Moboxen 40mg (Mobocertinib )

Description

COMPOSITION
Moboxen capsule: Each capsule contains Mobocertinib
Succinate INN equivalent to Mobocertinib 40 mg.
PHARMACOLOGY
Mechanism of Action
Mobocertinib is a kinase inhibitor of the epidermal growth
factor receptor (EGFR) that irreversibly binds to and inhibits
EGFR exon 20 insertion mutations at lower concentrations
than wild type (WT) EGFR. Two pharmacologically-active
metabolites (AP32960 and AP32914) with similar inhibitory
profiles to Mobocertinib have been identified in the plasma
after oral administration of Mobocertinib. In vitro, Mobocerti-
nib also inhibited the activity of other EGFR family members
(HER2 and HER4) and one additional kinase (BLK) at
clinically relevant concentrations (IC50 values <2 nM).
Pharmacokinetic properties
After single and multiple-dose administration, combined
molar C max and AUC 0-24h of Mobocertinib and its active
metabolites, AP32960 and AP32914, was dose-proportional
over the dose range of 5 to 180 mg once daily (0.03 to 1.1
times the approved recommended dosage). No clinically
meaningful accumulation was observed after administration
of Mobocertinib 160 mg once daily based on the AUC ratio
of Mobocertinib.
Absorption
The median (min, max) time to peak concentration (Tmax) of
Mobocertinib is 4 hours (1, 8 hours). The mean (%CV)
absolute bioavailability is 37% (50%).
Effect of food
No clinically meaningful differences in the combined molar
AUC and C max of Mobocertinib, AP32960, and AP32914
were observed following administration of a high-fat meal
(approximately 900 to 1000 calories, with 150 calories from
protein, 250 calories from carbohydrate and 500 to 600
calories from fat) or a low fat-meal (approximately 336
calories, with 37 calories from protein, 253 calories from
carbohydrate, and 46 calories from fat) compared to
administration after an overnight fast.
Distribution
Mobocertinib was bound to human plasma proteins in a
concentration independent manner in vitro from 0.5 to 5.0 μ
M. The mean (standard deviation) bound fraction was
99.3% (0.11%) for Mobocertinib, 99.5% (0.16%) for
AP32960 and 98.6% (0.36%) for AP32914 in vitro.
Elimination
The mean (%CV) plasma elimination half-life of Mobocerti-
nib was 18 hours (21%) at steady-state. The mean apparent
oral clearance (CL/F) (%CV) of Mobocertinib was 138 L/hr
(47%) at steady-state. The mean (%CV) plasma elimination
half-life of AP32960 was 24 hours (20%) at steady-state.
The mean apparent oral clearance (CL/F) (%CV) of
AP32960 was 149 L/hr (36%) at steady-state. The mean
(%CV) plasma elimination half-life of AP32914 was 18 hours
(21%) at steady-state. The mean apparent oral clearance
(CL/F) (%CV) of AP32914 was 159 L/hr (52%) at
steady-state.