Effects of ABT-089 on Smoking Abstinence Symptoms and Reward

Phase 2

Terminated

• Conditions: Nicotine Addiction
• Interventions: Drug: Placebo; Drug: ABT-089

• Registration Number: NCT01756053
• Lead Sponsor: University of Pennsylvania

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2012-12-19
• Study First Submitted QC: 2012-12-19
• Study First Posted: 2012-12-24
• Study Start: 2013-03
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Status Verified: 2014-02
• Results First Submitted: 2014-09-23
• Results First Submitted QC: 2014-10-23
• Last Update Submitted: 2014-10-23
• Results First Posted: 2014-10-29
• Last Update Posted: 2014-10-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	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.
ABT-089	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.

Primary Outcome Measures

Name	Time	Method
Change in Abstinence-induced Cognitive Deficits (N-Back Accuracy)	Baseline (Day 0) and Test Day (Days 6 & 37)	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)
Change in Abstinence-induced Cognitive Deficits (N-Back Correct Response Time)	Baseline (Day 0) and Test Day (Days 6 & 37)	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)

Secondary Outcome Measures

Name	Time	Method
Effects of ABT-089 on Smoking Urges/Craving	Days 6 and 37	QSU-B: The 10-item brief QSU (QSU-B) questionnaire was used to assess smoking urges. Each item is rated on a 7-point scale (1 = strongly disagree, 7 = strongly agree). A total score is calculated as the sum of the individual items (range: 10-70). Higher scores indicate more severe urges to smoke.
Effects of ABT-089 on Mood	Days 6 and 37	PANAS: The Positive and Negative Affect Schedule (PANAS), a 20-item Likert-format self-report measure, was used to assess Positive Affect (PA; 10 items, e.g., enthusiastic, strong) and Negative Affect (NA; 10 items, e.g., distressed, upset), two dominant and generally orthogonal dimensions of affect. Scores for the 10 items on each subscale were summed to create summary scores (range: 10-50); higher scores indicate greater intensity of mood (i.e., more positive or more negative affect). Higher ratings of positive affect and lower ratings of negative affect are considered better outcomes.
Effects of ABT-089 on Withdrawal Symptoms	Days 6 and 37	MNWS: The Minnesota Nicotine Withdrawal Scale - Revised version captures the current state of nicotine withdrawal. The scale assesses 15 items of nicotine withdrawal (including 7 DSM-IV items) such as: dysphoria or depressed mood, insomnia, irritability/frustration/anger, anxiety, difficulty concentrating, restlessness, and increased appetite/weight gain. Subjects will rate the intensity of their symptoms on the following scale: 0 = none, 1 = slight, 2 = mild, 3 = moderate, 4 = severe. A "withdrawal discomfort score" was calculated as the sum of the first 9 items (possible range: 0-36) and is a well-validated measure of nicotine withdrawal; a higher score indicates more severe withdrawal.
Effects of ABT-089 on Attention-deficit and Hyperactive Symptoms	Days 6 and 37	ADHD symptoms: The 27-item BAARS-IV scale was used to assess current attention-deficit and hyperactive symptoms. Participant rated the intensity of their symptoms using the following scale: 1= never or rarely, 2 = sometimes, 3 = often, or 4 = very often. A total score was calculated as the sum of the individual items (range: 27-108). Higher scores indicate more frequent ADHD symptoms.
Effects of ABT-089 on Cigarette Ratings	Days 6 and 37	Cigarette evaluation scale: The Cigarette Evaluation Scale (CES), developed to assess subjective effects of smoking, is an 11-item Likert-format measure. Questions include items for nausea and dizziness, craving relief, and enjoyment of airway sensations. Items are rated on a scale from 1 ("Not at all") to 7 ("Extremely); a summary score is calculated as the mean of all responses (range: 1-7). Higher scores indicate stronger subjective effects of smoking.
Effects of ABT-089 on Days of Biochemically-confirmed Abstinence	Days 7, 8, 9, 10, 38, 39, 40, & 41	Daily smoking rate will be assessed at each in-person visit using the Timeline Follow-Back assessment. Abstinence will be confirmed by exhaled carbon monoxide levels during a \~4-day monitored abstinence phase within each period.

Trial Locations

Locations (1)

Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States