Opioid Drug Interaction Study

Shanna Babalonis, PhD

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Drug Kinetics; Drug Interactions

Treatments: Drug: Placebo; Drug: Alprazolam; Drug: Oxycodone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06757140

97946

R01DA016718 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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25 participants in 9 patient groups, including a placebo group

Placebo / Placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo

Placebo / Oxycodone low oral dose (Percocet, Roxicodone)

Experimental group

Description:

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).

Treatment:

Drug: Oxycodone

Drug: Placebo

Placebo / Oxycodone high oral dose (Percocet, Roxicodone)

Experimental group

Description:

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).

Treatment:

Drug: Oxycodone

Drug: Placebo

Alprazolam low oral dose (Xanax) / Placebo

Experimental group

Description:

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).

Treatment:

Drug: Alprazolam

Drug: Placebo

Alprazolam high oral dose (Xanax) / Placebo

Experimental group

Description:

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).

Treatment:

Drug: Alprazolam

Drug: Placebo

Alprazolam low oral dose (Xanax) / Oxycodone low oral dose (Percocet, Roxicodone)

Experimental group

Description:

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).

Treatment:

Drug: Oxycodone

Drug: Alprazolam

Alprazolam high oral dose (Xanax) / Oxycodone low oral dose (Percocet, Roxicodone)

Experimental group

Description:

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).

Treatment:

Drug: Oxycodone

Drug: Alprazolam

Alprazolam low oral dose (Xanax) / Oxycodone high oral dose (Percocet, Roxicodone)

Experimental group

Description:

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).

Treatment:

Drug: Oxycodone

Drug: Alprazolam

Alprazolam high oral dose (Xanax) / Oxycodone high oral dose (Percocet, Roxicodone)

Experimental group

Description:

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).

Treatment:

Drug: Oxycodone

Drug: Alprazolam