逸達(簡銘達) Leuprolide Mesylate (LMIS 50mg) 皮下6個月劑型: phase III振奮

逸達前列腺癌新藥 三期臨床報喜 2017-01-17 09:29中央社 台北17日電 逸達生技宣布，治療前列腺癌新劑型新藥FP-001 LMIS 50毫克（六個月緩釋）全球多國多中心三期臨床試驗數據分析，完成其主要療效指標高達受試者的97%，數據佳。專精於緩釋針劑改良劑型及創新分子新藥開發的逸達生技今天宣布，已於16日順利完成首項產品FP-001LMIS 50毫克（6個月劑型）三期臨床實驗數據分析，主要療效指標（primary efficacy end point）高達受試者的97%。逸達生技董事長暨總經理簡銘達表示，逸達創新針劑藥物傳輸技術SIF（Stabilized Injectable Formulation）首項產品FP-001開發成果令他們非常振奮，證明逸達自行開發的SIF緩釋針劑平台技術，已成功克服三十年來高活性荷爾蒙柳菩林針劑保存與使用的技術障礙。正與全球多家廠商深入探討共同行銷及授權。後續將向歐美以505（b）2核准途徑申請新劑型新藥藥證，目前也積極與美、歐、中、韓等地廠商深入探討行銷合作及授權活動，布局未來產品上市推廣。FP-001所治療的前列腺癌隨著人口老化，已是全球最快速成長的疾病之一。目前全球前列腺癌藥物市值有75億美元，估計2025年將繼續成長至260億美元。

Safety, Efficacy, and Pharmacokinetic Behavior of Leuprolide Mesylate in Subjects With Advanced Prostate Carcinoma   Sponsor: Foresee Pharmaceuticals Co., Ltd. Collaborator: QPS-Qualitix Information provided by (Responsible Party): Foresee Pharmaceuticals Co., Ltd. ClinicalTrials.gov Identifier: NCT02234115 First received: September 1, 2014 Last updated: December 18, 2015 Last verified: December 2015 Purpose The study will evaluate if Leuprolide Mesylate is safe and effective in the treatment of subjects with advanced prostate carcinoma, when administered as two injections six months apart. Phase 3 Study Type: Interventional Study Design: Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment Official Title: An Open-Labeled, Singled-Arm Study of the Safety, Efficacy, and Pharmacokinetic Behavior of Leuprolide Mesylate for Injectable Suspension (LMIS 50 mg) in Subjects With Advanced Prostate Carcinoma

Primary Outcome Measures: Efficacy of Leuprolide Mesylate (LMIS 50mg) [ Time Frame: 336 days ] [ Designated as safety issue: No ] The percentage of subjects with a serum testosterone concentration suppressed to castrate levels (≤ 50 ng/dL) by Day 28 ± 1(day) following the first injection of LMIS 50 mg and the percentage of subjects with serum testosterone suppression (≤ 50 ng/dL) from Day 28 through Day 336 (remaining duration of the study).

Secondary Outcome Measures: Post-suppression excursions of serum testosterone [ Time Frame: 336 days ] [ Designated as safety issue: No ] The proportion of subjects exhibiting post-suppression excursions of serum testosterone to >50 ng/dL, either through "breakthrough" (i.e., episodes unrelated to LMIS 50 mg dosing), or through the "acute-on-chronic" phenomenon (i.e., related to the second dose of LMIS 50 mg); Effect of LMIS 50 mg on serum PSA levels; and Effect of LMIS 50 mg on serum LH levels Pharmacokinetics of Leuprolide Mesylate (LMIS 50mg) [ Time Frame: Days 0, 1, 2, 3, 7, 14, 21, 28, 56, 84, 112, 140, 168, 169, 170, 171, 196, 224, 252,280, 308, 336 ] [ Designated as safety issue: No ] Plasma leuprolide concentrations (ng/mL) in PK populationSafety and tolerability of LMIS 50 mg [ Time Frame: 336 days ] [ Designated as safety issue: Yes ] Determining the safety and tolerability of LMIS 50 mg based on adverse events (AEs), local tolerability, vital signs, electrocardiograms (ECGs), and clinical parameters Estimated Enrollment: 130 Study Start Date: August 2014 Estimated Study Completion Date: December 2016 Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure) Arms Assigned Interventions Experimental: Leuprolide Mesylate 50mg All subjects will be males with advanced prostate carcinoma. They will be injected twice with a depot formulation containing 50 mg of Leuprolide Mesylate. The first dose on day 0 the second dose on day 168 (six months apart). Subjects will be followed until day 336. Drug: Leuprolide Mesylate Subcutaneous injection of 50mg Leuprolide Mesylate

Detailed Description: This is a multi-center, open-label, single-arm study conducted in 2 parts. Part I was established to provide a vanguard of the first 30 subjects who will have more frequent monitoring of their safety. If safety is established, the remainder of the subjects will be entered into the clinical study (i.e., Part II). All subjects will be males with advanced prostate carcinoma judged to be candidates for medical androgen ablation therapy, and all will receive two injections of LMIS 50 mg six-month apart in an unblinded fashion.

Eligibility:  Ages Eligible for Study: 18 Years and older (Adult, Senior) Genders Eligible for Study: Male Accepts Healthy Volunteers: No Criteria Inclusion Criteria: Males aged ≥ 18 years old Males with histologically confirmed carcinoma of the prostate Subjects who are judged by the attending physician and/or Principal Investigator to be a candidate for androgen ablation therapy Baseline morning serum testosterone level > 150 ng/dL performed at Screening Visit Eastern Cooperative Oncology Group (ECOG) Performance score ≤ 2 Life expectancy of at least 18 months Laboratory values Absolute neutrophil count ≥ 1,500 cells/µL Platelets ≥ 100,000 cells/µL Hemoglobin ≥ 10 gm/dL Total bilirubin ≤ 1.5 × upper limit of normal (ULN) AST (SGOT) ≤ 2.5 × ULN ALT (SGPT) ≤ 2.5 × ULN Serum creatinine ≤ 1.5 mg/dL Lipid profile within acceptable range according to investigator's judgment HgbA1c within acceptable range according to investigator's judgment Clinical chemistries (K, Na, Mg, Ca and P) within acceptable range according to investigator's judgment Serum glucose within acceptable range according to investigator's judgement Urinalysis within normal range according to the investigator's judgment Agree to use male contraceptive methods during study trial Based on the Investigator's judgment, the ability to understand the nature of the study and any hazards of participation, and to communicate satisfactorily with the Investigator and to participate in, and to comply with, the requirements of the entire protocol All aspects of the protocol explained and written informed consent obtained Exclusion

Criteria: Receipt of chemotherapy, immunotherapy, cryotherapy, radiotherapy, or anti- androgen therapy concomitantly, or within 8 weeks prior to Screening Visit, for treatment of carcinoma of the prostate. Radiation for pain control will be allowed during the study. Receipt of any vaccination (including influenza) within 4 weeks of Baseline History of blood donation within 2 months of Baseline History of anaphylaxis to any LH-RH analogues Receipt of any LHRH suppressive therapy within 6 months of Baseline Major surgery, including any prostatic surgery, within 4 weeks of Baseline History and concomitant clinical and radiographic evidence of central nervous system/spinal cord metastases. Subjects at risk for spinal cord compression will be excluded.

Contraindication to leuprolide or an LHRH agonist as indicated on package labeling Use of 5-alpha reductase inhibitor within the last 6 months of Baseline History or presence of insulin-dependent diabetes mellitus (Type I). Presence of well controlled diabetes mellitus Type II will be allowed Use of systemic corticosteroids at a dose >10 mg/d or anti-androgens Use of any investigational agent within 4 weeks of Baseline Use of any over-the-counter (OTC) medication within 4 weeks of Baseline except for those listed in the permitted Concomitant Treatment section. Uncontrolled intercurrent illness that would jeopardize the subject's safety, interfere with the objectives of the protocol, or limit the subject's compliance with study requirements, as determined by the Investigator in consultation with the Sponsor

Responsible Party: Foresee Pharmaceuticals Co., Ltd. ClinicalTrials.gov Identifier: NCT02234115 History of Changes Other Study ID Numbers: FP01C-13-0012013-001790-25Study First Received: September 1, 2014 Last Updated: December 18, 2015 Health Authority: United States: Food and Drug Administration European Union: European Medicines Agency Taiwan : Food and Drug Administration Austria: Austrian Medicines and Medical Devices Agency Keywords provided by Foresee Pharmaceuticals Co., Ltd.: Prostate Neoplasm Cancer Carcinoma