Evaluation of Doxazosin to Alter the Abuse of Oxycodone

NCT03415581 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 7547
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Healthy, adult men and women, aged 21 to 59 years, who abuse opioids and are physically dependent on them will be recruited to participate in a study to examine the ability of doxazosin, an epinephrine receptor blocker, to alter the abuse potential of oxycodone. After participants complete the screening process, they will be scheduled for inpatient admission onto our clinical inpatient where they will reside during the 8-week study. During Weeks 1-2, participants will be transitioned from their normal opioid use regime onto oral morphine until withdrawal dissipates. At this time participants will also be stabilized on the first dose of doxazosin (0 or 16 mg/day; active doxazosin will be started at 4 mg and increased by 4 mg every 3 days). During Weeks 3-4, either active or placebo oxycodone will be available (in random order). Monday-Friday each these drugs will be tested using our sample and choice self-administration procedure. On Friday, participants will also complete a cue exposure session during which they will be presented drug cues to determine whether the study medication affects how participants react to them. To summarize, Weeks 1-2 and 5-6 will be stabilization weeks (0 or 16 mg doses of doxazosin administered in random order) and Weeks 3-4 and 7-8 will be test weeks under each of the doxazosin maintenance doses. At the conclusion of the study, participants will be given an exit interview, warnings about re-initiation of opioid use, and counseling about the different treatment options for Opioid Use Disorder. Within 1 week after discharge, investigators will assess adverse events using the a number of clinical assessments. At each weekly visits, investigators will assess participants' interest in treatment and drug use patterns.

Conditions

Opioid-use Disorder

Outcome Measures

Primary Outcomes (1)

• Opioid Self-administration

  Clinical laboratory task where the participant is asked to choose between drug and money. Shown as the mean percent of drug choices.

  Averaged across the 8-week trial.

Secondary Outcomes (1)

• Opioid Craving

  Averaged across the 8-week trial.

Study Arms (2)

Doxazosin (Placebo First)

PLACEBO COMPARATOR

Maintenance on a daily dose of oral doxazosin (0 mg) for 4 weeks, followed by 4-week maintenance on active doxasozin (up to 16mg/day or the highest tolerated dose. During this time subjects complete testing sessions (Self-administration, Cue session) assessing the abuse potential of intranasal oxycodone.

Drug: Intranasal Oxycodone; Behavioral: Cue Session

Doxazosin (Active First)

ACTIVE COMPARATOR

Maintenance on a daily dose of oral doxazosin (16 mg, or the highest tolerated dose) for 4-weeks, followed by 4-week maintenance on placebo doxasozin. During this time subjects complete testing sessions (Self-administration, Cue session) assessing the abuse potential of intranasal oxycodone.

Drug: Intranasal Oxycodone; Behavioral: Cue Session

Interventions

Intranasal Oxycodone DRUG

Under each doxazosin maintenance condition the effects of intranasal oxycodone will be assessed in order to determine if doxazosin reduces dependent measures assessing its abuse potential.

Also known as: Oxycodone HCl

Doxazosin (Active First); Doxazosin (Placebo First)

Cue Session BEHAVIORAL

During the cue exposure session participants are presented with neutral cues followed by drug-related cues. This procedure will allow the investigators to determine whether the study medication affects reactivity to drug-related cues.

Doxazosin (Active First); Doxazosin (Placebo First)

Eligibility Criteria

• Age: 21 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• years of age. Ascertained by: Self-reported age and/or verification with legal identification.
• Diagnostic criteria for Opioid Use Disorder moderate-severe (304.00) as per DSM-V Ascertained by: Clinical interviews (telephone, psychologist, nurse, physician), naloxone challenge test/visual evidence of opioid withdrawal.
• No current or past diagnosis of schizophrenia, schizoaffective disorder, or other psychotic disorder; bipolar I or bipolar II disorder, other major mood, psychotic, or anxiety disorder that might interfere with the study. Ascertained by: Clinical interview with physician or nurse.
• Physically healthy. Ascertained by: Clinical interview with physician, laboratory tests (urinalysis, blood chemistry, 12-lead ECG), physical examination, self-reported medical history.
• Able to perform study procedures. Ascertained by: Practice session or Clinical Judgement (Psychologist or Physician)
• Normal body weight. Ascertained by: Body Mass Index \<30.
• Current or history of intranasal opioid use. Ascertained by: Clinical interviews (telephone, psychologist, and psychiatric NP, or physician).
• Current intranasal or intravenous use of opioids in amounts and/or frequencies that meet or exceed those used in the proposed study (e.g., 3-4 tablets of a prescription opioid medication per day or 1-2 bags of heroin per day). Ascertained by: Clinical interviews (telephone, psychologist, psychiatric NP, or physician)
• If female and using oral contraceptives, must use alternative forms of contraception as well (e.g. condoms in combination with spermicide). Ascertained by: Clinical interviews (telephone, psychologist, nurse, physician), physical examination.
• Has not participated in another opioid laboratory study within the past 3 months. Ascertained by: Clinical interviews (psychologist physician, or psychiatric NP), review of laboratory records.

You may not qualify if:

• Meeting DSM-V criteria for substance use disorder (moderate-severe) on drugs other than opioids, nicotine or caffeine (must be less than 500 mg caffeine daily). Ascertained by: Clinical interview with physician or psychiatric NP, urine screen, observation.
• Participants requesting treatment. Ascertained by: Self-report during interview.
• Treatment with any investigational drug during the last 30 days. Ascertained by: Self-report during interview.
• Participants on parole or probation. Ascertained by: Self-report during interview, criminal background check upon admission.
• Currently pregnant or trying to conceive, or currently lactating. Ascertained by: Blood pregnancy testing at screening, on admission and (beta hCG), and self-report during interview and study visits.
• Current or recent history of significant violent or suicidal behavior and/or suicidal/homicidal risk. Ascertained by: Clinical interview with a psychiatrist or psychiatric NP, and C-SSRS, MINI, and Beck Depression Inventory (based on current state and history).
• Cannot read or understand the self-report assessment forms unaided, or are so severely disabled that they cannot comply with the requirements of the study. Ascertained by: Clinical interview (psychologist, physician, or psychiatric NP), or practice session.
• Elevated liver function tests (i.e., AST and ALT \> 3 times the upper limit of normal (ULN); bilirubin \> 2x ULN; hepatitis B or chronic hepatitis C). Ascertained by: Laboratory tests.
• Physical disorders that might make participation hazardous such as AIDS, cancer, baseline hypotension, orthostatic hypotension or syncope, hypertension (blood pressure \> 140/90), uncontrolled diabetes, pulmonary hypertension or heart disease (please note that participants will be asked about previous visits to a cardiologist, chest pain, or strong palpitations; if these exist, they will be referred to a cardiologist and excluded unless cleared for participation by a cardiologist). Ascertained by: Clinical interview (psychologist, physician, or psychiatric NP) physical examination, 12-lead ECG.
• Current major Axis I psychopathology other than opioid use disorder (e.g., mood disorder with functional impairment or suicide risk, schizophrenia), that might interfere with ability to participate in the study. Ascertained by: Clinical interviews (psychologist, physician, or psychiatric NP).
• Sensitivity, allergy, or contraindication to opioids, doxazosin, adrenergic antagonists or agonists, or similar compounds. Ascertained by: Clinical interview (psychologist, physician, or psychiatric NP).
• Planning to conceive within 6 months of study participation. Ascertained by: Clinical interview (psychologist, physician, or psychiatric NP).
• Use of any prescription, over-the-counter medication that affects CYP3A4 activity are prohibited for at least 7 days prior to the anticipated study start date; or the use of phosphodiesterase inhibitors and MAOIs 14 days prior to the study. Ascertained by: Medical History, Clinical Interview ((psychologist, physician, or psychiatric NP).

Sponsors & Collaborators

• New York State Psychiatric Institute: lead

Study Sites (1)

Jermaine Jones

Manhattan, New York, 10032, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Oxycodone

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Jermaine Jones PhD
• Organization: New York State Psychiatric Institute

jermaine.jones@nyspi.columbia.edu

6467746113

Study Officials

• Sandra D Comer, PhD

  NYSPI/CUMC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Scientist/Professor of Clinical Neurobiology (In Psychiatry)

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: January 30, 2018
• Study Start: February 12, 2017
• Primary Completion: December 23, 2019
• Study Completion: December 23, 2019
• Last Updated: April 12, 2021
• Results First Posted: April 12, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)