Buprenorphine's Dose Response Curve

Phase 2

Completed

• Conditions: Opioid-related Disorders
• Interventions: Drug: Buprenorphine; Drug: Morphine; Drug: Placebo

• Registration Number: NCT00460239
• Lead Sponsor: Johns Hopkins University

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).

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.

Study Timeline

• Study Start: 2007-01
• Study First Submitted: 2007-04-11
• Study First Submitted QC: 2007-04-11
• Study First Posted: 2007-04-13
• Primary Completion: 2009-07
• Study Completion: 2009-07
• Results First Submitted: 2012-08-18
• Status Verified: 2017-01
• Results First Submitted QC: 2017-01-11
• Last Update Submitted: 2017-01-11
• Results First Posted: 2017-03-03
• Last Update Posted: 2017-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Buprenorphine 32	Buprenorphine	All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Morphine 30	Morphine	All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Buprenorphine 16	Buprenorphine	All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Placebo	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).
Morphine 15	Morphine	All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Buprenorphine 48	Buprenorphine	All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Buprenorphine 8	Buprenorphine	All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Buprenorphine 60	Buprenorphine	All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).

Primary Outcome Measures

Name	Time	Method
Psychomotor/Cognitive Performance Effects Assessed by Digit Symbol Substitution Test (DSST)	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.
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 Oxygen Saturation	Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Peak Change From Baseline in Drug Effect Assessed by Visual Analog Scale (VAS)	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 Trails B	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 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 Pupil Diameter	Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

Trial Locations

Locations (1)

Johns Hopkins University (BPRU) Bayview Campus; 🇺🇸 Baltimore, Maryland, United States