Buprenorphine's Dose Response Curve

NCT00460239 | Completed Phase 2 Results

• 4 other identifiers: NIDA-08045-85R01DA008045-08R01DA008045DPMCDA
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Opioid-related Disorders

Keywords

Opioid addiction; Opioid dependence; Buprenorphine

Outcome Measures

Primary Outcomes (8)

• Peak Change From Baseline in Drug Effect Assessed by Visual Analog Scale (VAS)

  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.

  Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

• Psychomotor/Cognitive Performance Effects Assessed by Digit Symbol Substitution Test (DSST)

  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.

  Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

• Psychomotor/Cognitive Performance Effects Assessed by Trails B

  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.

  Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

• Physiologic Effects as Assessed by Blood Pressure

  Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

• Physiologic Effects as Assessed by Heart Rate

  Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

• Physiologic Effects as Assessed by Body Temperature

  Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

• Physiologic Effects as Assessed by Oxygen Saturation

  Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

• Physiologic Effects as Assessed by Pupil Diameter

  Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

Study Arms (8)

Placebo

EXPERIMENTAL

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

Drug: Placebo

Morphine 15

EXPERIMENTAL

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

Drug: Morphine

Morphine 30

EXPERIMENTAL

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

Drug: Morphine

Buprenorphine 8

EXPERIMENTAL

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

Drug: Buprenorphine

Buprenorphine 16

EXPERIMENTAL

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

Drug: Buprenorphine

Buprenorphine 32

EXPERIMENTAL

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

Drug: Buprenorphine

Buprenorphine 48

EXPERIMENTAL

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

Drug: Buprenorphine

Buprenorphine 60

EXPERIMENTAL

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

Drug: Buprenorphine

Interventions

Buprenorphine DRUG

Intramuscular, doses (8, 16, 32, 48, 60 mg) are blind; administered up to 1-2 times per week.

Buprenorphine 16; Buprenorphine 32; Buprenorphine 48; Buprenorphine 60; Buprenorphine 8

Morphine DRUG

Intramuscular; up to 1-2 times per week; doses (15, 30 mg) double blind

Morphine 15; Morphine 30

Placebo DRUG

Intramuscular; double blind; once per week

Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \. current opioid abuse but not physically dependent on opioids

You may not qualify if:

• 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 corrected QT interval (QTc)
• current significant alcohol or sedative/hypnotic drug use
• Forced expiratory volume at one second (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

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Johns Hopkins University (BPRU) Bayview Campus

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine; Morphine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Morphine Derivatives

Results Point of Contact

• Title: Eric C. Strain, M.D.
• Organization: Johns Hopkins University School of Medicine

ecsgss@aol.com

410-550-1191

Study Officials

• Eric C Strain, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2007
• First Posted: April 13, 2007
• Study Start: January 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: March 3, 2017
• Results First Posted: March 3, 2017

Record last verified: 2017-01

Locations

US (1)