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

Official title

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

Overview

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.

Detailed description

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.)

Interventions

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

Primary outcome measures

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

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Basic science

Study locations

Australia · 1 center

• Nucleus Network Brisbane — Herston

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗