Clinical trial NCT06757140: Opioid Drug Interaction Study
Official title: Opioid Drug Interactions: Safety, Abuse Potential and Pharmacokinetic Effects
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Drug Interactions
Drug Kinetics
Keywords: inpatient study
opioids
opiates
sedatives
opioid misuse
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2025-01-03
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Liking
timeFrame: 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 outcomes:
measure: Change in Subject-Rated Outcome: Visual Analog Scale (VAS) Drug Effect
timeFrame: 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).
measure: Change in Respiration Rate
timeFrame: Respiration rate recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 6.5 hours per session).
measure: Change in End-tidal Carbon Dioxide (EtCO2)
timeFrame: 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).
measure: Change in Oxygen Saturation
timeFrame: Oxygen Saturation recorded prior to and in regular intervals after drug administration for the duration of the session (approx. 6.5 hours per session).
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Shanna Babalonis, PhD
role: PRINCIPAL_INVESTIGATOR
References: