Test of Novel Drug for Smoking Cessation (UH3-P2)

Development of a Novel Therapeutic for Smoking Cessation

The study will assess a novel active drug vs. placebo on ability to reduce smoking and aid cessation during a one-week "practice" quit period for each condition in smokers with a high interest in quitting (i.e. crossover design). Medication effects on reducing withdrawal and cognitive impairment will help assess the mechanism to support quit smoking attempts.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: Active JNJ Drug; Drug: Placebo pill

Detailed Description

We aim to test the proof of principal that an alpha-7 PAM drug, JNJ-39393406, promotes smoking cessation when compared to placebo. We have developed, tested, and validated an efficient Phase 2a screening procedure that optimally combines the validity of randomized clinical trials with the practicality of lab- based medication studies. Notably, it employs a within-subject, cross-over design comparing active versus placebo effects on quitting smoking to maximize statistical power without a large sample, in contrast to the large samples needed for between-groups randomized treatment conditions. Using this procedure, we will evaluate effects of JNJ-39393406 vs. placebo on short-term smoking abstinence in smokers who already have a high interest in quitting soon. We predict that, compared with placebo, JNJ-39393406 will increase days of abstinence, identifying initial evidence of efficacy for smoking cessation. Our main dependent measure is days of very stringent biochemically validated (expired CO<5 ppm) 24-hr smoking abstinence, with post-quit withdrawal and cognitive function as secondary measures. Potential for adverse side-effects will be assessed at each visit.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Univ of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Healthy male and female dependent smokers wanting to quit soon

-

Exclusion Criteria:

• Use of non-smoked nicotine products

• Already enrolled in cessation program.

  • Recent alcohol or substance dependence (≤ 3 months)
  • Women who are pregnant, planning a pregnancy, or lactating; all female participants shall undergo a pregnancy test at screening and will be excluded if positive.
  • Serious or unstable medical disorder within the past 3 months

• Epilepsy

  • Current diagnosis (within last 6-months) of abnormal cardiac rhythms; unstable cardiovascular disease e.g. stroke, myocardial infarction in the last 6 months
  • Evidence impaired liver function test (LFT)
  • Evidence of kidney failure
  • Any subject with a history of hematological cancers examples: leukemia, lymphoma etc.
  • Any clinically significant hematological laboratory abnormality.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNJ Active Drug; 200 mg (100 mg b.i.d.) Active JNJ Drug used to assess quitting for one week, as part of crossover design. This JNJ experimental compound has NO name, just a company number.	Drug: Active JNJ Drug; 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.; Other Names: JNJ-39393406; Drug: Placebo pill; Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.
Experimental: Placebo Pill; Placebo pill used for one week quit attempt, as part of crossover design.	Drug: Active JNJ Drug; 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.; Other Names: JNJ-39393406; Drug: Placebo pill; Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quit Status	Complete abstinence from smoking for 24 hr is counted as a "quit day" and is assessed daily from Mon-Fri for just one week, on the JNJ active drug and one week on placebo. This same Mon-Fri procedure for one week (only) is done for both drug phases. Total outcome in each drug condition therefore is number of quit days out of the five assessment days (range 0-5).	up to one week each drug phase (0-5)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minnesota Nicotine Withdrawal Scale (MNWS) During Attempt to Quit on Active JNJ Drug and on Placebo	Severity of withdrawal symptoms will be assessed with standard self-report measure of Minnesota Nicotine Withdrawal Scale (MNWS) each quit day during one week only on active JNJ, and each quit day during one week on placebo. Ratings are made on 0-100 visual analog scale, with 0="not at all" to 100="very much", and are averaged to create a total score also ranging from 0-100. Higher scores indicate more severe withdrawal.	only on days quit while on JNJ or on placebo
Cognitive Function on Continuous Performance Task (CPT) for Those With CO<10 During First Assessment Day (Mon) of Attempt to Quit Smoking During Both JNJ and Plac Quit Periods	This measure of cognitive performance (mean of median speed of correct responding on computer keyboard to letters and numbers) was assessed only on Monday (day 1) of the 0-5 days during each drug/placebo condition. Data only from those shown to have CO<10 ppm were analyzed, to confirm responding during abstinence while on drug/placebo condition. Cognitive testing consisted of standard Continuous Performance Task (CPT), on active JNJ and on placebo phases. This measure is assessed to determine potential mechanism of drug efficacy in relieving disrupted cognitive processing function caused by tobacco deprivation and withdrawal.	first day during quit week on JNJ, and during quit week on placebo.

Collaborators and Investigators

• Sponsor: Chengappa, K.N. Roy, MD
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Kenneth Perkins, PhD, Univ of Pittsburgh

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: July 24, 2014
• First Submitted That Met QC Criteria: August 14, 2014
• First Posted (Estimate): August 15, 2014

Study Record Updates

• Last Update Posted (Actual): August 15, 2018
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: crossover
• Other Study ID Numbers: UH3-PRO14070319; UH3TR000958 (U.S. NIH Grant/Contract)