An Open-Label Single-Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of Viaca (Sildenafil + Cabergoline) Compared With Sildenafil and Cabergoline in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Participants with AEs/SAEs
研究概览
简要总结
This is a Phase 1, open-label, single-ascending-dose study evaluating the safety, tolerability, and pharmacokinetics (PK) of Viaca - a fixed-dose oral combination of sildenafil (a PDE5 inhibitor) and cabergoline (a dopamine D2 agonist) - versus sildenafil monotherapy and cabergoline monotherapy in healthy adult male volunteers. Approximately 30 participants are enrolled across 5 sequential cohorts (6 each). Each participant receives a single oral dose. The combination targets erectile dysfunction through both vascular and neuroendocrine pathways, aiming for efficacy at lower component doses.
详细描述
Five cohorts of 6 healthy male participants each (n≈30). Viaca dose cohorts: Cohort 1 (25/0.25 mg), Cohort 2 (50/0.5 mg), Cohort 3 (75/0.75 mg). Active-comparator cohorts: Cohort 4 (sildenafil 50 mg) and Cohort 5 (cabergoline 0.5 mg). Cohort 1 runs first; after Safety Review Committee (SRC) review of safety/tolerability/PK through Day 3, Cohorts 2, 4 and 5 may proceed in parallel; Cohort 3 proceeds after SRC review of Cohort 2. Participants fast ≥8 h overnight before dosing and 2 h after. They are confined to a Phase 1 unit and discharged on Day 5 (Cohorts 1-3 and 5) or Day 2 (Cohort 4), with a follow-up visit on Day 8 (±1). Total participation ~33 days including screening. (V2.0 amendment removed the former optional high-dose Viaca cohort.)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male participants, aged 18 to 65 years (inclusive) at the time of informed consent.
- •In good general health (Investigator judgement) with no significant medical history and no clinically significant abnormalities on physical examination, vital signs, or 12-lead ECG - including systolic blood pressure 110-140 mmHg (inclusive) at Screening and Day -1 - at Screening and/or before first IP administration.
- •BMI ≥ 18.0 and ≤ 32.0 kg/m² and weight ≥ 50 kg.
- •Nonsmoker or casual smoker (< 5 cigarettes/week equivalent) with no tobacco use within 2 months prior to Screening (Investigator discretion).
- •Clinical laboratory values within normal range (or not clinically significant per Investigator).
- •Fertile men agree to acceptable contraception from Screening until 90 days after last IP dose, and no sperm donation from first dose until ≥ 90 days after last dose.
- •Able and willing to attend required study visits.
- •Able and willing to provide written informed consent before any study procedures.
排除标准
- •Physical or psychological condition that would impair protocol compliance or study completion (Investigator judgement).
- •History of, or condition that would contraindicate study medication or interfere with study evaluations (Investigator judgement).
- •Previous history of any of: myocardial infarction; cerebrovascular accident; arrhythmia; congestive heart failure; unstable angina; recent (<6 months) need for calcium-channel/beta-blocker/nitrate/anti-epileptic therapy; uncontrolled hypertension (SBP >140 or DBP >100 mmHg); hypotension (SBP <90 or DBP <60 mmHg) incl. syncope/orthostatic/vasovagal; pulmonary/pericardial/retroperitoneal fibrotic disorders; sickle-cell disease or trait; cardiac valve disease; severe psychiatric disorders; Raynaud's/vasospastic disorders; bariatric surgery (cholecystectomy acceptable).
- •Blood/plasma donation or significant blood loss (450 mL) within 30 days prior to first IP dose.
- •Fever (>38°C) or symptomatic viral/bacterial infection within 2 weeks prior to Screening.
- •Infections requiring parenteral antibiotics within 1 month prior to Screening.
- •Concomitant use of an indwelling urethral catheter.
- •Concomitant nitrates/nitric-oxide donors, potent CYP3A4 inhibitors (e.g. ritonavir, indinavir, ketoconazole) or moderate inhibitors (e.g. erythromycin); unwilling to avoid St. John's wort and CYP3A4-active herbals (e.g. grapefruit) within 14 days prior and throughout the study.
- •Medications that significantly affect BP: nitrates (any form), alpha-blockers (e.g. doxazosin, terazosin, tamsulosin), guanylate cyclase stimulators (e.g. riociguat).
- •Positive HCV antibody, HBsAg, or HIV antibody.
- •Live vaccine within 4 weeks prior to first IP dose.
- •Poor pill-swallowing ability or poor venous access.
- •History of severe allergic/anaphylactic reactions or sensitivity to IP or constituents.
- •History of malignancy (except non-melanoma skin cancer excised >5 years prior to Screening).
- •Clinically significant abnormal Screening ECG (e.g. QRS ≥ 120 msec and/or QTcF > 450 msec, per Investigator).
- •History/evidence of renal disease or eGFR < 60 mL/min/1.73 m² at Screening (2021 CKD-EPI creatinine equation).
- •Immunosuppressive drug exposure (incl. experimental therapies) within 4 months or 5 half-lives (whichever longer) prior to Screening.
- •Positive urine toxicology panel (barbiturates, THC, amphetamines/methamphetamines, methadone, MDMA, phencyclidine, tricyclic antidepressants, benzodiazepines, opiates, cocaine) or positive alcohol breath test.
- •Unwilling to abstain from alcohol, caffeine and nicotine from 48 h prior to admission, during confinement, and 48 h prior to follow-up visits.
- •History of substance abuse/dependency or recreational IV drug use in the last 12 months (self-declared).
- •Unwilling to refrain from strenuous exercise (incl. weightlifting) 48 h prior to admission and follow-up visits.
- •Anything the Investigator considers would jeopardize participant safety, prevent full participation, or compromise data interpretation.
结局指标
主要结局
Participants with AEs/SAEs
时间窗: Day 1 (dosing) through Day 8
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Unit: participants (summarised by severity and relatedness).
Blood pressure
时间窗: Baseline through Day 8.
Change from Baseline in systolic and diastolic blood pressure. Unit: mmHg.
Pulse rate
时间窗: Baseline through Day 8.
Change from Baseline in pulse rate. Unit: beats/min.
Respiratory rate
时间窗: Baseline through Day 8.
Change from Baseline in respiratory rate. Unit: breaths/min.
Body temperature
时间窗: Baseline through Day 8.
Change from Baseline in body temperature. Unit: °C.
ECG heart rate
时间窗: Baseline through Day 8.
Change from Baseline in 12-lead ECG heart rate. Unit: beats/min.
ECG intervals
时间窗: Baseline through Day 8.
Change from Baseline in 12-lead ECG intervals (QTcF, PR, QRS). Unit: milliseconds.
Laboratory tests
时间窗: Baseline through Day 8.
Number of participants with clinically significant safety laboratory abnormalities. Unit: participants.
Physical examination
时间窗: Baseline through Day 8.
Number of participants with clinically significant physical examination findings. Unit: participants.
次要结局
- Cmax(Predose (Day 1) through 168 hours post-dose (Day 8).)
- Tmax(Predose (Day 1) through 168 hours post-dose (Day 8).)
- AUC0-t(Predose (Day 1) through 168 hours post-dose (Day 8))
- AUC0-24(Predose (Day 1) through 168 hours post-dose (Day 8).)
- AUC0-inf(Predose (Day 1) through 168 hours post-dose (Day 8).)
- %AUCextrap(Predose (Day 1) through 168 hours post-dose (Day 8).)
- t½(Predose (Day 1) through 168 hours post-dose (Day 8).)
- kel(Predose (Day 1) through 168 hours post-dose (Day 8).)
- CL/F(Predose (Day 1) through 168 hours post-dose (Day 8).)
- Vz/F(Predose (Day 1) through 168 hours post-dose (Day 8).)
- Cmax/D(Predose (Day 1) through 168 hours post-dose (Day 8).)
- AUC0-inf/D(Predose (Day 1) through 168 hours post-dose (Day 8).)
- AUC0-t/D(Predose (Day 1) through 168 hours post-dose (Day 8).)
- Dose proportionality(Predose (Day 1) through 168 hours post-dose (Day 8).)
研究者
Yanping Kong
MD, PhD, President, Kong's Pharmaceutical Co.
Kong's Pharmaceutical