A Study on Oral and Intranasal Forms of Oxycodone in Healthy Volunteers Using Pharmacokinetic Modeling

Physiologically Based Pharmacokinetic Modelling of Oral and Intranasal Formulations of Oxycodone in Healthy Volunteers

This is a single-dose, 2-period, 2-sequence, fasting, open label, crossover randomized design, comparing the pharmacokinetics (PK) and pharmacodynamics (PD) of intranasal and oral oxycodone solutions. The aim will be to characterize the PK and PD of two formulations of oxycodone (intranasal and oral) in healthy subjects, which will be used to verify/validate nasal-CNS-PBPK (Physiologically Based Pharmacokinetic) model predictions following intranasal dosing. A total of 8 healthy male/female subjects will be randomly assigned to one of two sequences in the crossover study. All subjects will receive the same dosage of oxycodone intranasal or oral and the sequence will be determined following randomization.

Inclusion Criteria:

• Healthy male or female volunteers according to physical examination, vital signs (blood pressure, heart rate and body temperature), ECG and safety laboratory parameters and results should be within normal ranges or considered as non-clinically relevant by the investigator.
• Age ≥ 18 and ≤ 55 years.
• Body weight up to 90 kg
• Body mass index (BMI) ≥ 18 and ≤ 30 kg/m2.
• Able/willing to be compliant with the study restrictions
• Able to read Spanish and adhere to study requirements.
• Signed informed consent prior to any study-mandated procedure.
• Prior therapeutic or recreational experience with opioids (i.e., tramadol, oxycodone, or buprenorphine)

Exclusion Criteria:

• Life-time (current and/or history of) substance use disorders (SUD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
• Use of any illegal drug within 30 days of screening and throughout participation in the study
• History of smoking or use of nicotine containing products within 3 months of screening and throughout participation in the study
• No acute, chronic, or allergic rhinitis
• Ongoing gastrointestinal diseases or history of gastrointestinal surgery affecting absorption.
• History of severe bronchial asthma or chronic obstructive pulmonary disease,
• Any anatomical abnormality or pathological condition of the nasal cavity based on medical history.
• History of hypothyroidism.
• Subjects with a clinically relevant disease or condition that in the judgment of the investigator might interfere with the safety or subject's ability to comply with study procedures or requirements and/or bias the interpretation of the study results and/or jeopardize the subject's safety.
• Current mental diseases that require prescription drugs.
• Any ophthalmologic condition that could interfere with pupillometry
• Being under any administrative or legal supervision.
• Pregnancy and breastfeeding
• Positive blood or urine test for drugs of abuse or alcohol breath test prior to study drug administration.
• Current and/or history of anxiety or depression not completely recovered within 12 months prior to study drug administration, as assessed by the Dual Diagnosis Screening Interview (DDSI).
• CYP2D6 poor or ultrarapid metabolizers.
• Any clinically relevant findings in physical examination, vital signs, 12-lead ECG and safety laboratory parameters.
• Positive hepatitis or HIV tests (Ag VHB, IgG VHC, Ac VIH).
• Known hypersensitivity to any drug or drug excipients.
• Use of drugs known to induce or inhibit hepatic drug metabolism (check drugs in Appendix 6) within one month prior to study administration or during the study and use of citrus juice during the study.
• Use of sedative medicines such as benzodiazepines or related drugs in the last 3 months.
• Any prescription or over-the-counter (OTC) product, not including oral contraceptives but including analgesics (paracetamol), aspirin, herbal, homeopathic, vitamins, minerals and nutritional supplements within one week prior to study drug administration.
• Intake of foods or beverages containing xanthine (more than 5 cups of coffee, tea or 5 bottles/cans cola drinks) per day.
• Donation of blood or plasma within two months prior to study drug administration
• Transfusion of blood or plasma for medical/surgical reasons in the past 120 days.
• Current or history of inadequate venous access and/or experience of difficulty donating blood.
• Subject included in a clinical trial within 3 months prior to study drug administration.