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

Patient Participation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04420871
• Other study ID #: QL-KPTB-150
• Status: Completed
• Phase: Phase 1
• Start date: December 10, 2018
• Est. completion date: January 26, 2019

Study information

• Verified date: June 2020
• Source: The Affiliated Hospital of Qingdao University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: January 26, 2019
• Est. primary completion date: December 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 28 Years to 69 Years

Eligibility

Inclusion Criteria:

• Patients with histologically or cytologically con?rmed 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).

Related Conditions & MeSH terms

• Patient Participation

Intervention

Drug:
• 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®.
• 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.

Locations

Country	Name	City	State
China	Phase ? Clinical Research Center	Qingdao	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Hospital of Qingdao University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak Plasma Concentration (Cmax)	Evaluation of Peak Plasma Concentration (Cmax)	18 days
Primary	Area under the plasma concentration versus time curve (AUC)0-t	Evaluation of Area under the plasma concentration versus time curve (AUC)0-t	18 days
Primary	Area under the plasma concentration versus time curve (AUC)0-8	Evaluation of Area under the plasma concentration versus time curve (AUC)0-8	18 days
Secondary	Incidence of Treatment-Emergent Adverse Events	Adverse events were recorded to evaluate the safety of the studied drugs.	18 days