Clinical Evaluation of NMDA Modulator NYX-783 for OUD: Randomized, Double-blind, Placebo-Controlled Study to Assess Safety, Tolerability, and Pharmacokinetics of NYX-783 in Combination With Oxycodone (Study 1)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Change in cardiac rate
研究概览
简要总结
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.
详细描述
Outcomes will be cardiovascular (ECG monitoring, heart rate, blood pressure), respiratory, Clinical Opioid Withdrawal Scale (COWS), treatment emergent adverse events (TEAEs), and PK of NYX-783 levels in combination with Oxycodone. Secondary outcomes will be drug effects, subjective opiate withdrawal scale (SOWS), Drug Effects Questionnaire (DEQ), pupillary diameter, the Opioid Symptom Checklist (OSC), craving, stress and pain, and study drug levels during NYX-783 and Oxycodone combination challenge sessions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blind, placebo controlled.
入排标准
- 年龄范围
- 21 Years 至 58 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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-
- •Screening QT interval corrected for heart rate (HR) by Fridericia's formula (QTcF) > 450 (males) or 470 (females) milliseconds (msec) or an ECG that is not suitable for QT measurements (e.g., poorly defined termination of T-wave in the investigator's opinion.
- •Heart rate ≤45 or >90 bpm at screening
- •Creatinine clearance <60ml/min at screening or history of renal disease as assessed by Investigator.
- •Uncontrolled Type I or Type II diabetes or uncontrolled hypertension characterized by fasting blood glucose > 126 mg/dl or postprandial blood glucose > 200 mg/dl, resting systolic blood pressure >160 mm Hg or resting diastolic >100 mm Hg, or clinically significant hypotension in the judgement of the Investigator as characterized by resting systolic blood pressure <90 mm Hg or resting diastolic blood pressure <60 mm Hg.
- •Impaired hepatic function characterized by a previous known diagnosis of chronic liver disease and/or the presence of:
- •direct bilirubin > 1.5x the upper limit of normal at screening
- •alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, or gamma-glutamyl transferase (GGT) > 2x the upper limit of normal at screening.
- •History of severe COVID-19 infection requiring hospitalization, treatment with oxygen or mechanical ventilation, that may interfere with study participation as assessment by the Investigator.
- •Any participant with a medical history of Covid-19 infection (positive test) within the last 2 months, or current symptoms consistent with Covid-19 infection, as assessed by the Investigator.
- •Donated blood during the past 8 weeks.
- •Participants who do not report an increase in subjective opioid effect, as measured by the Drug Effects Questionnaire (DEQ, see below) by minimum of 10% or more to initial challenge with oxycodone in Session 1 will be excluded from the DDI phase sessions 2-7.
研究组 & 干预措施
Placebo + Oxycodone
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.
干预措施: Placebo (Drug)
Placebo + Oxycodone
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.
干预措施: Oxycodone (Drug)
NYX-783: 50 mg dose + Oxycodone
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.
干预措施: NYX-783 (Drug)
NYX-783: 50 mg dose + Oxycodone
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.
干预措施: Oxycodone (Drug)
NYX-783: 150 mg dose + Oxycodone
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.
干预措施: NYX-783 (Drug)
NYX-783: 150 mg dose + Oxycodone
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.
干预措施: Oxycodone (Drug)
结局指标
主要结局
Change in cardiac rate
时间窗: over 6 sessions from baseline up to 3 weeks
Change in cardiac rate pre and post drug administration measured by EKG cardiac monitor
Change in oxygenation saturation
时间窗: over 6 sessions from baseline up to 3 weeks
Change in oxygenation saturation pre and post drug administration measured by pulse-oximeter
Change in body temperature
时间窗: over 6 sessions from baseline up to 3 weeks
Change in body temperature pre and post drug administration measured by temperature monitor
Change in cardiac rhythm
时间窗: over 6 sessions from baseline up to 3 weeks
Change in cardiac rhythm pre and post drug administration measured by EKG cardiac monitor
Change in blood pressure
时间窗: over 6 sessions from baseline up to 3 weeks
Change in blood pressure pre and post drug administration measured by blood pressure monitor
Change in heart rate
时间窗: over 6 sessions from baseline up to 3 weeks
Change in heart rate pre and post drug administration measured by blood pressure monitor
Change in respiratory rate
时间窗: over 6 sessions from baseline up to 3 weeks
Change in respiratory rate pre and post drug administration measured by counting breaths
次要结局
- Change in Subjective Opioid Withdrawal Scale (SOWS)(over 6 sessions from baseline up to 3 weeks)
- 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 Drug Effects Questionnaire (DEQ)(over 6 sessions from baseline up to 3 weeks)
- Change in Opioid Symptom Checklist (OSC)(over 6 sessions from baseline up to 3 weeks)
- Change in Visual Analog Scale (VAS)(over 6 sessions from baseline up to 3 weeks)
- Change in pupillary diameter(over 6 sessions from baseline up to 3 weeks)