Pharmacokinetics and Safety of Polaprezinc Granules Oral Administration in Healthy Chinese Volunteers Under Fasting and Fed Conditions

Abstract

The study aimed to demonstrate bioequivalence between generic and original polaprezinc granules by comparing pharmacokinetic (PK) profiles in healthy Chinese subjects under fasting and fed conditions. This PK investigation was conducted with two independent, randomized, open-label, single-dose, two-period, cross-over studies. Healthy Chinese fasting (N = 24, 75 mg) or fed (N = 24, 300 mg) subjects randomly received a single oral dose of the test or reference polaprezinc granules at each period. Blood samples were collected pre- and post-dose for up to 12 h. Blood zinc was determined using a validated ICP-MS method. Primary PK endpoints were calculated using non-compartmental methods, including peak concentration (C_max) and the areas under the plasma concentration-time curve (AUC_0-t, AUC_0-∞). The geometric mean ratios (GMR) in primary PK endpoints between the test and reference products with 90% confidence intervals (CI) were calculated. Treatment-emergent adverse events were assessed. In the fasting study, C_max, AUC_0-t and AUC_0-∞ were 1.30 ± 0.30 μg/mL, 4.06 ± 1.13 h·μg/mL, and 4.43 ± 1.04 h·μg/mL following 75 mg test product. In the fed study, C_max, AUC_0-t and AUC_0-∞ were 0.91 ± 0.26 μg/mL, 3.26 ± 1.06 h·μg/mL, and 3.37 ± 1.07 h·μg/mL following 300 mg test product. The reference product had comparable PK profiles. All 90% CIs of GMRs in C_max, AUC_0-t and AUC_0-∞ between the two products were within 80.0%-125.0%. Both study products were well-tolerated with no serious adverse events. The generic and original polaprezinc granules were bioequivalent by pharmacokinetic comparisons in healthy Chinese subjects under fasting and fed conditions. The two polaprezinc formulations were well-tolerated with no new safety signals. Trial Registration: CTR20210011.

Keywords: bioequivalence; pharmacokinetics; polaprezinc granules; safety; tolerability.

FIGURE 1

Subject enrolment flowchart. The fasting study included and randomized 24 healthy subjects (T‐R: 12; R‐T: 12), among which 21 completed the study per protocol requirements (test: 10; reference: 11). In the study, 3 subjects discontinued: K002 and K003 due to TEAE in the 1st treatment period and K019 withdrew consent at Day 4 in the 2nd treatment period. The FAS and SS included all 24 randomized subjects. The PKPS and the BES included 22 subjects. Two (2) subjects discontinued due to TEAE vomiting within the period covering 2 times × T _max of the study product and were excluded from the PKPS and the BES. The subject K019 completed the 1st treatment period with all data collected and was included in the PKPS and the BES. The fed study included and randomized 24 healthy subjects (T‐R: 12; R‐T: 12), among which all 24 completed the study per protocol requirements (test: 12; reference: 12). The FAS, the SS, the PKPS, and the BES included all 24 healthy subjects for the fed study. T: Test product; R: Reference drug.

FIGURE 2

(A) Zinc concentration‐time curve in the fasting study (mean ± SD). Adjusted for baseline blood zinc, PKCS; Test product n = 23; reference product n = 22; (B) Zinc concentration‐time curve in the fed study (mean ± SD). Adjusted for baseline blood zinc, PKCS; Test product n = 24; reference product n = 24.