PK/PD Comparison of Guanfacine ER and IR

Smoking Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01904526
• Other study ID #: 1110009133
• Secondary ID: R01DA035001P50DA
• Status: Completed
• Phase: Phase 2
• Start date: July 2013
• Est. completion date: December 2016

Study information

• Verified date: March 2020
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Smoking

Intervention

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.

Locations

Country	Name	City	State
United States	Yale Center for Clinical Investigations, Yale University	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)