Single Ascending Dose Study of NRS 033 in Healthy Volunteers

NCT05724797 | Completed Phase 1 FDA Drug

• 2 other identifiers: NRS-033-102UG3DA048234
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (13)

• 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

Study Arms (2)

NRS-033: Cohorts 1-3

EXPERIMENTAL

Cohorts 1-3: 6 participants in each cohort will receive active drug (NRS-033)

Drug: NRS-033

Placebo: Cohorts 1-3

PLACEBO COMPARATOR

Cohorts 1-3: 2 participants in each cohort will receive the matching placebo dose

Drug: Placebo

Interventions

NRS-033 DRUG

A single dose of NRS-033 will be administered

NRS-033: Cohorts 1-3

Placebo DRUG

A single dose of matching placebo will be administered

Placebo: Cohorts 1-3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Nirsum Labs: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Frontage Clinical Research Center

Secaucus, New Jersey, 07094, United States

Location

Study Officials

• N Shah, MD

  Nirsum Labs

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2023
• First Posted: February 13, 2023
• Study Start: April 17, 2023
• Primary Completion: December 4, 2024
• Study Completion: December 4, 2024
• Last Updated: December 8, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)