Clinical Trials

Inclusion Criteria

* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Male or female, aged 18 or older
* Diagnosed with either recurrent acute pancreatitis or chronic pancreatitis as defined by the American Pancreatic Association:

o Chronic Pancreatitis (any of the following): i. Moderate/marked pancreas imaging morphology (i.e. ductal and parenchymal abnormalities ii. Pancreatic calcifications iii. Histologic confirmation

o Recurrent Acute Pancreatitis: i. Two or more documented attacks of acute pancreatitis, separated by 3 months from one another, defined by at least 2 of the following 3:
1. amylase or lipase values, or both, that are greater than 3 times the upper limit of normal values
2. characteristic cross-sectional imaging
3. typically upper abdominal pain according to the revised Atlanta classification
* Currently smoking ≥ 5 cigarettes/day
* Explicitly express a desire to quit within 30 days
* Ability to take oral medication and be willing to adhere to the study intervention regimen
* Willing and able to comply with trial protocol and follow-up

Exclusion Criteria

* Age \< 18 years
* Ongoing acute pancreatitis or prior episode of pancreatitis in previous 30 days
* No desire to quit smoking
* Currently undergoing smoking cessation intervention (i.e. nicotine replacement therapy, varenicline, counseling, bupropion).
* Known allergic reactions to varenicline or bupropion SR
* History of seizures
* History of an eating disorder (anorexia or bulimia)
* Closed head trauma with any loss of consciousness or amnesia in the last 5 year
* Ever history of closed head trauma with \> 30 minutes of loss of consciousness or amnesia or resulting in skull fracture or subdural hematoma/brain contusion
* Ever history of alcohol withdrawal
* Ever history of chronic kidney disease (creatine clearance \< 30 mL/minute)
* Liver impairment (i.e. history of cirrhosis) with aminotransferase elevation ≥ 2 times the upper limit of normal and/or alkaline phosphatase elevation ≥ 2 times the upper limit of normal.
* History of bipolar disorder or psychosis
* Ongoing or recent use (prior 14 days) of any monoamine oxidase inhibitors (isocarboxazid, phenelzine, tranylcypromine, selegiline).
* Regular use of potent CYP2B6 inhibitors (i.e. clopidogrel, ticlopidine)
* Regular use of CYP2D6 substrates with narrow therapeutic indices (e.g. flecainide, propafenone, tricyclic antidepressants such as nortriptyline, thioridazine, vinblastine)
* History of acute angle closure glaucoma
* Meet criteria for depression as assessed by the Center for Epidemiologic Studies - Depression (CES-D) with a score of 16 or higher.
* Psychiatric hospitalization within 1 year of screening
* Participants who have a score of 3 or higher on the Columbus-Suicide Severity Rating Scale (C-SSRS) at enrollment or during any of the study assessments will be excluded
* Unable to provide consent for self Incarcerated
* Pregnant females. All female patients of childbearing potential must have a negative pregnancy test and must agree to use highly effective (failure rate \<1%) contraception during participation in the study.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 9/12/2025. Questions regarding updates should be directed to the study team contact.