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Buprenorphine's Dose Response Curve

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eric Strain, MD, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00460239
First received: April 11, 2007
Last updated: April 21, 2012
Last verified: April 2012
History of Changes
  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 2

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:

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: December 2012
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Buprenorphine
    IM, doses are blind; administered up to 1-2 times per week.
    Drug: Morphine
    IM; up to 1-2 times per week; doses double blind
    Drug: Placebo
    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:

  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
  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 Strain, MD, Professor, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00460239     History of Changes
Other Study ID Numbers: NIDA-08045-8, R01DA008045, DPMCDA
Study First Received: April 11, 2007
Last Updated: April 21, 2012
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 May 23, 2013