Safety Assessment of Atomoxetine With MA IV Administration

• Status: Terminated
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a study of 4 nontreatment seeking individuals who were MA-dependent and the safety and tolerability of atomoxetine. This double-blind, placebo-controlled, within-subjects study is to determine the safety and tolerability of atomoxetine.

MA abusing participants will undergo a 1-day outpatient screening and if it is safe for the participants to proceed with the study they will participate in two inpatient components of the study that will occur in the University of California Los Angeles (UCLA) General Clinical Research Center (GCRC). The first inpatient stay will be 15 days, and the second will be a 9 days stay that includes drug administration and assessments. There will be at least a two week interval between inpatient components. During the inpatient components participants will receive alternating study drugs; atomoxetine or placebo and four sessions of IV MA administration or saline.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, Los Angeles
• Collaborator: National Institute on Drug Abuse (NIDA)
• Treatments: Atomoxetine Hydrochloride; Methamphetamine

Criteria

Inclusion Criteria:

1. Be fluently English-speaking volunteers who meet DSM-IV criteria for MA abuse or dependence.

2. Be between 18 and 50 years of age.

3. Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures.

4. Have smoked or injected methamphetamine for more than two years.

5. Produce a methamphetamine-positive urine prior to study entry.

6. Have vital signs as follows: resting pulse between 50 and 90 bpm, blood pressures between 105-150mm Hg systolic and 45-90mm Hg diastolic. Note that a blood pressure of 150/90 and pulse of 90 is too high for randomization but will allow participants to be enrolled if an acceptable range is demonstrated on a separate occasion.

7. Have an ECG performed that demonstrates normal sinus rhythm, normal conduction, and no clinically significant arrhythmias.

8. Agree to abstain from MA during the study, evidenced by a MA-negative urine each morning of the study.

9. If female, have a negative pregnancy test and agree to use one of the following methods of birth control, or be postmenopausal, have had a hysterectomy or have been sterilized.

1. oral contraceptives

2. barrier (diaphragm or condom) with spermicide, or condom only

3. intrauterine progesterone,or non-hormonal contraceptive system

4. levonorgestrel implant

5. medroxyprogesterone acetate contraceptive injection

6. complete abstinence from sexual intercourse

NOTE: Recent intermittent alcohol or other illicit drug use without physical dependence is allowable (however a benzodiazepine-free urine should be produced to document absence of recent use).

Exclusion Criteria:

1. A current or past history of seizure disorder, including alcohol- or stimulant-related seizure, febrile seizure, or significant family history of idiopathic seizure disorder.

2. A history of head trauma that resulted in neurological sequelae (e.g., with loss of consciousness [LOC] > 15 minutes, or that required hospitalization. Also, individuals with 3 or more head injuries with LOC > 5 minutes will be excluded).

3. Do not meet DSM-IV criteria (by SCID) for drug dependence other than meth, with the exception of nicotine and/or marijuana dependence.

4. Any previous medically serious adverse reaction to MA including loss of consciousness, chest pain, or epileptic seizure resulting in hospitalization.

5. Meeting diagnostic criteria or receiving psychopharmacological treatment for the following Axis I disorders within the last 6 months: anorexia nervosa, bulimia, psychosis, bipolar I disorder, organic brain disease, dementia, major depression, schizoaffective disorder, or schizophrenia.

6. Evidence of clinically significant heart disease, hypertension or significant medical illness.

7. Have any history of hypersensitivity to atomoxetine, glaucoma, motor tics or with a family history or diagnosis of Tourette's syndrome.

8. Have any preexisting severe gastrointestinal narrowing, small bowel inflammatory disease, intestinal adhesions, past history of peritonitis, or cystic fibrosis.

9. Be pregnant or nursing.

10. Have a significant family history of early cardiovascular morbidity or mortality.

11. Have a diagnosis of adult asthma, including those with a history of acute asthma within the past two years, and those with current or recent (past 2 years) treatment with inhaled or oral beta-agonist or steroid therapy (due to potential serious adverse interactions with methamphetamine).

12. Be actively using albuterol or other beta agonist medications, regardless of formal diagnosis of asthma. (Inhalers are sometimes used by MA addicts to enhance MA delivery to the lungs.) If respiratory disease is excluded and the subject will consent to discontinue agonist use, s/he may be considered for inclusion.

13. For subjects suspect for asthma but without formal diagnosis, 1) have a history of coughing and/or wheezing, 2) have a history of asthma and/or asthma treatment two or more years before, 3) have a history of other respiratory illness, e.g., complications of pulmonary disease (exclude if on beta agonists), 4) use over-the-counter agonist or allergy medication for respiratory problems (e.g., Primatene Mist): a detailed history and physical exam, pulmonary consult, and pulmonary function tests should be performed prior to including or excluding from the study or 5) have an FEV1 <70 %.

14. Have any illness, condition, and/or use of medications that in the opinion of the site Principal Investigator and the admitting physician would preclude safe and/or successful completion of the study.

15. Have active syphilis that has not been treated or refuse treatment for syphilis.

16. Be undergoing HIV treatment with antiviral and non-antiviral therapy.

17. Have AIDS according to the current CDC criteria for AIDS - MMWR 1999;48 (#RR-13:29-31).

18. Have neurological disorders including Parkinson's disease.

19. Have evidence of significant liver or kidney dysfunction.

20. Have a history of urinary retention or bladder outlet obstruction.

21. Be UCLA students or staff.

22. Have evidence of active tuberculosis infection.