A phase III, two arm, multi centric, randomised, open label, parallel study to compare pharmacodynamics ofGoserelin 10.8 mg Injection (Eurofarma Laboratórios S.A) administered subcutaneously with the referencedrug ZOLADEX® 10.8 mg Injection (AstraZeneca) in patients with advanced prostate cancer.
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 94
- 试验地点
- 23
- 主要终点
- Evaluation and comparision of the pharmacodynamics of test product against
研究概览
简要总结
The current study is being conducted to evaluate the pharmacodynamics effect of test product (injection goserelin 10.8mg implant) against that of reference product and establish non-inferiority of test product as compared to reference product. Goserelin acetate is a synthetic analogue of gonadotropin-releasing hormone (GnRH). When given acutely, it transiently increases the plasma levels of luteinising hormone (LH) and follicle-stimulating hormone (FSH). Peak levels of LH and FSH usually occur 2 to 3 days after administration of a subcutaneous slow release depot formulation [1]. During continued administration of goserelin, the pituitary gland becomes refractory to further stimulation and serum levels of LH and FSH decline, leading to receptor desensitisation and/or down-regulation of the hypothalamic-pituitary gonadal axis. After about 2 weeks the LH and FSH serum levels reach pretreatment
values or lower. After this transient increase, the LH and follicle-stimulating hormone (FSH) production is down-regulated and testosterone production is inhibited. The decline in testosterone levels is similar to those observed after castration. Goserelin 10.8 mg Implant is a hybrid medicinal product. Bioavailability would be clinically not relevant as efficacy of GnRH analogues is independent of the pharmacokinetic profile as long as blood levels exceed a threshold level necessary to desensitise/downregulate pituitary receptors. There is no correlation between GnRH blood levels and the clinically meaningful suppression of testosterone below castration level. Therefore, the study is designed to establish pharmacodynamic comparability between the two products that can be maintained for the rest of the active treatment phase (once it has been achieved) rather than establishing pharmacokinetic comparability.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- Male
入选标准
- •Male patient with age of 18 to 75 years (Both inclusive)
- •Body mass index (BMI) between 18.5 and 30 kg/m².
- •(Both inclusive)
- •Patient with a confirmed advanced prostatic adenocarcinoma.
- •(TNM stage III or IV or recurrent metastatic disease) who are scheduled to start Goserelin therapy as per Investigator discretion.
- •Note: Stage III (T1–T2, N0, M0, PSA level is 20 or more, Grade Group 1–4 or T3– T4, N0, M0, any PSA, Grade Group 1–4 or any T, N0, M0, any PSA, Grade Group 5).
- •Stage IV (any T, N1, M0, any PSA, any Grade Group or any T, N0, M1, any PSA, any Grade Group)
- •Serum testosterone level >2.5 ng/mL for age of 20 to 49 (both inclusive) and >1.9 ng/mL for age ≥ 50 at screening.
- •(Screening sample for Serum testosterone level should be taken before 10:00 am in the morning).
- •Patient must be able to give informed consent for participation in the trial.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Adequate bone marrow function, renal function, liver function.
- •Patient should have recovered from any toxic effects of previous chemotherapy as judged by the Investigator.
- •Patients with life expectancy of at least 1 year as judged by the Investigator.
- •Patient or his partner willing to use an effective method as mentioned below of contraception during the study: a) Tubal sterilization (tubal ligation performed more than one month before Study Day 1; transcervical tubal occlusion procedure performed more than six months before Study Day 1) b) Barrier method (cervical cap, diaphragm, contraceptive sponge, vaginal spermicide, female condom, or male condom) c) Two barrier methods used together (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide plus a male or female condom) Absolute sexual abstinence (no sexual intercourse or genital contact with a female partner).
- •If the patient becomes sexually active during the study, then he is required to use a double barrier method of contraception.
排除标准
- •Evidence of severe urinary tract obstruction with anticipated urinary retention, in the opinion of the Investigator, taking into account medical history, clinical observations and symptoms.
- •Patients who are scheduled to receive any chemotherapy/radiotherapy in addition to goserelin.
- •Patients who are already on GnRH receptor agonist or antagonist therapy directed for prostate cancer.
- •Patients who have previously failed on GnRH receptor agonist or antagonist therapy for prostate cancer.
- •Presence of life-threatening metastatic visceral disease, defined as extensive hepatic involvement, or any degree (proven or suspected) of brain or leptomeningeal involvement (past or present) or symptomatic pulmonary lymhangitic spread.
- •Patients with discrete pulmonary parenchymal metastases are eligible, provided their respiratory function is not compromised as a result of disease.
- •Patients who are intended to be started on any medication apart from study drug that can have impact on any of the study endpoints.
- •Patients with spinal cord compression (in the opinion of the Investigator), taking into account medical history, clinical observations and symptoms.
- •Excruciating, severe bone pain which is due to extensive metastatic osseous deposits.
- •Patient has "currently active" second malignancy, other than non-melanoma skin cancer.
- •Patients are not considered to have a "currently active" malignancy if they have completed therapy >5 years previously and have no known evidence of residual or recurrent disease.
- •Patients with confirmed signs or symptoms related to cerebral metastasis or radiographically confirmed brain metastasis.
- •Patients with a clinically significant medical condition other than advanced prostate cancer including but not limited to renal, hepatic, gastrointestinal, endocrine, cardiovascular, neurological or psychiatric disease, alcohol or substance abuse, or any other condition that may affect the patient’s health or the outcome of the trial as judged by the investigator.
- •History of orchiectomy, adrenalectomy or hypophysectomy.
- •Patients receiving anticoagulation medications.
- •Patients with uncontrolled diabetes mellitus (HbA1c > 8 % as per ADA) at randomization (those who have controlled blood sugar (fasting) will be eligible for randomization)
- •Uncontrolled hypertension (systolic blood pressure [BP] >140 or diastolic BP >90mm Hg) or uncontrolled cardiac arrhythmias.
- •(Patients with hypertension controlled by antihypertensive therapies are eligible).
- •Patients with a QTc>450ms on the ECG at screening.
- •History of clinically significant cardiovascular disorder.
- •Use of any recreational drugs (cocaine, amphetamines, barbiturates, benzodiazepines, cannabinoids and morphine) or history of drug or alcohol abuse within the past 1 year, as judged by the Investigator, or a positive result on the urine drug/alcohol screen which is not consistent with current medical treatment.
- •Concomitant use of medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin, antipsychotics.
- •Patients who test positive for HIV and/or syphilis.
- •The receipt of an investigational product, or participation in a drug research study within a period of 30 days prior screening or 5 half-lives within the last dose of investigational product, whichever is longer.
- •Current use of any drugs that are known to interfere with goserelin metabolism or to cause a drug-drug interaction.
- •Donation / loss of blood/plasma or blood product (without replenishment) (1 unit or 350 mL) within 180 days prior to receiving the first dose of study medicine.
- •Presence of clinically significant findings on the physical exam, laboratory testing, medical history, ECG that in the opinion of the Investigator may interfere with trial conduct, patient safety, or interpretation of results.
- •Any contraindications for goserelin administration.
- •Note: Any clinically significant findings should be discussed with the Medical Monitor.
结局指标
主要结局
Evaluation and comparision of the pharmacodynamics of test product against
时间窗: Pre-dose and Day 1, Day 2, Day 8, Day 15, Day 22, Day 29, Day 43, day 57, day 71, day 85 day 86, day 89, day 99, day 113, day 127, day 141, day 155 and day 169 hours post dose
reference product and establish non-inferiority.
时间窗: Pre-dose and Day 1, Day 2, Day 8, Day 15, Day 22, Day 29, Day 43, day 57, day 71, day 85 day 86, day 89, day 99, day 113, day 127, day 141, day 155 and day 169 hours post dose
次要结局
- Evaluation of the pharmacokinetic and safety of(the test product as compared to reference)