2) | 1.88 | 1.97 | 1.98 | 1.98 | 1.97 |
| Estimated TSF for test 4 (TSF = 4) | 3.45 | 3.94 | 3.97 | 3.95 | 3.96 |
| 95% CIs including 1 for placebo (TSF = 1) (%) | 87 | 95 | 92 | 94 | 94 |
| 95% CIs including 2 for placebo (TSF = 1) (%) | 83 | 0.44 | 7.0 | 2.5 | 0.9 |
| 95% CIs including 2 for selegiline (TSF = 2) (%) | 92 | 95 | 93 | 94 | 94 |
| 95% CIs including 1 for selegiline (TSF = 2) (%) | 51 | 2.2 | 8.2 | 3.0 | 0.9 |
| 95% CIs including 2 for test 4 (TSF = 4) (%) | 58 | 2.1 | 8.0 | 2.9 | 0.9 |
| Mean number of doses in Period 3 | 3.5–5.4 | 2.7–4.7 | 3.0–4.4 | ||
Note: For the estimated TSFs, geometric means are presented, as well as proportions of 95% confidence intervals including 1 or including 2 for placebo and active treatments. For the simulated designs, mean number of doses per treatment in Period 3 are presented. All simulations assumed that 13% of the subjects receiving 12.5 mg of tyramine in Period 3 meet the CFB SBP stopping criterion.
Abbreviations: CFB SBP, change in systolic blood pressure from baseline; CI, confidence interval; C max, tyramine peak plasma concentration; gmean, geometric mean; TSF, tyramine sensitivity factor; TSF30, tyramine sensitivity factor, defined as the ratio of TYR30 at baseline (Period 1) over TYR30 during treatment (Period 3); TSFCx, tyramine sensitivity factor, defined as the ratio of TYRCx at baseline (Period 1) over TYRCx during treatment (Period 3).