Clinical trial NCT04420871: Pharmacokinetic and Safety Comparison of Two Capecitabine Tablets in Patients With Colorectal or Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Patient Participation
Keywords: Capecitabine
Bioequivalence
Pharmacokinetics
Lead sponsor: The Affiliated Hospital of Qingdao University
Sponsor class: OTHER
First posted: 2020-06-09
Enrollment: 48
Sex: ALL
Minimum age (years): 28
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A multicenter, randomized, open-label, three-period, and reference-replicated crossover study
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Peak Plasma Concentration (Cmax)
timeFrame: 18 days
measure: Area under the plasma concentration versus time curve (AUC)0-t
timeFrame: 18 days
measure: Area under the plasma concentration versus time curve (AUC)0-∞
timeFrame: 18 days
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 18 days
Other outcomes:
Locations:
city: Qingdao
country: China
facility: Phase Ⅰ Clinical Research Center
state: Shandong
Study officials:
affiliation: the study director of phase I clinical research center
name: yu Cao, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.