Back to resultsLow-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia
Primary Purpose
Analgesia, Abuse Opioids, Pain
Status
Not yet recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Buccal Buprenorphine 300 mcg
Buccal Buprenorphine 600 mcg
Buccal Buprenorphine 900 mcg
Buccal Placebo
Oral Placebo
Oral immediate-release oxycodone 10mg
Sponsored by
About this trial
This is an interventional other trial for Analgesia
Eligibility Criteria
Inclusion Criteria: Intact cognitive status and ability to provide informed consent Ability to read and write in English sufficiently to understand and complete study questionnaires Age 18-65 Opioid-naive status (defined as no use of full mu-opioid receptor (MOR) agonist, partial MOR agonist, or mixed agonist/antagonist medications for the prior 3 months by patient report Exclusion Criteria: Liver/kidney disease Chronic pain Current/prior substance use disorder Pregnancy (to avoid fetal drug exposure, with pregnancy tests conducted to confirm eligibility) Seizure disorder Certain psychiatric conditions (severe depression, bipolar disorder, psychotic disorders) Recent use of medications that may interfere with study drug metabolism Recent benzodiazepine or opioid use (confirmed via rapid urine screening prior to each lab session) The presence of any medical conditions felt by the study physician to render participant unsafe Prior allergic reaction or intolerance to oxycodone, buprenorphine, or their analogs
Sites / Locations
- Vanderbilt University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Placebo Comparator
Arm Label
Buccal Buprenorphine 300mcg and oral Placebo
Buccal Buprenorphine 600mcg and oral Placebo
Buccal Buprenorphine 900mcg and oral Placebo
Oral immediate release oxycodone 10mg and buccal placebo
Oral placebo and buccal placebo
Arm Description
In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.
In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.
In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.
In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.
In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.
Outcomes
Primary Outcome Measures
Difference in mean maximum effect score (Emax) of the drug liking visual analog scale (VAS) between oxycodone 10 mg and an equianalgesic dose of buprenorphine
Difference in mean Emax of the drug liking VAS between oxycodone 10 mg and an equianalgesic dose of buprenorphine conditions. Drug liking VAS is a bipolar scale designed to assess a participant's liking for a given study intervention at the time the question is being asked (that is, at this moment). It is scored as an integer ranging from 0 (strong disliking) to 100 (strong liking).
Quantitative sensory testing (QST) thermal pain tolerance in seconds
Mean time in seconds elapsed from onset of the heat pain stimulus to participants withdrawal from the stimulus. Heat pain tolerance is an indicator of pain sensitivity. This will determine the equianalgesic dose of buccal buprenorphine compared to oxycodone 10 mg. Equivalence to oxycodone will be defined as the buprenorphine does that produces a mean thermal pain tolerance increase within 0.5 standard deviation of the oxycodone. response.
Secondary Outcome Measures
Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between equianalgesic dose of buprenorphine and placebo conditions
Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between equianalgesic dose of buprenorphine and placebo conditions. Drug liking VAS is a bipolar scale designed to assess a participant's liking for a given study intervention at the time the question is being asked (that is, at this moment). It is scored as an integer ranging from 0 (strong disliking) to 100 (strong liking).
Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between oxycodone 10 mg and placebo conditions
Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between oxycodone 10 mg and placebo conditions. Drug liking VAS is a bipolar scale designed to assess a participant's liking for a given study intervention at the time the question is being asked (that is, at this moment). It is scored as an integer ranging from 0 (strong disliking) to 100 (strong liking).
QST heat pain threshold
Mean time in seconds elapsed from onset of the thermal stimulus to the point at which heat stimulus is first experienced as painful. Thermal pain threshold is an indicator of pain sensitivity.
Visual Analog Scale (VAS) pain intensity
Difference in mean Emax of the pain intensity VAS between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. The VAS pain intensity is a measure of experienced pain intensity on 0 to 100 scale when 0 is no pain and 100 is worst pain imaginable.
VAS pain unpleasantness
Difference in mean Emax of the pain unpleasantness VAS between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. The VAS pain unpleasantness is a measure of experienced pain unpleasantness on 0 to 100 scale, when 0 is no unpleasantness and 100 is most unpleasant imaginable.
McGill Pain Questionnaire - Short Form
Mean of maximum McGill Pain Questionnaire - Short Form score between oxycodone 10mg, equianalgesic dose of buprenorphine and placebo. The score ranges from 0-33 where 0 represents no pain and 33 represents most intense pain. Positive change values indicate decreased pain responsiveness.
VAS alertness/drowsiness
Difference in mean Emax of the VAS alertness/drowsiness between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. The VAS alertness/drowsiness assesses alertness and drowsiness following drug administration on 0 to 100 sale, when 0 is extreme drowsiness, 50 is neutral, and 100 is extreme alertness.
VAS any drug effects
Difference in mean Emax of the VAS any drug effects between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS any drug effects assesses presence of any drug effects felt by participant on 0 to 100 scale, when 0 is no drug effects and 100 is extreme drug effects.
VAS good effects
Difference in mean Emax of the VAS good effects between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS good effects assesses presence of drug effects characterized as good felt by participant on scale 0 to 100 when 0 is no good drug effects and 100 is extreme good drug effects.
VAS feeling high
Difference in mean Emax of the VAS feeling high between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS feeling high assesses presence of "feeling high" by participant on 0 to 100 scale when o is not feeling high at all and 100 is feeling extremely high.
VAS bad effects
Difference in mean Emax of the VAS bad effects between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS bad effects assesses presence of drug effects characterized as bad felt by participant on 0 to 100 scale when 0 is no bad drug effects and 100 is extreme bad drug effects.
VAS desire to use opioids
Difference in mean Emax of the VAS desire to use opioids between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS desire to use opioids assesses participant's desire to use opioids on a 0-100 scale when 0 is no desire to use opioids and 100 is extreme desire to use opioids.
Opioid Adjective Rating Scale
Difference in mean Emax of the VAS Opioid Adjective Rating Scale between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS Opioid Adjective Rating Scale is a 12 item questionnaire which evaluates common sensory and somatic effects of opioid (e.g., itching, vomiting, sweating, nausea, dry mouth). Each effect is rated on 0 to 4 scale when 0 is not at all and 4 is extremely.
Temporal summation of pain (TSP)
Change in pain intensity between first and most painful TSP stimuli (mean of two TSP trials) compared between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo conditions. Pain intensity will be measured on a 0-10 Numeric Rating Scale when when 0 is no pain and 100 is worst pain imaginable.
Full Information
NCT ID
NCT05988710
First Posted
August 1, 2023
Last Updated
October 19, 2023
Sponsor
Vanderbilt University Medical Center
Collaborators
National Institute on Drug Abuse (NIDA)
1. Study Identification
Unique Protocol Identification Number
NCT05988710
Brief Title
Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia
Official Title
Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
October 2026 (Anticipated)
Study Completion Date
October 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
Collaborators
National Institute on Drug Abuse (NIDA)
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The goal of this study is to compare the abuse potential of low-dose equianalgesic buccal buprenorphine to a commonly used full mu opioid receptor (MOR) agonist in a highly controlled experimental setting. This is a translational study in which healthy participants are phenotyped for psychosocial and Opioid-Use-Disorder-risk-related metrics. In a within-subjects crossover design, 60 participants will receive a standard postoperative oral oxycodone dose (10 mg), placebo, and 3 different doses of buccal buprenorphine across 5 separate sessions. Quantitative Sensory Testing (QST) will be used to evaluate alterations in pain responsiveness relative to placebo across buprenorphine doses and oxycodone, and will compare abuse potential (indexed by the standard FDA drug liking metric) following equianalgesic doses of the two drugs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Analgesia, Abuse Opioids, Pain
7. Study Design
Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
randomized, double blind, double-dummy, placebo-controlled, crossover
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
72 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Buccal Buprenorphine 300mcg and oral Placebo
Arm Type
Experimental
Arm Description
In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.
Arm Title
Buccal Buprenorphine 600mcg and oral Placebo
Arm Type
Experimental
Arm Description
In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.
Arm Title
Buccal Buprenorphine 900mcg and oral Placebo
Arm Type
Experimental
Arm Description
In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.
Arm Title
Oral immediate release oxycodone 10mg and buccal placebo
Arm Type
Active Comparator
Arm Description
In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.
Arm Title
Oral placebo and buccal placebo
Arm Type
Placebo Comparator
Arm Description
In randomized order (crossover) across 5 laboratory sessions approximately 5 days apart, participants will receive: 1) Buccal buprenorphine 300 mcg and oral placebo, 2) Buccal buprenorphine 600 mcg and oral placebo, 3) Buccal buprenorphine 900 mg and oral placebo, 4) oral immediate-release oxycodone 10mg and oral placebo, or 5) buccal placebo and oral placebo.
Intervention Type
Drug
Intervention Name(s)
Buccal Buprenorphine 300 mcg
Intervention Description
buprenorphine for 300mcg buccal administration
Intervention Type
Drug
Intervention Name(s)
Buccal Buprenorphine 600 mcg
Intervention Description
buprenorphine for 600mcg buccal administration
Intervention Type
Drug
Intervention Name(s)
Buccal Buprenorphine 900 mcg
Intervention Description
buprenorphine for 900mcg buccal administration
Intervention Type
Drug
Intervention Name(s)
Buccal Placebo
Intervention Description
Placebo for buccal administration
Intervention Type
Drug
Intervention Name(s)
Oral Placebo
Intervention Description
Placebo for oral administration
Intervention Type
Drug
Intervention Name(s)
Oral immediate-release oxycodone 10mg
Intervention Description
Immediate-release oxycodone for 10 mg oral administration
Primary Outcome Measure Information:
Title
Difference in mean maximum effect score (Emax) of the drug liking visual analog scale (VAS) between oxycodone 10 mg and an equianalgesic dose of buprenorphine
Description
Difference in mean Emax of the drug liking VAS between oxycodone 10 mg and an equianalgesic dose of buprenorphine conditions. Drug liking VAS is a bipolar scale designed to assess a participant's liking for a given study intervention at the time the question is being asked (that is, at this moment). It is scored as an integer ranging from 0 (strong disliking) to 100 (strong liking).
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
Quantitative sensory testing (QST) thermal pain tolerance in seconds
Description
Mean time in seconds elapsed from onset of the heat pain stimulus to participants withdrawal from the stimulus. Heat pain tolerance is an indicator of pain sensitivity. This will determine the equianalgesic dose of buccal buprenorphine compared to oxycodone 10 mg. Equivalence to oxycodone will be defined as the buprenorphine does that produces a mean thermal pain tolerance increase within 0.5 standard deviation of the oxycodone. response.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Secondary Outcome Measure Information:
Title
Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between equianalgesic dose of buprenorphine and placebo conditions
Description
Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between equianalgesic dose of buprenorphine and placebo conditions. Drug liking VAS is a bipolar scale designed to assess a participant's liking for a given study intervention at the time the question is being asked (that is, at this moment). It is scored as an integer ranging from 0 (strong disliking) to 100 (strong liking).
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between oxycodone 10 mg and placebo conditions
Description
Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between oxycodone 10 mg and placebo conditions. Drug liking VAS is a bipolar scale designed to assess a participant's liking for a given study intervention at the time the question is being asked (that is, at this moment). It is scored as an integer ranging from 0 (strong disliking) to 100 (strong liking).
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
QST heat pain threshold
Description
Mean time in seconds elapsed from onset of the thermal stimulus to the point at which heat stimulus is first experienced as painful. Thermal pain threshold is an indicator of pain sensitivity.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
Visual Analog Scale (VAS) pain intensity
Description
Difference in mean Emax of the pain intensity VAS between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. The VAS pain intensity is a measure of experienced pain intensity on 0 to 100 scale when 0 is no pain and 100 is worst pain imaginable.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
VAS pain unpleasantness
Description
Difference in mean Emax of the pain unpleasantness VAS between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. The VAS pain unpleasantness is a measure of experienced pain unpleasantness on 0 to 100 scale, when 0 is no unpleasantness and 100 is most unpleasant imaginable.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
McGill Pain Questionnaire - Short Form
Description
Mean of maximum McGill Pain Questionnaire - Short Form score between oxycodone 10mg, equianalgesic dose of buprenorphine and placebo. The score ranges from 0-33 where 0 represents no pain and 33 represents most intense pain. Positive change values indicate decreased pain responsiveness.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
VAS alertness/drowsiness
Description
Difference in mean Emax of the VAS alertness/drowsiness between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. The VAS alertness/drowsiness assesses alertness and drowsiness following drug administration on 0 to 100 sale, when 0 is extreme drowsiness, 50 is neutral, and 100 is extreme alertness.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
VAS any drug effects
Description
Difference in mean Emax of the VAS any drug effects between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS any drug effects assesses presence of any drug effects felt by participant on 0 to 100 scale, when 0 is no drug effects and 100 is extreme drug effects.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
VAS good effects
Description
Difference in mean Emax of the VAS good effects between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS good effects assesses presence of drug effects characterized as good felt by participant on scale 0 to 100 when 0 is no good drug effects and 100 is extreme good drug effects.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
VAS feeling high
Description
Difference in mean Emax of the VAS feeling high between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS feeling high assesses presence of "feeling high" by participant on 0 to 100 scale when o is not feeling high at all and 100 is feeling extremely high.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
VAS bad effects
Description
Difference in mean Emax of the VAS bad effects between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS bad effects assesses presence of drug effects characterized as bad felt by participant on 0 to 100 scale when 0 is no bad drug effects and 100 is extreme bad drug effects.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
VAS desire to use opioids
Description
Difference in mean Emax of the VAS desire to use opioids between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS desire to use opioids assesses participant's desire to use opioids on a 0-100 scale when 0 is no desire to use opioids and 100 is extreme desire to use opioids.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
Opioid Adjective Rating Scale
Description
Difference in mean Emax of the VAS Opioid Adjective Rating Scale between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo. VAS Opioid Adjective Rating Scale is a 12 item questionnaire which evaluates common sensory and somatic effects of opioid (e.g., itching, vomiting, sweating, nausea, dry mouth). Each effect is rated on 0 to 4 scale when 0 is not at all and 4 is extremely.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
Title
Temporal summation of pain (TSP)
Description
Change in pain intensity between first and most painful TSP stimuli (mean of two TSP trials) compared between oxycodone 10 mg, equianalgesic dose of buprenorphine and placebo conditions. Pain intensity will be measured on a 0-10 Numeric Rating Scale when when 0 is no pain and 100 is worst pain imaginable.
Time Frame
Baseline through 3.5 hours after study drug administration on each medication condition
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Intact cognitive status and ability to provide informed consent
Ability to read and write in English sufficiently to understand and complete study questionnaires
Age 18-65
Opioid-naive status (defined as no use of full mu-opioid receptor (MOR) agonist, partial MOR agonist, or mixed agonist/antagonist medications for the prior 3 months by patient report
Exclusion Criteria:
Liver/kidney disease
Chronic pain
Current/prior substance use disorder
Pregnancy (to avoid fetal drug exposure, with pregnancy tests conducted to confirm eligibility)
Seizure disorder
Certain psychiatric conditions (severe depression, bipolar disorder, psychotic disorders)
Recent use of medications that may interfere with study drug metabolism
Recent benzodiazepine or opioid use (confirmed via rapid urine screening prior to each lab session)
The presence of any medical conditions felt by the study physician to render participant unsafe
Prior allergic reaction or intolerance to oxycodone, buprenorphine, or their analogs
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daniel Larach, MD, MSTR, MA
Phone
615-322-6033
Email
daniel.larach@vumc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Gail Mayo
Phone
6159361705
Email
gail.mayo@vumc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Larach, MD, MSTR, MA
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37069
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Larach Larach, MD, MSTR, MA
Phone
615-322-6033
Email
daniel.larach@vumc.org
First Name & Middle Initial & Last Name & Degree
Gail Mayo
Phone
6159361705
Email
gail.mayo@vumc.org
12. IPD Sharing Statement
Plan to Share IPD
No
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Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia
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