Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia

• ClinicalTrials.gov Identifier: NCT05988710
• Recruitment Status: Recruiting
• First Posted: August 14, 2023
• Last Update Posted: October 27, 2023
• Sponsor: Vanderbilt University Medical Center
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Daniel Larach, Vanderbilt University Medical Center

Tracking Information

• First Submitted Date: August 1, 2023
• First Posted Date: August 14, 2023
• Last Update Posted Date: October 27, 2023
• Actual Study Start Date: October 19, 2023
• Estimated Primary Completion Date: October 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 8, 2023)

• 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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 8, 2023)

• Difference in mean maximum effect score (Emax) of the drug liking visual analog scale between equianalgesic dose of buprenorphine and placebo conditions [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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 [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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) [ Time Frame: Baseline through 3.5 hours after study drug administration on each medication condition ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia
• Official Title: Low-dose Buccal Buprenorphine: Relative Abuse Potential and Analgesia
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

randomized, double blind, double-dummy, placebo-controlled, crossover

Masking: Double (Participant, Investigator)
Primary Purpose: Other

Condition

• Analgesia
• Abuse Opioids
• Pain

Intervention

• Drug: Buccal Buprenorphine 300 mcg
  buprenorphine for 300mcg buccal administration
• Drug: Buccal Buprenorphine 600 mcg
  buprenorphine for 600mcg buccal administration
• Drug: Buccal Buprenorphine 900 mcg
  buprenorphine for 900mcg buccal administration
• Drug: Buccal Placebo
  Placebo for buccal administration
• Drug: Oral Placebo
  Placebo for oral administration
• Drug: Oral immediate-release oxycodone 10mg
  Immediate-release oxycodone for 10 mg oral administration

Study Arms

• Experimental: Buccal Buprenorphine 300mcg 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.
  Interventions:

  • Drug: Buccal Buprenorphine 300 mcg
  • Drug: Oral Placebo
• Experimental: Buccal Buprenorphine 600mcg 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.
  Interventions:

  • Drug: Buccal Buprenorphine 600 mcg
  • Drug: Oral Placebo
• Experimental: Buccal Buprenorphine 900mcg 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.
  Interventions:

  • Drug: Buccal Buprenorphine 900 mcg
  • Drug: Oral Placebo
• Active Comparator: Oral immediate release oxycodone 10mg and buccal 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.
  Interventions:

  • Drug: Buccal Placebo
  • Drug: Oral immediate-release oxycodone 10mg
• Placebo Comparator: Oral placebo and buccal 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.
  Interventions:

  • Drug: Buccal Placebo
  • Drug: Oral Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 8, 2023): 72
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2026
• Estimated Primary Completion Date: October 2026 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Daniel Larach, MD, MSTR, MA; 615-322-6033; daniel.larach@vumc.org

Contact: Gail Mayo; 6159361705; gail.mayo@vumc.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05988710
• Other Study ID Numbers: 222204; 1K23DA057387 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Daniel Larach, Vanderbilt University Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Vanderbilt University Medical Center
• Original Study Sponsor: Same as current
• Collaborators: National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Daniel Larach, MD, MSTR, MA; Vanderbilt University Medical Center

• PRS Account: Vanderbilt University Medical Center
• Verification Date: October 2023