Buprenorphine's Dose Response Curve

Opioid-related Disorders Clinical Trial

Official title:

Evaluation of Opioid Antagonist Activity in Humans

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00460239
• Other study ID #: NIDA-08045-8
• Secondary ID: R01DA008045DPMCD
• Status: Active, not recruiting
• Phase: Phase 2
• First received: April 11, 2007
• Last updated: April 21, 2012
• Start date: January 2007
• Est. completion date: December 2012

Study information

• Verified date: April 2012
• Source: National Institute on Drug Abuse (NIDA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: December 2012
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Opioid-related Disorders

Intervention

Drug:
• Buprenorphine
IM, doses are blind; administered up to 1-2 times per week.
• Morphine
IM; up to 1-2 times per week; doses double blind
• Placebo
IM; double blind; once per week

Locations

Country	Name	City	State
United States	Johns Hopkins University (BPRU) Bayview Campus	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Opioid agonist effects (measured by Visual Analog Scales and other subjective ratings)		72 hours	Yes
Primary	Physiologic effects (blood pressure, heart rate, temperature, respiratory rate, oxygen saturation, pupil diameter)		6.5 hours	Yes
Primary	Psychomotor/cognitive performance effects (measured by tasks such as the DSST and Trails B)		6.5 hours	Yes
Secondary	Pharmacokinetics (blood levels of buprenorphine and norbuprenorphine)		72 hours	No