Pharmacokinetic and Safety Comparison of Two Capecitabine Tablets in Patients With Colorectal or Breast Cancer

Phase 1

Completed

• Conditions: Patient Participation
• Interventions: Drug: 150 mg of Xeloda®; Drug: 150 mg of capecitabine

• Registration Number: NCT04420871
• Lead Sponsor: The Affiliated Hospital of Qingdao University

Brief Summary

A multicenter, randomized, open-label, three-period, and reference-replicated crossover study was conducted in 48 patients with colorectal or breast cancer under fed conditions to assess the bioequivalence between two formulations of capecitabine.

Detailed Description

This was a multicenter, open, random, balanced, three-period, three-sequence and semi-repetitive cross study with 48 subjects. Eligible subjects were randomly assigned in a 1:1:1 ratio to receive one period of test formulation or two period of reference formulation, followed by a 1-day washout period and administration of the alternate formulation. Serial blood samples for pharmacokinetic assessment were collected at 0 hours (predose) up to 8 hours postdose. The plasma concentrations of capecitabine were analyzed by LC/MS-MS. Pharmacokinetic parameters (non-compartmental model) were assessed with WinNonlin software. The pharmacokinetic parameters assessed were area under the plasma concentration-time curve from time 0 to the time of last measurable concentration (AUC0-t), AUC from time zero to infinity (AUC0-∞), the peak plasma concentration of the drug (C max ), time needed to reach maximum concentration (Tmax), the elimination half-life (t1/2), and terminal elimination rate (λz). All were analyzed using an ANOVA model after logarithmic transformation of the data. For establishing bioequivalence (BE) for capecitabine， reference-scaled average bioequivalence (RSABE) acceptance criteria and average bioequivalence (ABE) acceptance criteria were used. Safety and tolerability was assessed during the entire study period.

Study Timeline

• Study Start: 2018-12-10
• Primary Completion: 2018-12-28
• Study Completion: 2019-01-26
• Status Verified: 2020-06
• Study First Submitted: 2020-06-04
• Study First Submitted QC: 2020-06-04
• Last Update Submitted: 2020-06-04
• Study First Posted: 2020-06-09
• Last Update Posted: 2020-06-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

• Patients with histologically or cytologically confirmed colorectal or breast cancer receiving capecitabine monotherapy or combination chemotherapy.
• Eligible patients were within 18-70 years of age.
• ECOG score was 0-2.
• Left ventricular ejection fraction (LVEF) > 50%.
• There was no serious persistent toxicity to capecitabine treatment before screening (laboratory tests ≤ grade 1 (NCI CTCAE 5.0 standard)
• Hand-foot syndrome ≤ grade 2 after recovery from the previous treatment period).

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Exclusion Criteria

• Patients were known allergy to fluorouracil or 5-fluorouracil.
• Patients with complete lack of known dihydropyrimidine dehydrogenase (DPD) activity.
• Patients with abnormal hepatic and renal function (serum creatinine≤ 1.5 ×ULN; CLcr ≥ 51 mL/min; bilirubin≤ 1.5 ×ULN; AST, ALT≤2.5×ULN)
• Needed to accept phenytoin, warfarin, other coumarin derivatives anticoagulants, folic acid, and CYP2C9 substrates during the research.
• Patients with brain metastases or other metastases of the central nervous system (except those who were treated at least 6 months prior to the start of the study and were stable and asymptomatic).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
capecitabine reference formulation at a single dose of 150 mg	150 mg of Xeloda®	150 mg of Xeloda® produced by Genentech USA, Inc., a subsidiary of the company, was used as the reference intervention in this study.
capecitabine test formulation at a single dose of 150 mg	150 mg of capecitabine	The tablet of 150 mg of capecitabine from Qilu Pharmaceutical Co., Ltd. (17H0053DE4, Jinan, Shandong Province, China) was used as the test formulation.

Primary Outcome Measures

Name	Time	Method
Peak Plasma Concentration (Cmax)	18 days	Evaluation of Peak Plasma Concentration (Cmax)
Area under the plasma concentration versus time curve (AUC)0-t	18 days	Evaluation of Area under the plasma concentration versus time curve (AUC)0-t
Area under the plasma concentration versus time curve (AUC)0-∞	18 days	Evaluation of Area under the plasma concentration versus time curve (AUC)0-∞

Secondary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	18 days	Adverse events were recorded to evaluate the safety of the studied drugs.

Trial Locations

Locations (1)

Phase Ⅰ Clinical Research Center; 🇨🇳 Qingdao, Shandong, China