Evaluation of food effect on the oral bioavailability of pradigastat, a diacylglycerol acyltransferase 1 inhibitor.

Pradigastat, a diacylglycerol acyltransferase 1 inhibitor, is being developed for the treatment of familial chylomicronemia syndrome. The results of two studies that evaluated the effect of food on the oral bioavailability of pradigastat using randomized, open-label, parallel group designs in healthy subjects (n=24/treatment/study) are presented. In study 1, a single dose of 20 mg pradigastat was administered under the fasted condition or with a high-fat meal. In study 2, a single dose of 40 mg pradigastat was administered under the fasted condition or with a low- or high-fat meal. At the 20 mg dose, the pradigastat Cmax and AUClast increased by 38% and 41%, respectively, with a high-fat meal. When 40 mg pradigastat was administered with a low-fat meal, the Cmax and AUClast increased by 8% and 18%, respectively, whereas with a high-fat meal the increase was 20% and 18%, respectively. The population pharmacokinetic analysis with the pooled data from 13 studies indicated that administration of pradigastat with a meal resulted in an increase of 30% in both the Cmax and AUC parameters. Based on these results, food overall increased pradigastat exposure in the range of less than 40%, which is not considered clinically significant. Both 20 and 40 mg doses of pradigastat were well tolerated under fasted or fed conditions.

Bioequivalence of canakinumab liquid pre-filled syringe and reconstituted lyophilized formulations following 150 mg subcutaneous administration: a randomized study in healthy subjects.

BACKGROUND: Canakinumab is a human anti-interleukin-1beta antibody approved for the treatment of cryopyrin associated periodic syndrome currently formulated as a lyophilized powder requiring reconstitution. A new formulation (solution for injection as pre-filled syringe) has been developed to avoid reconstitution. OBJECTIVE: The objective of this study was to evaluate the bioequivalence of pre-filled syringe and reconstituted formulations following 150 mg administration in healthy subjects. METHODS: This was an open-labeled, randomized, single dose, parallel-group study in 130 healthy subjects, followed for 120 days. Subjects received a single subcutaneous injection of 150 mg canakinumab after either reconstitution or in pre-filled syringe formulation, followed by pharmacokinetics/pharmacodynamics evaluations and safety assessments. The main outcome measure for the study was the pharmacokinetic bioequivalence of the two formulations, which was concluded if the 90% confidence intervals for the ratios of AUC(last) (area under the serum concentration-time curve from time zero to time of last measurable concentration) and C(max) (maximum serum concentration) were entirely contained within the interval, 0.80-1.25. RESULTS: The arithmetic mean values for the exposure parameters C(max) and AUC(last) were similar for the two formulations. The geometric mean ratio (pre-filled syringe vs. lyophilized form) of C(max) and AUC(last) were 0.99 and 1.01. The associated 90% confidence intervals were 0.90 to 1.08 and 0.94 to 1.09, respectively. Most common adverse events were headache and nasopharyngitis. Neutropenia occurred in 2 cases (reported as serious adverse events). No deaths occurred. CONCLUSION: The 150 mg liquid pre-filled syringe and lyophilized formulations of canakinumab are bioequivalent.