Reversal of opioid-induced respiratory depression with opioid antagonists - a pharmacokinetic pharmacodynamic modeling study in opioid naïve individuals and chronic opioid users under real-life conditions

Ki vehet részt

• Healthy 1. Signed the informed consent form (ICF) and able to comply with the study requirements and restrictions listed therein
• Chronic opioid users 4. BMI 18 to 32 kg/m2, inclusive
• Chronic opioid users 5. Opioid tolerant patients administered prescription opioids at daily doses ≥ 60 mg oral morphine equivalents
• Chronic opioid users 6. Stable as defined by the Investigator, based on a medical evaluation that includes the subject’s medical and surgical history, physical examination, vital signs, 12-lead ECG, hematology, and blood chemistry
• Chronic opioid users 7. positive opioid urine drug screening
• Chronic opioid users 8. positive naloxone challenge
• Healthy 2. Male and female subjects, age 18 to 70 years, inclusive
• Healthy 3. 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
• Healthy 4. Body Mass Index (BMI) 18 to 30 kg/m2, inclusive
• Healthy 5. Healthy as defined by the Investigator, based on a medical evaluation that includes the subject’s medical and surgical history, physical examination, vital signs, lab chemistry: estimated glomerular filtration rate >60 mL/min as estimated by the CKD-EPI equation, and AST or ALT levels < 3.0 times the upper limit of normal at screening, and negative serology tests for HIV, acute hepatitis B, or acute hepatitis C
• Healthy 6. No history of substance use disorder
• Chronic opioid users 1. Signed the consent form and able to comply with the requirements and restrictions listed therein
• Chronic opioid users 2. Males or females age 18 to 70 years, inclusive
• Chronic opioid users 3. 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 3 months after the last dose of study drug

Ki nem vehet részt

• Healthy 10. 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
• Chronic opioid users 2. Any active medical condition, organ disease or concurrent medication or treatment that may either compromise subject safety or interfere with study endpoints
• Chronic opioid users 4. Currently receiving medication-assisted treatment for the treatment of opioid-use disorder
• Chronic opioid users 5. Significant traumatic injury, major surgery, or open biopsy within the prior 4 weeks of informed consent
• Chronic opioid users 6. 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
• Healthy 2. Any other active medical condition, organ disease or concurrent medication or treatment that may either compromise subject safety or interfere with study endpoints
• Chronic opioid users 14. 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
• Healthy 4. Previous or current treatment with opioid agonist, partial agonist, or antagonist treatment within 30 days prior to the first study drug administration
• Healthy 5. Significant traumatic injury, major surgery, or open biopsy within the prior 4 weeks of informed consent
• Healthy 6. 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
• Healthy 1. Currently meet the criteria for diagnosis of substance use disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria on any substance
• Chronic opioid users 1. Currently meet the criteria for diagnosis of moderate or severe substance use disorder according to the DSM-5 criteria on any substances other than opioids, caffeine, or nicotine
• Chronic opioid users 8. History or presence of allergic response to fentanyl, sufentanil, nalmefene or naloxone
• Chronic opioid users 9. Opioid tolerant patients who have demonstrated allergic reactions (e.g., food, drug, atopic reactions or asthmatic episodes) which, in the opinion of the Investigator and sponsor, interfere with their ability to participate in the trial
• Chronic opioid users 12. Positive serology tests for HIV, acute hepatitis B, or acute hepatitis C (OT patients with asymptomatic hepatitis B or C infection may be enrolled)
• Healthy 8. History or presence of allergic response to fentanyl, sufentanil or naloxone or nalmefene
• Healthy 9. Subjects who have demonstrated allergic reactions (e.g., food, drug, atopic reactions or asthmatic episodes) which, in the opinion of the Investigator and sponsor, interfere with their ability to participate in the trial
• Chronic opioid users 13. AST or ALT levels >3.0 times the upper limit of normal at screening
• Healthy 11. Site staff or subjects affiliated with, or a family member of, site staff directly involved in the study
• Chronic opioid users 3. 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)
• Chronic opioid users 7. Measured systolic blood pressure greater than 160 or less than 95 mmHg or diastolic pressure greater than 95 mmHg at screening
• Chronic opioid users 10. Estimated glomerular filtration rate <60 mL/min as estimated by the CKD-EPI equation
• Chronic opioid users 11. Anemia at screening or donation of > 250 mL of blood or plasma within the last 3 months
• Chronic opioid users 15. Site staff or subjects affiliated with, or a family member of, site staff directly involved in the study
• Healthy 3. Consume, on average, >27 units/week of alcohol in men and >13 units/week of alcohol in women (1 unit = 1 glass (250 mL) beer, 125 mL glass of wine or 25 mL of 40% spirit)
• Healthy 7. Measured systolic blood pressure greater than 160 or less than 95 mmHg or diastolic pressure greater than 95 mmHg at screening