Single Ascending Dose Study of NRS 033 in Healthy Volunteers

A Phase 1, First in Human, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of NRS 033 in Healthy Volunteers

This is a phase 1, first in human, randomized, double-blind, placebo-controlled, single ascending dose (SAD) study in healthy adult male and female subjects 18 to 55 years of age, inclusive.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: NRS-033; Drug: Placebo

Detailed Description

Subjects will provide written informed consent and undergo a screening visit within 28 days of receiving study drug. Eligible subjects must have a negative urine drug screen (UDS) and a negative naloxone challenge test at Screening and at the check-in visit (Day -1). Upon completion of screening, eligible subjects will be admitted to the clinical research unit (CRU) on Day -1 and remain confined in the CRU through completion of all scheduled procedures on Day 4 to allow for safety labs, pharmacokinetic (PK) blood draws, ECGs, injection site assessments, and adverse event monitoring.

Study medication dosing will occur in the morning on Day 1 and serial blood samples for plasma concentration determination for PK analysis will be taken during this time at pre-dose and 0.25, 0.50, 1, 1.5, 2, 4, 8, 10, 12, 24 (day 2), 48 (day 3), and 72 (day 4) hours post dose. Additional blood PK samples will be taken at follow-up visits. A Safety Review Committee (SRC) will review blinded, preliminary data from Cohort 1 to make recommendations regarding escalation to Cohorts 2 and 3.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Secaucus, New Jersey, United States, 07094
      • Frontage Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female ≥18 and ≤55 years of age at time of consent
• Body mass index ≥18.0 to ≤35.0 kg/m2
• Medically healthy based on the absence of clinically significant abnormal vital sign
• Females must have a negative serum pregnancy test at time of screening and negative urine pregnancy test upon admission; also, females of childbearing potential must agree to use a highly effective means of contraception from Screening until 9 months after receiving the study medication.
• Male subjects with female partners of childbearing potential must agree to use a male condom and will be advised of the benefit for a female partner to use a highly effective method of contraception
• Agree to stay within National Institute on Alcohol Abuse and Alcoholism (NIAAA) low risk drinking criteria. For women, low-risk drinking is no more than 3 drinks on any single day and no more than 7 drinks per week. For men, it is defined as no more than 4 drinks on any single day and no more than 14 drinks per week.
• Agree not to take opioid analgesics.

Exclusion Criteria:

• Clinically significant medical or psychiatric diagnosis (assessed on history, physical exam, ECG, and/or blood tests; includes significant history of cardiovascular, pulmonary, hepatic, gallbladder, or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychiatric disease, or active sexually transmitted disease).
• Significant neuropsychiatric diagnosis (e.g., major depression, suicidal ideation, multiple sclerosis, dementia) as reported by the subject, or a past history of suicide attempt.
• Females who are pregnant, lactating, or likely to become pregnant during the study.
• History over last 30 days of consuming alcohol >3 drinks day per day or >7 drinks per week if female; if male >4 drinks per day or >14 drinks per week.
• Currently uses tobacco or nicotine containing products, including but not limited to cigarettes, electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum.
• Reported history of a significant traumatic injury, major surgery, or open biopsy within the 4 weeks prior to signing the informed consent form.
• Subject reported history of any use of long-term use of opioids agonists or antagonists; e.g., methadone, oxycodone, hydrocodone, naltrexone, buprenorphine.
• Subject reported history of any medications to treat opioid use disorder (MOUD); e.g., methadone, naltrexone, buprenorphine, kratom.
• Subject reports anticipated need for opioid analgesia in the next 12 months (e.g., planned surgery).
• Subject reports history or presence of allergic or adverse response (including rash or anaphylaxis) to naloxone, naltrexone, nalmefene, morphinan opioid agonists, benzyl alcohol or sesame oil.
• Positive urine drug screen (UDS) for barbiturates, benzodiazepines, cocaine, methamphetamine, or opioids.
• Positive alcohol breath test.
• Received an investigational drug within the last 30 days or 5 half-lives of the drug, whichever is longer, prior to administration of study medication.
• Has taken exclusionary prohibited medications within the last 30 days or 5 half-lives of the drug, whichever is longer.
• Subjects with a history of syncope, or have a history of symptomatic hypotension or symptomatic hypoglycemia.
• Subjects who test positive for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HbsAg), or Hepatitis C virus (HCV) antibody.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NRS-033: Cohorts 1-3; Cohorts 1-3: 6 participants in each cohort will receive active drug (NRS-033)	Drug: NRS-033; A single dose of NRS-033 will be administered
Placebo Comparator: Placebo: Cohorts 1-3; Cohorts 1-3: 2 participants in each cohort will receive the matching placebo dose	Drug: Placebo; A single dose of matching placebo will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Adverse Events (TEAEs)	Number of Participants with TEAEs	From predose through end of study visit, assessed up to study completion, an average of 15 months
Severity of TEAEs	Severity of TEAEs	From predose through end of study visit, assessed up to study completion, an average of 15 months
Serious Adverse Events (SAEs)	Number of Participants with SAEs	From predose through end of study visit, assessed up to study completion, an average of 15 months
Discontinuation Due to Adverse Events (AEs)	Number of Participants who discontinue the study due to AEs	From predose through end of study visit, assessed up to study completion, an average of 15 months
Pharmacokinetics: AUC0-last	Area under the plasma concentration-time curve (AUC) from time 0 to last measurable plasma concentration	From predose through end of study visit, assessed up to study completion, an average of 15 months
Pharmacokinetics: AUC0-infinity	Area under the plasma concentration-time curve from time 0 to infinity, calculated as AUC0-last + AUCt-inf	From predose through end of study visit, assessed up to study completion, an average of 15 months
Pharmacokinetics: AUC0-inf %extrapolation	Percentage of AUC0-inf due to extrapolation from Tlast to infinity	From predose through end of study visit, assessed up to study completion, an average of 15 months
Pharmacokinetics: Cmax	Maximum observed plasma concentration (Cmax)	From predose through end of study visit, assessed up to study completion, an average of 15 months
Pharmacokinetics: Tmax	Time of Cmax	From predose through end of study visit, assessed up to study completion, an average of 15 months
Pharmacokinetics: t1/2	Terminal half-life (t1/2)	From predose through end of study visit, assessed up to study completion, an average of 15 months
Pharmacokinetics: Kel (λz)	Apparent terminal rate-constant, calculated using linear regression on the terminal portion of the Log-concentration versus time curve	From predose through end of study visit, assessed up to study completion, an average of 15 months
Pharmacokinetics: Vz/F	Apparent volume of distribution (Vz/F)	From predose through end of study visit, assessed up to study completion, an average of 15 months
Pharmacokinetics: CL/F	Apparent clearance (CL/F)	From predose through end of study visit, assessed up to study completion, an average of 15 months

Collaborators and Investigators

• Sponsor: Nirsum Labs
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Study Director: N Shah, MD, Nirsum Labs

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2023
• Primary Completion (Actual): December 4, 2024
• Study Completion (Actual): December 4, 2024

Study Registration Dates

• First Submitted: February 1, 2023
• First Submitted That Met QC Criteria: February 10, 2023
• First Posted (Actual): February 13, 2023

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: NRS-033-102; UG3DA048234 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No