RATIONALE FOR DOSE SELECTION Sample Clauses

RATIONALE FOR DOSE SELECTION. 5.2.1 Initial dose (see Appendix A) 5.2.2 Subsequent doses (see Appendices A and B)‌ Due to the expected target-mediated drug disposition (TMDD) effect and to the high inter-individual variability of IFNγ concentrations in HLH patients, doses subsequent to the initial one can be increased to 3 mg/kg, if required, based on clinical and laboratory criteria (see Table 4). After a minimum of two infusions at 3 mg/kg, if upon re-assessmen, the same clinical and laboratory criteria are found to still apply, the dose of NI-0501 may be increased to 6 mg/kg for up to four infusions, with a regular monitoring of the clinical and laboratory HLH parameters. If clinical and laboratory response criteria are no longer applicable, the dose of NI-0501 will be decreased back to 3 mg/kg, On the other hand, if criteria still apply, based on careful benefit/risk assessment, the Investigator may propose either i) to continue treatment at 6 mg/kg for additional infusions or ii) to increase NI-0501 dose above 6 mg/kg if PK and PD evidence indicates extremely high IFNγ levels and, consequently, fast NI-0501 elimination.

RATIONALE FOR DOSE SELECTION. The dose levels selected for the study described herein are: • Cohort 1: 750 mg AT-752/placebo 3 times a day (TID) for 5 days • Cohort 2: up to 1000 mg AT-752/placebo twice a day (BID) or TID for 5 days • Cohort 3: up to 1500 mg AT-752/placebo BID for 5 days Based on the PK results of the AT-02A-001 study (see Section 1.2.1), the AT-752 starting dose of 750 mg TID (2250 mg total daily dose) is anticipated to demonstrate antiviral activity in dengue patients. This dose rapidly achieved and maintained plasma AT-273 troughs above the target 200 ng/mL (in vitro EC90 of AT-281 against DENV-2 is 0.64 μM or approximately CCI