Effects of ABT-089 on Smoking Abstinence Symptoms and Reward

NCT01756053 | Terminated Phase 2 Results DMC

• 1 other identifier: 815238
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Nicotine Addiction

Keywords

Smoking; Tobacco

Outcome Measures

Primary Outcomes (2)

• Change in Abstinence-induced Cognitive Deficits (N-Back Accuracy)

  We will assess whether ABT-089 ameliorates the cognitive deficits due to smoking abstinence. To assess, all subjects will complete a computerized N-Back task 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. Each of the task conditions (0-, 1-, 2-, and 3-back) will be administered in a pseudorandomized counterbalanced order. Each difficulty level will consist of one block of 50 trials, preceded by a practice block of 20 trials. The primary dependent variables for this task are total number of correct responses (out of 60) and reaction time (milliseconds). All computerized neurocognitive tasks are completed in a quiet, standardized environment in our clinic. NOTE: Each PPT completes 1 Baseline (no tx.) and 2 Testing Days (ABT/Placebo)

  Baseline (Day 0) and Test Day (Days 6 & 37)

• Change in Abstinence-induced Cognitive Deficits (N-Back Correct Response Time)

  We will assess whether ABT-089 ameliorates the cognitive deficits due to smoking abstinence. To assess, all subjects will complete a computerized N-Back task 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. Each of the task conditions (0-, 1-, 2-, and 3-back) will be administered in a pseudorandomized counterbalanced order. Each difficulty level will consist of one block of 50 trials, preceded by a practice block of 20 trials. The primary dependent variables for this task are total number of correct responses (out of 60) and reaction time (milliseconds). All computerized neurocognitive tasks are completed in a quiet, standardized environment in our clinic. NOTE: Each PPT completes 1 Baseline (no tx.) and 2 Testing Days (ABT/Placebo)

  Baseline (Day 0) and Test Day (Days 6 & 37)

Secondary Outcomes (6)

• Effects of ABT-089 on Mood

  Days 6 and 37

• Effects of ABT-089 on Withdrawal Symptoms

  Days 6 and 37

• Effects of ABT-089 on Smoking Urges/Craving

  Days 6 and 37

• Effects of ABT-089 on Attention-deficit and Hyperactive Symptoms

  Days 6 and 37

• Effects of ABT-089 on Cigarette Ratings

  Days 6 and 37

Study Arms (2)

ABT-089

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

ABT-089 DRUG

Selective neuronal nicotinic receptor agonist.

Also known as: Pozanicline

ABT-089

Placebo DRUG

Matched placebo capsules supplied by study drug supplier.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible subjects will be:
• 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.
• Healthy as determined by the Study Physician, based on relevant medical history, physical examination (including vitals), and basic screening tests (CBC, CHEM7, AST/ALT).
• 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.
• Able to communicate fluently in English (speaking, writing, and reading).
• Plan to live in the area for the next 2 months.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form.

You may not qualify if:

• Subjects who self-report and/or present with the following criteria will not be eligible to participate in the study:
• Smoking behavior.
• Current enrollment or firm plans to quit smoking and/or enroll in a smoking cessation program within the next 2 months.
• Current and/or anticipated use of any nicotine substitutes and/or smoking cessation treatments/medications within the next 2 months.
• Provide a Carbon Monoxide (CO) reading less than 11 parts per million (ppm) at Intake.
• 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.
• Self-report smoking during the mandatory abstinence period at either Testing Visit (Days 6 and 37).
• Regular use of chewing tobacco or snus.
• Alcohol/Drugs.
• 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.
• Current alcohol consumption that exceeds 25 standard drinks/week.
• 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).
• 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.
• Medical.
• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• CIRNA Center homepage

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking

Interventions

pozanicline

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavior

Limitations and Caveats

The study was terminated early due to the results of an interim futility analysis.

Results Point of Contact

• Title: Benjamin Albelda (Project Manager)
• Organization: Center for Interdisciplinary Research on Nicotine Addiction

albeldab@mail.med.upenn.edu

2157467173

Study Officials

• Caryn Lerman, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2012
• First Posted: December 24, 2012
• Study Start: March 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: October 29, 2014
• Results First Posted: October 29, 2014

Record last verified: 2014-02

Locations

US (1)