Erectile Dysfunctions, Healthy Volunteer
Conditions
Keywords
viaca, sildenafil, cabergoline, erectile dysfunction, PDE5 inhibitor, dopamine agonist, fixed-dose combination, single ascending dose, pharmacokinetics, healthy volunteers, Phase 1
Brief summary
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
DRUGSildenafil 50 mg
single oral dose
single oral dose
DRUGViaca
fixed-dose oral tablet of sildenafil + cabergoline (low-dose 25/0.25 mg; high-dose 50/0.5 mg). Single oral dose.
Sponsors
Yanping Kong
Novotech (Australia) Pty Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants with AEs/SAEs | 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 | Baseline through Day 8. | Change from Baseline in systolic and diastolic blood pressure. Unit: mmHg. |
| Pulse rate | Baseline through Day 8. | Change from Baseline in pulse rate. Unit: beats/min. |
| Respiratory rate | Baseline through Day 8. | Change from Baseline in respiratory rate. Unit: breaths/min. |
| Body temperature | Baseline through Day 8. | Change from Baseline in body temperature. Unit: °C. |
| ECG heart rate | Baseline through Day 8. | Change from Baseline in 12-lead ECG heart rate. Unit: beats/min. |
| ECG intervals | Baseline through Day 8. | Change from Baseline in 12-lead ECG intervals (QTcF, PR, QRS). Unit: milliseconds. |
| Laboratory tests | Baseline through Day 8. | Number of participants with clinically significant safety laboratory abnormalities. Unit: participants. |
| Physical examination | Baseline through Day 8. | Number of participants with clinically significant physical examination findings. Unit: participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | Predose (Day 1) through 168 hours post-dose (Day 8). | Maximum observed plasma concentration (Cmax). Unit: e.g. ng/mL. |
| Tmax | Predose (Day 1) through 168 hours post-dose (Day 8). | Time to maximum plasma concentration (Tmax). Unit: hours. |
| AUC0-t | Predose (Day 1) through 168 hours post-dose (Day 8) | Area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t). Unit: e.g. ng·h/mL. |
| AUC0-24 | Predose (Day 1) through 168 hours post-dose (Day 8). | AUC from time 0 to 24 hours (AUC0-24). Unit: e.g. ng·h/mL. |
| AUC0-inf | Predose (Day 1) through 168 hours post-dose (Day 8). | AUC from time 0 extrapolated to infinity (AUC0-inf). Unit: e.g. ng·h/mL. |
| %AUCextrap | Predose (Day 1) through 168 hours post-dose (Day 8). | Percentage of AUC0-inf obtained by extrapolation (%AUCextrap). Unit: percentage. |
| t½ | Predose (Day 1) through 168 hours post-dose (Day 8). | Apparent terminal elimination half-life (t½). Unit: hours. |
| kel | Predose (Day 1) through 168 hours post-dose (Day 8). | Terminal elimination rate constant (kel). Unit: 1/hour. |
| CL/F | Predose (Day 1) through 168 hours post-dose (Day 8). | Apparent total clearance after oral dosing (CL/F). Unit: e.g. L/h. |
| Vz/F | Predose (Day 1) through 168 hours post-dose (Day 8). | Apparent volume of distribution during the terminal phase after oral dosing (Vz/F). Unit: e.g. L. |
| Cmax/D | Predose (Day 1) through 168 hours post-dose (Day 8). | Dose-normalised maximum plasma concentration (Cmax/D). Unit: e.g. ng/mL per mg. |
| AUC0-inf/D | Predose (Day 1) through 168 hours post-dose (Day 8). | Dose-normalised AUC0-inf (AUC0-inf/D). Unit: e.g. ng·h/mL per mg. |
| AUC0-t/D | Predose (Day 1) through 168 hours post-dose (Day 8). | Dose-normalised AUC0-t (AUC0-t/D). Unit: e.g. ng·h/mL per mg. |
| Dose proportionality | Predose (Day 1) through 168 hours post-dose (Day 8). | Dose proportionality of Cmax and AUC across Viaca dose levels. Unit: e.g. slope (power-model estimate). |
Countries
Australia
Contacts
CONTACTClinical Research Coordinator at Nucleus Network Brisbane
PRINCIPAL_INVESTIGATOREmma Trowbridge, MD
Nucleus Network Brisbane
Outcome results
None listed