Opioid Drug Interaction Study

Opioid Drug Interactions: Safety, Abuse Potential and Pharmacokinetic Effects

This study will examine the effects of doses of opioid/placebo and doses of alprazolam/placebo, alone and in combination. The primary outcomes are pharmacodynamic measures (subjective ratings of drug liking and other abuse-related effects; physiological outcomes) and pharmacokinetic outcomes (from blood samples) to determine the interaction effects of these compounds.

Study Overview

• Status: Recruiting
• Conditions: Drug Interactions; Drug Kinetics
• Intervention / Treatment: Drug: Placebo; Drug: Oxycodone; Drug: Alprazolam

Detailed Description

Alprazolam (Xanax®) is a short-acting benzodiazepine that is the commonly prescribed in the U.S. (>15 million prescriptions in 2021) and CDC reporting indicates that alprazolam was associated with the greatest increase in number of ED presentations of the benzodiazepines. This study will examine the effects of a widely prescribed and abused mu opioid agonist, oxycodone, and a widely prescribed and abused benzodiazepine, alprazolam, when given alone and in combination to experienced drug using volunteers. Key safety outcomes, including expired CO2, pharmacodynamic measures related to abuse potential, and cognitive/psychomotor performance will be thoroughly examined over a range of doses for both drugs alone and in combination. Pharmacokinetic data will also be collected and analyzed to assess the potential pharmacokinetic interaction as an underlying mechanism of action.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Paul A Nuzzo; Phone Number: (859) 323-0002; Email: paul.nuzzo@uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40508
      • Recruiting
      • University Of Kentucky
      • Contact: Paul A Nuzzo; Phone Number: 859-323-0002; Email: paul.nuzzo@uky.edu
      • Principal Investigator: Shanna Babalonis, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• English-speaking and literate participants, able to understand and sign Informed Consent Document
• ages 18 to 55 years old inclusive
• BMI of greater than/equal to 17 and approximately less than or equal to 30
• self-reported opioid use
• self-reported sedative-like drug use
• women of childbearing potential must not be pregnant or breastfeeding at screening and be using an effective form of contraception throughout study participation
• otherwise healthy as determined by the medical/research team based on medical history, physical examination, vital signs, laboratory chemistries (blood chemistry with liver function tests and hematology, urinalysis and microscopic evaluation, 12-lead electrocardiogram)
• willing and able to comply with all testing requirements defined in the protocol
• adequate venous access (determined by RN) for pharmacokinetic blood draws

Exclusion Criteria:

• physical dependence on alcohol, opioids, benzodiazepines or sedative/hypnotics requiring medical management/detoxification
• seeking treatment for opioid or any other drug use
• acute medical problem (e.g., infection) or chronic medical problem requiring daily medication or ongoing medical care (e.g., hypertension, cardiovascular disease, diabetes, respiratory disorders [e.g., asthma, COPD])
• clinically significant abnormal ECG (as determined by study physician/cardiologist)
• clinically significant abnormal laboratory findings (e.g., liver function tests greater than 3x the upper limits of normal range)
• current or past history of major psychiatric disorder that would limit ability to participate in the study (e.g., bipolar disorder).
• recent use of CYP2C9, CYP2D6 and CYP3A4 inhibitor or inducer that is long-acting and not amenable to a wash-out period after enrollment
• known hypersensitivity to any of the study drugs
• currently pregnant or breastfeeding
• currently under parole or probation with urine testing requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo / Placebo; Participants will receive 2 drug administrations, neither will be active. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).	Drug: Placebo; Participants will receive inactive oral doses
Experimental: Placebo / Oxycodone low oral dose (Percocet, Roxicodone); Participants will receive 2 drug administrations, one dose oral placebo and one low dose oral oxycodone. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).	Drug: Placebo; Participants will receive inactive oral doses; Drug: Oxycodone; Participants will receive varying non-therapeutic experimental doses of oral oxycodone, alone and in combination with oral alprazolam; Other Names: Roxicodone; Percocet
Experimental: Placebo / Oxycodone high oral dose (Percocet, Roxicodone); Participants will receive 2 drug administrations, one dose oral placebo and one high dose oral oxycodone. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).	Drug: Placebo; Participants will receive inactive oral doses; Drug: Oxycodone; Participants will receive varying non-therapeutic experimental doses of oral oxycodone, alone and in combination with oral alprazolam; Other Names: Roxicodone; Percocet
Experimental: Alprazolam low oral dose (Xanax) / Placebo; Participants will receive 2 drug administrations, one dose oral placebo and one low dose oral alprazolam. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).	Drug: Placebo; Participants will receive inactive oral doses; Drug: Alprazolam; Participants will receive varying non-therapeutic experimental doses of oral alprazolam, alone and in combination with oral oxycodone; Other Names: Xanax
Experimental: Alprazolam high oral dose (Xanax) / Placebo; Participants will receive 2 drug administrations, one dose oral placebo and one high dose oral alprazolam. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).	Drug: Placebo; Participants will receive inactive oral doses; Drug: Alprazolam; Participants will receive varying non-therapeutic experimental doses of oral alprazolam, alone and in combination with oral oxycodone; Other Names: Xanax
Experimental: Alprazolam low oral dose (Xanax) / Oxycodone low oral dose (Percocet, Roxicodone); Participants will receive 2 non-therapeutic oral drug administrations, one low dose alprazolam, and one low dose oxycodone. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).	Drug: Oxycodone; Participants will receive varying non-therapeutic experimental doses of oral oxycodone, alone and in combination with oral alprazolam; Other Names: Roxicodone; Percocet; Drug: Alprazolam; Participants will receive varying non-therapeutic experimental doses of oral alprazolam, alone and in combination with oral oxycodone; Other Names: Xanax
Experimental: Alprazolam high oral dose (Xanax) / Oxycodone low oral dose (Percocet, Roxicodone); Participants will receive 2 non-therapeutic oral drug administrations, one high dose alprazolam, and one low dose oxycodone. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).	Drug: Oxycodone; Participants will receive varying non-therapeutic experimental doses of oral oxycodone, alone and in combination with oral alprazolam; Other Names: Roxicodone; Percocet; Drug: Alprazolam; Participants will receive varying non-therapeutic experimental doses of oral alprazolam, alone and in combination with oral oxycodone; Other Names: Xanax
Experimental: Alprazolam low oral dose (Xanax) / Oxycodone high oral dose (Percocet, Roxicodone); Participants will receive 2 non-therapeutic oral drug administrations, one low dose alprazolam, and one high dose oxycodone. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).	Drug: Oxycodone; Participants will receive varying non-therapeutic experimental doses of oral oxycodone, alone and in combination with oral alprazolam; Other Names: Roxicodone; Percocet; Drug: Alprazolam; Participants will receive varying non-therapeutic experimental doses of oral alprazolam, alone and in combination with oral oxycodone; Other Names: Xanax
Experimental: Alprazolam high oral dose (Xanax) / Oxycodone high oral dose (Percocet, Roxicodone); Participants will receive 2 non-therapeutic oral drug administrations, one high dose alprazolam, and one high dose oxycodone. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).	Drug: Oxycodone; Participants will receive varying non-therapeutic experimental doses of oral oxycodone, alone and in combination with oral alprazolam; Other Names: Roxicodone; Percocet; Drug: Alprazolam; Participants will receive varying non-therapeutic experimental doses of oral alprazolam, alone and in combination with oral oxycodone; Other Names: Xanax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking	Participants rated their subjective drug liking on a standardized VAS scale (0 to 100) with higher scores equating to increased liking. Raw data transformed to peak scores.	This outcome was recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 6.5 hours per session).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect	Participants rated their subjective drug effect on a standardized VAS scale (0 to 100) with higher scores equating to increased effect. Raw data transformed to peak scores.	This outcome was recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 6.5 hours per session).
Change in Respiration Rate	Respiration rate monitored throughout each session. Raw data transformed to trough scores.	Respiration rate recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 6.5 hours per session).
Change in End-tidal Carbon Dioxide (EtCO2)	Change in End-tidal Carbon Dioxide (EtCO2) monitored throughout each session. Raw data transformed to peak scores.	End-tidal Carbon Dioxide (EtCO2) recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 6.5 hours per session).
Change in Oxygen Saturation	Oxygen Saturation monitored throughout each session. Raw data transformed to trough scores.	Oxygen Saturation recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 6.5 hours per session).

Collaborators and Investigators

• Sponsor: Shanna Babalonis, PhD
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Shanna Babalonis, PhD, University Of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: December 9, 2024
• First Submitted That Met QC Criteria: January 1, 2025
• First Posted (Actual): January 3, 2025

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: opioids; opiates; opioid misuse; sedatives; inpatient study
• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Benzazepines; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Benzodiazepines; Morphine Derivatives; Codeine; Oxycodone; Alprazolam; oxycodone-acetaminophen
• Other Study ID Numbers: 97946; R01DA016718 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No