PK/PD Comparison of Guanfacine ER and IR
Condition: Smoking
Intervention: Guanfacine
Intervention description: 3mg/day IR with 3-week lead-in period. Maintained at steady state to complete lab session. After completion of lab session, 1-week lead-in medication period to 4mg/day ER. Maintained at steady state to complete lab session. After completion of lab session, 1-week lead-in medication period to 6mg/day ER. Maintained at steady state to complete lab session. 5-day taper after lab.
Intervention MeSH terms: Guanfacine
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Guanfacine; PK/PD; Smokers

Summary:

      Evaluate whether a 4mg/day or 6/mg day dose of extended-release guanfacine produces
      pharmacokinetic/dynamic (PK/PD) properties similar to 3mg/day immediate release guanfacine.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18-65

          -  Able to read, write and comprehend English

          -  Smoker

          -  Able to take oral medications and willing to adhere to medication regimen

          -  Provide evidence of a stable living residence in the last 2 months, have reasonable
             transportation to the study site, and have no plans to move within the next 3 months
             or unresolved legal problems.

        Exclusion Criteria:

          -  Any significant current medical conditions that would contraindicate smoking

          -  Current Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) abuse or
             dependence of other substances, other than nicotine dependence or alcohol abuse

          -  Positive test results at intake appointment on urine drug screens for illicit drugs

          -  Past 30 day use of psychoactive drugs including anxiolytics and antidepressants

          -  Women who are pregnant or nursing

          -  Suicidal, homicidal or evidence of current mental illness such as schizophrenia,
             bipolar disorder or major depression, or anxiety disorders

          -  Meeting DSM-IV criteria for current attention deficit hyperactivity disorder (ADHD)

          -  Individuals who are currently taking medications known to be effective for smoking
             cessation or are regular users of other tobacco products in the past 30 days

          -  Only one member per household can participate in the study

          -  Specific exclusions for administration of guanfacine not already specified include:

               -  EKG evidence at baseline screening of any clinically significant conduction
                  abnormalities or arrhythmias

               -  Known intolerance for guanfacine or any alpha blocker

               -  History of fainting, syncopal attacks

               -  Heart failure or myocardial infarction

               -  Impaired liver (as indicated by aspartate aminotransferase (AST), alanine
                  aminotransferase (ALT) >3x normal)

               -  Renal function (as indicated by estimated creatinine clearance <60cc/min)

               -  Treatment with any antihypertensive drug or any alpha-adrenergic blocker

               -  Use of any central nervous system depressant (e.g., phenothiazines, barbiturates,
                  benzodiazepines)

               -  Use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole) or
                  inducers (e.g., rifampin), or consumption of grapefruit juice

          -  Subjects may have not donated blood in the past 8 weeks or have been involved in other
             investigational studies that involve substantial blood draws or medications unknown to
             us