Trial Outcomes & Findings for Varenicline for Cognitive Deficits and Cigarette Smoking in Schizophrenia - Efficacy and Predictors (NCT NCT00802919)

NCT ID: NCT00802919

Last Updated: 2017-12-02

Results Overview

plasma cotinine

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 93 participants
• Primary outcome timeframe: Baseline, 4 weeks, 8 weeks
• Results posted on: 2017-12-02

Participant Flow

Overall, 93 subjects were consented, 2 withdrew consent before randomization, and 87 provided evaluable data on at least one outcome measure. The number enrolled 93, is less than the number started 91, because 2 patients withdrew consent before randomization

Participant milestones

Measure	Varenicline Varenicline 1-2 mg/day Varenicline: Varenicline 1-2 mg/day	Matched Placebo placebo for varenicline Placebo for varenicline: Placebo
Overall Study STARTED	45	46
Overall Study COMPLETED	42	45
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Varenicline for Cognitive Deficits and Cigarette Smoking in Schizophrenia - Efficacy and Predictors

Baseline characteristics by cohort

Measure	Varenicline n=42 Participants Varenicline 1-2 mg/day Varenicline: Varenicline 1-2 mg/day	Matched Placebo n=45 Participants placebo for varenicline Placebo for varenicline: Placebo	Total n=87 Participants Total of all reporting groups
Age, Continuous	46.6 years STANDARD_DEVIATION 8.9 • n=5 Participants	43.6 years STANDARD_DEVIATION 10.6 • n=7 Participants	44.7 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	39 Participants n=7 Participants	74 Participants n=5 Participants
Race/Ethnicity, Customized white	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Race/Ethnicity, Customized black-AA	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Race/Ethnicity, Customized hispanic	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized chinese han	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	27 participants n=7 Participants	49 participants n=5 Participants
Region of Enrollment China	8 participants n=5 Participants	8 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Israel	12 participants n=5 Participants	10 participants n=7 Participants	22 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 4 weeks, 8 weeks

Population: Data were available for cotinine analysis in mixed model analysis of co covariance on 34 participants in the varenicline arms and 36 participants in the placebo arm.

plasma cotinine

Outcome measures

Measure	Varenicline n=34 Participants Varenicline 1-2 mg/day Varenicline: Varenicline 1-2 mg/day	Matched Placebo n=36 Participants placebo for varenicline Placebo for varenicline: Placebo
Cotinine Level baseline	257.9 cotinine ng/ml Standard Error 15.9	258.6 cotinine ng/ml Standard Error 18.4
Cotinine Level week4	176.0 cotinine ng/ml Standard Error 16.0	252.1 cotinine ng/ml Standard Error 18.7
Cotinine Level week8	147.0 cotinine ng/ml Standard Error 17.9	264.6 cotinine ng/ml Standard Error 18.9

PRIMARY outcome

Timeframe: basline and 8 weeks (or end of study iif patient ended participation before the 8-weeks)

Population: N's varied from 25-32 in varenicline group and 29-35 in placebo group because all subjects did not complete all parts of MATRICS battery.Maximum number of participants is entered for number of participants because this cell entry does not allow entry of variable number of participations ( e.g. 25-32). for different scores..

The MATRICS Consensus Cognitive Battery (MCCB)(Measurement and Treatment Research to Improve Cognition in Schizophrenia) was used to measure cognitive performance. Six Domain scores and a Composite score are calculated by the proprietary MCCB Computer Scoring Program (modified beta version) from raw scores on 10 individually administered subtests. The social cognition test was not assessed in this study. The Domain T-scores are percentile-ranked and range from <20 (<0.1 percentile) to >80 (>99.9 percentile). The Composite scores are also percentile-ranked and range from <213 (T<20, <0.1 percentile) to >487 (T>80, >99.9 percentile). Higher scores after baseline represent better outcomes. Here we report difference scores from post-treatment and baseline with positive difference scores representing better outcomes.

Outcome measures

Measure	Varenicline n=32 Participants Varenicline 1-2 mg/day Varenicline: Varenicline 1-2 mg/day	Matched Placebo n=35 Participants placebo for varenicline Placebo for varenicline: Placebo
Change From Baseline in Cognitive Performance MATRICS composite score diff from baseline	-0.19 T scores from MATRICS battery Standard Error 2.14	1.97 T scores from MATRICS battery Standard Error 1.86
Change From Baseline in Cognitive Performance MATRICS Speed of Processing diff from baseline	3.03 T scores from MATRICS battery Standard Error 1.52	4.08 T scores from MATRICS battery Standard Error 1.56
Change From Baseline in Cognitive Performance MATRICS attention-vigilance diff from baseline	2.49 T scores from MATRICS battery Standard Error 1.99	4.33 T scores from MATRICS battery Standard Error 1.95
Change From Baseline in Cognitive Performance MATRICS working memory diff from baseline	0.95 T scores from MATRICS battery Standard Error 1.82	5.29 T scores from MATRICS battery Standard Error 1.88
Change From Baseline in Cognitive Performance MATRICS visual learning diff from baseline	4.75 T scores from MATRICS battery Standard Error 2.26	7.85 T scores from MATRICS battery Standard Error 2.30
Change From Baseline in Cognitive Performance MATRICS reasoning-rob sol diff from baseline	0.38 T scores from MATRICS battery Standard Error 0.78	2.79 T scores from MATRICS battery Standard Error 0.81
Change From Baseline in Cognitive Performance MATRICS verbal learning diff from baseline	0.94 T scores from MATRICS battery Standard Error 1.00	0.01 T scores from MATRICS battery Standard Error 1.04

SECONDARY outcome

Timeframe: baseline, 4 weeks, 8 weeks

The Positive and Negative Syndrome Scale (PANSS) was used to measure psychiatric symptoms. Item scores ranged from 1 (Absent) to 6 (Severe) for symptoms on the Positive Scale (total subscale range: 7-42), the Negative Scale (total subscale range: 7-42), and the General Psychopathology Scale (total subscale range:16-96). All three subscales were summed for the PANSS total score (total scale range: 30-180). Scores closer to 30 after baseline represented better outcomes. Here we report difference scores from post-treatment and baseline with negative difference scores representing better outcomes.

Outcome measures

Measure	Varenicline n=39 Participants Varenicline 1-2 mg/day Varenicline: Varenicline 1-2 mg/day	Matched Placebo n=38 Participants placebo for varenicline Placebo for varenicline: Placebo
Change From Baseline in Psychiatric Symptoms PANSS Total wk4 -baseline diff	-3.56 units on a scale Standard Error 1.29	-0.86 units on a scale Standard Error 1.42
Change From Baseline in Psychiatric Symptoms PANSS Total wk8-baseline diff	-3.05 units on a scale Standard Error 1.35	-0.97 units on a scale Standard Error 1.40
Change From Baseline in Psychiatric Symptoms PANSS Depression Factor wk4-basline diff	-0.67 units on a scale Standard Error 0.24	0.23 units on a scale Standard Error 0.26
Change From Baseline in Psychiatric Symptoms PANSS depressor factor wk8-baseline diff	-0.67 units on a scale Standard Error 0.25	-0.10 units on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: baseline, 4 weeks, 8 weeks

Population: Not all patients had relevant responses on Calgary Depression Scale. Data are analyzed for 36 subjects randomized to varenicline and 38 subjects randomized to placebo (total N=74).

The Calgary Depression Scale for Schizophrenia. The scale has 9 items with ratings of 0 to 3 on each item. Total score can vary from 0 to 27. Higher scores indicate more depression. Negative change scores indicate decreasing depression.

Outcome measures

Measure	Varenicline n=36 Participants Varenicline 1-2 mg/day Varenicline: Varenicline 1-2 mg/day	Matched Placebo n=38 Participants placebo for varenicline Placebo for varenicline: Placebo
Change From Basellne in Calgary Depression Scale Score Calgrapy Dep totl wk4-baseline diff	-0.63 Scores on a scale Standard Error 0.24	-0.72 Scores on a scale Standard Error 0.27
Change From Basellne in Calgary Depression Scale Score calgrapy dep wk8-baseline diff	-0.79 Scores on a scale Standard Error 0.26	-0.88 Scores on a scale Standard Error 0.26

Adverse Events

Varenicline

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Matched Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Varenicline n=45 participants at risk Varenicline 1-2 mg/day Varenicline: Varenicline 1-2 mg/day	Matched Placebo n=46 participants at risk placebo for varenicline Placebo for varenicline: Placebo
Psychiatric disorders psychiatric decompensation not study drug related	2.2% 1/45 • Number of events 1	0.00% 0/46
Psychiatric disorders auditory hallucination not study drug related	2.2% 1/45 • Number of events 1	0.00% 0/46
Psychiatric disorders verbal agression	0.00% 0/45	2.2% 1/46 • Number of events 1

Other adverse events

Adverse event data not reported

Additional Information

Robert C. Smith MD

Nathan Kline Institute for Psychiatric Research

Phone: 845-398-6531

Email: rsmith@nki.rfmh.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place