A Phase 2, Randomized, Open-Label, Dose-Finding Study of Debio 4228, an Extended-Release Formulation of Gonadotropin-Releasing Hormone Antagonist in Participants With Advanced Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 57
- 主要终点
- Maximum Plasma Concentration (Cmax) of Debio 4228
研究概览
简要总结
The primary purpose of this study is to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of Debio 4228.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Participant with histologically confirmed diagnosis of prostate cancer, with one of the following:
- •Newly diagnosed androgen-sensitive locally advanced or metastatic disease; or
- •Localized disease not suitable for local primary intervention with curative intent.
- •Participant judged by the Study Investigator to be candidate for continuous androgen deprivation therapy (ADT).
- •Baseline morning serum testosterone levels >150 ng/dL at screening visit.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Life expectancy of at least 6 months.
- •Adequate bone marrow, hepatic, and renal function at the screening visit.
- •[Note: Other protocol and subprotocol-defined criteria apply]
排除标准
- •Previous ADT (neoadjuvant or adjuvant hormonal therapy) for ≥6 months duration and <6 months treatment-free interval before start of screening.
- •Participant requires combination with androgen deprivation therapy with the exception of enzalutamide.
- •History of bilateral orchiectomy, adrenalectomy, or hypophysectomy.
- •Received chemotherapy or cryotherapy within 8 weeks prior to the start of screening for the treatment of prostate cancer.
- •Abnormal cardiovascular function or diabetes.
- •Use of exogenous testosterone within 6 months before the start of screening.
- •Major surgery within 4 weeks before the start of screening.
- •Cancer disease within the last two years except for prostate cancer and some skin cancers.
- •[Note: Other protocol and subprotocol-defined criteria apply]
研究组 & 干预措施
Cohort 2: Debio 4228 Dose Level 2
Participants will receive a single IM administration of dose level 2 Debio 4228 on Day 1.
干预措施: Debio 4228 (Drug)
Cohort 1: Debio 4228 Dose Level 1
Participants will receive a single intramuscular (IM) administration of dose level 1 Debio 4228 on Day 1. Enrolment for cohort 1 was discontinued as per protocol amendment v5.0
干预措施: Debio 4228 (Drug)
Cohort 3
If any alternative dose is deemed necessary based on preliminary data, participants may be enrolled in Cohort 3 to receive Debio 4228 loading dose IM, on Day 1 followed by a maintenance dose IM, 12 weeks after receiving the loading dose (Day 85).
干预措施: Debio 4228 (Drug)
结局指标
主要结局
Maximum Plasma Concentration (Cmax) of Debio 4228
时间窗: Cohorts 1 and 2: Predose and at multiple time points post-dose up to Day 169; Cohort 3: Predose and at multiple time points post-dose up to Day 169
Area Under the Concentration-time Curve of Debio 4228 Over 12 weeks (AUC84d)
时间窗: Cohorts 1 and 2: Predose and at multiple time points post-dose up to Day 84; Cohort 3: Predose and at multiple time points post-dose up to Day 169
Plasma Concentration of Debio 4228 at Week 12 (C84d)
时间窗: Cohorts 1 and 2: Post-dose on Day 84; Cohort 3: Post-dose on Days 84 and 168
Serum Concentration of Testosterone
时间窗: Cohorts 1 and 2: Predose and at multiple time points post-dose from Days 1 to 85; Cohort 3: Predose and at multiple time points post-dose from Days 1 to 169
次要结局
- Number of Participants who Achieved and Maintained a Testosterone Castration (Testosterone Level of <50 [Nanograms per Deciliter] ng/dL and <20 ng/dL)(Cohorts 1, 2, and 3: Days 29 to 85)
- Number of Participants who Maintained a Testosterone Castration (Testosterone Level of <50 ng/dL and <20 ng/dL)(Cohort 3: Days 29 to 169)
- Time to Achieve Testosterone Castration (Testosterone Level of <50 ng/dL and <20 ng/dL)(Cohorts 1 and 2: Day 1 up to Day 85; Cohort 3: Day 1 up to Day 169)
- Number of Participants who Experience Local Reactions Categorized as Erythema, Swelling, and Induration at the Injection Site(Cohorts 1 and 2: Immediately, at 2 and 24 hours post-injection on Day 1; Cohort 3: Immediately, at 2 and 24 hours post-injection on Days 1 and 85)
- Number of Participants who Experience Pain at Injection Site(Cohorts 1 and 2: Immediately, at 2 and 24 hours post-injection on Day 1; Cohort 3: Immediately, at 2 and 24 hours post-injection on Days 1 and 85)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity(Cohorts 1 and 2: Up to Day 169; Cohort 3: Up to Day 197)
- Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, and Electrocardiogram (ECG) Parameters(Cohorts 1 and 2: Up to Day 169; Cohort 3: Up to Day 197)
- Number of Participants With Related TEAEs, Serious TEAEs, Adverse Events of Special Interest (AESIs), TEAEs Leading to Treatment Delay, and/or Discontinuation, and Death(Cohorts 1 and 2: Up to Day 169; Cohort 3: Up to Day 197)
- Percent Change From Baseline in Serum Prostate-Specific Antigen (PSA) Over Time(Cohorts 1 and 2: Baseline up to Day 85; Cohort 3: Baseline up to Day 169)
- Change From Baseline of Serum Luteinizing Hormone (LH) Over Time(Cohorts 1 and 2: Baseline up to Day 85; Cohort 3: Baseline up to Day 169)
- Change From Baseline in Serum Follicle-Stimulating Hormone (FSH) Over Time(Cohorts 1 and 2: Baseline up to Day 85; Cohort 3: Baseline up to Day 169)