In an early stage clinical trial in

In an early stage clinical trial in patients (Study3144A1-200WW) ，ninety two (92) subjects with PK collected had evaluable Cmin at steadystate (day 1 month 2) after 240 mg daily administration of neratinib.The diarrhea was reversible and managed with non-ma ndatory co­ medications including loperamide during the studγ. On day 1 month 2 among the 92 patients，30 patients were still with or during episode of anγgrade diarrhea and 62 patients had no symptom of diarrhea or had been recovered from prior diarrhea .The exposure (Cmin) comparison between patients with or without diarrhea at day 1month 2 indicated no apparent difference of Cmin for neratinib at steady state (Figure 4). This analysis could not rule out the confounding effects of anti-diarrhea co-medications and/or dehydrations from diarrhea on PK of neratinib. However，since most patients experienced diarrhea had taken anti-diarrheal medications during the trial the effect of prophylactic use of loperamide is considered to be similar and expected to have no clinically meaningful effect on the neratinib exposure.