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

• Oxycodone IN (Drug): 0.1 mg/kg intravenously oxycodone solution administered intranasally
• oxycodone (Drug): oral solution 0.1 mg/kg

Primary outcomes

• AUC(0-24h) [up to 24 hours]: Area under the curve from 0 time to the last measurable concentration (of intranasal and oral oxycodone), calculated from individual plasma PK concentrations.
• Tmax [Blood samples were taken pre-dose and up to 24 hours after start of each Dose]: Time of maximum observed concentration (of intranasal and oral oxycodone), calculated from individual plasma PK concentrations.
• Cmax [Blood samples were taken pre-dose and up to 24 hours after start of each Dose]: The mean maximum observed concentration (of intranasal and oral oxycodone), calculated from individual plasma PK concentrations

Secondary outcomes

• Adverse Effects (AE) [Up to 24 hours]: AE was performed including number and percentage.

Other outcomes

• Pupil Diameter [up to 24 hours]: To assess the effects of oxycodone on pupil size; only results at 24 hours will be reported.

Sex: All, ages: 18 Years to 55 Years, accepts healthy volunteers

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.

Participant flow

Outcome results

• AUC(0-24h) (Primary), Mean, ng·min/mL: Group: Oral 7373.6 +/- 1954.6; Group Intranasal 7195.7 +/- 1824.8
• Tmax (Primary), Median, min: Group: Oral 40 (10 to 180); Group Intranasal 50 (30 to 60)
• Cmax (Primary), Mean, ng/mL: Group: Oral 24.0 +/- 5.9; Group Intranasal 26.6 +/- 6.0
• Adverse Effects (AE) (Secondary), Count of participants, Participants: Group: Oral 1; Group: Intranasal 1
• Pupil Diameter (Other pre specified), Mean, mm: Group: Oral 3.5 +/- 0.9; Group Intranasal 3.2 +/- 0.6

Adverse events

Time frame: From Day 1 to End of Study, up to 24 hours.

Other adverse events by term

• Study Protocol (PDF, 2025-03-24)
• Statistical Analysis Plan (PDF, 2025-09-15)
• Informed Consent Form (PDF, 2025-02-03)

• Rafael De la Torre, PhD, Principal investigator, Hospital del Mar Research Institute Barcelona