A Bioequivalence Study of Capecitabine Tablets 500 mg in Adult Cancer Patients Under Fed Condition

NCT03435666 | Unknown Phase 1 FDA Drug

• 1 other identifier: 17-VIN-0855
• Study Type: interventional
• Target: 45
• Locations: 0 countries
• Sites: N/A

Brief Summary

Purpose: To demonstrate the bioequivalence between Capecitabine Tablets 500 mg of Qilu Pharmaceutical Co., Ltd, China in comparison with XELODA® (Capecitabine) Tablets 500 mg, Distributed by Genentech USA, Inc. Design: two treatment, three period, three sequence, reference replicate crossover, single dose. Test Drug: Capecitabine Tablets; Reference drug: XELODA Sample size: Around 45 patients will be enrolled to have at least 39 evaluable patients in the study.

Conditions

Colon Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Cmax

  Maximum plasma Capecitabine concentration.

  Pre-dose, 0.17 (10 min), 0.33 (20 min), 0.50 (30 min), 0.67 (40 min), 0.83 (50 min), 1.00, 1.25 (1h15min), 1.50 (1h30min), 1.75 (1h45min), 2, 2.25 (2h15min), 2.5 (2h30min), 2.75 (2h45min), 3.00, 3.50 (3h30min), 4.00, 5.00, 6.00, 7.00, and 8.00 hours

• AUC0-t

  The area under the plasma concentration time curve from zero to the last measurable concentration.

  Pre-dose, 0.17 (10 min), 0.33 (20 min), 0.50 (30 min), 0.67 (40 min), 0.83 (50 min), 1.00, 1.25 (1h15min), 1.50 (1h30min), 1.75 (1h45min), 2, 2.25 (2h15min), 2.5 (2h30min), 2.75 (2h45min), 3.00, 3.50 (3h30min), 4.00, 5.00, 6.00, 7.00, and 8.00 hours

Secondary Outcomes (5)

• AUC0-∞

  Pre-dose, 0.17 (10 min), 0.33 (20 min), 0.50 (30 min), 0.67 (40 min), 0.83 (50 min), 1.00, 1.25 (1h15min), 1.50 (1h30min), 1.75 (1h45min), 2, 2.25 (2h15min), 2.5 (2h30min), 2.75 (2h45min), 3.00, 3.50 (3h30min), 4.00, 5.00, 6.00, 7.00, and 8.00 hours

• Tmax

  Pre-dose, 0.17 (10 min), 0.33 (20 min), 0.50 (30 min), 0.67 (40 min), 0.83 (50 min), 1.00, 1.25 (1h15min), 1.50 (1h30min), 1.75 (1h45min), 2, 2.25 (2h15min), 2.5 (2h30min), 2.75 (2h45min), 3.00, 3.50 (3h30min), 4.00, 5.00, 6.00, 7.00, and 8.00 hours

• Kel

  Pre-dose, 0.17 (10 min), 0.33 (20 min), 0.50 (30 min), 0.67 (40 min), 0.83 (50 min), 1.00, 1.25 (1h15min), 1.50 (1h30min), 1.75 (1h45min), 2, 2.25 (2h15min), 2.5 (2h30min), 2.75 (2h45min), 3.00, 3.50 (3h30min), 4.00, 5.00, 6.00, 7.00, and 8.00 hours

• t½

  Pre-dose, 0.17 (10 min), 0.33 (20 min), 0.50 (30 min), 0.67 (40 min), 0.83 (50 min), 1.00, 1.25 (1h15min), 1.50 (1h30min), 1.75 (1h45min), 2, 2.25 (2h15min), 2.5 (2h30min), 2.75 (2h45min), 3.00, 3.50 (3h30min), 4.00, 5.00, 6.00, 7.00, and 8.00 hours

• AUC_%Extrap_obs

  Pre-dose, 0.17 (10 min), 0.33 (20 min), 0.50 (30 min), 0.67 (40 min), 0.83 (50 min), 1.00, 1.25 (1h15min), 1.50 (1h30min), 1.75 (1h45min), 2, 2.25 (2h15min), 2.5 (2h30min), 2.75 (2h45min), 3.00, 3.50 (3h30min), 4.00, 5.00, 6.00, 7.00, and 8.00 hours

Study Arms (2)

Capecitabine

EXPERIMENTAL

Capecitabine is the test product.In period 1, period 2 and period 3, 13 of 39 Subjects were given Single oral dose (1250 mg/m2) Capecitabine.

Drug: Capecitabine; Drug: XELODA

XELODA

ACTIVE COMPARATOR

XELODA is the reference product.In period 1, period 2 and period 3, 13 of 39 Subjects were given Single oral dose (1250 mg/m2) XELODA.

Drug: Capecitabine; Drug: XELODA

Interventions

Capecitabine DRUG

Single oral dose (1250mg/m2) Capecitabine or XELODA in each period.

Capecitabine; XELODA

XELODA DRUG

Single oral dose (1250mg/m2) Capecitabine or XELODA in each period.

Capecitabine; XELODA

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or non-pregnant, non-lactating female patient of age between 18 to 60 years (both inclusive).
• Patients with have histopathologically /cytologically confirmed Dukes' C colon cancer who have undergone complete resection of the primary tumor when treatment with fluoropyrimidine therapy alone is preferred.
• Or Patients with histopathologically /cytologically confirmed colorectal carcinoma with evidence of metastasis when treatment with fluoropyrimidine therapy alone is preferred Or Patients with histopathologically /cytologically confirmed breast cancer with evidence of metastasis
• Resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant to paclitaxel and for whom further anthracycline therapy is not indicated (e.g., patients who have received cumulative doses of 400 mg/m2 of doxorubicin or doxorubicin equivalents). Resistance is defined as progressive disease while on treatment, with or without an initial response, or relapse within 6 months of completing treatment with an anthracycline-containing adjuvant regimen.
• Cancer patients already receiving a stable twice-daily dosing regimen of capecitabine (who have completed at least one cycle of chemotherapy) as prescribed by the reference product label (i.e. 1250 mg/m2, twice daily, equivalent to 2500 mg/m2 total daily dose, for two-weeks followed by a one-week rest period given as three-week cycles)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate cardiac function \[left ventricular ejection fraction (LVEF) ≥ 50 %\]
• Patient with adequate bone marrow(ANC ≥ 1500/mm3, Platelet count ≥ 100,000/mm3 , Hemoglobin ≥ 9.0 g/ dL); renal (Serum Creatinine ≤ 1.5 times ULN and creatinine clearance ≥ 51 to 80 mL/min \[Cockroft and Gault\]) and hepatic function (Bilirubin ≤ 1.5 times ULN, ALT/AST ≤ 3 times ULN (≤ 5 x ULN if liver metastases present)) .
• Patient willing and able to give written informed consent for participation in the study and comply with the study protocol.
• No persistent clinically significant toxicities from prior medications at screening.
• Subject with clinically acceptable chest X-Ray (P/A view) whose X-Ray was taken not more than 3 months prior to screening.
• Females of child-bearing potential (FOCP) must agree to use an acceptable method of birth control such as sexual abstinence or at least 2 reliable modes of contraception, one of which must be a double-barrier method (e.g., condom with spermicidal gel or diaphragm with spermicidal gel) or IUD or vaginal spermicidal suppository from screening until 6 months after last dose of study drug. \[Note: Use of hormonal contraception (pills/hormonal intrauterine device etc,) is not allowed\].
• OR Post-menopausal females defined as at least 12 consecutive months with no menses without an alternative medical cause OR Surgically sterilized females with documented evidence of hysterectomy / bilateral salpingectomy / bilateral oophorectomy. Females without documented evidence of surgery and those who have undergone tubal ligation will be considered of child bearing potential.
• Male patient must agree to use an acceptable method of birth control such as sexual abstinence or barrier method of contraception (i.e. condom) from screening until 3 months after last dose of study drug. Subject agrees to accept the risk that pregnancy in female partner could still result despite using birth control devices.
• Cancer patients should preferably be on monotherapy. However, cancer patients receiving concomitant drug(s) are allowed to participate, provided:

You may not qualify if:

• Known hypersensitivity or contraindication to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil, or
• Patients with known DPD (Dihydropyrimidine Dehydrogenase) deficiency.
• Prior unanticipated severe reaction to Capecitabine or metabolites and to fluoropyrimidine therapy
• Patients with a prior history of coronary artery disease,
• Patients receiving phenytoin, warferin, other coumarin-derivative anticoagulants, leucoverin, CYP2C9 at the time of screening or anticipated use of these drugs during the study period. \[If the subject was on any of these drugs before screening, a wash out period of at least 5 half-lives must have elapsed since the last dose of such drug.\]
• Known symptomatic or untreated or recently treated (≤ 6 months of screening) central nervous system (CNS) metastases. Patients with previously treated (\> 6 months of screening) CNS metastases and are now stable and asymptomatic are allowed.
• Presence of active infections
• Any of the following cardiac conditions:
• Unstable angina
• Myocardial infarction within the past 6 months
• NYHA (New York State Heart Association) class II-IV heart failure
• Severe uncontrolled ventricular arrhythmias
• Clinically significant pericardial disease
• Electrocardiographic evidence of acute ischemic or active conduction system abnormalities
• Any other cardiac illness that could lead to a safety risk to the patient in case of enrolment in the study

Sponsors & Collaborators

• Qilu Pharmaceutical Co., Ltd.: lead

MeSH Terms

Conditions

Colonic Neoplasms; Breast Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2018
• First Posted: February 19, 2018
• Study Start: May 1, 2018
• Primary Completion: October 1, 2018
• Study Completion: November 1, 2018
• Last Updated: February 19, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share