Effects of ABT-089 on Smoking Abstinence Symptoms and Reward

This study has been terminated.
(Trial discontinued based on the results of an interim futility analysis.)
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01756053
First received: December 19, 2012
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Nicotine Addiction
Drug: ABT-089
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Pilot Feasibility Study of the Effects of ABT-089 on Smoking Abstinence Symptoms and Reward

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Change in abstinence-induced cognitive deficits [ Time Frame: Days 6 & 37 ] [ Designated as safety issue: No ]

    We will assess whether ABT-089 ameliorates the cognitive deficits due to smoking abstinence.

    To assess, all subjects will complete computerized neurocognitive tasks during the Testing Day Session (Days 6 & 37) in each study medication period. Each Testing Day session occurs after 24 hours of abstinence from smoking. During one study medication period, subjects will take active ABT-089; during the other period, subjects will take a matched placebo.

    We will identify changes in neurocognitive task performance, within each subject, across the two medication conditions.

    All subjects will complete a baseline assessment of these tasks during the Baseline Visit (Day 0), providing us with cognitive task performance while the subjects are smoking-as-usual.

    All computerized neurocognitive tasks are completed in a quiet, standardized environment in our clinic.



Secondary Outcome Measures:
  • Effects of ABT-089 on mood [ Time Frame: Days 0, 3, 6 (part 1), 7, 8, 10, 34, 37 (part 1), 38, 39, & 41 ] [ Designated as safety issue: No ]
    Subjects' mood will be assessed using The Positive and Negative Affect Schedule (PANAS), a 20-item Likert-format, self-report questionnaire.

  • Effects of ABT-089 on withdrawal symptoms [ Time Frame: Days 0, 3, 5, 6 (part 1), 7, 8, 10, 34, 36, 37 (part 1), 38, 39, & 41 ] [ Designated as safety issue: No ]
    We will assess nicotine withdrawal symptoms using The Minnesota Nicotine Withdrawal Scale - Revised Version (MNWS-R).

  • Effects of ABT-089 on smoking urges/craving [ Time Frame: Days 0, 3, 5, 6 (parts 1 & 2)*, 7, 8, 10, 34, 36, 37 (parts 1 & 2)*, 38, 39, & 41 ] [ Designated as safety issue: No ]
    We will assess smoking urges and craving using the 10-item Questionnaire of Smoking Urges - Brief (QSU-B).

  • Effects of ABT-089 on attention-deficit and hyperactive symptoms [ Time Frame: Days 0, 3, 6 (part 1), 7, 8, 10, 34, 37 (part 1), 38, 39, & 41 ] [ Designated as safety issue: No ]
    ADHD symptoms have been associated with smoking behavior and likelihood to relapse in prior studies. We will assess attention-deficit and hyperactive symptoms using the 27-item Barkley Adult ADHD Rating Scale-IV (BAARS-IV).

  • Effects of ABT-089 on cigarette ratings [ Time Frame: Days 0, 3, 5, 6 (part 2), 7, 8, 10, 34, 36, 37 (part 2), 38, 39 & 41 ] [ Designated as safety issue: No ]
    We will assess subjective effects of smoking cigarettes using the 11-item Likert-format Cigarette Evaluation Scale (CES).

  • Effects of ABT-089 on daily smoking rate [ Time Frame: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 32, 33, 34, 35, 36, 37, 38, 39, 40, & 41 ] [ Designated as safety issue: No ]
    Daily smoking rate will be assessed at each in-person visit using the Timeline Follow-Back assessment.


Enrollment: 17
Study Start Date: March 2013
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ABT-089

During both 10-day study medication periods (Days 1-10 & Days 32-41), subjects will take 4 capsules daily. Administration of study medication will be double-blind and in counter-balanced order.

Those randomized to active ABT-089 during study medication period 1 will take four 10mg capsules daily (40mg daily) during the 10-day medication period. During study medication period 2, these subjects will take four capsules of the matched placebo capsules.

Drug: ABT-089
Selective neuronal nicotinic receptor agonist.
Other Name: Pozanicline
Placebo Comparator: Placebo

These are matched placebo capsules manufactured by the study drug supplier.

During both 10-day study medication periods (Days 1-10 & Days 32-41), subjects will take 4 capsules daily. Administration of study medication will be double-blind and in counter-balanced order.

Those randomized to matched placebo during study medication period 1 will take four capsules daily during the 10-day medication period. During study medication period 2, these subjects will take four 10mg capsules (40mg daily) of the active ABT-089 capsules.

Drug: Placebo
Matched placebo capsules supplied by study drug supplier.

Detailed Description:

This is a single-site, phase IIa, double-blind, within-subject, cross-over, human laboratory study. Subjects will be healthy, treatment-seeking female and male adult smokers, ages 18 to 65 years old. Subjects deemed eligible for participation after an Intake Visit (~Day -7) will complete baseline assessments and receive period 1 medication (ABT-089 or placebo) at the Baseline Visit (Day 0). Subjects will take 40mg of ABT-089 or placebo, based on random assignment, every day for two identical 10-day study treatment periods.

Subjects will begin period 1 study medication on Day 1. On Days 3 and 5, subjects will complete in-clinic medication run-up and monitoring assessments. On Day 5, subjects will begin a ~24-hour period of mandatory abstinence from smoking. Day 6 is conducted in two parts. Part 1 will consist of confirmation of smoking abstinence, testing for abstinence-induced cognitive deficits and the collection of subjective assessments. Part 2 will begin with a programmed smoking lapse, after which the subjective rewarding value of the programmed lapse cigarette will be assessed. Before leaving the clinic on Day 6, subjects will receive brief cessation counseling and be instructed to try to remain abstinent from 10pm that evening until after the final Observation Visit on Day 10.

During the ~4-day monitored abstinence/observation phase, subjects will complete in-clinic observation visits (subjective assessments, medication adherence, etc.) on Days 7, 8, and 10.

After a ~3-week medication washout period and Period 2 Medication Pick-up Visit on ~Day 31, subjects will begin study medication (either ABT-089 or placebo; but will always be the opposite of the assigned study medication in period 1) and participate in period 2 of the study following the same procedures as period 1.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01756053

Locations
United States, Pennsylvania
Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Caryn Lerman, PhD University of Pennsylvania
  More Information

Additional Information:
No publications provided

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01756053     History of Changes
Other Study ID Numbers: 815238
Study First Received: December 19, 2012
Last Updated: February 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
Smoking
Tobacco

Additional relevant MeSH terms:
Tobacco Use Disorder
Behavior, Addictive
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Compulsive Behavior
Impulsive Behavior

ClinicalTrials.gov processed this record on August 20, 2014