Pharmacokinetics, Pharmacodynamics and Safety of LY01005 in Patients With Prostate Cancer Compared to ZOLADEX®

NCT05140512 | Completed Phase 1

• 1 other identifier: LY01005/CT-CHN-104
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label and parallel phase I study to compare pharmacokinetics (PK), pharmacodynamics (PD) and safety of goserelin acetate sustained-release microspheres for injection (LY01005) and ZOLADEX® following multiple administration in patients with prostate cancer.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; LY01005; PK/PD; Safety

Outcome Measures

Primary Outcomes (11)

• Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Plasma concentration of goserelin over time.

  from baseline to Day 85

• Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Cmax.

  from baseline to Day 85

• Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Ctrough.

  from baseline to Day 85

• Pharmacokinetic Profile of LY01005 versus ZoLADEX®: AUC0-t.

  from baseline to Day 85

• Pharmacokinetic Profile of LY01005 versus ZoLADEX®: AUC0-∞.

  from baseline to Day 85

• Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Tmax.

  from baseline to Day 85

• Pharmacokinetic Profile of LY01005 versus ZoLADEX®: T1/2.

  from baseline to Day 85

• Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Vz/F.

  from baseline to Day 85

• Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Cl/F.

  from baseline to Day 85

• Pharmacokinetic Profile of LY01005 versus ZoLADEX®: MRT0-∞.

  from baseline to Day 85

• Pharmacokinetic Profile of LY01005 versus ZoLADEX®: accumulation of goserelin.

  from baseline to Day 85

Secondary Outcomes (16)

• Pharmacodynamic Profile of LY01005 versus ZoLADEX®: AUEC of serum testosterone.

  from baseline to Day 85

• Pharmacodynamic Profile of LY01005 versus ZoLADEX®: Emax of serum testosterone.

  from baseline to Day 85

• Pharmacodynamic Profile of LY01005 versus ZoLADEX®: TEmax of serum testosterone.

  from baseline to Day 85

• Pharmacodynamic Profile of LY01005 versus ZoLADEX®: AUEC of serum LH.

  from baseline to Day 85

• Pharmacodynamic Profile of LY01005 versus ZoLADEX®: Emax of serum LH.

  from baseline to Day 85

Study Arms (2)

LY01005 3.6 mg

EXPERIMENTAL

Intramuscular injections of LY01005 3.6 mg every 28 days for a maximum of 3 consecutive doses.

Drug: LY01005

ZOLADEX® 3.6 mg

ACTIVE COMPARATOR

Subcutaneous injections of ZOLADEX® 3.6 mg every 28 days for a maximum of 3 consecutive doses.

Drug: ZOLADEX® 3.6 mg

Interventions

LY01005 DRUG

LY01005 was administered as 3 intramuscular (IM) injections, 28 days apart. As concomitant medications, Casodex® (50 mg/day) was orally administered during the whole study period.

Also known as: Goserelin Acetate Sustained-Release Microspheres for Injection

LY01005 3.6 mg

ZOLADEX® 3.6 mg DRUG

ZOLADEX® was administered as 3 Subcutaneous (SC) injections, 28 days apart. As concomitant medications, Casodex® (50 mg/day) was orally administered during the whole study period.

Also known as: Goserelin Acetate Implant 3.6 mg

ZOLADEX® 3.6 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older.
• Patients with locally advanced or metastatic prostate cancer suitable for endocrine therapy, including those who are suitable for endocrine therapy (such as patients with biochemical recurrence after adjuvant endocrine therapy and radical therapy) following radical therapy.
• Serum testosterone level ≥ 150 ng/dL (1.50 ng/mL or 5.2 nmol/L) at the screening visit.
• Life expectancy of at least 9 months.
• ECOG score of ≤ 2.
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, platelet count ≥ 90 x 10\^9/L, white blood cell count ≥ 3 x 10\^9/L, hemoglobin ≥ 90 g/L, total bilirubin (TBIL) ≤ 1.5×ULN, ALT and AST ≤ 2.5×ULN (or ≤ 5.0×ULN for patients with liver metastases), and Creatinine clearance ≥50 mL/min at the screening visit.
• Subjects of childbearing potential must agree to use a reliable method of contraception with their female sexual partners during the study period and at least 3 months after the last administration.
• Patients who voluntarily sign an IRB-approved informed consent form before any trial-related activities, are willing to abide by the restrictions of the study, and complete the prescribed examinations.

You may not qualify if:

• Patients with prostate cancer who receive previous or ongoing endocrine therapy (surgical castration or other endocrine therapy including GnRH receptor agonists, GnRH receptor antagonists, anti-androgens, estrogens, megestrol acetate, etc.), except for patients with prostate cancer undergoing prostatectomy, radiotherapy or cryotherapy who have received neoadjuvant/adjuvant endocrine therapy for no more than 6 months and discontinued the above therapy more than 6 months before screening.
• Patients with confirmed or suspected hormone-resistant prostate cancer.
• Patients who have received prostatic surgery within 4 weeks prior to the first dose, or plan to receive major surgical treatment during the trial.
• Patients who have previously received hypophysectomy or adrenalectomy, or who have pituitary lesions or adrenal dysfunction.
• History of severe asthma, anaphylaxis, or severe urticaria and/or angioedema.
• Other cancer diseases diagnosed within 5 years before the screening visit, except for surgically removed basal or squamous cell carcinoma of the skin.
• History of the following medical histories within 6 months prior to the screening visit: stroke, transient ischemic attack (TIA), myocardial infarction, unstable angina, coronary revascularization, New York Heart Association (NYHA) class ≥ II cardiac insufficiency, severe unstable arrhythmia.
• Hypertensive patients with poor blood pressure control (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg at the screening visit).
• Patients with type 1 diabetes or type 2 diabetes with poor glycemic control (glycosylated hemoglobin \> 8% at the screening visit).
• Patients who have received treatment with 5-α reductase inhibitors (finasteride, dutasteride, enalidomide, epristeride, etc.) within 4 weeks before the first dose.
• Has previously received goserelin.
• Is receiving coumarin anticoagulants at the screening visit.
• Has congenital long QT syndrome or QT/QTc interval prolongation (QTc ≥ 450 ms) at the screening visit; Or has received drugs that may prolong QT/QTc interval at the screening visit.
• Known to be allergic to the active ingredients or any excipients of GnRH agonists or bicalutamide.
• Patients who are seropositive for hepatitis B surface antigen (HBsAg), and must meet the following 2 conditions at the same time: 1. HBV DNA level: HBeAg-positive patients, HBV DNA ≥ 20,000 IU/ml \[equivalent to 10\^5 copies/mL\]; HBeAg-negative patients, HBV DNA ≥ 2,000 IU/ml \[equivalent to 10\^4 copies/mL\]; 2. ALT ≥ 2 x ULN); Patients who are seropositive for human immunodeficiency virus (HIV) antibody.

Sponsors & Collaborators

• Luye Pharma Group Ltd.: lead

Study Sites (1)

Sun Yat-sen Memorial Hospital of Sun Yat-sen University

Guangzhou, China

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Injections; Goserelin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Design

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

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: December 1, 2021
• Study Start: February 4, 2021
• Primary Completion: September 15, 2021
• Study Completion: November 26, 2021
• Last Updated: May 16, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)