Buprenorphine's Dose Response Curve - Full Text View

Sponsor:	National Institute on Drug Abuse (NIDA)
Information provided by:	National Institute on Drug Abuse (NIDA)
ClinicalTrials.gov Identifier:	NCT00460239

Purpose

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).

Condition	Intervention	Phase
Opioid-Related Disorders	Drug: Buprenorphine Drug: Morphine Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Evaluation of Opioid Antagonist Activity in Humans

Resource links provided by NLM:

Drug Information available for: Buprenorphine Buprenorphine hydrochloride

U.S. FDA Resources

Further study details as provided by National Institute on Drug Abuse (NIDA):

Primary Outcome Measures:

Opioid agonist effects (measured by Visual Analog Scales and other subjective ratings) [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
Physiologic effects (blood pressure, heart rate, temperature, respiratory rate, oxygen saturation, pupil diameter) [ Time Frame: 6.5 hours ] [ Designated as safety issue: Yes ]
Psychomotor/cognitive performance effects (measured by tasks such as the DSST and Trails B) [ Time Frame: 6.5 hours ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetics (blood levels of buprenorphine and norbuprenorphine) [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	January 2007
Estimated Study Completion Date:	July 2010
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Intervention Details:

IM, doses are blind; administered up to 1-2 times per week.

IM; up to 1-2 times per week; doses double blind

IM; double blind; once per week

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

Ages Eligible for Study:	21 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. current opioid abuse but not physically dependent on opioids

Exclusion Criteria:

evidence of significant medical (e.g., insulin dependent diabetes) or psychiatric (e.g., schizophrenia) illness
anemia defined as a hematocrit less than 30%
females are required to provide a negative pregnancy test prior to study participation
baseline electrocardiogram (ECG) showing prolongation of the QTc interval
current significant alcohol or sedative/hypnotic drug use
FEV1 of less than 50% at the time of screening
applicants seeking treatment for their substance abuse will not be admitted to the study, and should be provided information about treatment services available

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00460239

Locations

United States, Maryland
Johns Hopkins University (BPRU) Bayview Campus
Baltimore, Maryland, United States, 21224

Sponsors and Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

Principal Investigator:

Eric C Strain, M.D.

Johns Hopkins University

More Information

No publications provided

Responsible Party:	Eric C. Strain/Principal Investigator, Johns Hopkins University School of Medicine
ClinicalTrials.gov Identifier:	NCT00460239 History of Changes
Other Study ID Numbers:	NIDA-08045-8, R01DA008045, DPMCDA
Study First Received:	April 11, 2007
Last Updated:	June 2, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute on Drug Abuse (NIDA):

Opioid addiction
Opioid dependence
Buprenorphine

Additional relevant MeSH terms:

Opioid-Related Disorders
Substance-Related Disorders
Mental Disorders
Buprenorphine
Morphine
Analgesics, Opioid
Narcotic Antagonists
Analgesics

Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Narcotics

ClinicalTrials.gov processed this record on February 09, 2012