Clinical trial NCT00460239: Buprenorphine's Dose Response Curve
Official title: Evaluation of Opioid Antagonist Activity in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opioid-related Disorders
Keywords: Opioid addiction
Opioid dependence
Buprenorphine
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2007-04-13
Enrollment: 12
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility 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 corrected QT interval (QTc)
5. current significant alcohol or sedative/hypnotic drug use
6. Forced expiratory volume at one second (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

Primary outcomes:
measure: Peak Change From Baseline in Drug Effect Assessed by Visual Analog Scale (VAS)
timeFrame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
measure: Psychomotor/Cognitive Performance Effects Assessed by Digit Symbol Substitution Test (DSST)
timeFrame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
measure: Psychomotor/Cognitive Performance Effects Assessed by Trails B
timeFrame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
measure: Physiologic Effects as Assessed by Blood Pressure
timeFrame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
measure: Physiologic Effects as Assessed by Heart Rate
timeFrame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
measure: Physiologic Effects as Assessed by Body Temperature
timeFrame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
measure: Physiologic Effects as Assessed by Oxygen Saturation
timeFrame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
measure: Physiologic Effects as Assessed by Pupil Diameter
timeFrame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University (BPRU) Bayview Campus
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Eric C Strain, M.D.
role: PRINCIPAL_INVESTIGATOR
References: