Vyvance: Open-Label Pilot Study of Lisdexamfetamine for Cocaine Dependence

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01486810
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 17
• Location: 1
• Arm: 1
• Duration (Months): 24
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The proposed protocol is an open-label pilot study of the treatment of cocaine dependence using lisdexamfetamine (LDX), a prodrug of d-amphetamine. The investigators plan to enroll 12 patients in an eight-week open-label trial to obtain preliminary data regarding the safety, tolerability, and potential utility of lisdexamfetamine for treatment of cocaine dependence and to determine an effective dosage range.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence	Drug: Lisdexamfetamine; Behavioral: medication management	Phase 1/Phase 2

Detailed Description

In an eight-week open label outpatient pilot trial, we will evaluate the safety, tolerability, and potential utility of LDX in the treatment of cocaine dependence. Patients will receive a flexible-fixed dosing schedule under open-label conditions. Patients will be titrated to the tolerated dose over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks, followed by a two week run-down period. All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders.

The primary outcome measures will be 1) the maximum total lisdexamfetamine dose achieved during the study period defined as the highest amount of medication per day maintained for a seven day period 2) lisdexamfetamine tolerability as measured by adverse effects reported on the Systematic Assessment for Treatment and Emergent Events (SAFTEE). Secondary outcome measures will be 1) cocaine use as recorded by the number of days of use on the Timeline Follow-Back method (Sobell & Sobell, 1992) and confirmed by urine toxicology, 2) cocaine craving as measured by the Cocaine Craving Scale (CCS) and Cocaine Craving Questionnaire (CCQ) and 3) alternate measures of cocaine use, such as the dollar value of cocaine used per day, as measured by the Timeline Follow-Back method, and the proportion of urine toxicology samples negative for cocaine.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label Pilot Study of Lisdexamfetamine for Cocaine Dependence
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Lisdexamfetamine and medication management Patients will be titrated to the tolerated dose of Lisdexamfetamine over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks. All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders.

Drug: Lisdexamfetamine; Patients will be titrated to the tolerated dose over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks; Other Names: Vyvance ; Behavioral: medication management; All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Maintained on the Maximum Lisdexamfetamine Daily Dose. [during 1 week of study participation]

   Number of participants achieving and maintained for a seven day period during the trial on the maximum daily dose of 140 mg..

2. Mean Maximum Maintained Dose of Lisdexamfetamine for at Least 1 Week of Trial. [during 8 weeks of trial or length of participation]

   The mean maximum daily dose of lisdexamfetamine that was maintained for at least 1 week of trial.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Individuals must be treatment seeking

• Men and women between the ages of 18-60 who meet DSM-IV criteria for current cocaine dependence

• Used cocaine at least four days in the past month

• Individuals must be in good general health

• Individuals must be capable of giving informed consent and capable of complying with study procedures

• Women of child-bearing age must agree to use a method of contraception with proven efficacy, consisting of one of the following: 1) Any form of hormonal contraception;

1. Intra-uterine device; 3) Sterilization; 4) Double-barrier contraception which is a combination of two of the following: condoms, spermicide, diaphragm. Pregnancy tests will be performed monthly and if a woman becomes pregnant, the study medication will be discontinued.

Exclusion Criteria:

• Individuals who meet DSM-IV-TR criteria for bipolar disorder, schizophrenia, any psychotic disorder other than transient psychosis due to drug abuse, or current major depressive disorder

• Individuals with any other current Axis I psychiatric disorder as defined by DSM-IV-TR that in the investigator's judgment are unstable, or would be disrupted by study medication, or are likely to require pharmacotherapy during the study period

• Individuals physiologically dependent on any other drugs (excluding nicotine or cannabis) which require medical intervention

• Individuals with current psychostimulant abuse or dependence (other than cocaine dependence)

• Individuals with current suicidal risk

• Individuals with coronary vascular disease as indicated by history or suspected by abnormal ECG or history of cardiac symptoms

• Unstable physical disorders which might make participation hazardous such as uncontrolled hypertension (SBP > 140, DBP> 90, or HR > 100 when sitting quietly), acute hepatitis (patients with chronic mildly elevated transaminases < 1.5x upper limit of normal are acceptable), or uncontrolled diabetes

• Individuals with a history of seizures, hyperthyroidism and/or glaucoma

• Individuals with a family history of sudden cardiac death

• History of allergic reaction to study medication

• Women who are pregnant or nursing

• Currently being prescribed psychotropic medication by another physician (other than sleep medication)

• Individuals who are legally mandated (e.g., to avoid incarceration) to participate in substance abuse treatment program

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	STARS	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: John Mariani, M.D., Columbia University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: John Mariani MD, research psychiatrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01486810
• Other Study ID Numbers: #6154; P50DA009236-18
• First Posted: Dec 7, 2011
• Last Update Posted: Apr 24, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by John Mariani MD, research psychiatrist, New York State Psychiatric Institute: cocaine; lisdexamfetamine
• Additional relevant MeSH terms: Cocaine-Related Disorders; Lisdexamfetamine Dimesylate

Study Results

Participant Flow

Arm/Group Title	Lisdexamfetamine and Medication Management
Arm/Group Description	Patients will be titrated to the tolerated dose of Lisdexamfetamine over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks. All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders. Lisdexamfetamine: Patients will be titrated to the tolerated dose over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks medication management: All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders.
Period Title: Overall Study
STARTED	17
COMPLETED	9
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Lisdexamfetamine and Medication Management
Arm/Group Description	Patients will be titrated to the tolerated dose of Lisdexamfetamine over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks. All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders. Lisdexamfetamine: Patients will be titrated to the tolerated dose over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks medication management: All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders.
Overall Participants	17
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.8 (8.4)
Sex: Female, Male (Count of Participants)
Female	2 11.8%
Male	15 88.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 17.6%
Not Hispanic or Latino	14 82.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 5.9%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	10 58.8%
White	3 17.6%
More than one race	3 17.6%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Maintained on the Maximum Lisdexamfetamine Daily Dose.
Description	Number of participants achieving and maintained for a seven day period during the trial on the maximum daily dose of 140 mg..
Time Frame	during 1 week of study participation

Outcome Measure Data

Analysis Population Description

Although 17 participants were enrolled, one participant was lost to follow-up without any post-enrollment study data, therefore 16 participants were analyzed.

Arm/Group Title	Lisdexamfetamine and Medication Management
Arm/Group Description	Patients will be titrated to the tolerated dose of Lisdexamfetamine over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks. All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders. Lisdexamfetamine: Patients will be titrated to the tolerated dose over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks medication management: All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders.
Measure Participants	16
Count of Participants [Participants]	12 70.6%

2. Primary Outcome

Title	Mean Maximum Maintained Dose of Lisdexamfetamine for at Least 1 Week of Trial.
Description	The mean maximum daily dose of lisdexamfetamine that was maintained for at least 1 week of trial.
Time Frame	during 8 weeks of trial or length of participation

Outcome Measure Data

Analysis Population Description

data available for 16 participants.

Arm/Group Title	Lisdexamfetamine and Medication Management
Arm/Group Description	Patients will be titrated to the tolerated dose of Lisdexamfetamine over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks. All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders. Lisdexamfetamine: Patients will be titrated to the tolerated dose over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks medication management: All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders.
Measure Participants	16
Mean (Standard Deviation) [mgs/day]	118.1 (40.4)

Adverse Events

Arm/Group Title	Lisdexamfetamine and Medication Management
Arm/Group Description	Patients will be titrated to the tolerated dose of Lisdexamfetamine over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks. All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders. Lisdexamfetamine: Patients will be titrated to the tolerated dose over a two week period, with a maximum of 140mg daily, and then maintained on the highest tolerated dose for four weeks medication management: All participants will receive medication management counseling and individual therapy using a structured compliance enhancement manual designed for pharmacotherapy trials in subjects with substance use disorders.
All Cause Mortality
	Lisdexamfetamine and Medication Management
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lisdexamfetamine and Medication Management
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Lisdexamfetamine and Medication Management
	Affected / at Risk (%)	# Events
Total	13/16 (81.3%)
Cardiac disorders
increased heart rate	2/16 (12.5%)	2
increased blood pressure	1/16 (6.3%)	1
Gastrointestinal disorders
abdominal pain	1/16 (6.3%)	1
constipation	1/16 (6.3%)	1
diarrhea	2/16 (12.5%)	2
nausea	1/16 (6.3%)	1
vomiting	1/16 (6.3%)	1
General disorders
appetite change	6/16 (37.5%)	6
dry mouth	2/16 (12.5%)	2
headache	1/16 (6.3%)	1
insomnia	3/16 (18.8%)	3
jittery	5/16 (31.3%)	5
fatigue	1/16 (6.3%)	1

Limitations/Caveats

As this was an open label trial, future studies should evaluate lisdexamfetamine for the treatment cocaine use disorder under double-blind conditions.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.