First-In-Human Study to Evaluate Safety of a New Drug Intended for Treatment of Acute Ischemic Stroke
Conditions
Brief summary
The purpose of this clinical trial is to evaluate the safety, tolerability and pharmacokinetics of a single ascending intravenous dose of NoNO-42 administered to healthy adults. Participants will be administered a single intravenous dose of NoNO-42 or placebo. Participants will be confined for 24 hours post dose with a follow-up visit at Day 4 and Day 28.
Detailed description
The trial was a single, adaptive dose, dose escalation study in healthy male and female adults. The trial was randomized, double-blind, placebo controlled and evaluated the safety, tolerability, and PK of IV NoNO-42 in healthy adults. Each healthy volunteer was administered a single IV dose of study drug or placebo. It was planned that up to 10 dosing cohorts would be evaluated. A cohort may have been repeated or added if necessary. Cohort 1 included 4 healthy volunteers (1:1 randomization of NoNO-42 to placebo) with a sentinel dose of 2 healthy volunteers (1:1). Cohorts 2 to 10 were to include 10 new healthy volunteers dosed at each dose level (4:1 randomization of NoNO-42 to placebo) during the single dose escalation. Sentinel dosing with 2 healthy volunteers (1:1) occurred at each dose escalation. Both the dose concentration and the dosing duration may have been adjusted.
Interventions
DRUGNoNO-42
A single intravenous infusion weight-based dose of NoNO-42 administered over 10±1 minute
DRUGPlacebo
A volume of 0.9% normal saline matching the volume required for a weight-based dosing of NoNO-42, administered as a single 10±1 minute intravenous infusion.
Sponsors
NoNO Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures, clinic visits, blood draws, and availability for the duration of the study * Healthy adult male or female aged 18 to 60 years old. * Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively * Body weight less than or equal to 120 kg * Good bilateral venous access sufficient for IV infusions as judged by the investigator or designee * Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by an investigator
Exclusion criteria
* Female who is lactating or pregnant * History of significant hypersensitivity to NoNO-42 or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs * Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability * History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, renal, hepatic, or dermatologic disease * Presence of clinically significant ECG abnormalities, or any QT interval abnormalities, at the screening visit, as defined by medical judgment * Immunization with a COVID-19 vaccine in the 14 days prior to the first study drug administration or plans for vaccination * Blood pressure below 100 mmHg systolic and 60 mmHg diastolic, and any upper limit is deemed clinically significant by the investigator * Estimated glomerular filtration rate (eGFR) of \<60 mL/min.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of AEs, abnormal laboratory findings and abnormal vital signs | 28 days | * Incidence, severity, and causal relationship of AEs. * Incidence of abnormal laboratory findings, including histamine. * Incidence of abnormal vital signs (blood pressure, heart rate, temperature) and electrocardiogram (ECG) parameters |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics of NoNO-42 following administration of a single ascending IV dose | 24 hours |
Countries
Canada
Outcome results
None listed