A Comparison of the Addiction Liability of Hydrocodone and Sustained Release Morphine

University of California (UC) Davis

Status and phase: Completed; Phase 4

Conditions: Chronic Pain

Treatments: Drug: ER Morphine; Drug: hydrocodone plus acetaminophen; Drug: placebo; Behavioral: Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity

Study type: Interventional

Funder types: Other

Identifiers

NCT00314340

200513430

Details and patient eligibility

About

Characterize the relative abuse liability of a short versus a long acting opioid in chronic pain patients.

Full description

A placebo-controlled, double-blind, crossover trial will be conducted providing study subjects either hydrocodone/acetaminophen 30mg/975mg, sustained release morphine 45mg or placebo on separate GCRC visits. A long acting comparator (slow-release morphine sulfate 45 mg) will be chosen because of its putative equianalgesic effects to the dose of hydrocodone (30 mg) selected. Subjects will participate in the three sessions at the UC Davis/Mather Medical Center General Clinical Research Center (GCRC) at intervals of 7-10 days. Sessions will be approximately 360 min in duration. Subjects will receive either hydrocodone/acetaminophen or sustained release morphine around-the-clock for 7-10 days prior to the experimental session. At each experimental session, an assessment of abuse liability will be completed before the intake of medications, as well as at 0, 60, 120, 180, 240 minutes after the ingestion of the study medication.

Enrollment: 12 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Patients with chronic pain for periods greater than 6 months
• Patients taking greater than 80 mg morphine equivalents of a short acting opioid (>8 vicodin or 4 oxycodone/day)
• Referral to Pain or Substance Abuse Clinic for self-escalation of opioids

Exclusion criteria

• Inability to understand and comprehend spoken English
• Patients with Munchausen's syndrome
• Patient has a history of Peripheral Vascular Disease
• Patient has a history of Raynaud's Phenomenon
• Liver Disease; Child's classification greater than 1 (liver cirrhosis) will be excluded
• Renal disease (BUN >25 or Cr >1.5)
• Congestive Heart Failure; Subjects with New York Heart Association (NYHA)Heart Failure Symptom Classification System Level of Impairment II, III and IV will be excluded
• Coronary artery disease; recent MI within the past six months or recent history of angina not controlled with NTG within the past six months
• Hypertension; 1)previously normotensive subject; systolic bp >140 mm Hg and diastolic bp > 90 mm Hg 2) Hx of active treatment with antihypertensive medications; systolic bp >150 mm Hg and diastolic bp > 100 mm Hg
• Cerebrovascular disease; recent history within the past year of a transient ischemic attack or recent history within the past year of a cerebrovascular event
• Malignancy requiring active treatment
• Patient is pregnant (as ascertained by a self-report and a mandatory commercial pregnancy test before any study medication is consumed)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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12 participants in 3 patient groups, including a placebo group

extended-release morphine

Active Comparator group

Description:

Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity On one of three study dates, subjects received ER morphine tablets, 45 mg (Mallinckrodt Pharmaceuticals, St. Louis, MO). The dose of ER morphine sulfate (45 mg) was selected because of its approximate equianalgesic effect to the dose of hydrocodone-acetaminophen (30/925 mg).

Treatment:

Behavioral: Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity

Drug: ER Morphine

hydrocodone

Active Comparator group

Description:

Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity On the day of the study session, patients received hydrocodone 30 mg plus N-acetyl-para-aminophenol 975 mg (APAP;Qualitest Pharmaceuticals Inc, Huntsville, AL).

Treatment:

Behavioral: Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity

Drug: hydrocodone plus acetaminophen

placebo

Placebo Comparator group

Description:

Subjects received a placebo pill if randomized to this arm. Both opioid medications and the placebo were administered in identical capsules.

Treatment:

Behavioral: Markers of Abuse Liability, Neuropsych Testing, and Cue Reactivity

Drug: placebo