Smoking
Conditions
Keywords
Guanfacine, PK/PD, Smokers
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.
Interventions
DRUGGuanfacine
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.
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Trough Levels of Guanfacine | +24 hours on Lab Session days (Days 22, 49, 58) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Heart Rate | Last day of titration period 1 (Day 21) to the last day of titration period 3 (Day 57) | Evaluate the safety and tolerability of guanfacine by measuring physiologic reactivity (e.g., heart rate) |
| Systolic Blood Pressure | Last day of titration period 1 (Day 21) to the last day of titration period 3 (Day 57) | Evaluate the safety and tolerability of guanfacine by measuring physiologic reactivity (e.g., systolic blood pressure) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Guanfacine 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. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Guanfacine |
|---|---|
| Age, Continuous | 45.8 Years STANDARD_DEVIATION 2.49 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 3 / 5 | 4 / 5 | 4 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 5 |
Outcome results
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
Time frame: +24 hours on Lab Session days (Days 22, 49, 58)
Population: 3 mg/day IR (Day 22) followed by 4mg/day ER (Day 49) followed by 6mg/day ER (Day 58)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guanfacine 3mg/Day Immediate Release | Plasma Trough Levels of Guanfacine | 3.40 ng/ml | Standard Error 0.33 |
| Guanfacine 4mg/Day Extended Release | Plasma Trough Levels of Guanfacine | 3.46 ng/ml | Standard Error 0.67 |
| Guanfacine 6mg/Day Extended Release | Plasma Trough Levels of Guanfacine | 5.92 ng/ml | Standard Error 1.02 |
Secondary
Heart Rate
Evaluate the safety and tolerability of guanfacine by measuring physiologic reactivity (e.g., heart rate)
Time frame: Last day of titration period 1 (Day 21) to the last day of titration period 3 (Day 57)
Population: Last day of titration period: 3 mg/day IR (Day 21) followed by 4mg/day ER (Day 48) followed by 6mg/day ER (Day 57)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guanfacine 3mg/Day Immediate Release | Heart Rate | 59.6 beats per minute | Standard Error 1.75 |
| Guanfacine 4mg/Day Extended Release | Heart Rate | 58.8 beats per minute | Standard Error 3.97 |
| Guanfacine 6mg/Day Extended Release | Heart Rate | 61.6 beats per minute | Standard Error 5.3 |
Secondary
Systolic Blood Pressure
Evaluate the safety and tolerability of guanfacine by measuring physiologic reactivity (e.g., systolic blood pressure)
Time frame: Last day of titration period 1 (Day 21) to the last day of titration period 3 (Day 57)
Population: Last day of titration period: 3 mg/day IR (Day 21) followed by 4 mg/kg ER (Day 48) followed by 6 mg/day ER (Day 57)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Guanfacine 3mg/Day Immediate Release | Systolic Blood Pressure | 101.0 mmHg | Standard Error 3.73 |
| Guanfacine 4mg/Day Extended Release | Systolic Blood Pressure | 107.4 mmHg | Standard Error 7.51 |
| Guanfacine 6mg/Day Extended Release | Systolic Blood Pressure | 108.4 mmHg | Standard Error 7.16 |