127 Pharmacokinetic and pharmacodynamic profile of CTX-4430 in two phase 1 studies

Abstract

Objectives CTX-4430 is a new anti-inflammatory drug under development for treatment of CF. It is an inhibitor of Leukotriene A4 Hydrolase, the enzyme responsible for production of Leukotriene B4. Pharmacokinetics (PK) and pharmacodynamics (PD) of CTX-4430 have been studied in two phase 1 trials including a 14 day study in healthy volunteers (NCT01748838) and a 15 day study in CF patients (NCT01944735). Methods CTX-4430 was administered orally once daily as a capsule. Plasma PK was studied in 36 healthy volunteers at doses of 50, 100, 150 and 200 mg over 14 days and in 12 CF patients at doses of 50 and 100 mg over 15 days. Matched PK and PD samples were collected on days 1, 7 and 14 in healthy volunteers or days 1, 8 and 15 in CF patients. Blood PD was studied by measuring LTB4 in ex vivo ionophore-stimulated whole blood. A food effect substudy at doses of 50 and 100 mg was carried out as part of the healthy volunteer study. Results In both healthy volunteers and CF patients, CTX-4430 is rapidly absorbed after oral administration and is eliminated with a half-life consistent with once-daily dosing. PK and PD profiles are similar between CF patients and healthy volunteers. The 100 mg dose produced a near-maximal PD response in blood, while the 50 mg dose produced a moderate PD response. Consumption of a high fat meal prior to CTX-4430 administration delays drug absorption but does not substantially alter exposure. Conclusion These data support continued clinical development of once-daily oral CTX-4430 at a dose of 100 mg.