Influence of Oxycodone on Individuals Taking an SSRI
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 55
- 主要终点
- Ve55 Paroxetine 1 week
研究概览
简要总结
This study will determine whether selective serotonin reuptake inhibitors (SSRI) exacerbate opioid induced respiratory depression in patients initiating treatment for underlying conditions such as depression or an anxiety disorder. Next to paroxetine which has been evaluated in a previous study in healthy volunteers sertraline, citalopram and escitalopram will be evaluated with regards to its influence on opioid induced respiratory depression.
详细描述
Primary Objective:
To determine the effect of low-dose (10 mg) oxycodone versus placebo in individuals that use paroxetine on ventilation at an extrapolated end-tidal carbon dioxide concentration of 55 mmHg at 1 week (4-10 days) of SSRI treatment.
Secondary objectives:
To determine the effect of low-dose (10 mg) oxycodone versus placebo in individuals that either use sertraline, citalopram or escitalopram on ventilation at an extrapolated end-tidal carbon dioxide concentration of 55 mmHg at 1 week (4-10 days) of SSRI treatment.
To determine the effect of low dose (10 mg) oxycodone versus placebo in individuals that either use paroxetine, sertraline, citalopram or escitalopram on ventilation at an extrapolated end-tidal carbon dioxide concentration of 55 mmHg following at 1 month (25- 45 days) following initiation of SSRI treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed the informed consent form (ICF) and able to comply with the study requirements and restrictions listed therein;
- •Male and female subjects, age 18 to 75 years, inclusive;
- •Women of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to informed consent) must have a negative serum pregnancy test prior to enrolment and must agree to use a medically acceptable means of contraception from screening through at least 1 month after the last dose of study drug;
- •Body Mass Index (BMI) 18 to 35 kg/m2, inclusive;
- •Stable as defined by the Investigator, based on a medical evaluation that includes the subject's medical and surgical history, physical examination, vital signs;
- •Using sertraline (minimal dose 50 mg), paroxetine minimal dose 20 mg), citalopram (minimal dose 20 mg) or escitalopram (minimal dose 10 mg).
排除标准
- •Currently meet the criteria for diagnosis of moderate or severe substance use disorder according to the DSM-5 criteria on any substances other than caffeine, or nicotine;
- •Any active medical condition, organ disease or concurrent medication or treatment that may either compromise subject safety or interfere with study endpoints;
- •Consume, on average, >27 units/week of alcohol in men and >20 units/week of alcohol in women (1 unit = 1 glass (250 mL) beer, 125 mL glass of wine or 25 mL of 40% spirit);
- •Currently receiving medication-assisted treatment for the treatment of opioid-use disorder;
- •Require on-going prescription or over-the-counter medications that are clinically relevant CYP P450 3A4 or CYP P450 2C8 inducers or inhibitors (e.g., rifampicin, azole antifungals [e.g., ketoconazole], macrolide antibiotics [e.g., erythromycin]);
- •Significant traumatic injury, major surgery, or open biopsy within the prior 4 weeks of informed consent;
- •History of substance use disorder;
- •History of suicidal ideation within 30 days prior to informed consent or history of a suicide attempt in the 6 months prior to informed consent;
- •Measured systolic blood pressure greater than 160 or less than 95 mmHg or diastolic pressure greater than 95 mmHg at screening;
- •History or presence of allergic response to study medication;
- •Treatment with another investigational drug within 3 months prior to dosing or having participated in more than 4 investigational drug studies within 1 year prior to screening;
- •Site staff or subjects affiliated with, or a family member of, site staff directly involved in the study.
- •Current use of any opioid.
- •Opioid use less than 4 weeks prior to dosing with oxycodone in the current study.
研究组 & 干预措施
SSRI 1 month following initiation placebo
Patients will be included day 25-45 following initiation of treatment with either Paroxetine, Sertraline, Escitalopram or Citalopram and and will be administered placebo comparator.
干预措施: Placebo (Drug)
SSRI 1 week following initiation placebo
Patients will be included day 25-45 following initiation of treatment with either Paroxetine, Sertraline, Escitalopram or Citalopram and and will be administered placebo comparator
干预措施: Placebo (Drug)
SSRI 1 month following initiation oxycodone
Patients will be included day 25-45 following initiation of treatment with either Paroxetine, Sertraline, Escitalopram or Citalopram and and will be administered oxycodone 10 mg IR.
干预措施: Oxycodone Hydrochloride (Drug)
SSRI 1 week following initiation oxycodone
Patients will be included day 4-10 following initiation of treatment with either Paroxetine, Sertraline, Escitalopram or Citalopram and will be administered oxycodone 10 mg IR
干预措施: Oxycodone Hydrochloride (Drug)
结局指标
主要结局
Ve55 Paroxetine 1 week
时间窗: two hours following ingestion of the Paroxetine either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.
After one week of starting Paroxetine, extrapolated ventilation at an end-tidal carbon dioxide concentration of 55 mmHg will be measured, followed by oxycodone or placebo ingestion. The extrapolated ventilation at an end-tidal carbon dioxide concentration of 55 mmHg will be assessed two hours after oxycodone/placebo ingestion. The change from the baseline will be determined.
次要结局
- Ve55 Sertraline, Citalopram, Escitalopram 1 week(two hours following ingestion of the Sertraline or Citalopram or Escitalopram either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.)
- Ve55 Paroxetine, Sertraline, Citalopram, Escitalopram at 1 month(two hours following ingestion of the Sertraline or Citalopram or Escitalopram either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.)
- Pupillometry(Will be determined from pupillometry at t= 0,30,60,90,120,150,180,210,240,270,300 minutes)
- Plasma concentration oxycodone(Will be determined from blood samples drawn at t= 0,15,30,45,60,120,180,240,300 minutes)
- Ve55 over course Treatment(two hours following ingestion of the Sertraline or Citalopram or Escitalopram either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.)
研究者
Albert Dahan
MD PhD
Leiden University Medical Center