Quetiapine for the Reduction of Cocaine Use (AZC)

This placebo-controlled trial will test the effectiveness of Seroquel XR™ for the treatment of cocaine dependence in non-psychotic individuals who are cocaine dependent.

Cocaine abuse continues to be an epidemic. Co-morbid psychiatric disorders and high risks behaviors compound the morbidity, economic costs, and social destruction associated with this public health crisis. This is a 12 week, prospective, intent-to-treat, double-blind, randomized, placebo-controlled study of Seroquel XR™ versus matched placebo, combined with cognitive-behavioral group therapy, for the treatment of cocaine dependence in non-psychotic individuals.

We will conduct this study at the American Lake (Tacoma) and Seattle campuses of the VA Puget Sound Health Care System, recruiting veteran and non-veteran participants currently using cocaine from the greater Pierce and King Counties region. It is anticipated that 120 subjects will be consented and screened for study participation and that 60 subjects will be randomized to treatment.

After subjects have provided informed consent, they will enter a 1 week screening phase during which medical, psychiatric, and substance use measures and assessments will be administered to determine study eligibility. At baseline, we will assess cocaine use, cocaine craving, psychiatric symptoms, and high risk behaviors. Also at this visit, subjects will be randomly assigned to treatment with quetiapine (target dose 400 mg/day) or placebo. During the treatment phase, subjects will visit the clinic once a week for safety monitoring, completion of ratings and questionnaires, UDS's, and participation in a cognitive-behavioral therapy group. At end of study, week 12, a physical examination will be administered and a UDS and clinical laboratory values obtained. In addition, substance use, psychiatric symptoms, and high risk behaviors will be assessed. To monitor safety and further evaluate treatment effects, we will ask participants to return for a follow-up visit at week 16.

• Cocaine Dependence
• Cocaine Abuse
• Cocaine Addiction
• Drug Abuse
• Substance Abuse

• Drug: quetiapine fumarate
  At baseline, subjects in the experimental group will initially be administered 50 mg/day of Seroquel XR™ (extended release formulation of quetiapine fumarate), to be titrated up to 400 mg/day of Seroquel XR™ by the end of the second week. By the end of week 2, subjects will be stabilized on a dose of 400 mg/day or alternatively 300, 200, 100, or 50 mg/day of study drug, as tolerated. If a subject is unable to tolerate the 50 mg/day dose, he or she will be discontinued from the drug portion of the study.
  Other Name: Serorquel XR
• Drug: Matched Placebo
  Subjects randomized to the placebo comparator group will follow the same titration and dosing procedures as the experimental group, but will receive matched placebo tablets.
• Behavioral: Cognitive-behavioral Therapy
  During the 12 week treatment phase, all subjects will also attend weekly group cognitive-behavioral therapy sessions. This therapy platform will utilize the cognitive-behavioral therapy manual, Seeking Safety. Seeking Safety was originally designed as a psychotherapeutic intervention for women dually diagnosed with PTSD and substance abuse disorders but it has also been successfully used with dually diagnosed men. Seeking Safety has been shown to effectively reduce substance use and to improve psychological functioning in a variety of populations. In addition, Seeking Safety has been shown to be as effective as cognitive-behavioral relapse prevention therapy. Seeking Safety's focus on increasing emotional regulation and teaching cognitive, behavioral and interpersonal coping skills that provide ready alternatives to substance use make it an appropriate psychotherapeutic intervention for any person in early recovery from a substance use disorder.

• Experimental: Study Drug
  Interventions:

  • Drug: quetiapine fumarate
  • Behavioral: Cognitive-behavioral Therapy
• Placebo Comparator: Placebo
  Interventions:

  • Drug: Matched Placebo
  • Behavioral: Cognitive-behavioral Therapy

Inclusion Criteria:

1. Provision of written informed consent
2. Males and females aged 18-65 years
3. Female subjects of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at the screening and baseline visits and agree to use one of the following methods of birth control: a) oral contraceptive, b) patch, c) intrauterine progesterone or non-hormonal contraceptive system, d) levonorgestrel implant, e) medroxyprogesterone acetate contraceptive injection, or f) complete abstinence from sexual intercourse
4. A diagnosis of current cocaine dependence; as determined by the Structured Clinical Interview for DSM-IV-TR Axis I Disorders 69 (SCID-I/P)
5. Has used cocaine within the 30 days prior to screening
6. Able to understand and comply with the requirements of the study
7. Is seeking treatment for cocaine dependence
8. Is able to provide a reliable primary contact phone number and is able to provide a reliable alternate contact address and phone number, such as for a relative or close friend
9. Anticipates no life changes that would preclude study completion

Exclusion Criteria:

1. Pregnancy or lactation
2. Currently hospitalized or in a detoxification program
3. Physiological dependence on alcohol, sedative/hypnotic, or any other substance requiring medical detoxification
4. Current diagnosis of psychotic disorder, including bipolar disorder with psychotic features, as determined by the SCID-I/P or clinical interview
5. Subjects who are judged by the investigator to be psychiatrically unstable, including posing an imminent risk of suicide or a danger to self or others, as determined by the SCID-I/P, CGI-S, Hamilton Anxiety Rating Scale(HAM-A), Hamilton Rating Scale for Depression(HAM-D), or clinical interview
6. Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator
7. Has a history of neuroleptic malignant syndrome or other serious adverse reaction to antipsychotic medication
8. Use of any antipsychotic medication within the 30 days preceding baseline
9. Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days prior to baseline including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluoxetine, fluvoxamine, paroxetine, and saquinavir
10. Use of any of the following cytochrome P450 inducers in the 14 days prior to baseline including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids
11. Evidence of any clinically relevant disease (e.g., renal, hepatic, gastrointestinal, pulmonary, cardiac, or cerebrovascular disease, AIDS, cancer, asthma, neurological or neuromuscular disease, seizure disorder, or clinically significant abnormal laboratory value) or any clinical finding that in the judgment of the investigator could potentially be negatively affected by study participation or that could potentially affect study participation

• VA Puget Sound Health Care System
• AstraZeneca