Phendimetrazine and Cocaine

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
Safety and Tolerability of Cocaine During Phendimetrazine Maintenance

Conditions
-----------------
Cocaine Use Disorder

Intervention / Treatment
-----------------
* Drug: Cocaine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and phendimetrazine.<br>Drug: Placebo<br>* The pharmacodynamic effects of placebo will be determined during maintenance on placebo and phendimetrazine.<br>|
| Experimental: Phendimetrazine Dose 1<br>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<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and phendimetrazine.<br>Drug: Placebo<br>* The pharmacodynamic effects of placebo will be determined during maintenance on placebo and phendimetrazine.<br>|
| Experimental: Phendimetrazine Dose 2<br>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<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and phendimetrazine.<br>Drug: Placebo<br>* The pharmacodynamic effects of placebo will be determined during maintenance on placebo and phendimetrazine.<br>|
| Experimental: Phendimetrazine Dose 3<br>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<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and phendimetrazine.<br>Drug: Placebo<br>* The pharmacodynamic effects of placebo will be determined during maintenance on placebo and phendimetrazine.<br>|

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. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cocaine, phendimetrazine, pharmacotherapy