Safety, Tolerability and Pharmacokinetics of NYX-783 and Oxycodone DDI Study

NCT05447286 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: 2000033008UG3DA050322NYX-783-1009
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This study proposes to examine the safety, tolerability, and pharmacokinetics (PK) of NYX-783 50 mg and 150 mg versus Placebo (PBO) in combination with acute Oxycodone 15 mg and 30 mg in an inpatient randomized, cross-over study in non-treatment seeking non-dependent, opioid experienced individuals with current recreational use.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (7)

• Change in respiratory rate

  Change in respiratory rate pre and post drug administration measured by counting breaths

  over 6 sessions from baseline up to 3 weeks

• Change in oxygenation saturation

  Change in oxygenation saturation pre and post drug administration measured by pulse-oximeter

  over 6 sessions from baseline up to 3 weeks

• Change in blood pressure

  Change in blood pressure pre and post drug administration measured by blood pressure monitor

  over 6 sessions from baseline up to 3 weeks

• Change in heart rate

  Change in heart rate pre and post drug administration measured by blood pressure monitor

  over 6 sessions from baseline up to 3 weeks

• Change in body temperature

  Change in body temperature pre and post drug administration measured by temperature monitor

  over 6 sessions from baseline up to 3 weeks

• Change in cardiac rate

  Change in cardiac rate pre and post drug administration measured by EKG cardiac monitor

  over 6 sessions from baseline up to 3 weeks

• Change in cardiac rhythm

  Change in cardiac rhythm pre and post drug administration measured by EKG cardiac monitor

  over 6 sessions from baseline up to 3 weeks

Secondary Outcomes (7)

• treatment emergent adverse events (TEAES) from Systematic Assessment for Treatment Emergent Effects (SAFTEE)

  over 6 sessions from baseline up to 3 weeks

• Change in Clinical Opiate Withdrawal Scale (COWS)

  over 6 sessions from baseline up to 3 weeks

• Change in Subjective Opioid Withdrawal Scale (SOWS)

  over 6 sessions from baseline up to 3 weeks

• Change in Drug Effects Questionnaire (DEQ)

  over 6 sessions from baseline up to 3 weeks

• Change in Visual Analog Scale (VAS)

  over 6 sessions from baseline up to 3 weeks

Other Outcomes (1)

• Pharmacokinetic (PK) levels of study medication

  across 3 sessions during the 3 weeks assessment period

Study Arms (3)

Placebo + Oxycodone

PLACEBO COMPARATOR

Participants will receive placebo with + 15 mg oxycodone then placebo + 30 mg oxycodone in separate inpatient randomized sessions in this, cross-over study over 6 experimental sessions.

Drug: Placebo; Drug: Oxycodone

NYX-783: 50 mg dose + Oxycodone

ACTIVE COMPARATOR

Participants will receive NYX-783 50 mg dose with + 15 mg oxycodone then NYX-783 50 mg + 30 mg oxycodone in separate inpatient randomized sessions in this, cross-over study over 6 experimental sessions.

Drug: NYX-783; Drug: Oxycodone

NYX-783: 150 mg dose + Oxycodone

ACTIVE COMPARATOR

Participants will receive NYX-783 150 mg dose with + 15 mg oxycodone then NYX-783 150 mg + 30 mg oxycodone in separate inpatient randomized sessions in this, cross-over study over 6 experimental sessions.

Drug: NYX-783; Drug: Oxycodone

Interventions

NYX-783 DRUG

This study proposes to examine the safety, tolerability, and pharmacokinetics (PK) of NYX-783 at 50 mg and 150 mg doses versus Placebo (PBO) in combination with acute Oxycodone 15 mg and 30 mg in an inpatient randomized, cross-over study over 6 experimental sessions.

Also known as: ((2S, 3R)-3-hydroxy-2-((S)-5-isobutyryl-1-oxo-2,5-diazaspiro[3.4]octan-2-yl)butanamide)

NYX-783: 150 mg dose + Oxycodone; NYX-783: 50 mg dose + Oxycodone

Placebo DRUG

This study proposes to examine the safety, tolerability, and pharmacokinetics (PK) of NYX-783 at 50 mg and 150 mg doses versus Placebo (PBO) in combination with acute Oxycodone 15 mg and 30 mg in an inpatient randomized, cross-over study over 6 experimental sessions.

Placebo + Oxycodone

Oxycodone DRUG

This study proposes to examine the safety, tolerability, and pharmacokinetics (PK) of NYX-783 at 50 mg and 150 mg doses versus Placebo (PBO) in combination with acute Oxycodone 15 mg and 30 mg in an inpatient randomized, cross-over study over 6 experimental sessions.

NYX-783: 150 mg dose + Oxycodone; NYX-783: 50 mg dose + Oxycodone; Placebo + Oxycodone

Eligibility Criteria

• Age: 21 Years - 58 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Voluntary, written, informed consent.
• full scale and verbal IQs \> 80 (Shipley Institute of Living IQ Screening Test).
• Non-treatment seeking, non-dependent, opioid-experienced participants with low, opioid use via smoking or oral pills routes and with no need for medical detoxification from opiates and without past 12-month history of overdoses or medical detoxification for opioid withdrawal.
• Participants must agree to use dual contraceptive methods during the study and refrain from donating sperm or ova during study or for 28 days after final dose of drug for ova and for 90 days after final dose of drug for sperm. Dual contraceptive methods include the use of a barrier contraceptive (i.e., condoms) in addition to another effective method that can prevent pregnancy (i.e., oral or parenteral contraceptives, intrauterine devices, spermicide, etc.).
• Ability to understand and comply with study requirements and restrictions and provide a secondary contact if they cannot be reached.

You may not qualify if:

• Meet current DSM-5 criteria of moderate to severe Substance Use Disorder (SUD) on either sedative, hypnotics, cocaine, methamphetamine, opiates or alcohol.
• Daily heroin, fentanyl use requiring opiate detoxification and treatment.
• Regular daily prescribed use of anticonvulsants, sedatives/hypnotics, other antihypertensives, anti-arrhythmics, antiretroviral medications, naltrexone, antabuse, grapefruit juice and St. John's wort products, glucocorticoids, stimulants (amphetamine like compounds), CNS active medications (other than stabilized use of antidepressants and anti-anxiety medications), metformin, or other medications such as benzodiazepines and sedating antidepressants that in the opinion of the investigators interfere with the study.
• Women who are pregnant or nursing (as assessed by pregnancy tests during initial intake and upon CNRU admissions).
• HIV seropositivity, hepatitis or other acute ongoing infectious disease considered clinically significant by the investigator.
• Traumatic brain injury with loss of consciousness.
• Individuals with current or past history of seizure disorders.
• Current or recent diagnosis within past 6-months of Major Depressive Disorder (MDD), bipolar disorder, schizophrenia, and schizoaffective disorder.
• History of a neurodegenerative or neuro-inflammatory disorder including Huntington's, Parkinson's, Alzheimer's disease, or multiple sclerosis.
• Known familial history or known presence of long QT syndrome, or a known history of past or current clinically significant arrhythmias or ischemic heart disease.
• History of gastrointestinal disease or surgery (except simply appendectomy or hernia repair), leading to impaired drug absorption.
• Uncorrected hypothyroidism or hyperthyroidism. Participants with compensated hypothyroidism with normal thyroid-stimulating hormone levels may be enrolled.
• Sensitivity, allergy, or intolerance to N-methyl-D-aspartate receptor (NMDAR) ligands including ketamine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone and magnesium. Use of NMDAR-binding drugs within 60 days prior to dosing or during the study.
• Received an investigational product or device within 30 days of dosing (or 5 half-lives whichever is longer).
• Previously received NYX-783.

Sponsors & Collaborators

• Yale University: lead

Study Sites (2)

Cmhc/Cnru

New Haven, Connecticut, 06519, United States

Location

The Yale Stress Center: Yale University

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Oxycodone

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Rajita Sinha, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind, placebo controlled.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PROFESSOR

Study Record Dates

• First Submitted: June 21, 2022
• First Posted: July 7, 2022
• Study Start: May 15, 2023
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)