A Phase 1, Blinded, Randomized, Placebo Controlled, Parallel-Group, Single-Dose, Dose-Escalation Study to Investigate Safety, Tolerability, and Pharmacokinetics of Emodepside (BAY 44-4400) After Oral Dosing in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 79
- 试验地点
- 1
- 主要终点
- Safety and Tolerability as Measured by 12-lead ECG
研究概览
简要总结
This study will investigate the safety, tolerability, and pharmacokinetics of single ascending doses of emodepside (BAY 44-4400) in healthy male volunteers. This study will also conduct an exploratory investigation of the relative bioavailability of emodepside administered as tablets and determine the effect of food on the pharmacokinetics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male, Caucasian volunteers, deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine. Optionally, after further evaluation during the study, at the sponsor's discretion other ethnic groups may be recruited.
- •Aged 18 to 55 years.
- •With a body mass index (BMI; Quetelet index) in the range of 18 to 30.1 kg/m2 at screening.
- •Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
- •Willingness to give written consent to participate, after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate
排除标准
- •Participation in another clinical trial within 3 months prior and during the study, or 5-times the half-life of the drug tested in the previous clinical trial, whichever is longer (time calculated relative to the last dose in the previous clinical trial)
- •Clinically relevant abnormal medical history, concurrent medical condition, acute or chronic illness or history of chronic illness sufficient to invalidate the subject's participation in the trial or make it unnecessarily hazardous.
- •Surgery (eg stomach bypass) or medical condition that might affect absorption of study drug taken orally.
- •Presence of abnormal physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.
- •Positive tests for hepatitis B & C, HIV
- •Presence or history of drug or alcohol abuse during the last 10 years, or intake of more than 21 units of alcohol weekly.
- •Regular daily consumption of more than one liter of xanthine-containing beverages
- •Regular daily consumption of more than 5 cigarettes daily, or use more than 3 grams (1/8 ounce) of tobacco
- •Use of a prescription medicine during the 28 days before the first dose of trial medication or use of an over-the-counter medicine, with the exception of acetaminophen (paracetamol), during the 7 days before the first dose of trial medication
- •Use of dietary supplements or herbal remedies (such as St John's Wort) known to interfere with the CYP3A4 and/or P-gp metabolic pathways during the 28 days before the first dose of trial medication (see list in Study Procedures Manual)
- •Additional exclusion criteria for cohort with ophthalmological assessments:
- •No contact lenses wear within 1 month prior to first dose of IMP. Contact lenses wear is not permitted during the study
- •Any ocular disorder for which topical ocular therapy is currently or chronically prescribed, including inflammatory eye disease (dry eye allergic conjunctivitis [seasonal allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis], uveitis and glaucoma)
- •Past history of ocular disease requiring ongoing treatment
- •Past ocular surgery including laser or other refractive corneal surgery
- •Evidence of eye irritation, visual difficulties, corneal opacity, ocular surface (corneal or conjunctival damage, with or without ocular symptoms)
- •Evidence of narrow anterior chamber angles causing increased risk of acute glaucoma
- •Evidence of ocular media opacity including lens opacity/vitreous opacities
- •Evidence of retinal or optic nerve pathology
- •Evidence of pronounced colour blindness, as indicated by an Ishihara score of 9/13 or below
研究组 & 干预措施
placebo of emodepside (BAY 44-4400)
Up to 10 cohorts with single ascending dose
干预措施: placebo (Drug)
emodepside (BAY 44-4400)
Up to 10 cohorts with single ascending dose
干预措施: emodepside (BAY 44-4400) (Drug)
结局指标
主要结局
Safety and Tolerability as Measured by 12-lead ECG
时间窗: Up to 14 days post dose (may be extended to 21 days)
The following variables were recorded in 12-lead ECGs and extracted from continuous 12-lead ECG recordings: ventricular rate, PR interval, QRS interval, QTcB and QTcF interval.
Safety and Tolerability as Measured by Clinical Laboratory Parameters
时间窗: Up to 14 days post dose (may be extended to 21 days)
Clinical laboratory parameters included hematology, biochemistry, serology and coagulation in blood samples and urinalysis in urine samples
Safety and Tolerability as Measured by Physical and Neurological Examination Findings
时间窗: Up to 14 days post dose (may be extended to 21 days)
Abnormal or clinically significant neurological examination findings during the study or reported as an AE
Safety and Tolerability as Measured by Ophthalmological Examination Findings in One Study Arm Only
时间窗: Up to 14 days post dose (may be extended to 21 days)
Subjects attended a specialist eye hospital for ophthalmology assessments by a Consultant Ophthalmologist. Opthalmology assessments included:ocular symptoms, past ocular history, auto-refraction, best corrected distance visual acuity, color vision assessment, amsler grid assessment, ocular alignment and ocular motility assessment, confrontation visual field assessment, slit lamp examination (anterior segment), intraocular pressure (Goldmann Tonometry), optical coherence scanning of tomography, post mydriatic ocular media (at Screening visit 2 only) and retinal examination with slit lamp and lens.
Safety and Tolerability as Measured by Adverse Events
时间窗: Up to 14 days post dose (may be extended to 21 days)
Deaths, serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs)
Safety and Tolerability as Measured by Vital Signs
时间窗: Up to 14 days post dose (may be extended to 21 days)
Vital signs included heart rate, systolic and diastolic blood pressure,
次要结局
- The t½ of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The MRT of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The AUC 0-24 of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- Frel of the IR (Immediate Release) Tablet of Emodepside(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The Cmax/D of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The Tmax of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The AUC∞ of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The AUC∞/D of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The Cmax of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The Cmax, Norm of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The CL/F of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The AUC 0-24/D of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The AUC 24, Norm of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The AUC Last of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The AUC Last, Norm of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- Effect of Food on the Bioavailability (Cmax) of Emodepside (BAY 44-4400) After Single Oral Dose Administered as Solution or IR Tablets in One Arm Only(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- The Vz/F of Emodepside in Plasma(From pre-dose until 336h post-dose (may be extended to 504h post-dose))
- Effect of Food on the Bioavailability (AUC24) of Emodepside (BAY 44-4400) After Single Oral Dose Administered as Solution or IR Tablets in One Arm Only(From pre-dose until 336h post-dose (may be extended to 504h post-dose))