Trial Outcomes & Findings for Combined Behavioral and Analgesic Trial for Fibromyalgia (NCT NCT01598753)

Last Updated: 2019-06-26

Results Overview

The primary outcome is a reduction of at least 30% on the pain score (mean for 5-day daily pain diary) or improvement of 20% physical function (FIQR) from baseline (pre-treatment) to post-treatment. Individuals who achieve such decrease in pain or increase in function are labeled "responders."

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

134 participants

Primary outcome timeframe

Baseline (one week prior to drug titration) to post-treatment (approximately 11 weeks after baseline).

Results posted on

2019-06-26

Participant Flow

Participants with fibromyalgia (FM) were enrolled at 2 sites, the University of Washington in Seattle WA and the University of Rochester in Rochester NY.

Participants underwent a physical exam to rule out conflicting medical conditions and confirm a diagnosis of FM (1990 ACR criteria). A 5-day baseline diary was distributed and required a mean daily pain score ≥ 4 and ≤ 9. A urine drug test with no illicit drugs and a negative urine pregnancy test (when applicable) were also required at baseline.

Participant milestones

Participant milestones
Measure	Placebo and Health Education Participants received a matching placebo and 8 weekly 50 minute sessions of health education on Fibromyalgia.	Tramadol and Health Education Participants received between 200mg and 400mg of Tramadol daily and 8 weekly 50 minute sessions of health education on Fibromyalgia.	Placebo and Cognitive Behavioral Therapy Participants received matching placebo and 8 weekly 50 minute sessions of Cognitive Behavioral Therapy that had been specifically tailored for Fibromyalgia patients.	Tramadol and Cognitive Behavioral Therapy Participants received between 200mg and 400mg of Tramadol daily and 8 weekly 50 minute sessions of Cognitive Behavioral Therapy that had been specifically tailored for Fibromyalgia patients.
Overall Study STARTED	37	31	32	34
Overall Study COMPLETED	25	16	24	19
Overall Study NOT COMPLETED	12	15	8	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo and Health Education Participants received a matching placebo and 8 weekly 50 minute sessions of health education on Fibromyalgia.	Tramadol and Health Education Participants received between 200mg and 400mg of Tramadol daily and 8 weekly 50 minute sessions of health education on Fibromyalgia.	Placebo and Cognitive Behavioral Therapy Participants received matching placebo and 8 weekly 50 minute sessions of Cognitive Behavioral Therapy that had been specifically tailored for Fibromyalgia patients.	Tramadol and Cognitive Behavioral Therapy Participants received between 200mg and 400mg of Tramadol daily and 8 weekly 50 minute sessions of Cognitive Behavioral Therapy that had been specifically tailored for Fibromyalgia patients.
Overall Study Adverse Event	1	9	1	7
Overall Study Lost to Follow-up	4	3	7	5
Overall Study Physician Decision	0	1	0	2
Overall Study Withdrawal by Subject	7	2	0	1

Baseline Characteristics

Combined Behavioral and Analgesic Trial for Fibromyalgia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo and Health Education n=37 Participants Participants received a matching placebo and 8 weekly 50 minute sessions of health education on Fibromyalgia.	Tramadol and Health Education n=31 Participants Participants received between 200mg and 400mg of Tramadol daily and 8 weekly 50 minute sessions of health education on Fibromyalgia.	Placebo and Cognitive Behavioral Therapy n=32 Participants Participants received matching placebo and 8 weekly 50 minute sessions of Cognitive Behavioral Therapy that had been specifically tailored for Fibromyalgia patients.	Tramadol and Cognitive Behavioral Therapy n=34 Participants Participants received between 200mg and 400mg of Tramadol daily and 8 weekly 50 minute sessions of Cognitive Behavioral Therapy that had been specifically tailored for Fibromyalgia patients.	Total n=134 Participants Total of all reporting groups
Age, Continuous	50.3 years STANDARD_DEVIATION 12.9 • n=5 Participants	51.2 years STANDARD_DEVIATION 10.8 • n=7 Participants	48.9 years STANDARD_DEVIATION 13.1 • n=5 Participants	44.64 years STANDARD_DEVIATION 13.1 • n=4 Participants	48.7 years STANDARD_DEVIATION 12.7 • n=21 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	28 Participants n=7 Participants	30 Participants n=5 Participants	31 Participants n=4 Participants	123 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	11 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=5 Participants	29 Participants n=7 Participants	30 Participants n=5 Participants	33 Participants n=4 Participants	128 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) White	35 Participants n=5 Participants	25 Participants n=7 Participants	29 Participants n=5 Participants	28 Participants n=4 Participants	117 Participants n=21 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (one week prior to drug titration) to post-treatment (approximately 11 weeks after baseline).

Outcome measures

Outcome measures
Measure	Placebo and Health Education n=37 Participants Participants received a matching placebo and 8 weekly 50 minute sessions of health education on Fibromyalgia.	Tramadol and Health Education n=31 Participants Participants received between 200mg and 400mg of Tramadol daily and 8 weekly 50 minute sessions of health education on Fibromyalgia.	Placebo and Cognitive Behavioral Therapy n=32 Participants Participants received matching placebo and 8 weekly 50 minute sessions of Cognitive Behavioral Therapy that had been specifically tailored for Fibromyalgia patients.	Tramadol and Cognitive Behavioral Therapy n=34 Participants Participants received between 200mg and 400mg of Tramadol daily and 8 weekly 50 minute sessions of Cognitive Behavioral Therapy that had been specifically tailored for Fibromyalgia patients.
Number of Participants With a 30% Improvement in Pain or 20% Improvement in Function	24 Participants	13 Participants	21 Participants	15 Participants

Adverse Events

Placebo and Health Education

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Tramadol and Health Education

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Placebo and Cognitive Behavioral Therapy

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Tramadol and Cognitive Behavioral Therapy

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dennis C. Turk, Ph.D.

University of Washington

Phone: (206)616-2626

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Placebo and Health Education n=37 participants at risk Participants received a matching placebo and 8 weekly 50 minute sessions of health education on Fibromyalgia.	Tramadol and Health Education n=31 participants at risk Participants received between 200mg and 400mg of Tramadol daily and 8 weekly 50 minute sessions of health education on Fibromyalgia.	Placebo and Cognitive Behavioral Therapy n=32 participants at risk Participants received matching placebo and 8 weekly 50 minute sessions of Cognitive Behavioral Therapy that had been specifically tailored for Fibromyalgia patients.	Tramadol and Cognitive Behavioral Therapy n=34 participants at risk Participants received between 200mg and 400mg of Tramadol daily and 8 weekly 50 minute sessions of Cognitive Behavioral Therapy that had been specifically tailored for Fibromyalgia patients.
Gastrointestinal disorders Abdominal Pain	2.7% 1/37 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	5.9% 2/34 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Skin and subcutaneous tissue disorders Skin abrasions	5.4% 2/37 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	6.2% 2/32 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Psychiatric disorders Agitation	2.7% 1/37 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Psychiatric disorders Anxiety	8.1% 3/37 • Number of events 3 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	6.5% 2/31 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	6.2% 2/32 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	8.8% 3/34 • Number of events 3 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Musculoskeletal and connective tissue disorders Back pain	5.4% 2/37 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	6.2% 2/32 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Gastrointestinal disorders Bloating	2.7% 1/37 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.1% 1/32 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Renal and urinary disorders Blood in stool	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Nervous system disorders Blurry vision	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Musculoskeletal and connective tissue disorders Body ache	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Respiratory, thoracic and mediastinal disorders Bronchitis	2.7% 1/37 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Skin and subcutaneous tissue disorders Bruise	10.8% 4/37 • Number of events 4 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.1% 1/32 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Skin and subcutaneous tissue disorders Burn	2.7% 1/37 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.1% 1/32 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Skin and subcutaneous tissue disorders Burning sensation	2.7% 1/37 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Respiratory, thoracic and mediastinal disorders Change in respiration	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Cardiac disorders Chest pain	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Endocrine disorders Chills	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	6.5% 2/31 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	6.2% 2/32 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Respiratory, thoracic and mediastinal disorders Cold	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.1% 1/32 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Respiratory, thoracic and mediastinal disorders Congestion	5.4% 2/37 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.1% 1/32 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Gastrointestinal disorders Constipation	2.7% 1/37 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	25.8% 8/31 • Number of events 8 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	17.6% 6/34 • Number of events 6 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Respiratory, thoracic and mediastinal disorders Cough	10.8% 4/37 • Number of events 4 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	6.2% 2/32 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Gastrointestinal disorders Cramps	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Gastrointestinal disorders Decreased appetite	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	6.5% 2/31 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Nervous system disorders Decreased taste sensation	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.1% 1/32 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
General disorders Dental pain	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Psychiatric disorders Depression	5.4% 2/37 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	5.9% 2/34 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Gastrointestinal disorders Diarrhea	8.1% 3/37 • Number of events 4 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	12.9% 4/31 • Number of events 4 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	9.4% 3/32 • Number of events 3 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	11.8% 4/34 • Number of events 4 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Nervous system disorders Difficulty concentrating	5.4% 2/37 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	6.5% 2/31 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.1% 1/32 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Musculoskeletal and connective tissue disorders Difficulty swallowing	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.1% 1/32 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Nervous system disorders Dissociative state	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Nervous system disorders Dizziness	5.4% 2/37 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	16.1% 5/31 • Number of events 5 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	11.8% 4/34 • Number of events 4 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Nervous system disorders Drowsiness	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	12.9% 4/31 • Number of events 4 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	9.4% 3/32 • Number of events 3 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	11.8% 4/34 • Number of events 4 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Eye disorders Dry eyes	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Gastrointestinal disorders Dry mouth	2.7% 1/37 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	6.5% 2/31 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
General disorders Dry nose	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Gastrointestinal disorders Emesis	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Psychiatric disorders Extra emotional	2.7% 1/37 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.1% 1/32 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Eye disorders Eye pain	5.4% 2/37 • Number of events 2 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/34 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Nervous system disorders Fatigue	2.7% 1/37 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Nervous system disorders Fever	0.00% 0/37 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.2% 1/31 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/32 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.
Gastrointestinal disorders Flatus	2.7% 1/37 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	0.00% 0/31 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	3.1% 1/32 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.	2.9% 1/34 • Number of events 1 • Adverse events were reported from signing the informed consent until the completion of the 6-month follow-up visit.