The results from Study D1001054 on healthy subjects showed that food had a significant effect on lurasidone levels compared with the fasted state. The results from D1050294 showed that medium fat meal resulted in smaller increase in levels compared to a high fat/high calorie meal. The PSC noted the lack of absolute bioavailability and the lack of a justification for not providing such a study. The sponsor had been asked for a justification but this was unavailable for the meeting. The absence of an absolute bioavailability study may be permissible, as long as this was supported by sound justification. The sponsor has not provided such a justification at the present time. It appears that 14C-labelled oral doses have been administered. Although from the information presented in the summaries presented to the PSC it is impossible to tell if they might provide some measure of bioavailability. Population pharmacokinetics The PSC advised that detailed population PK analysis showed liner PK. Non linearity in the different dosing might be due to the different point estimate and the limited number of subjects. PSC discussion There might be an issue with one of the proposed packaging (Al/Al). Product Information (PI) The PSC advised that the food effect demonstrated should be included in the PI. PSC recommendation The PSC resolved to recommend to the Advisory Committee on Prescription Medicines (ACPM) and the TGA that: The PSC endorsed all the questions raised by the TGA in relation to the quality and biopharmaceutic aspects of the submission by Commercial Eyes Pty Ltd to register Latuda film coated tablets containing 20 mg, 40 mg and 80 mg of lurasidone (as hydrochloride). The PSC advised that all outstanding issues should be addressed to the satisfaction of the TGA. There is no requirement for this submission to be reviewed again by the PSC before it is presented for consideration by the ACPM. Quality summary and conclusions There are no objections in respect of Chemistry, Manufacturing, Controls and Biopharmaceutics to registration of these products.
The results from Study D1001054 on healthy subjects showed that food had a significant effect on lurasidone levels compared with the fasted state. The results from D1050294 showed that medium fat meal resulted in smaller increase in levels compared to a high fat/high calorie meal. The PSC noted the lack of absolute bioavailability and the lack of a justification for not providing such a study. The sponsor had been asked for a justification but this was unavailable for the meeting. The absence of an absolute bioavailability study may be permissible, as long as this was supported by sound justification. The sponsor has not provided such a justification at the present time. It appears that 14C-labelled oral doses have been administered. Although from the information presented in the summaries presented to the PSC it is impossible to tell if they might provide some measure of bioavailability. Population pharmacokinetics The PSC advised that detailed population PK analysis showed liner PK. Non linearity in the different dosing might be due to the different point estimate and the limited number of subjects. PSC discussion There might be an issue with one of the proposed packaging (Al/Al). Product Information (PI) The PSC advised that the food effect demonstrated should be included in the PI. PSC recommendation The PSC resolved to recommend to the Advisory Committee on Prescription Medicines (ACPM) and the TGA that: The PSC endorsed all the questions raised by the TGA in relation to the quality and biopharmaceutic aspects of the submission by Commercial Eyes Pty Ltd to register Latuda film coated tablets containing 20 mg, 40 mg and 80 mg of lurasidone (as hydrochloride). The PSC advised that all outstanding issues should be addressed to the satisfaction of the TGA. There is no requirement for this submission to be reviewed again by the PSC before it is presented for consideration by the ACPM. Quality summary and conclusions There are no objections in respect of Chemistry, Manufacturing, Controls and Biopharmaceutics to registration of these products.
auspar-lurasidone-hydrochloride-140620.docx