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

NCT ID: NCT04420871

Last Updated: 2020-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-10
• Study Completion Date: 2019-01-26

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.

Conditions

Patient Participation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

capecitabine reference formulation at a single dose of 150 mg

150 mg of Xeloda® produced by Genentech USA, Inc., a subsidiary of the company, was used as the reference intervention in this study.

Group Type: ACTIVE_COMPARATOR

150 mg of Xeloda®

Intervention Type: DRUG

Subjects were allocated to one of three groups randomly and equally with a 1-day wash time period. 150 mg of Xeloda® produced by Genentech USA, Inc., a subsidiary of the company, was used as the reference intervention in this study.The subjects randomly received single oral administration of 150 mg of Xeloda®.

capecitabine test formulation at a single dose of 150 mg

The tablet of 150 mg of capecitabine from Qilu Pharmaceutical Co., Ltd. (17H0053DE4, Jinan, Shandong Province, China) was used as the test formulation.

Group Type: EXPERIMENTAL

150 mg of capecitabine

Intervention Type: DRUG

Subjects were allocated to one of three groups randomly and equally with a 1-day wash time period.The tablet of 150 mg of capecitabine from Qilu Pharmaceutical Co., Ltd. (17H0053DE4, Jinan, Shandong Province, China) was used as the test formulation.The subjects randomly received single oral administration of 150 mg of capecitabine.

Interventions

150 mg of Xeloda®

Subjects were allocated to one of three groups randomly and equally with a 1-day wash time period. 150 mg of Xeloda® produced by Genentech USA, Inc., a subsidiary of the company, was used as the reference intervention in this study.The subjects randomly received single oral administration of 150 mg of Xeloda®.

Intervention Type: DRUG

150 mg of capecitabine

Subjects were allocated to one of three groups randomly and equally with a 1-day wash time period.The tablet of 150 mg of capecitabine from Qilu Pharmaceutical Co., Ltd. (17H0053DE4, Jinan, Shandong Province, China) was used as the test formulation.The subjects randomly received single oral administration of 150 mg of capecitabine.

Intervention Type: DRUG

Eligibility Criteria

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).

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).

• Minimum Eligible Age: 28 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Affiliated Hospital of Qingdao University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

yu Cao, Doctor

Role: PRINCIPAL_INVESTIGATOR

the study director of phase I clinical research center

Locations

Phase Ⅰ Clinical Research Center

Qingdao, Shandong, China

Countries

China

References

Wang CJ, Li T, Lin PP, Tao Y, Jiang X, Li X, Wen Q, Cao Y. Pharmacokinetic and Safety Comparison of Two Capecitabine Tablets in Patients with Colorectal or Breast Cancer Under Fed Conditions: A Multicenter, Randomized, Open-Label, Three-Period, and Reference-Replicated Crossover Study. Adv Ther. 2021 Sep;38(9):4798-4814. doi: 10.1007/s12325-021-01817-4. Epub 2021 Aug 4.

Reference Type: DERIVED

PMID: 34347254 (View on PubMed)

Other Identifiers

QL-KPTB-150

Identifier Type: -

Identifier Source: org_study_id