Combining Varenicline and Guanfacine for Smoking Cessation

NCT04198116 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 2000026630R01DA047986
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

The novel design of this study combines a laboratory paradigm to evaluate stress-induced smoking behavior and smoking-related reinforcement, followed by a 12-week treatment phase to evaluate clinical outcomes.

Conditions

Smoking Cessation

Outcome Measures

Primary Outcomes (1)

• Latency

  Latency (in minutes) to time of first cigarette smoked during the delay period.

  50 minutes

Study Arms (2)

Varenicline + Guanfacine ER

EXPERIMENTAL

Varenicline (2mg/day) + Guanfacine extended release (6mg/day ER). Varenicline (2mg/day) administered orally twice a day at 8:00 AM and 8:00 PM while titrating to full dose. Titration schedule: Days 1-9 0mg/day; 0mg/dose, Days 10-12 0.5mg/day; 0.5mg/dose 8:00 PM, Days 13-15 1mg/day; 0.5mg/dose, Days 16-21 2mg/day; 1mg/dose. Guanfacine ER (6mg/day) administered orally twice daily at 8:00 AM and 8:00 PM while titrating to the full dose. Titration schedule: Days 1-3 1mg/day; 0.5mg/dose, Days 4-6 2mg/day; 1mg/dose, Days 7-9 3mg/day; 1.5mg/dose, Days 10-12 4mg/day; 2mg/dose; Days 13-15 5mg/day; 2.5mg/dose and Days 16-23 6mg/day; 3mg/dose. Once at steady state, administration is orally once per day at 8:00 PM for both medications.

Drug: Varenicline; Drug: Guanfacine ER

Varenicline

ACTIVE COMPARATOR

Varenicline (2mg/day). Varenicline (2mg/day) administered orally twice a day at 8:00 AM and 8:00 PM while titrating to full dose. Titration schedule: Days 1-9 0mg/day; 0mg/dose, Days 10-12 0.5mg/day; 0.5mg/dose 8:00 PM, Days 13-15 1mg/day; 0.5mg/dose, Days 16-21 2mg/day; 1mg/dose. Once at steady state, administration is orally once per day at 8:00 PM.

Drug: Varenicline

Interventions

Varenicline DRUG

Varenicline 2mg/day

Also known as: Chantix

Varenicline; Varenicline + Guanfacine ER

Guanfacine ER DRUG

Guanfacine Extended Release (6mg/day ER)

Also known as: Intuniv

Varenicline + Guanfacine ER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18+
• Able to read and write English
• SMOKER: 10 or more cigarettes per day for at least the past year, Carbon Monoxide (CO) \> 10 ppm at intake
• Able to take oral medications and willing to adhere to medication regimen
• Provide evidence of a stable living residence in the last 2 months prior to randomization, have reasonable transportation arrangements to the study site, have no plans to move within the next 3 months, and have no unresolved legal problems
• Motivated to quit smoking (8 or greater on the Contemplation Ladder)

You may not qualify if:

• Subjects with any significant current medical conditions (neurological, cardiovascular \[including hypertension or hypotension: sitting BP \>160/100 or \<90/60mmHg at baseline screening\], endocrine, thyroid, renal, liver), seizures, delirium or hallucinations, or other unstable medical conditions
• Current Diagnostic and Statistical Manual of Mental Disorders (DSM-V) alcohol or substances use disorders, other than mild alcohol use disorder or tobacco use disorder
• Subjects who have a positive test result at intake appointment on urine drug screens conducted for illicit drugs
• Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives \[oral, implant, injection, patch, or ring\], contraceptive sponge, double barrier \[diaphragm or condom plus spermicide\], or IUD)
• Suicidal, homicidal or evidence of current (past 6-month) severe mental illness such as schizophrenia or bipolar disorder
• meeting DSM-V criteria for current (past-6 month) attention deficit hyperactivity disorder (ADHD)
• Individuals who are currently taking medications known to be effective for smoking cessation (e.g., FDA smoking cessation medications, nortriptyline, clonidine) or are regular users of e-cigarettes or other tobacco projects (pipe, cigar, smokeless tobacco) in the past 30 days
• Only one member per household can participate in the study

Sponsors & Collaborators

• Yale University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Conditions

Smoking Cessation

Interventions

Varenicline; Guanfacine

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines; Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids

Study Officials

• Sherry McKee, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 13, 2019
• Study Start: November 1, 2020
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)