Efficacy, Safety, and Pharmacokinetics of FP-014, 11.25 mg in Patients With Advanced Prostate Cancer

This is a study in male patients with advanced prostate cancer who are eligible for androgen ablation therapy. The study duration will be up to 26 weeks.

Eligibility will be assessed during a screening period of up to 28 days. Up to 2 doses of a long-acting FP-014, 11.25 mg formulation will be given to the patients by separate SC injections 12 weeks apart in an unblinded manner. The first dose of FP-014, 11.25 mg, will be administered on Day 0 (Visit 2/Week 1). When patients have tolerated the first dose of FP-014, 11.25 mg and have achieved castrate levels of serum testosterone, a second dose will be administered on Day 84 (Visit 13/Week 12) to achieve castrate levels of serum testosterone concentrations (\< 50 ng/dL). Patients will be followed for efficacy, safety, tolerability, and ancillary clinical and laboratory markers for an additional 12-week observation period (Day 168/Week 24/ Visit 22).

Blood samples will be collected at Baseline (Day 0/Week 1) at least 30 minutes before the first FP-014, 11.25 mg administration, immediately thereafter and at specified time points through Day 168 (Week 24) to determine pharmacokinetic (PK) (triptorelin) and pharmacodynamic (PD) (testosterone, PSA, and LH) profiles.

To evaluate the sustained castration testosterone level after two administrations of FP-014, 11.25 mg, the first 30 enrolled patients will be considered as a subset for safety and PK assessments. Furthermore, these 30 patients will be extended for another 2 weeks post Day 168 (Day 182 ± 2 days/Week 26/Visit 23) to obtain the extended PK/PD profiles of serum triptorelin mesylate and testosterone levels.

To evaluate the sustained castration testosterone level after two administrations of FP-014, 11.25 mg, the first 30 enrolled patients will be considered as a subset for safety and PK assessments. Furthermore, these 30 patients will be extended for another 2 weeks post Day 168 (Day 182 ± 2 days/Week 26/Visit 23) to obtain the extended PK/PD profiles of serum triptorelin mesylate and testosterone levels.

The efficacy assessments will be performed in both Intent-to-Treat (ITT) and Per-Protocol (PP) populations. Efficacy assessment will include the percentage of patients who reached the castrate levels (\< 50 ng/dL) of serum testosterone on Day 28 (± 2 days; Week 4) post the first dosing of FP-014, 11.25 mg. Furthermore, the effect of FP-014, 11.25 mg on serum levels of PSA, and LH will be assessed post the first and the second dosing of FP-014, 11.25 mg, respectively. Urinary tract signs and symptoms will be evaluated for efficacy using the International Prostate Symptom Score (I-PSS) and will be recorded in the electronic case report forms (eCRFs). The acute-on-chronic (surge) effect of serum testosterone and LH levels will also be monitored in all patients. In addition, the impact of FP-014, 11.25 mg, on the percentage (rate) of patients with PSA relapse, on the percentage of patients that achieves normal serum PSA level, and on the percentage of patients with an enhanced serum testosterone concentration suppression (\< 20 ng/dL) will be determined at the end of study.

All treatment emergent adverse events (TEAEs), including AEs of interest (AEoI), that occur during the study period and serious adverse events (SAEs) that occur during the study period will be recorded in the electronic case report forms (eCRFs) and followed until they are resolved or considered stable. In addition, all SAEs will be recorded and reported as required by local and international regulatory requirements.

Other safety assessments and their results, including safety clinical laboratory parameters, vital signs, physical examination, resting 12-lead electrocardiogram (ECG), injection site reactions and bone pain assessed using visual analog scale (VAS) will also be recorded in the eCRF.

Patients who discontinue early should be encouraged to remain in the study for safety evaluations.

A Data Safety Monitoring Board (DSMB) composed of independent experts will review available safety results every 3 months, and on an ad hoc basis if deemed necessary, from the moment onwards when one month data is available from approximately 5% of enrolled patients until the last patient completes the study. The composition and responsibilities of the DSMB will be defined in a separate DSMB charter.