Buprenorphine's Dose Response Curve

Condition(s) targeted: Opioid-Related Disorders

Intervention: Buprenorphine (Drug); Morphine (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Institute on Drug Abuse (NIDA)

Official(s) and/or principal investigator(s):
Eric C Strain, M.D., Principal Investigator, Affiliation: Johns Hopkins University

Overall contact:
Sarah Ilk, Phone: 410-550-0159, Email: silk1@jhmi.edu

This is a residential study that looks at the effects of buprenorphine in persons who abuse but are not dependent on opioids. Animal studies show that very high doses of buprenorphine produce less effects than mid-range doses. This suggests that buprenorphine can be a very safe medication. However, no studies in humans have tested higher doses in a similar way. The goal of this study is to show the effects of single doses of buprenorphine, across a range of doses, in persons who are not physically dependent on opioids (but do abuse opioids).

Official title: Evaluation of Opioid Antagonist Activity in Humans

Study design: Treatment, Randomized, Double Blind (Subject, Outcomes Assessor), Active Control, Crossover Assignment, Pharmacokinetics/Dynamics Study

Primary outcome:

Opioid agonist effects (measured by Visual Analog Scales and other subjective ratings)

Physiologic effects (blood pressure, heart rate, temperature, respiratory rate, oxygen saturation, pupil diameter)

Psychomotor/cognitive performance effects (measured by tasks such as the DSST and Trails B)

Secondary outcome: Pharmacokinetics (blood levels of buprenorphine and norbuprenorphine)

Detailed description: Preclinical studies have demonstrated for a variety of measures that buprenorphine has a bell-shaped dose response curve. However, human studies with buprenorphine have not shown such an effect, although controlled studies have generally not tested higher acute doses of buprenorphine. Current clinical recommendations generally place an upper limit of daily buprenorphine dosing at 32 mg of sublingual tablets, although considerably higher acute doses have been administered to humans (primarily in clinical studies of less than daily dosing). Determining the relationship between higher doses of buprenorphine in humans and effects produced would be valuable; it would be scientifically interesting to demonstrate a bell-shaped curve in humans, and it would help guide clinical practice (for example, with respect to dosing, safety, and side effect considerations. The purpose of this study is to characterize the dose response curve for buprenorphine in humans, utilizing acute single doses of parenteral buprenorphine.

Minimum age: 21 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. current opioid abuse but not physically dependent on opioids

Exclusion Criteria:

1. evidence of significant medical (e. g., insulin dependent diabetes) or psychiatric (e. g., schizophrenia) illness

2. anemia defined as a hematocrit less than 30%

3. females are required to provide a negative pregnancy test prior to study participation

4. baseline electrocardiogram (ECG) showing prolongation of the QTc interval

5. current significant alcohol or sedative/hypnotic drug use

6. FEV1 of less than 50% at the time of screening

7. applicants seeking treatment for their substance abuse will not be admitted to the study, and should be provided information about treatment services available

Sarah Ilk, Phone: 410-550-0159, Email: silk1@jhmi.edu

Johns Hopkins University (BPRU) Bayview Campus, Baltimore, Maryland 21224, United States; Recruiting
Sarah Ilk, Phone: 410-550-0159, Email: silk1@jhmi.edu
Eric C Strain, M.D., Email: ecsgss@aol.com

Starting date: January 2007
Ending date: March 2010
Last updated: October 15, 2009