Phendimetrazine and Cocaine

Safety and Tolerability of Cocaine During Phendimetrazine Maintenance

This study will determine the safety and tolerability of phendimetrazine (Bontril®) as a pharmacotherapy for cocaine use disorder. A rigorous, inpatient human laboratory study will be conducted in which the subjective and physiological effects of cocaine are evaluated during maintenance on placebo and phendimetrazine.

Study Overview

• Status: Completed
• Conditions: Cocaine Use Disorder
• Intervention / Treatment: Drug: Cocaine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40507
      • University of Kentucky Laboratory of Human Behavioral Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recent cocaine use

Exclusion Criteria:

• Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant
• Current or past histories of substance abuse or dependence that are deemed by the study physicians to interfere with study completion
• History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation
• Females not currently using effective birth control
• Contraindications to cocaine or phendimetrazine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects will be maintained on oral placebo. Cocaine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance.	Drug: Cocaine; The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and phendimetrazine.; Drug: Placebo; The pharmacodynamic effects of placebo will be determined during maintenance on placebo and phendimetrazine.
Experimental: Phendimetrazine Dose 1; Subjects will be maintained on the low phendimetrazine dose. Cocaine will be administered acutely during low dose phendimetrazine maintenance. Placebo will be administered acutely during low dose phendimetrazine maintenance.	Drug: Cocaine; The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and phendimetrazine.; Drug: Placebo; The pharmacodynamic effects of placebo will be determined during maintenance on placebo and phendimetrazine.
Experimental: Phendimetrazine Dose 2; Subjects will be maintained on the intermediate phendimetrazine dose. Cocaine will be administered acutely during intermediate dose phendimetrazine maintenance. Placebo will be administered acutely during intermediate dose phendimetrazine maintenance.	Drug: Cocaine; The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and phendimetrazine.; Drug: Placebo; The pharmacodynamic effects of placebo will be determined during maintenance on placebo and phendimetrazine.
Experimental: Phendimetrazine Dose 3; Subjects will be maintained on the high phendimetrazine dose. Cocaine will be administered acutely during high dose phendimetrazine maintenance. Placebo will be administered acutely during high dose phendimetrazine maintenance.	Drug: Cocaine; The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and phendimetrazine.; Drug: Placebo; The pharmacodynamic effects of placebo will be determined during maintenance on placebo and phendimetrazine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Systolic Pressure	Systolic blood pressure was measured with an automated monitor. Higher values represent greater systolic pressure. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo maintenance conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Diastolic Pressure	Diastolic blood pressure was measured with an automated monitor. Higher values represent greater diastolic pressure. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo maintenance conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Heart Rate	Heart rate was measured with an automated monitor. Higher values represent greater heart rate. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo maintenance conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Temperature	Oral temperature was measured with an automated monitor. Higher values represent greater temperature. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo maintenance conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Score on Sedative Subscale of the Adjective Rating Scale	Subjects completed 16 items that loaded into the Sedative Subscale of the Adjective Rating Scale. The items were rated 0-4 on a Likert-type scale and the sum for the 16 "sedative" items was summed to yield the Sedative Subscale score. The maximum score for this scale was 64, the minimum was 0. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Score on Stimulant Subscale of the Adjective Rating Scale	Subjects completed 16 items that loaded into the Stimulant Subscale of the Adjective Rating Scale. The items were rated 0-4 on a Likert-type scale and the sum for the 16 "stimulant" items was summed to yield the Stimulant Subscale score. The maximum score for this scale was 64, the minimum was 0. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Active, Alert, Energetic" on the Visual Analog Scale	Subjects rated their feelings of "Active, Alert, Energetic" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Any Effect" on the Visual Analog Scale	Subjects rated their feelings of "Any Effect" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Bad Effect" on the Visual Analog Scale	Subjects rated their feelings of "Bad Effect" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Euphoric" on the Visual Analog Scale	Subjects rated their feelings of "Euphoric" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Good Effect" on the Visual Analog Scale	Subjects rated their feelings of "Good Effect" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "High" on the Visual Analog Scale	Subjects rated their feelings of "High" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Irregular/Racing Heartbeat" on the Visual Analog Scale	Subjects rated their feelings of "Irregular/Racing Heartbeat" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Like Drug" on the Visual Analog Scale	Subjects rated their feelings of "Like Drug" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Nauseated/Queasy/Sick to Stomach" on the Visual Analog Scale	Subjects rated their feelings of "Nauseated/Queasy/Sick to Stomach" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Nervous/Anxious" on the Visual Analog Scale	Subjects rated their feelings of "Nervous/Anxious" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Willing to Pay For" on the Visual Analog Scale	Subjects rated their feelings of "Willing to Pay For" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Performance Impaired" on the Visual Analog Scale	Subjects rated their feelings of "Performance Impaired" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Performance Improved" on the Visual Analog Scale	Subjects rated their feelings of "Performance Improved" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Restless" on the Visual Analog Scale	Subjects rated their feelings of "Restless" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Rush" on the Visual Analog Scale	Subjects rated their feelings of "Rush" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Shaky/Jittery" on the Visual Analog Scale	Subjects rated their feelings of "Shaky/Jittery" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Sluggish/Fatigued/Lazy" on the Visual Analog Scale	Subjects rated their feelings of "Sluggish/Fatigued/Lazy" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Stimulated" on the Visual Analog Scale	Subjects rated their feelings of "Stimulated" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Willing to Take Again" on the Visual Analog Scale	Subjects rated their feelings of "Willing to Take Again" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.
Peak Ratings of "Talkative/Friendly" on the Visual Analog Scale	Subjects rated their feelings of "Talkative/Friendly" on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both phendimetrazine and placebo conditions.	This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions.

Collaborators and Investigators

• Sponsor: William Stoops
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: September 3, 2014
• First Submitted That Met QC Criteria: September 5, 2014
• First Posted (Estimate): September 8, 2014

Study Record Updates

• Last Update Posted (Actual): September 27, 2017
• Last Update Submitted That Met QC Criteria: September 26, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: pharmacotherapy; cocaine; phendimetrazine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Anesthetics, Local; Dopamine Uptake Inhibitors; Vasoconstrictor Agents; Cocaine
• Other Study ID Numbers: BED (IN) 29