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Effects of ABT-089 on Smoking Abstinence Symptoms and Reward

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01756053
Recruitment Status : Terminated (Trial discontinued based on the results of an interim futility analysis.)
First Posted : December 24, 2012
Results First Posted : October 29, 2014
Last Update Posted : October 29, 2014
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Nicotine Addiction
Interventions Drug: ABT-089
Drug: Placebo
Enrollment 17
Recruitment Details Fifty three subjects were consented and screened for eligibility at an Intake Visit between April 2013 and December 2013 at the Center for Interdisciplinary Research on Nicotine Addiction (Philadelphia, PA).
Pre-assignment Details Seventeen of the 53 subjects were randomized and received study medication. Of those NOT randomized, 30 were deemed ineligible and 6 withdrew from the study.
Arm/Group Title ABT-089, Then Placebo Placebo, Then ABT-089
Hide Arm/Group Description

Those randomized to active ABT-089 during study medication period 1 will take four 10mg capsules daily (40mg daily) during a 10-day medication period. After a washout period of ~21 days, these subjects will then take four capsules of matching placebo daily for a second 10-day medication period.

ABT-089: Selective neuronal nicotinic receptor agonist.

Those randomized to placebo (matching ABT-089 10 mg capsules) during study medication period 1 will take four capsules daily during a 10-day medication period. After a washout period of ~21 days, these subjects will then take four 10 mg capsules (40 mg) daily of ABT-089 for a second 10-day study medication period.

Placebo: Matching placebo capsules supplied by study drug supplier.

Period Title: Period 1 (10 Days)
Started 8 9
Completed 7 8
Not Completed 1 1
Reason Not Completed
Protocol Violation             1             1
Period Title: Washout Period (~21 Days)
Started 7 8
Completed 7 8
Not Completed 0 0
Period Title: Period 2 (10 Days)
Started 7 8
Completed 7 6
Not Completed 0 2
Reason Not Completed
Protocol Violation             0             2
Arm/Group Title All Study Subjects
Hide Arm/Group Description Subjects who were randomized and received their Period 1 study medication (ABT-089 or matching placebo).
Overall Number of Baseline Participants 17
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants
41.76471  (11.20563)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
Female
5
  29.4%
Male
12
  70.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
13
  76.5%
White
4
  23.5%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 17 participants
17
1.Primary Outcome
Title Change in Abstinence-induced Cognitive Deficits (N-Back Accuracy)
Hide Description

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)

Time Frame Baseline (Day 0) and Test Day (Days 6 & 37)
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants completing both study periods (n=13) were included in the analyses.
Arm/Group Title ABT-089 Placebo
Hide Arm/Group Description:
Subjects who were assigned to active ABT-089 (four 10 mg capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Subjects who were assigned to matched placebo (four capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: Number of correct responses (out of 60)
Baseline (Day 0) 44.2  (7.2) 44.2  (7.2)
Test Days (Days 6 & 37) 47.5  (8.4) 47.5  (8.4)
2.Primary Outcome
Title Change in Abstinence-induced Cognitive Deficits (N-Back Correct Response Time)
Hide Description

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)

Time Frame Baseline (Day 0) and Test Day (Days 6 & 37)
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants completing both study periods (n=13) were included in the analyses.
Arm/Group Title ABT-089 Placebo
Hide Arm/Group Description:
Subjects who were assigned to active ABT-089 (four 10 mg capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Subjects who were assigned to matched placebo (four capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: Milliseconds
Baseline (Day 0) 612.4  (125.5) 612.4  (125.5)
Test Days (Days 6 & 37) 646.5  (143.3) 638.9  (129.5)
3.Secondary Outcome
Title Effects of ABT-089 on Mood
Hide Description 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.
Time Frame Days 6 and 37
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants completing both study periods (n=13) were included in the analyses.
Arm/Group Title ABT-089 Placebo
Hide Arm/Group Description:
Subjects who were assigned to active ABT-089 (four 10 mg capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Subjects who were assigned to matched placebo (four capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
PANAS: Positive Affect 25.4  (9.2) 26.2  (9.6)
PANAS: Negative Affect 13.2  (3.6) 13.5  (4.6)
4.Secondary Outcome
Title Effects of ABT-089 on Withdrawal Symptoms
Hide Description 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.
Time Frame Days 6 and 37
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants completing both study periods (n=13) were included in the analyses.
Arm/Group Title ABT-089 Placebo
Hide Arm/Group Description:
Subjects who were assigned to active ABT-089 (four 10 mg capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Subjects who were assigned to matched placebo (four capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
6.8  (6.1) 6.6  (6.7)
5.Secondary Outcome
Title Effects of ABT-089 on Smoking Urges/Craving
Hide Description 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.
Time Frame Days 6 and 37
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants completing both study periods (n=13) were included in the analyses.
Arm/Group Title ABT-089 Placebo
Hide Arm/Group Description:
Subjects who were assigned to active ABT-089 (four 10 mg capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Subjects who were assigned to matched placebo (four capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
37.4  (17.2) 38.3  (15.8)
6.Secondary Outcome
Title Effects of ABT-089 on Attention-deficit and Hyperactive Symptoms
Hide Description 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.
Time Frame Days 6 and 37
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants completing both study periods (n=13) were included in the analyses.
Arm/Group Title ABT-089 Placebo
Hide Arm/Group Description:
Subjects who were assigned to active ABT-089 (four 10 mg capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Subjects who were assigned to matched placebo (four capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
33.2  (6.8) 35.4  (9.6)
7.Secondary Outcome
Title Effects of ABT-089 on Cigarette Ratings
Hide Description 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.
Time Frame Days 6 and 37
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants completing both study periods (n=13) were included in the analyses.
Arm/Group Title ABT-089 Placebo
Hide Arm/Group Description:
Subjects who were assigned to active ABT-089 (four 10 mg capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Subjects who were assigned to matched placebo (four capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
2.8  (0.78) 2.9  (0.76)
8.Secondary Outcome
Title Effects of ABT-089 on Days of Biochemically-confirmed Abstinence
Hide Description 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.
Time Frame Days 7, 8, 9, 10, 38, 39, 40, & 41
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants completing both study periods (n=13) were included in the analyses.
Arm/Group Title ABT-089 Placebo
Hide Arm/Group Description:
Subjects who were assigned to active ABT-089 (four 10 mg capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Subjects who were assigned to matched placebo (four capsules daily) in either Period 1 or Period 2 of the study. Each study period is 10 days.
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: Days of abstinence
1.2  (1.7) 1.2  (1.8)
Time Frame 10 days for each study medication period (ABT-089/Placebo in counter-balanced order)
Adverse Event Reporting Description

The safety population described within this section includes all subjects who received at least one dose of ABT-089 (n=16) or Placebo (n=16).

Systematic Assessment: Subjects completed a side effect checklist at every in-person study visit over the course of the treatment period. Subjects could also spontaneously report AEs at any time.

 
Arm/Group Title ABT-089 Placebo
Hide Arm/Group Description

Subjects were assigned to take four 10 mg capsules daily (40 mg daily) during a 10-day medication period.

ABT-089: Selective neuronal nicotinic receptor agonist.

Subjects were assigned to take four placebo capsules (matching ABT-089 10 mg) daily during a 10-day medication period.

Placebo: Matched placebo capsules supplied by study drug supplier.

All-Cause Mortality
ABT-089 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
ABT-089 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/16 (0.00%)      0/16 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
ABT-089 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/16 (75.00%)      14/16 (87.50%)    
Gastrointestinal disorders     
Diarrhea   2/16 (12.50%)  2 1/16 (6.25%)  1
Nausea   2/16 (12.50%)  4 3/16 (18.75%)  4
Constipation   0/16 (0.00%)  0 1/16 (6.25%)  1
General disorders     
Fatigue   2/16 (12.50%)  3 3/16 (18.75%)  4
Irritability   8/16 (50.00%)  22 11/16 (68.75%)  30
Pyrexia  [1]  1/16 (6.25%)  1 0/16 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Muscle Weakness   2/16 (12.50%)  3 1/16 (6.25%)  2
Myalgia  [2]  0/16 (0.00%)  0 1/16 (6.25%)  1
Nervous system disorders     
Headache   2/16 (12.50%)  7 6/16 (37.50%)  12
Psychiatric disorders     
Anxiety   6/16 (37.50%)  18 8/16 (50.00%)  20
Hostility   3/16 (18.75%)  7 7/16 (43.75%)  17
Tension   5/16 (31.25%)  16 7/16 (43.75%)  21
Depressed Mood   1/16 (6.25%)  1 1/16 (6.25%)  1
Agitation   9/16 (56.25%)  20 9/16 (56.25%)  21
Vivid Dreams   4/16 (25.00%)  4 4/16 (25.00%)  6
Insomnia   2/16 (12.50%)  6 4/16 (25.00%)  6
Respiratory, thoracic and mediastinal disorders     
Cough   1/16 (6.25%)  3 0/16 (0.00%)  0
Rhinorrhoea  [3]  1/16 (6.25%)  3 0/16 (0.00%)  0
Throat Irritation  [4]  0/16 (0.00%)  0 3/16 (18.75%)  5
Indicates events were collected by systematic assessment
[1]
Fever
[2]
Muscle pain
[3]
Runny Nose
[4]
Sore Throat
The study was terminated early due to the results of an interim futility analysis.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Benjamin Albelda (Project Manager)
Organization: Center for Interdisciplinary Research on Nicotine Addiction
Phone: 2157467173
EMail: albeldab@mail.med.upenn.edu
Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01756053    
Other Study ID Numbers: 815238
First Submitted: December 19, 2012
First Posted: December 24, 2012
Results First Submitted: September 23, 2014
Results First Posted: October 29, 2014
Last Update Posted: October 29, 2014