Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion (AUVELITY) as an Adjunctive Treatment for Buprenorphine/Naloxone for Opioid Use Disorder
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Safety- as measured by pulse oximetry
研究概览
简要总结
The overall goal of this project is to collect initial human data on the effects of novel compounds on safety (interactions with an opioid drug, e.g., buprenorphine) and early efficacy signals (subjective effects on negative affect, craving, and opioid withdrawal) in OUD subjects currently in MOUD treatment with buprenorphine.
详细描述
The overall goal of this project is to collect initial human data on the effects of novel compounds on safety (interactions with an opioid drug, e.g., buprenorphine) and early efficacy signals (subjective effects on negative affect, craving, and opioid withdrawal) in OUD subjects currently in MOUD treatment with buprenorphine. The compound to be studied in this protocol will be a pre-configured combination of 45mg dextromethorphan with 105 mg Bupropion (AuvelityTM, hereafter referred as Auvelity). Notably, other NMDA receptor antagonists such as ketamine have also been shown to rapidly improve mood and reduce suicidality. OUD has also been linked to histories of trauma and syndromes of negative mood, where opioid use in many individuals was initially motivated by a desire to alleviate a negative mood state. Lastly, using the NIDA Phenotyping Battery, our group has also found negative emotionality to be part of a constellation of neurofunctional domains that are associated with SUD severity. Taken together, providing AUVELITY as an adjunctive treatment to buprenorphine could be an avenue to target crucial underlying mechanisms of OUD and improve OUD treatment outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and female subjects between 18 - 65 years of age;
- •Understand the study procedures and provide written informed consent in the English language.
- •Meet current DSM-5 criteria for OUD, of at least moderate severity, currently engaged in MOUD treatment at a buprenorphine-naloxone sublingual film total daily dose ranging from 8mg/2mg to 24mg/6mg or buprenorphine sublingual tablet 5.7mg/1.4mg to 17.1/4.3 daily for at least 2 weeks at screening. Or on a stable dose of depot injectable buprenorphine for at least four months, with at least one week since last depot buprenorphine injection.
- •Have a positive urine drug screen for buprenorphine during screening and upon presenting for the first laboratory day on the clinical research unit to document buprenorphine use;
- •Quick Inventory of Depressive Symptomatology (16-Item) (QIDS-SR16) score of mild or greater (>6)
- •Females must be non-pregnant and non-lactating. Additionally, for females with childbearing potential (ie., have not undergone sterilization via hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or at least 1 year post-menopausal), participants must agree to use an acceptable form of contraception during study participation and to continue its use for at least 30 days after the last dose of the study drug (e.g, abstinence, intrauterine device, hormonal implant, hormonal patch/ring/pill, condoms (male or female).
排除标准
- •Contraindications for participation as determined by medical history and physical exam performed by study NP or study physician;
- •Pregnant or nursing women;
- •Baseline ECG with clinically significant abnormal conduction;
- •Uncontrolled serious psychiatric or major medical disorder; including uncontrolled hypertension, seizure disorder, anorexia nervosa or bulimia, bipolar disorder, schizoaffective disorder, or schizophrenia;
- •Taking antidepressant medications (tricyclic antidepressants, SSRIs, SNRIs, MAOIs), antibiotic linezolid, antiepileptics, or CNS stimulants (amphetamine, methylphenidate) within the two weeks prior to initiation of study medication
- •History of adverse reaction or allergy to dextromethorphan or bupropion
- •Current severe alcohol use disorder or current benzodiazepine use or recent (within last 3 months) discontinuation of alcohol with severe alcohol use disorder or discontinuation of benzodiazepines with severe benzodiazepine use disorder
- •Current DSM-5 diagnosis of any psychoactive substance use disorder other than opioids, cocaine, marijuana, or nicotine, or mild or moderate alcohol use disorder. Diagnosis of mild to moderate use disorder for alcohol will not be considered exclusionary.
- •Significant current suicidal or homicidal ideation (C-SSRS "yes" answers on questions 4 or 5) or a history of suicide attempt within the past 6 months.
- •Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
研究组 & 干预措施
Auvelity
Orally-administered combination of dextromethorphan with Bupropion (trade name Auvelity)
干预措施: Auvelity (Drug)
Placebo
Subjects who are randomized to placebo will receive identical capsules to the test product at the same time periods noted above, administered orally.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety- as measured by pulse oximetry
时间窗: During each PK study visit from visit start to end, up to approximately 8 hours
pulse oximetry
Safety- as measured by respiratory rate
时间窗: During each PK study visit from visit start to end, up to approximately 8 hours
respiratory rate
Safety- as measured by blood pressure
时间窗: During each PK study visit from visit start to end, up to approximately 8 hours
blood pressure
Safety- as measured by Adverse events
时间窗: During each PK study visit from visit start to end, up to approximately 8 hours; and from baseline to end of study participation
adverse events
Safety- as measured by heart rate
时间窗: During each PK study visit from visit start to end, up to approximately 8 hours
Heart rate (HR)
Safety- as Measured by Average Heart Rate (Pulse) at Each Testing Visit
时间窗: Baseline and Day 8 (PK testing visits)
Measuring pulse is crucial for providing real-time, objective data. It acts as a baseline indicator to detect irregularities and monitor for stress and fatigue levels. The healthy resting heart rate (RHR) for most adults is 60-100 beats per minute (bpm). A lower rate usually indicates better cardiovascular fitness. A poor score is falling above the 60-100bpm range.
Safety- as Measured by Average Blood Pressure at Each Testing Visit
时间窗: Baseline and Day 8 (PK testing visits)
Systolic blood pressure is the first (top/upper) number. It measures the pressure your blood is pushing against your artery walls when the heart beats. Diastolic blood pressure is the second (bottom/lower) number. It measures the pressure your blood is pushing against your artery walls while the heart muscle rests between beats. A good, healthy blood pressure for most adults is generally considered to be less than 120/80 mm Hg. It ensures participant safety by monitoring for extreme hypertension or hypotension, validating cardiovascular drug effects. Anything abovethe 130/80 mmHg is considered a high or bad reading. A high reading means that your heart is working too hard to pump blood and putting excessive strain on the arteries.
Safety- as Measured by Average Pulse Oximetry at Each Testing Visit
时间窗: Baseline and Day 8 (PK testing visits)
Measuring pulse oximetry (SpO2) for research safety provides real-time, noninvasive monitoring of oxygen saturation, crucial for identifying "silent hypoxia," detecting respiratory decline from interventions, and ensuring participant safety during trials. The normal range is 95%-100%. Anything below the 95% is out of normal range and cause for concern.
Safety- as Measured by Average Respiratory Rate at Each Testing Visit
时间窗: Baseline and Day 8 (PK testing visits)
A good, normal respiratory rate for research safety data in resting adults is 12 to 20 breaths per minute (bpm). Rates consistently under 12 or over 25 bpm are often flagged in clinical studies as potential safety concerns.
Safety- as Measured by Total Number of Adverse Events
时间窗: Baseline to Week 2 follow-up
Tracking adverse event (AE) rates in research is essential to ensure participant safety, determine the risk-benefit ratio of interventions, and maintain data integrity for regulatory approval. Analyzing these rates allows investigators to identify trends, detect unexpected risks early, and modify studies to prevent harm. .
次要结局
- Buprenorphine PK(During each PK study visit from visit start to end, up to approximately 8 hours)