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.
This is a randomized, open-label, active-controlled phase I trial. A total of 23 patients with locally advanced or metastatic prostate cancer who were suitable for endocrine therapy were enrolled into the screening period from D-21 to D-10 (±3d) before administration. Eligible subjects were treated with bicalutamide tablets (Casodex®, 50 mg/day) from D-10 (± 3d) to the end of the trial and randomized in a 1:1 ratio to receive LY01005 3.6 mg or ZOLADEX ® 3.6 mg after completion of pretreatment. All subjects were administered once every 28 days for three doses. Blood samples were collected at the specified time points in the trial protocol to detect PK parameters of goserelin, and PD parameters (serum testosterone, LH and FSH). Safety evaluation (including vital signs, physical examination, laboratory tests, 12 ECG, adverse events, etc.) was conducted as required in the protocol. This study aimed to compare PK/PD and safety of LY01005 and ZOLADEX® in patients with locally advanced or metastatic prostate cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
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.
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.
Sun Yat-sen Memorial Hospital of Sun Yat-sen University
Guangzhou, China
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Plasma concentration of goserelin over time.
Time frame: from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Cmax.
Time frame: from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Ctrough.
Time frame: from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: AUC0-t.
Time frame: from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: AUC0-∞.
Time frame: from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Tmax.
Time frame: from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: T1/2.
Time frame: from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Vz/F.
Time frame: from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: Cl/F.
Time frame: from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: MRT0-∞.
Time frame: from baseline to Day 85
Pharmacokinetic Profile of LY01005 versus ZoLADEX®: accumulation of goserelin.
Time frame: from baseline to Day 85
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Pharmacodynamic Profile of LY01005 versus ZoLADEX®: AUEC of serum testosterone.
Time frame: from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: Emax of serum testosterone.
Time frame: from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: TEmax of serum testosterone.
Time frame: from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: AUEC of serum LH.
Time frame: from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: Emax of serum LH.
Time frame: from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: TEmax of serum LH.
Time frame: from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: AUEC of serum FSH.
Time frame: from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: Emax of serum FSH.
Time frame: from baseline to Day 85
Pharmacodynamic Profile of LY01005 versus ZoLADEX®: TEmax of serum FSH.
Time frame: from baseline to Day 85
The percentage of subjects with serum testosterone ≤50 ng/dL (1.735 nmol/L) on Day 29 after the first dose.
Time frame: Day 29 after the first dose
The cumulative percentage of subjects with the maintenance of serum testosterone ≤50 ng/dL (1.735 nmol/L) from Day 29 to Day 85.
Time frame: from Day 29 to Day 85
Significant Castration Rate.
The percentage of subjects with serum testosterone ≤20 ng/dL (0.7 nmol/L) on Day 29 after the first dose, and the cumulative percentage of subjects with the maintenance of serum testosterone ≤20 ng/dL (0.7 nmol/L) from Day 29 to Day 85.
Time frame: from Day 29 to Day 85
The percentage of subjects with serum testosterone > 50 ng/dL on 1 hour, 4 hours, Day 3 and Day 7 after the second dose and the third dose.
Time frame: 1 hour, 4 hours, Day 3 and Day 7 after the second dose and the third dose
Percentage changes compared to baseline in serum FSH level after each administration.
Time frame: Day 29, Day 57 and Day 85
Percentage changes compared to baseline in serum LH level after each administration.
Time frame: Day 29, Day 57 and Day 85
Adverse events throughout the study.
Time frame: up to Day 85