A Phase 1 Study to Evaluate Safety and Tolerability of NoNO-42 in Healthy Adults

A Phase 1, Randomized, Placebo Controlled, Double-Blind, Single Dose Escalation Study of NoNO-42 in Healthy Adults

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.

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.

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.