Buprenorphine's Dose Response Curve

Johns Hopkins University

Status and phase: Completed; Phase 2

Conditions: Opioid-related Disorders

Treatments: Drug: Morphine; Drug: Buprenorphine; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00460239

R01DA008045 (U.S. NIH Grant/Contract)

NIDA-08045-8

5R01DA008045-08 (U.S. NIH Grant/Contract)

DPMCDA

Details and patient eligibility

About

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).

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 21 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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12 participants in 8 patient groups

Placebo

Experimental group

Description:

All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).

Treatment:

Drug: Placebo

Morphine 15

Experimental group

Description:

All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).

Treatment:

Drug: Morphine

Morphine 30

Experimental group

Description:

All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).

Treatment:

Drug: Morphine

Buprenorphine 8

Experimental group

Description:

All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).

Treatment:

Drug: Buprenorphine

Buprenorphine 16

Experimental group

Description:

All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).

Treatment:

Drug: Buprenorphine

Buprenorphine 32

Experimental group

Description:

All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).

Treatment:

Drug: Buprenorphine

Buprenorphine 48

Experimental group

Description:

All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).

Treatment:

Drug: Buprenorphine

Buprenorphine 60

Experimental group

Description:

All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).

Treatment:

Drug: Buprenorphine