Effects of ABT-089 on Smoking Abstinence Symptoms and Reward
Condition: Nicotine Addiction
MeSH terms: Tobacco Use Disorder
Intervention: ABT-089; Placebo
Intervention description: Selective neuronal nicotinic receptor agonist.; Matched placebo capsules supplied by study drug supplier.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Smoking; Tobacco

Summary:

      This Phase IIa within-subject, cross-over pilot study will evaluate the effects of ABT-089
      (an experimental medication not approved by the FDA) when administered as 40mg oral once
      daily dose for 10 days, compared to placebo, on the following: abstinence-induced cognitive
      deficits, smoking withdrawal, smoking urges, smoking reward, and a brief, monitored quit
      attempt (~4 days). The key cognitive domains include: working memory, sustained attention,
      and response inhibition.
    

Eligibility criteria:

        Inclusion Criteria.

        Eligible subjects will be:

          1. Male and female smokers who are between 18 and 65 years of age and self-report smoking
             at least 10 cigarettes (menthol and/or non-menthol) per day for at least the last 6
             months.

          2. Healthy as determined by the Study Physician, based on relevant medical history,
             physical examination (including vitals), and basic screening tests (CBC, CHEM7,
             AST/ALT).

          3. Smokers who wish to quit smoking in the next 2-6 months (treatment-seeking), because
             our prior work suggests that motivated subjects are more sensitive to medication
             effects on smoking behavior. Using a scale from 0 to 100 (100, being extremely
             interested), subjects must rate their interest in quitting smoking within the next 6
             months greater than 50.

          4. Able to communicate fluently in English (speaking, writing, and reading).

          5. Plan to live in the area for the next 2 months.

          6. Capable of giving written informed consent, which includes compliance with the
             requirements and restrictions listed in the combined consent and HIPAA form.

        Exclusion Criteria.

        Subjects who self-report and/or present with the following criteria will not be eligible to
        participate in the study:

          1. Smoking behavior.

               1. Current enrollment or firm plans to quit smoking and/or enroll in a smoking
                  cessation program within the next 2 months.

               2. Current and/or anticipated use of any nicotine substitutes and/or smoking
                  cessation treatments/medications within the next 2 months.

               3. Provide a Carbon Monoxide (CO) reading less than 11 parts per million (ppm) at
                  Intake.

               4. Provide a CO reading of 10 ppm or greater at either Testing Visit (Days 6 and
                  37). If the CO reading is greater than or equal to 10 ppm, but there is a 50%
                  reduction from the CO reading collected at the Baseline/Period 1 Medication
                  Pick-Up Visit, this will be sufficient and the subject may continue as scheduled.

               5. Self-report smoking during the mandatory abstinence period at either Testing
                  Visit (Days 6 and 37).

               6. Regular use of chewing tobacco or snus.

          2. Alcohol/Drugs.

               1. History of substance abuse in the past 6 months and/or currently receiving
                  treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or
                  stimulants). Subjects reporting a history of substance abuse must be in remission
                  at least 6 months or greater.

               2. Current alcohol consumption that exceeds 25 standard drinks/week.

               3. Provide a breath alcohol concentration (BrAC) reading of greater than or equal to
                  0.01 at Intake, Baseline/Period 1 Medication Pick-Up, or Testing Visits (Days 6
                  and 37).

               4. A positive urine drug screen for cocaine, PCP, amphetamines, methamphetamines,
                  tricyclic antidepressants, opiates, methadone, benzodiazepines, and/or
                  barbiturates at Intake, Baseline/Period 1 Medication Pick-Up, Period 2 Medication
                  Pick-Up, and Observation Visits on Days 10 and 41.

          3. Medical.

               1. Women who are pregnant, planning a pregnancy, and/or breast feeding. All female
                  subjects will undergo a urine pregnancy test at Intake, after which only females
                  determined to be of childbearing potential will complete a urine pregnancy test
                  at Baseline/Period 1 Medication Pick-Up, Period 2 Medication Pick-Up, and
                  Observation Visits on Days 10 and 41. By signing the combined consent and HIPAA
                  form, women of childbearing potential agree to use an approved method of
                  contraception during the study.

               2. Men who do not agree to use an approved method of contraception during the study.
                  Men who are sexually active must be surgically sterile (vasectomy) or using a
                  barrier method (condom) of birth control for the duration of the study. By
                  signing the combined consent and HIPAA form, men agree to use an approved method
                  of contraception.

               3. Current treatment of cancer or diagnosed with cancer (except basal cell
                  carcinoma) in the past 6 months.

               4. Any impairment including, but not limited to, visual, physical, and/or
                  neurological impairments preventing neurocognitive task performance.

               5. Color blindness.

               6. History of brain injury.

               7. History of epilepsy or a seizure disorder.

               8. Low or borderline intellectual functioning - determined by receiving a score of
                  less than 90 on the Shipley Institute of Living Scale (SILS, administered at
                  Intake), which correlates with the Wechsler Adult Intelligence Scale-Revised
                  (WAIS-R) Estimated IQ Test.

               9. Serious or unstable disease within the past 6 months (i.e., heart disease,
                  liver/kidney failure).

              10. Recent history (last 6 months) of abnormal heart rhythms, tachycardia, and/or
                  cardiovascular disease (stroke, angina, heart attack) may result in
                  ineligibility. These conditions will be evaluated on a case-by-case basis by the
                  Study Physician.

              11. Clinically significant abnormalities determined by physical examination and
                  collection of vital signs at Intake. Abnormalities will be assessed by the Study
                  Physician and eligibility will be determined on a case-by-case basis.

              12. Uncontrolled hypertension (Systolic Blood Pressure [SBP] greater than or equal to
                  160 mmHg and/or Diastolic Blood Pressure [DBP] greater than or equal to 100
                  mmHg).

              13. Heart rate/pulse greater than or equal to 110 beats per minute (bpm).

              14. Clinically significant abnormalities in clinical chemistry (CBC, CHEM7, and
                  AST/ALT). Results greater than 20% outside of normal range will be evaluated for
                  clinical significance by the Study Physician and eligibility will be determined
                  on a case-by-case basis.

              15. Inability to provide an assessable blood sample for basic screening tests (CBC,
                  CHEM7, and AST/ALT) at Intake.

          4. Psychiatric.

             As determined by self-report, the Mini International Neuropsychiatric Interview
             (MINI), and/or Columbia-Suicide Severity Rating Scale (C-SSRS):

               1. Any suicide risk score on the MINI.

               2. Current (past month) suicidal ideation or lifetime suicidal behavior on the
                  C-SSRS.

               3. Lifetime history or current diagnosis of psychosis, bipolar disorder, and/or
                  schizophrenia.

               4. Current diagnosis of major depression and/or recurrent major depression. Persons
                  with a history of a single episode of major depression, in remission for 6 months
                  or longer, are eligible provided they are not excluded based on medications (see
                  Medication Exclusion Criteria).

               5. Current or past hypomanic/manic episode.

               6. History or current diagnosis of posttraumatic stress disorder (PTSD).

               7. Prior or current diagnosis of attention deficit hyperactivity disorder (ADHD).

          5. Medication.

               1. Current use or recent discontinuation (within the last 14 days at the time of
                  Intake) of:

                    -  Smoking cessation medication (e.g., Zyban, Wellbutrin, Wellbutrin SR,
                       Chantix).

                    -  Anti-anxiety or panic disorder medications.

                    -  Anti-psychotic medications.

                    -  Medications used to treat depression (e.g., Wellbutrin, MAOIs, SSRIS,
                       tricyclic antidepressants).

                    -  Prescription stimulants (e.g., Provigil, Ritalin, Adderall).

                    -  Systemic corticosteroids.

               2. Current use of:

                    -  Nicotine replacement therapy (NRT).

               3. Daily use of:

                    -  Opiate-containing medications for chronic pain.

                    -  Inhaled corticosteroids.