An Open-label, Single-dose Bioavailability Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety Following Subcutaneous Injection of TOL3022 in Patients with Advanced Prostate Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 48
- 试验地点
- 14
研究概览
简要总结
This is an open label, single dose bioavailability study designed to assess the pharmacokinetics, pharmacodynamics, and safety of TOL3022 after subcutaneous injection in subjects with advanced prostate cancer. A total of 6 to 12 subjects will be enrolled in each cohort.
The study will include two main cohorts and up to two optional cohorts:
Cohort 1: TOL3022 240 mg
Cohort 1a (optional): TOL3022 120 mg
Cohort 2: TOL3022 480 mg
Cohort 3 (optional): One of the following cohorts or Cohort 1a
Cohort 3a: TOL3022 loading dose paradigm
Cohort 3b: TOL3022 360 mg
Progression to the next dose level will be based on review of safety, PK, and available PD data at Week 4 for at least three subjects from Cohort 1.
If the TOL3022 240 mg dose is well tolerated, Cohort 2 (TOL3022 480 mg) will be initiated.
If the TOL3022 240 mg dose is not well tolerated, the next cohort will be a dose de escalation to Cohort 1a (TOL3022 120 mg).
If, after completion of Cohorts 1 and 2, the TOL3022 240 mg dose is well tolerated, shows testosterone suppression for three months or longer, and meets other sponsor defined criteria, Cohort 1a may be initiated as an alternative to Cohort 3a or 3b.
Cohort 3 is an optional cohort consisting of two possible dose levels. Enrollment in Cohorts 3a or 3b will begin only after review of safety, PK, and available PD data from at least six subjects in each of Cohorts 1 and 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 90.00 Year(s)（—）
- 性别
- Male
入选标准
- •To be eligible for study entry, subjects must meet all of the following criteria during screening:
- •Must be able and willing to provide written informed consent prior to participation and comply with the study protocol and procedures.
- •Is a male patient with histologically confirmed carcinoma of the prostate who is a candidate for androgen deprivation therapy (except for neoadjuvant hormonal therapy).
- •Has an Eastern Cooperative Oncology Group (ECOG) score of two or less.
- •Has a serum testosterone level within the age-specific normal range.
- •Has a prostate-specific antigen (PSA) value of four nanograms per milliliter or higher.
- •Has a hemoglobin level of ten grams per deciliter or higher.
- •Has a life expectancy of at least twelve months.
排除标准
- •Subjects will be excluded from the study if one or more of the following criteria are applicable during screening:
- •Has previously received or is currently receiving hormonal treatment for prostate cancer.
- •Has recently received, within three months prior to screening, or is currently receiving treatment with any drugs (prescription or over-the-counter) that modify the testosterone level.
- •Is currently being treated with a five alpha reductase inhibitor or has had prior use within the last six months.
- •Is a candidate for curative therapy, that is, radical prostatectomy or radiotherapy.
- •Has elevated serum alanine aminotransferase level three times the upper limit of normal or serum total bilirubin level one and a half times the upper limit of normal.
- •Has abnormal laboratory results which, in the judgment of the Investigator, would affect the subject’s health or the outcome of the study.
- •Has a known or suspected hepatic symptomatic biliary disease.
- •Presents with significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, endocrine, hematological, neurological, psychological, or dermatological disorder, or an active infection.
- •In addition, has any other condition such as excessive alcohol or drug abuse (based on subject reported history) that may interfere with study participation or influence the conclusion of the study as judged by the Investigator.
- •Has a current or medical history of congenital long QT syndrome, with a QTc of more than four hundred fifty milliseconds, or the presence of severe cardiovascular disease defined as having required cardiovascular surgery or the occurrence of incapacitating myocardial infarction within the past twelve months prior to study enrollment.
- •Has a history of severe asthma, defined as a need for daily treatment with oral or inhalation steroids to control the asthma, anaphylactic reactions, angioedema, angioneurotic edema, or Quincke’s edema.
- •Has any known hypersensitivity to any component of TOL
- •Is currently under treatment for any cancers, except for certain skin cancers, other than prostate cancer.
- •Has received an investigational drug within the last three months preceding the screening visit.
- •Has had a loss of three hundred fifty milliliters or more of blood within ninety days prior to receiving the investigational product of the current study.
- •Has a positive serology for hepatitis B, defined as hepatitis B surface antigen or hepatitis B core antibody, hepatitis C virus, or human immunodeficiency virus.
- •Note: Subjects with a hepatitis B core antibody positive result can be enrolled only if a confirmatory negative test is obtained, suggestive of no active infection currently.
- •Has a mental incapacity or language barrier precluding adequate understanding or cooperation.
- •Male subjects sexually active with a female partner of childbearing potential who are not willing to use one of the following acceptable contraceptive methods from the time of initial screening until six months after receiving TOL3022: Simultaneous use of a condom and, for the female partner, a hormonal contraceptive such as oral, patch, depot injection, implant, vaginal ring, or intrauterine device, or a non-hormonal intrauterine device.
- •Simultaneous use of a condom and, for the female partner, a diaphragm or cervical cap with spermicide.
研究者
Dr Sandeep Singh
CBCC Global Research