A Study to Assess the Safety, Tolerability and Pharmacokinetics of Viaca (Sildenafil + Cabergoline) Compared With Sildenafil and Cabergoline

Официальное название

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

Обзор

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.

Подробное описание

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.)

Вмешательства

• Препарат Viaca
  fixed-dose oral tablet of sildenafil + cabergoline (low-dose 25/0.25 mg; high-dose 50/0.5 mg). Single oral dose.
• Препарат Sildenafil 50 mg
  single oral dose
• Препарат Cabergoline 0.5 MG
  single oral dose

Первичные конечные точки

• Participants with AEs/SAEs [Срок оценки: Day 1 (dosing) through Day 8]
• Blood pressure [Срок оценки: Baseline through Day 8.]
• Pulse rate [Срок оценки: Baseline through Day 8.]
• Respiratory rate [Срок оценки: Baseline through Day 8.]
• Body temperature [Срок оценки: Baseline through Day 8.]
• ECG heart rate [Срок оценки: Baseline through Day 8.]
• ECG intervals [Срок оценки: Baseline through Day 8.]
• Laboratory tests [Срок оценки: Baseline through Day 8.]
• Physical examination [Срок оценки: Baseline through Day 8.]

Вторичные конечные точки (12)

• Cmax [Срок оценки: Predose (Day 1) through 168 hours post-dose (Day 8).]
• Tmax [Срок оценки: Predose (Day 1) through 168 hours post-dose (Day 8).]
• AUC0-t [Срок оценки: Predose (Day 1) through 168 hours post-dose (Day 8)]
• AUC0-24 [Срок оценки: Predose (Day 1) through 168 hours post-dose (Day 8).]
• AUC0-inf [Срок оценки: Predose (Day 1) through 168 hours post-dose (Day 8).]
• %AUCextrap [Срок оценки: Predose (Day 1) through 168 hours post-dose (Day 8).]
• t½ [Срок оценки: Predose (Day 1) through 168 hours post-dose (Day 8).]
• kel [Срок оценки: Predose (Day 1) through 168 hours post-dose (Day 8).]
• CL/F [Срок оценки: Predose (Day 1) through 168 hours post-dose (Day 8).]
• Vz/F [Срок оценки: Predose (Day 1) through 168 hours post-dose (Day 8).]
• Cmax/D [Срок оценки: Predose (Day 1) through 168 hours post-dose (Day 8).]
• AUC0-inf/D [Срок оценки: Predose (Day 1) through 168 hours post-dose (Day 8).]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Австралия · 1 центр

• Nucleus Network Brisbane — Herston

Идентификаторы

NCT: NCT07732387 · CR-067-001 · EC00372 · 462/26

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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