Trial Outcomes & Findings for Treatment for Nicotine Addiction in Women (NCT NCT02448654)

Last Updated: 2020-11-24

Results Overview

The MNWS was the 8 item version, using VAS scales for each item (1-100), and MNWS score calculated as an average of all items (range of possible scores for MWNS at each timepoint was 0-100, with higher MNWS scores at each timepoint indicating more withdrawal symptoms (worse outcome). Timepoints reflect 1.) the baseline (beginning of the trial, not yet receiving any pills, not yet being asked to abstain from smoking; calculated as average of scores from two visits: ad libitum baseline visit and pill day 1 measure which was collected prior to administration of pills) and 2.) the abstinence period (tolcapone or placebo pill days 6-8, during the 60-hr abstinence phase; calculated as average of scores from 3 visits: pill days 6, 7, and 8). Greater increases in scores (increases in withdrawal symptoms) during abstinence period compared to baseline reflects a worse outcome; reduced or stable scores (decreases or a lack of increases in withdrawal symptoms) during the abstinence period compa

Recruitment status

COMPLETED

Study phase

Target enrollment

36 participants

Primary outcome timeframe

Baseline (ad libitum baseline and pill day 1 (pre-pill)); Abstinent Period (pill days 6, 7, 8)

Results posted on

2020-11-24

Participant Flow

36 consented to be in the study, completed a baseline session, and were randomized to a study arm. However, 4 subjects never actually began the medication trial (i.e., stopped participating prior to receiving any pills (tolcapone or placebo)). 32 subjects began the pill portion of the trial (i.e., started tolcapone or placebo).

Participant milestones

Participant milestones
Measure	Tolcapone 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8	Sugar Pill Sugar pill (placebo) three times a day for 7 days then once on day 8
Overall Study STARTED	19	17
Overall Study Started Pills (Tolcapone or Placebo)	17	15
Overall Study COMPLETED	16	13
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatment for Nicotine Addiction in Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tolcapone n=19 Participants 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8	Sugar Pill n=17 Participants Sugar pill (placebo) three times a day for 7 days then once on day 8	Total n=36 Participants Total of all reporting groups
Age, Continuous	32.16 years STANDARD_DEVIATION 7.88 • n=5 Participants	33.35 years STANDARD_DEVIATION 7.77 • n=7 Participants	32.72 years STANDARD_DEVIATION 7.74 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants	13 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants	7 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (ad libitum baseline and pill day 1 (pre-pill)); Abstinent Period (pill days 6, 7, 8)

Population: Study completers (participants who were eligible, randomized to a treatment condition, and completed the study).

Outcome measures

Outcome measures
Measure	Tolcapone n=16 Participants 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8	Sugar Pill n=13 Participants Sugar pill (placebo) three times a day for 7 days then once on day 8
Withdrawal Symptoms (MNWS Score) Baseline (no pills, not abstinent)	13.33 score on a scale Standard Deviation 8.48	9.40 score on a scale Standard Deviation 8.12
Withdrawal Symptoms (MNWS Score) Abstinent Period (on pills, nicotine abstinent))	11.95 score on a scale Standard Deviation 11.80	13.29 score on a scale Standard Deviation 13.07

PRIMARY outcome

Timeframe: Baseline (ad libitum baseline and pill day 1 (pre-pill)); Abstinent Period (pill days 6, 7, 8)

Population: Study completers (participants who were eligible, randomized to a treatment condition, and completed the study).

The Brief Questionnaire on Smoking Urges (BQSU) is a 10 item scale. Factor 1 reflects the urge to smoke for its rewarding properties. Factor 1 is calculated as the sum of five items (items 1, 3, 6, 7, 10), with each item score ranging from 1-7, so Factor 1 scores range from 5-35. Higher scores reflect higher smoking urges and represent a worse outcome. Timepoints reflect 1.) baseline (beginning of trial, not yet receiving pills, not yet abstaining from smoking; calculated as average of scores from ad libitum baseline visit and pill day 1 which was collected prior to administration of pills) and 2.) abstinence period (pill days 6-8, during 60-hr abstinence phase; calculated as average of scores from pill days 6, 7, and 8). Greater increases in scores (increases in smoking urges) during abstinence period compared to baseline reflects a worse outcome; decreases or a lack of increases in smoking urges during the abstinence period compared to baseline reflects a better outcome.

Outcome measures

Outcome measures
Measure	Tolcapone n=16 Participants 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8	Sugar Pill n=13 Participants Sugar pill (placebo) three times a day for 7 days then once on day 8
Smoking Urges (BQSU Factor 1) Baseline (no pills, not abstinent)	19.69 score on a scale Standard Deviation 9.89	13.42 score on a scale Standard Deviation 7.44
Smoking Urges (BQSU Factor 1) Abstinent Period (on pills, nicotine abstinent))	14.50 score on a scale Standard Deviation 10.42	16.04 score on a scale Standard Deviation 9.58

PRIMARY outcome

Timeframe: Pill-Day 8 (end of trial)

Population: Study completers (participants who were eligible, randomized to a treatment condition, and completed the study).

The Smoking Choice Paradigm was done once at the end of the trial (Pill Day 8, at the end of the 60 hr abstinence period). Subjects are given forced choice options between 2 puffs of their own-brand cigarette vs. a token with a monetary value, spaced over a 90 minute period. The maximum amount subjects can earn from this task ranges from $0 to $7.50 (10 forced choice opportunities: smoke 2 puffs vs. earn 75 cent at each choice opportunity). Higher earnings reflect choice of the tokens over smoking, so this reflects a better outcome (i.e., reduced smoking choice).

Outcome measures

Outcome measures
Measure	Tolcapone n=16 Participants 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8	Sugar Pill n=13 Participants Sugar pill (placebo) three times a day for 7 days then once on day 8
Smoking Choice Paradigm: Amount Earned ($)	7.41 Dollars ($) Standard Deviation 0.26	7.06 Dollars ($) Standard Deviation 0.57

Adverse Events

Tolcapone

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Sugar Pill

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Elise E. DeVito, Ph.D./ Associate Research Scientist

Yale University

Phone: 203-737-4882

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Tolcapone n=17 participants at risk 100mg tolcapone three times a day for 7 days then 100mg once a day on day 8	Sugar Pill n=15 participants at risk Sugar pill (placebo) three times a day for 7 days then once on day 8
Gastrointestinal disorders Stomach pain	17.6% 3/17 • Number of events 4 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	6.7% 1/15 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Gastrointestinal disorders Upset stomach	5.9% 1/17 • Number of events 2 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	26.7% 4/15 • Number of events 6 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Gastrointestinal disorders Vomiting	11.8% 2/17 • Number of events 3 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	6.7% 1/15 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Gastrointestinal disorders Loss of appetite	11.8% 2/17 • Number of events 3 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	13.3% 2/15 • Number of events 3 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Gastrointestinal disorders Constipation	5.9% 1/17 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	6.7% 1/15 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Gastrointestinal disorders Diarrhea	11.8% 2/17 • Number of events 3 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	13.3% 2/15 • Number of events 2 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Psychiatric disorders Nervousness	0.00% 0/17 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	33.3% 5/15 • Number of events 9 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Psychiatric disorders Restlessness	11.8% 2/17 • Number of events 2 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	46.7% 7/15 • Number of events 12 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Psychiatric disorders Difficulty sleeping	17.6% 3/17 • Number of events 3 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	60.0% 9/15 • Number of events 12 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Psychiatric disorders Feeling drowsy	29.4% 5/17 • Number of events 6 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	33.3% 5/15 • Number of events 9 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Psychiatric disorders Extreme tiredness (fatigue)	29.4% 5/17 • Number of events 6 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	20.0% 3/15 • Number of events 4 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Psychiatric disorders Anger or irritability	5.9% 1/17 • Number of events 2 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	33.3% 5/15 • Number of events 10 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Psychiatric disorders Depressed mood	5.9% 1/17 • Number of events 2 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	26.7% 4/15 • Number of events 11 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Eye disorders Teary or dry eyes	11.8% 2/17 • Number of events 2 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	13.3% 2/15 • Number of events 11 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
General disorders Nosebleed	5.9% 1/17 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	6.7% 1/15 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
General disorders Runny nose	0.00% 0/17 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	26.7% 4/15 • Number of events 5 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Musculoskeletal and connective tissue disorders Back muscle or bone pain	29.4% 5/17 • Number of events 9 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	20.0% 3/15 • Number of events 7 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
General disorders Sweating	11.8% 2/17 • Number of events 3 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	6.7% 1/15 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Skin and subcutaneous tissue disorders Rash or skin problem	11.8% 2/17 • Number of events 4 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	20.0% 3/15 • Number of events 11 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Gastrointestinal disorders Excessive Hunger	23.5% 4/17 • Number of events 4 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	20.0% 3/15 • Number of events 6 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Psychiatric disorders Inability to respond to things around you	0.00% 0/17 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	6.7% 1/15 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Gastrointestinal disorders Dry Mouth	17.6% 3/17 • Number of events 4 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	20.0% 3/15 • Number of events 4 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Gastrointestinal disorders Change in ability to taste food	11.8% 2/17 • Number of events 4 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	13.3% 2/15 • Number of events 2 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Psychiatric disorders Headache	17.6% 3/17 • Number of events 3 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	66.7% 10/15 • Number of events 12 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
General disorders Tremors or shakiness	5.9% 1/17 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	0.00% 0/15 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Eye disorders Blurred vision	5.9% 1/17 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	0.00% 0/15 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Psychiatric disorders Slowed thinking	5.9% 1/17 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	0.00% 0/15 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
General disorders Tingling in fingers or toes	17.6% 3/17 • Number of events 6 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	6.7% 1/15 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
General disorders Sore Throat	11.8% 2/17 • Number of events 3 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	20.0% 3/15 • Number of events 7 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
General disorders Fever	5.9% 1/17 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	13.3% 2/15 • Number of events 3 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
General disorders Chills	11.8% 2/17 • Number of events 4 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	13.3% 2/15 • Number of events 2 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Cardiac disorders Slow heart rate	5.9% 1/17 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	0.00% 0/15 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Eye disorders Crossed eyes	11.8% 2/17 • Number of events 4 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	6.7% 1/15 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Gastrointestinal disorders Gas	17.6% 3/17 • Number of events 5 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	20.0% 3/15 • Number of events 8 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Cardiac disorders Irregular or pounding heartbeat	11.8% 2/17 • Number of events 2 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	6.7% 1/15 • Number of events 1 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
General disorders Feeling dizzy or faint or lighheaded	11.8% 2/17 • Number of events 3 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	20.0% 3/15 • Number of events 4 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Metabolism and nutrition disorders Weightloss	11.8% 2/17 • Number of events 3 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	0.00% 0/15 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Musculoskeletal and connective tissue disorders Weakness	5.9% 1/17 • Number of events 2 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	0.00% 0/15 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
Eye disorders Eye pain	5.9% 1/17 • Number of events 2 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	0.00% 0/15 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.
General disorders Numbness or tingling around mouth	5.9% 1/17 • Number of events 2 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.	0.00% 0/15 • During the medication phase (8 days) and follow-up (1 week). Patients 'at risk' for all adverse events are the 'safety population'- which consists of any patient that received study drug post randomization. This would be a total of 32 of 36 patients, 17 in Tolcapone arm and 15 in Sugar Pill arm.