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Buprenorphine's Dose Response Curve

This study has been completed.
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00460239
First received: April 11, 2007
Last updated: January 11, 2017
Last verified: January 2017
April 11, 2007
January 11, 2017
January 2007
July 2009   (Final data collection date for primary outcome measure)
  • Peak Change From Baseline in Drug Effect Assessed by Visual Analog Scale (VAS) [ Time Frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks) ]
    Opioid agonist effects measured by peak change from baseline drug effect visual analog scale. Scores range from 0 (not all all) to 100 (extremely); higher scores indicate a stronger drug effect.
  • Psychomotor/Cognitive Performance Effects Assessed by Digit Symbol Substitution Test (DSST) [ Time Frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks) ]
    Digit Symbol Substitution Test (DSST) is a sub-test within the Wechsler Adult Intelligence Scale and is frequently used to assess psychomotor performance changes associated with drug effects. The higher the percent correct on this measure the better the performance.
  • Psychomotor/Cognitive Performance Effects Assessed by Trails B [ Time Frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks) ]
    The Trails B task specifically measures set shifting and executive functioning within the Trail-Making Test. Part B consists of 25 circles distributed over a sheet of paper. Participants are asked to connect the circles in an ascending pattern, alternating between numbers and letters (i.e., 1-A-2-B-3-C, etc.). Results are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment.
  • Physiologic Effects as Assessed by Blood Pressure [ Time Frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks) ]
  • Physiologic Effects as Assessed by Heart Rate [ Time Frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks) ]
  • Physiologic Effects as Assessed by Body Temperature [ Time Frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks) ]
  • Physiologic Effects as Assessed by Oxygen Saturation [ Time Frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks) ]
  • Physiologic Effects as Assessed by Pupil Diameter [ Time Frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks) ]
  • Opioid agonist effects (measured by Visual Analog Scales and other subjective ratings)
  • Physiologic effects (blood pressure, heart rate, temperature, respiratory rate, oxygen saturation, pupil diameter)
  • Psychomotor/cognitive performance effects (measured by tasks such as the DSST and Trails B)
Complete list of historical versions of study NCT00460239 on ClinicalTrials.gov Archive Site
Not Provided
Pharmacokinetics (blood levels of buprenorphine and norbuprenorphine)
Not Provided
Not Provided
 
Buprenorphine's Dose Response Curve
Evaluation of Opioid Antagonist Activity in Humans
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).
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.
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Opioid-related Disorders
  • Drug: Buprenorphine
    Intramuscular, doses (8, 16, 32, 48, 60 mg) are blind; administered up to 1-2 times per week.
  • Drug: Morphine
    Intramuscular; up to 1-2 times per week; doses (15, 30 mg) double blind
  • Drug: Placebo
    Intramuscular; double blind; once per week
  • Experimental: Placebo
    All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
    Intervention: Drug: Placebo
  • Experimental: Morphine 15
    All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
    Intervention: Drug: Morphine
  • Experimental: Morphine 30
    All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
    Intervention: Drug: Morphine
  • Experimental: Buprenorphine 8
    All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
    Intervention: Drug: Buprenorphine
  • Experimental: Buprenorphine 16
    All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
    Intervention: Drug: Buprenorphine
  • Experimental: Buprenorphine 32
    All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
    Intervention: Drug: Buprenorphine
  • Experimental: Buprenorphine 48
    All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
    Intervention: Drug: Buprenorphine
  • Experimental: Buprenorphine 60
    All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
    Intervention: Drug: Buprenorphine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
July 2009
July 2009   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
21 Years to 55 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00460239
NIDA-08045-8
5R01DA008045-08 ( U.S. NIH Grant/Contract )
R01DA008045 ( U.S. NIH Grant/Contract )
DPMCDA ( Other Identifier: NIDA )
No
Not Provided
Not Provided
Johns Hopkins University
Johns Hopkins University
National Institute on Drug Abuse (NIDA)
Principal Investigator: Eric C Strain, M.D. Johns Hopkins University
Johns Hopkins University
January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP