Clinical trial NCT01904526: PK/PD Comparison of Guanfacine ER and IR
Official title: Pharmacokinetic/Dynamic (PK/PD) Comparison of Guanfacine Extended Release (ER) and Immediate Release (IR) in Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Smoking
Keywords: Guanfacine
PK/PD
Smokers
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2013-07-22
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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

Primary outcomes:
measure: Plasma Trough Levels of Guanfacine
timeFrame: +24 hours on Lab Session days (Days 22, 49, 58)
Secondary outcomes:
measure: Heart Rate
timeFrame: Last day of titration period 1 (Day 21) to the last day of titration period 3 (Day 57)
measure: Systolic Blood Pressure
timeFrame: Last day of titration period 1 (Day 21) to the last day of titration period 3 (Day 57)
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Center for Clinical Investigations, Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: Sherry A McKee, PhD
role: PRINCIPAL_INVESTIGATOR
References: