Comparing the Pharmacokinetic Profile of LY01612 and CAELYX® in Chinese Subjects With Advanced Breast Cancer

A Multicenter, Randomized, Open-lable, Single-dose, Two-cycle, Double-cross Bioequivalence Study Comparing the Pharmacokinetic Profile of LY01612 and CAELYX® in Chinese Subjects With Advanced Breast Cancer

A multicenter, randomized, open-lable, single-dose, two-cycle, double-cross bioequivalence study comparing the pharmacokinetic profile of LY01612 (Doxorubicin hydrochloride liposome injection) and CAELYX® in Chinese subjects with advanced breast cancer

Study Overview

• Status: Completed
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: Doxorubicin hydrochloride liposome injection

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shijiazhuang, China
    • The Fourth Hospital of Hebei Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary agreement to provide written informed consent;
2. Patients aged ≥18 years and ≤75 years with locally advanced or metastatic breast cancer diagnosed by histology or cytology，and who may benefit from monotherapy of Doxorubicin liposomes;
3. Life expectancy of at least 3 months; Eastern Cooperative Oncology Group (ECOG) performance status (PS)<2;
4. adequate bone marrow function [leukocyte ≥3,000/mm3, absolute neutrophil count (ANC) ≥1,500/mm3, hemoglobin ≥90g/L, and platelet count ≥90,000/mm3；
5. adequate renal function (serum creatinine ≤1.5×Institutional upper limit of normal (ULN));
6. adequate coagulation function [prothrombin time (PT), activated partial thromboplastin time (APTT) ≤1.5×ULN];
7. adequate hepatic function [aspartate aminotransferase (AST), alanine aminotransferase (ALT) level ≤ 2.5×ULN (or ≤5×ULN for subjects with liver metastases), and total bilirubin level ≤ 1.5×ULN (or ≤ 3×ULN for subjects with liver metastases).

Exclusion Criteria:

1. Patients with a diagnosis of severe cardiovascular, lung, liver, kidney, gastrointestinal, endocrine, immune system, skin, musculoskeletal, neurological or psychiatric conditions that the researchers did not consider appropriate for inclusion;
2. With a history of myocardial infarction, unstable angina pectoris, coronary revascularization, New York Heart Association (NYHA) grade ≥Ⅱ cardiac insufficiency, severe pericardial disease, and severe unstable ventricular arrhythmia, cerebrovascular accident or transient cerebral ischemia or pulmonary embolism within 6 months before randomization;
3. Unstable brain metastases;
4. Electrocardiogram (ECG) QTC >480ms; left ventricular ejection fraction <50% or below the lower limit of study center value;
5. The total cumulative dose of doxorubicin was ﹥350mg/m2 before screening；
6. Persistent or active infection requiring systemic treatment;
7. Pregnancy or breast feeding;
8. Other situations that investigators consider as contra-indication for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxorubicin hydrochloride liposome injection(LY01612); 20mg/10mL, 50mg/m2, intravenously for 90min (±3min) with an infusion pump on day 1 and day 29 of the trial.	Drug: Doxorubicin hydrochloride liposome injection; Doxorubicin hydrochloride liposome injection was administered intravenously for 90min (±3min) with an infusion pump on day 1 and day 29 of the trial. Doxorubicin hydrochloride liposome injection was diluted with 250mL 5% glucose injection.
Active Comparator: Doxorubicin hydrochloride liposome injection(CAELYX®); 20mg/10mL, 50mg/m2, intravenously for 90min (±3min) with an infusion pump on day 1 and day 29 of the trial	Drug: Doxorubicin hydrochloride liposome injection; Doxorubicin hydrochloride liposome injection was administered intravenously for 90min (±3min) with an infusion pump on day 1 and day 29 of the trial. Doxorubicin hydrochloride liposome injection was diluted with 250mL 5% glucose injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
plasma maximum concentration (Cmax) of encapsulated doxorubicin.	from baseline to day 56
Area under Plasma d concentration-time curves of encapsulated doxorubicin	from baseline to day 56
plasma maximum concentration (Cmax) of unencapsulated doxorubicin.	from baseline to day 56
Area under Plasma concentration-time curves of unencapsulated doxorubicin.	from baseline to day 56

Secondary Outcome Measures

Outcome Measure	Time Frame
plasma maximum concentration（Cmax） of total doxorubicin；	from baseline to day 56
Area under plasma concentration-time curves of total doxorubicin；	from baseline to day 56
Partial area under plasma concentration-time curves （AUC0-48h and AUC48h-t）of encapsulated doxorubicin	from baseline to day 56
Encapsulated doxorubicin、unencapsulated doxorubicin and total doxorubicin Tmax	from baseline to day 56
Encapsulated doxorubicin、unencapsulated doxorubicin and total doxorubicin t1/2z	from baseline to day 56
Adverse event	from baseline to day 56

Collaborators and Investigators

• Sponsor: Luye Pharma Group Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2022
• Primary Completion (Actual): February 9, 2023
• Study Completion (Actual): February 9, 2023

Study Registration Dates

• First Submitted: October 18, 2023
• First Submitted That Met QC Criteria: October 18, 2023
• First Posted (Actual): October 24, 2023

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: LY01612/CT-CHN-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No