A Phase I, Open-label, Single Centre Study Investigating the PK, Safety and PD of a Single Dose of Teverelix TFA, a GnRH Antagonist, Via s.c. or i.m. Route of Administration in Healthy Male Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Antev Ltd.
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Cmax
研究概览
简要总结
A Phase I, open-label, single centre study investigating the pharmacokinetics, safety and pharmacodynamics of a single dose of teverelix TFA, a gonadotrophin releasing hormone antagonist, via subcutaneous or intramuscular route of administration in healthy male volunteers
详细描述
The primary objective of the study is:
• To characterise the pharmacokinetic (PK) profile of teverelix following single dose, subcutaneous (s.c.) and intramuscular (i.m.) administration of teverelix TFA in healthy male subjects
The secondary objectives of the study are:
- To assess the safety and tolerability of teverelix TFA after single s.c. and i.m. injections in healthy male subjects
- To evaluate pharmacodynamics (PD) effects of teverelix following single dose, s.c. and i.m. administration of teverelix TFA in healthy male subjects
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Provide voluntarily agreement to participate in this study and sign an Independent Ethics Committee (IEC)-approved informed consent prior to performing any of the screening procedures.
- •Males of any ethnic origin, between 40 to 70 years of age (inclusive) at the screening visit.
- •Healthy, determined by pre-study medical evaluation (medical history, vital signs, physical examination, standard 12-lead ECG and clinical laboratory evaluations).
- •If a vital sign or ECG assessment is outside of the reference range at the screening visit or admission, the assessment may be repeated once to rule out any error.
- •Body mass index (BMI) between 20.0 and 34.9 kg/m2 (inclusive) at the screening visit and on admission.
排除标准
- •Clinically relevant history of cardiovascular, respiratory, hepatic, renal, pancreatic, gastrointestinal, metabolic, endocrine, neurological, dermatological, immunological, psychiatric or other diseases/disorders as determined by the Principal Investigator or designee, or evidence of such diseases/disorders during the screening period.
- •Any disorder or clinically relevant surgical history that would interfere with the absorption, distribution, metabolism or excretion of the study drug.
- •History of proneness to orthostatic dysregulation, fainting or blackouts.
- •History or physical evidence of chronic or clinically relevant acute infection.
- •Screening total testosterone <3.0 ng/mL (<10.4 nmol/L).
- •History of anaphylactoid reactions or hypersensitivity to teverelix or GnRH antagonists or any of the excipients of the products tested.
- •History of clinically relevant allergies or idiosyncrasies to medication or food.
- •History of regular alcohol consumption exceeding 21 units per week within 2 years of study entry.
- •History of illicit drug abuse within 2 years of study entry.
- •Any ECG abnormality of clinical relevance; ECG QT interval corrected for heart rate using Fridericia's correction (QTcF) > 450 ms at the screening visit.
- •Any clinically relevant findings in the laboratory tests, as judged by the Principal Investigator, at the screening visit and on admission; alanine aminotransferase (ALT) > 1.5 x the upper limit of normal (ULN) and/or aspartate aminotransferase (AST) > 1.5 x ULN and/or total bilirubin > 1.0 x ULN, as confirmed by subsequent repeat assessment, at the screening visit and on admission. If a laboratory assessment is outside of the reference range at the screening visit or admission, the assessment may be repeated once to rule out laboratory error.
- •An estimated glomerular filtration rate (eGFR) < 90 mL/min, based on creatinine clearance calculation by the Cockcroft Gault formula and normalised to an average surface area of 1.73m2, at the screening visit.
- •Positive results in any of the tests for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), hepatitis C antibody (anti-HCV) or human immunodeficiency virus (HIV) antibodies, at the screening visit.
- •Positive urine test for ethanol and/or drugs of abuse at the screening visit or admission.
- •Use of prescription, non-prescription and over-the-counter (OTC) medications (including vitamins or herbal remedies) within 2 weeks prior to dosing is prohibited.
- •Receiving an investigational product in a clinical trial within 3 months prior to the screening visit.
- •Donation of blood (> 500 mL) or blood products within 2 months (56 days) prior to the screening visit.
- •Unwilling to avoid consumption of coffee and caffeine-containing products within 48 hours prior to admission until discharge from the study centre, as well as from 48 hours before ambulatory visits.
- •Unwilling to avoid use of alcohol or alcohol-containing foods, medications or beverages, within 48 hours prior to admission until discharge from the study centre, as well as from 48 hours before ambulatory visits.
- •Unwilling to abstain from vigorous exercise from 72 hours prior to admission until discharge from the study centre, as well as from 72 hours before ambulatory visits.
- •Unable to understand the protocol requirements, instructions and study related restrictions, the nature, scope and possible consequences of the clinical study.
- •Subject is unlikely to comply with the protocol requirements, instructions and study related restrictions; e.g., uncooperative attitude, inability to return for follow-up visits and improbability of completing the clinical study.
- •Subject has any concurrent condition that, in the opinion of the Principal Investigator, would make the subject unsuitable for participation in the clinical study.
- •Subject is an employee or the close relative of an employee of the Sponsor or the clinical research organisation (CRO) involved in the clinical study.
- •Vulnerable subjects defined as individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate (e.g., persons in detention, minors and those incapable of giving consent).
研究组 & 干预措施
90 mg s.c.
A single s.c. injection of 90 mg teverelix TFA administered on Day 1
干预措施: teverelix TFA (Drug)
60 mg s.c.
A single s.c. injection of 60 mg teverelix TFA administered on Day 1
干预措施: teverelix TFA (Drug)
90 mg i.m.
A single i.m. injection of 90 mg teverelix TFA administered on Day 1
干预措施: teverelix TFA (Drug)
120 mg s.c.
A single s.c. injection of 120 mg teverelix TFA administered on Day 1
干预措施: teverelix TFA (Drug)
结局指标
主要结局
Cmax
时间窗: 12 weeks
Maximum observed concentration after administration
Tmax,t1-t
时间窗: 12 weeks
Time to reach Cmax,t1-t after dosing
Cmax,0-t1
时间窗: 12 weeks
Maximum observed concentration after administration from zero up to time point t1
AUC0-t1
时间窗: 12 weeks
Area under the concentration time-curve from time zero up to concentration at time point t1 after which the concentrations start to rise again towards a second peak, t1 will be determined after review of the concentration-time profiles (immediate release component of total observed AUC)
AUCt1-t
时间窗: 12 weeks
Area under the concentration time-curve from time point t1 up to time point t (slow release component of total observed AUC)
Tmax
时间窗: 12 weeks
Time to reach Cmax after dosing
t½
时间窗: 12 weeks
Apparent terminal plasma half-life
AUC0-t
时间窗: 12 weeks
Area under the concentration time-curve from time zero up to the last measurable concentration at time point t Area under the concentration time-curve from time zero up to the last measurable concentration at time point t Area under the concentration time-curve from time zero up to the last measurable concentration at time point t
AUC0-∞
时间窗: 12 weeks
Area under the concentration time-curve from time zero up to infinity (∞)
Cmax,t1-t
时间窗: 12 weeks
Maximum observed concentration after administration from time point t1 up to time point t
Tmax,0-t1
时间窗: 12 weeks
Time to reach Cmax,0-t1 after dosing
λz
时间窗: 12 weeks
Apparent terminal rate constant
次要结局
- Local tolerability - Standardised Injection Site Reaction Scoring System (4-point) plus photography(12 weeks)
- Cardiac assessments(12 weeks)
- Systemic tolerability - Incidence of Treatment-Emergent Adverse Events(12 weeks)
- 24 hour Holter monitoring(Day -1 to Day 1)