A Phase 1, Two-Part, Single-Center, Open-Label, Randomized, Cross-Over, Single Ascending Doses (SAD), Followed by a Multiple Ascending Doses (MAD) Safety and Pharmacokinetic Study of RT234 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Number of participants with treatment related adverse events as assessed by CTCAE v5.0
研究概览
简要总结
The objective of this two part study was to demonstrate safety, tolerability, and pharmacokinetics of RT234 in healthy volunteers.
This study is also known as Vardenafil Inhaled for Pulmonary Arterial Hypertension PRN Phase 1 (VIPAH-PRN 1) study
详细描述
This study was designed to evaluate safety and tolerability and to characterize the PK profiles of single and repeated doses of inhaled vardenafil as RT234. In addition, vardenafil PK after single 0.6 mg doses of RT234 was compared to that following administration of a single 20 mg dose of oral vardenafil tablets.
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female, 18 to 45 years of age (inclusive at time of informed consent)
- •Normal heart, lung, kidney, and liver function based on physical examination
- •Systolic blood pressure of 100-145 mmHg, diastolic blood pressure of 50-90 mmHg, and a resting heart rate of 40-100 bpm at Screening
- •A body mass index (BMI) of ≤18 to ≥30 kg/m2 at Screening
- •Must be a non-smoker or ex-smoker with less than a 5-pack year history of smoking (including the use of electronic cigarettes) and have ceased smoking ≥1 year prior to Screening; or a social smoker (defined as less than 10 cigarettes in the previous 12 months)
排除标准
- •Has serum transaminase (i.e., alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma-glutamyl transferase [GGT]) levels greater than three times the upper level of normal
- •Abnormal orthostatic vital signs (at screening) defined as a decrease of ≥20 mmHg in systolic blood pressure and/or a decrease of ≥10 mmHg in diastolic blood pressure and/or >25 bpm increase in heart rate within 3 minutes of standing, or with symptoms of light-headedness, dizziness, or fainting upon standing.
- •History of hypotension including fainting, syncope, orthostatic hypotension, and/or vasovagal reactions
- •History of retinitis pigmentosa
- •Vision loss due to non-arteritic anterior ischemic optic neuropathy (NAION) or other optic perfusion impairment
- •History of priapism or anatomical deformation of the penis
- •History of sudden sensorineural hearing loss (SSHL), need for hearing aids, and/or other documented hearing loss
- •A corrected QT interval using Fridericia's formula (QTcF) >450 msec
- •Has evidence of significant obstructive lung disease on spirometry. Subjects with any of the following criteria will be excluded:
- •FEV1 <60% (predicted) (pre-bronchodilators); or
- •FEV1/FVC <65% (pre-bronchodilators)
研究组 & 干预措施
RT234 0.6 mg followed by oral vardenafil 20mg on day 3, SAD
Part 1, SAD Cohort 2A1
干预措施: Vardenafil Oral Tablet (Drug)
Oral vardenafil 20mg followed by RT234 0.6 mg on day 3, SAD
Part 1, SAD Cohort 2A2
干预措施: Vardenafil Oral Tablet (Drug)
结局指标
主要结局
Number of participants with treatment related adverse events as assessed by CTCAE v5.0
时间窗: Up to to 10 days
Adverse events reported by participants and those observed by the investigator in relation to laboratory tests, vital signs, ECGs, medications used to treat adverse events, and physical examinations were analyzed.
次要结局
- Total volume of distribution at the terminal phase(Up to 10 days)
- Half life (t1/2)(Up to 10 days)
- Time to reach maximum concentration (Tmax)(Up to 10 days)
- Total body clearance (CL/F)(Up to 10 days)
- Peak plasma concentration (Cmax)(Up to 10 days)
- Area under the curve (AUC)(Up to 10 days)
- Terminal elimination rate constant (Kel)(Up to 10 days)