A Phase 1, Randomized, Double-blind, Placebo-controlled Study Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of VNA-318 in Healthy Male Subjects
Overview
- Phase
- Phase 1
- Intervention
- VNA-318
- Conditions
- Not specified
- Sponsor
- Vandria SA
- Enrollment
- 92
- Locations
- 1
- Primary Endpoint
- Safety and tolerability of single dose
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
This is a phase 1, randomized, double-blind, placebo-controlled study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses (SAD) and multiple ascending doses (MAD) of VNA-318 in healthy male subjects.
Detailed Description
The First-in-Human phase I, single center study investigating VNA-318, administered orally, will consist of 2 parts: * Part 1 SAD, conducted in 5 to 8 cohorts of 8 healthy male subjects per dose level, including one optional exploratory cohort with cerebrospinal fluid (CSF) sampling * Part 2 MAD, conducted in 3 to 4 cohorts of 12 healthy male subjects per dose level Subjects will be included in either Part 1 or 2. A Study Safety Committee is involved and will make recommendations on the study advancement, i.e. the dose for the next planned cohort. The doses of the MAD part will be selected by this Study Safety Committee and will be based upon safety and tolerability assessments, the observed PK and, if available and applicable, PD data from SAD.
Investigators
Chief Executive Officer
Scientific
Vandria SA
Eligibility Criteria
Inclusion Criteria
- •Subjects able and willing to provide written informed consent prior any other clinical study procedures.
- •Subjects able and willing to comply with the clinical study protocol (hospitalization periods, scheduled visits, IMP administration, clinical laboratory tests, and other study procedures including lifestyle considerations) according to International Council of Harmonization (ICH) and local regulations.
- •Healthy male.
- •Aged 18-65 years (inclusive) on the day of signing the informed consent form (ICF). - Aged 18-45 years (inclusive) for the SAD optional exploratory cohort with CSF sampling
- •Have a body mass index (BMI) between 18.5-30.0 kg/m2 (inclusive) at screening and D
- •Health Status
- •Have normal physical examination and vital signs (VS) results within normal ranges at screening and D˗
- •If outside normal ranges, it must be considered by the Investigator without clinically significant abnormal findings.
- •Have a clinical laboratory of blood and urine within normal ranges at screening and D-
- •If outside normal ranges, it must be considered by the Investigator without clinically significant abnormal findings.
Exclusion Criteria
- •Medical History
- •Any condition or disease detected during the medical interview/physical examination that could relapse during or immediately after the study, or would render the subject unsuitable for the study, place the subject at undue risk, or interfere with the ability of the subject to complete the clinical study, as determined by the Investigator.
- •Have a history of and/or current clinically significant disease/disorder determined by the Investigator: gastrointestinal, endocrine, renal, hepatic, immunological, cardiovascular, hematological, respiratory, neurologic, metabolic, urologic, dermatologic, psychiatric disorder, or allergic disease, hypersensitivity, or allergic reactions excluding mild asymptomatic seasonal allergies (either spontaneous or following drug administration), or malignancy (including lymphoma, leukemia, and skin cancer) unless remission over 10 years.
- •Have a personal or family history of prolonged QT interval syndrome or Torsade de Pointes, or family history of sudden death.
- •Have current presence of an illness, such as a common cold, isolated headache, diarrhea, etc., within 14 days prior to D1 that is categorized as clinically significant by the Investigator.
- •History or presence of regular use of recreational or illicit drugs within 1 year before study D
- •Donation of blood or blood loss (i.e., \> 450 ml) within 90 days, or donated plasma within 7 days prior to D-
- •Known significant hypersensitivity or other contraindication to any of the components of the study drug.
- •History of suicidal behavior or any risk of suicidal behavior in the opinion of a certified clinician or as evidenced by a "yes" to any questions of Columbia-Suicide Severity Rating Scale (C-SSRS) taken at screening (MAD part only).
- •Confirmed coronavirus disease 2019 (COVID-19) infection within 90 days of screening or contact with an individual with COVID-19 infection in the past 14 days at D-
Arms & Interventions
Part 1 (SAD): Active
Single oral dose of VNA-318
Intervention: VNA-318
Part 1 (SAD): Placebo
Single oral dose of Matching Placebo
Intervention: Placebo
Part 2 (MAD): Active
Multiple oral doses of VNA-318
Intervention: VNA-318
Part 2 (MAD): Placebo
Multiple oral doses of Matching Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Safety and tolerability of single dose
Time Frame: From Day 1 to Day 7
• Percentage of subjects who meet the abnormal criteria for safety electrocardiogram (ECG) parameters at least once post-dose.
Safety and tolerability of multiple dose
Time Frame: From Day 1 to Day 19
• Percentage of subjects who meet the abnormal criteria for safety electrocardiogram (ECG) parameters at least once post-dose.
Secondary Outcomes
- SAD - Cmax(Day 1)
- SAD tmax(Day 1)
- SAD Clast(Day 1)
- SAD Tlast(Day 1)
- SAD AUC0-inf(Day 1)
- SAD AUC0-t(Day 1)
- SAD ke(Day 1)
- SAD t½(Day 1)
- SAD CL/F(Day 1)
- SAD Vz/F(Day 1)
- MAD Cmax(Day 1 and Day 12)
- MAD tmax(Day 1 and Day 12)
- MAD Ctrough(Day 1 and Day 12)
- MAD AUC0-24h(Day 1 and Day 12)
- MAD AUC0-inf(Day 1 and Day 12)
- MAD ke(Day 1 and Day 12)
- MAD t½(Day 1 and Day 12)
- MAD CL/F(Day 1 and Day 12)
- Characterize MAD PK profiles of VNA-318(Day 1 and Day 12)
- MAD Vss(Day 12)
- MAD accumulation ratio(Day 12)