Opioid Drug Interactions: Safety, Abuse Potential and Pharmacokinetic Effects
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Drug Interactions
- Sponsor
- Shanna Babalonis, PhD
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
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.
Investigators
Shanna Babalonis, PhD
Associate Professor
University of Kentucky
Eligibility Criteria
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
Arms & Interventions
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).
Intervention: Placebo
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).
Intervention: Oxycodone
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).
Intervention: Placebo
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).
Intervention: Oxycodone
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).
Intervention: Placebo
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).
Intervention: Alprazolam
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).
Intervention: Placebo
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).
Intervention: Alprazolam
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).
Intervention: Placebo
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).
Intervention: Alprazolam
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).
Intervention: Oxycodone
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).
Intervention: Alprazolam
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).
Intervention: Oxycodone
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).
Intervention: Alprazolam
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).
Intervention: Oxycodone
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).
Intervention: Alprazolam
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).
Intervention: Oxycodone
Outcomes
Primary Outcomes
Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking
Time Frame: 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).
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.
Secondary Outcomes
- Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect(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 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)(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 recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 6.5 hours per session).)