PK/PD Comparison of Guanfacine ER and IR

Pharmacokinetic/Dynamic (PK/PD) Comparison of Guanfacine Extended Release (ER) and Immediate Release (IR) in Smokers

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.

Study Overview

• Status: Completed
• Conditions: Smoking
• Intervention / Treatment: Drug: Guanfacine

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale Center for Clinical Investigations, Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Guanfacine; Guanfacine 3 mg/day immediate release followed by Guanfacine 4mg/day extended release followed by Guanfacine 6 mg/day extended release

Drug: Guanfacine; 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.; Other Names: Intuniv; Tenex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Trough Levels of Guanfacine	Evaluate whether a 4mg/day or 6mg/day dose of extended-release guanfacine produces pharmacokinetic (PK) properties similar to 3mg/day immediate release guanfacine by measuring plasma trough levels of guanfacine for each dose	+24 hours on Lab Session days (Days 22, 49, 58)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate	Evaluate the safety and tolerability of guanfacine by measuring physiologic reactivity (e.g., heart rate)	Last day of titration period 1 (Day 21) to the last day of titration period 3 (Day 57)
Systolic Blood Pressure	Evaluate the safety and tolerability of guanfacine by measuring physiologic reactivity (e.g., systolic blood pressure)	Last day of titration period 1 (Day 21) to the last day of titration period 3 (Day 57)

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: July 12, 2013
• First Submitted That Met QC Criteria: July 17, 2013
• First Posted (Estimate): July 22, 2013

Study Record Updates

• Last Update Posted (Actual): March 6, 2020
• Last Update Submitted That Met QC Criteria: March 4, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Smokers; Guanfacine; PK/PD
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Guanfacine
• Other Study ID Numbers: 1110009133; R01DA035001 (U.S. NIH Grant/Contract); P50DA033945 (U.S. NIH Grant/Contract)