Trial Outcomes & Findings for New Treatment for Alcohol and Nicotine Dependence (NCT NCT01182766)

Last Updated: 2025-10-31

Results Overview

No smoking in the last 4 weeks of the 18-week treatment with an expired carbon monoxide level of \<10 ppm as the biochemical verification. We used the intent-to-treat assumption, where missing smoking data were considered as smoking.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

236 participants

Primary outcome timeframe

Week 15 - 18 of the 18-week medication treatment

Results posted on

2025-10-31

Participant Flow

Participants were 236 adults who met the DSM-5 criteria for Alcohol Use Disorder and Tobacco Use Disorder and recruited from three metropolitan areas in the U.S., including San Diego, California, Houston, Texas, and Charlottesville, Virginia. A Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of mild to severe alcohol use disorder was required and participants must have smoked an average of 5 or more cigarettes/day in the 30 days prior to randomization.

Of 646 individuals who screened, 410 were excluded or uninterested. A total of 236 participants were enrolled and randomized into one of three study arms. Randomization was achieved using a block randomization procedure in which treatment groups were stratified to achieve a balance on age of onset for alcoholism (less than 26 years old or 26 years and older), gender, and drinks per drinking day (DDD) (\< 8 DDD or ≥ 8 DDD) and the number of cigarettes smoked (\<20 or \>20 cigarettes/day).

Participant milestones

Participant milestones
Measure	Placebo Participants received the 18-week placebo treatment with brief behavioral enhancement therapy	Low-Dose Topiramate Participants received the 18-week low-dose topiramate treatment (up to 125 mg/day) with brief behavioral enhancement therapy	High-Dose Topiramate Participants received the 18-week high-dose topiramate treatment (up to 250 mg/day) with brief behavioral enhancement therapy
Overall Study STARTED	84	75	77
Overall Study COMPLETED	36	35	41
Overall Study NOT COMPLETED	48	40	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received the 18-week placebo treatment with brief behavioral enhancement therapy	Low-Dose Topiramate Participants received the 18-week low-dose topiramate treatment (up to 125 mg/day) with brief behavioral enhancement therapy	High-Dose Topiramate Participants received the 18-week high-dose topiramate treatment (up to 250 mg/day) with brief behavioral enhancement therapy
Overall Study Lost to Follow-up	32	36	29
Overall Study Withdrawal by Subject	14	3	6
Overall Study Physician Decision	1	0	0
Overall Study Non-compliance	1	1	1

Baseline Characteristics

New Treatment for Alcohol and Nicotine Dependence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=84 Participants Placebo with brief behavioral enhancement therapy	Low-Dose Topiramate n=75 Participants Low-dose Topiramate (up to 125 mg/day) with brief behavioral enhancement therapy	High-Dose Topiramate n=77 Participants High-dose Topiramate (up to 250 mg/day) with brief behavioral enhancement therapy	Total n=236 Participants Total of all reporting groups
Age, Continuous	47.68 years STANDARD_DEVIATION 10.35 • n=5 Participants	48.07 years STANDARD_DEVIATION 10.34 • n=7 Participants	48.77 years STANDARD_DEVIATION 9.86 • n=5 Participants	48.16 years STANDARD_DEVIATION 10.15 • n=4 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	23 Participants n=7 Participants	25 Participants n=5 Participants	76 Participants n=4 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	52 Participants n=7 Participants	52 Participants n=5 Participants	160 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	13 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	76 Participants n=5 Participants	67 Participants n=7 Participants	70 Participants n=5 Participants	213 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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	2 Participants n=4 Participants
Race (NIH/OMB) Black or African American	29 Participants n=5 Participants	31 Participants n=7 Participants	22 Participants n=5 Participants	82 Participants n=4 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants	36 Participants n=7 Participants	48 Participants n=5 Participants	130 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	22 Participants n=4 Participants
Employment Employed or student	46 Participants n=5 Participants	42 Participants n=7 Participants	55 Participants n=5 Participants	143 Participants n=4 Participants
Employment Unemployed or retired	36 Participants n=5 Participants	28 Participants n=7 Participants	18 Participants n=5 Participants	82 Participants n=4 Participants
Employment Employment unknown	2 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Baseline Smoking (CPD)	21.34 cigarettes per day STANDARD_DEVIATION 9.96 • n=5 Participants	19.18 cigarettes per day STANDARD_DEVIATION 10.47 • n=7 Participants	20.33 cigarettes per day STANDARD_DEVIATION 10.02 • n=5 Participants	20.32 cigarettes per day STANDARD_DEVIATION 10.14 • n=4 Participants
Baseline Drinking (SDU)/day	10.02 standard drink units/day STANDARD_DEVIATION 6.76 • n=5 Participants	9.84 standard drink units/day STANDARD_DEVIATION 5.51 • n=7 Participants	9.88 standard drink units/day STANDARD_DEVIATION 5.96 • n=5 Participants	9.92 standard drink units/day STANDARD_DEVIATION 6.10 • n=4 Participants
Mean Fagerström Test for Cigarette Dependence (FTCD) Score	5.32 scores on a scale STANDARD_DEVIATION 1.92 • n=5 Participants	5.27 scores on a scale STANDARD_DEVIATION 2.38 • n=7 Participants	5.69 scores on a scale STANDARD_DEVIATION 2.30 • n=5 Participants	5.42 scores on a scale STANDARD_DEVIATION 2.21 • n=4 Participants
AUDIT	21.39 scores on a scale STANDARD_DEVIATION 7.61 • n=5 Participants	21.43 scores on a scale STANDARD_DEVIATION 7.23 • n=7 Participants	19.40 scores on a scale STANDARD_DEVIATION 6.18 • n=5 Participants	20.75 scores on a scale STANDARD_DEVIATION 7.08 • n=4 Participants

PRIMARY outcome

Timeframe: Week 15 - 18 of the 18-week medication treatment

Outcome measures

Outcome measures
Measure	Placebo n=84 Participants Placebo with brief behavioral enhancement therapy	Low-Dose Topiramate n=75 Participants Low-dose Topiramate (up to 125 mg/day) with brief behavioral enhancement therapy	High-Dose Topiramate n=77 Participants High-dose Topiramate (up to 250 mg/day) with brief behavioral enhancement therapy
Continuous Smoking Abstinence in the Last 4 Weeks of Treatment Continuous Smoking Abstinence in the Last 4 Weeks of Treatment	2 participants	5 participants	6 participants

PRIMARY outcome

Timeframe: Week 15 - 18 of the 18-week medication treatment

A heavy drinking day is defined as \>= 5 standard drinking units for men and \>= 4 standard drinking units for women. We calculated the PHDD used the intent-to-treat assumption, where missing drinking data were considered as heavy drinking.

Outcome measures

Outcome measures
Measure	Placebo n=84 Participants Placebo with brief behavioral enhancement therapy	Low-Dose Topiramate n=75 Participants Low-dose Topiramate (up to 125 mg/day) with brief behavioral enhancement therapy	High-Dose Topiramate n=77 Participants High-dose Topiramate (up to 250 mg/day) with brief behavioral enhancement therapy
Percentage of Heavy Drinking Days (PHDD) in the Last 4 Weeks of Treatment	62.8 percentage of heavy drinking days Standard Deviation 45.4	65.1 percentage of heavy drinking days Standard Deviation 44	59.3 percentage of heavy drinking days Standard Deviation 47.3

SECONDARY outcome

Timeframe: Week 15 - 18 of the 18-week medication treatment

We used the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) to measure quality of life in the last 4 weeks of treatment. Scoring involves summing the individual item scores on a 5-point scale, with higher scores indicating greater life satisfaction and enjoyment (better outcome). We report here a percent score of subscales contained within the Q-LES-Q, with higher scores indicating a better outcome. The subscales within the questionnaire have different numbers of items, resulting in different ranges of raw scores, so using a percent score, which used the following formula: (raw\_score - scale\_min\_possible\_score) / (scale\_max\_possible\_score - scale\_min\_possible\_score), helped normalize such differences, improving interpretation using the same range (i.e., 0 - 100) between subscales.

Outcome measures

Outcome measures
Measure	Placebo n=84 Participants Placebo with brief behavioral enhancement therapy	Low-Dose Topiramate n=75 Participants Low-dose Topiramate (up to 125 mg/day) with brief behavioral enhancement therapy	High-Dose Topiramate n=77 Participants High-dose Topiramate (up to 250 mg/day) with brief behavioral enhancement therapy
Quality of Life in the Last 4 Weeks of Treatment Coursework	40.2 percent score on a scale Standard Deviation 6.9	37.1 percent score on a scale Standard Deviation 10.3	35.4 percent score on a scale Standard Deviation 14.4
Quality of Life in the Last 4 Weeks of Treatment General Activities	57.7 percent score on a scale Standard Deviation 8.7	54.2 percent score on a scale Standard Deviation 10.7	57.9 percent score on a scale Standard Deviation 8.6
Quality of Life in the Last 4 Weeks of Treatment Household Duties	43.6 percent score on a scale Standard Deviation 5.1	42 percent score on a scale Standard Deviation 7.2	41.6 percent score on a scale Standard Deviation 8.7
Quality of Life in the Last 4 Weeks of Treatment Physical Health	25.2 percent score on a scale Standard Deviation 3.7	24.1 percent score on a scale Standard Deviation 4.9	23.4 percent score on a scale Standard Deviation 5.5
Quality of Life in the Last 4 Weeks of Treatment Social Relations	51.7 percent score on a scale Standard Deviation 8.4	50.4 percent score on a scale Standard Deviation 10.3	50.8 percent score on a scale Standard Deviation 11.7
Quality of Life in the Last 4 Weeks of Treatment Subjective Feelings	45.3 percent score on a scale Standard Deviation 6.7	43.6 percent score on a scale Standard Deviation 8.9	44.5 percent score on a scale Standard Deviation 10
Quality of Life in the Last 4 Weeks of Treatment Work	59.2 percent score on a scale Standard Deviation 8.5	58 percent score on a scale Standard Deviation 10.2	58.9 percent score on a scale Standard Deviation 11.8

SECONDARY outcome

Timeframe: Week 15 - 18 of the 18-week medication treatment

We used the Visual Analog Scales (VAS) to assess the craving levels for alcohol and cigarettes, respectively. VAS uses a 100 millimeter line, where 0 mm = no craving (minimum value) and 100 mm = strongest craving ever (maximum value). Participants are asked to make a mark on the line that best represents their current level of craving. Research staff then measure the distance in millimeters from the "No Craving" anchor (0 mm) to the participant's mark, which is their score. A higher score is equal to higher craving (worse outcome). Mean scores of the last 4 weeks of treatment are reported.

Outcome measures

Outcome measures
Measure	Placebo n=84 Participants Placebo with brief behavioral enhancement therapy	Low-Dose Topiramate n=75 Participants Low-dose Topiramate (up to 125 mg/day) with brief behavioral enhancement therapy	High-Dose Topiramate n=77 Participants High-dose Topiramate (up to 250 mg/day) with brief behavioral enhancement therapy
Craving for Alcohol and Cigarettes in the Last 4 Weeks of Treatment Craving for alcohol	12.3 score on VAS scale Standard Deviation 13.9	18.4 score on VAS scale Standard Deviation 20.2	14.3 score on VAS scale Standard Deviation 14.8
Craving for Alcohol and Cigarettes in the Last 4 Weeks of Treatment Craving for cigarettes	17.4 score on VAS scale Standard Deviation 18	24.6 score on VAS scale Standard Deviation 23.3	18.2 score on VAS scale Standard Deviation 17.8

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 63 other events

Deaths: 0 deaths

Low-Dose Topiramate

Serious events: 7 serious events

Other events: 59 other events

Deaths: 0 deaths

High-Dose Topiramate

Serious events: 7 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Nassima Ait-Daoud Tiouririne

University of Virginia School of Medicine

Phone: (434) 243-0570

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=84 participants at risk Placebo with brief behavioral enhancement therapy	Low-Dose Topiramate n=75 participants at risk Low-dose Topiramate (up to 125 mg/day) with brief behavioral enhancement therapy	High-Dose Topiramate n=77 participants at risk High-dose Topiramate (up to 250 mg/day) with brief behavioral enhancement therapy
Gastrointestinal disorders Abdominal Pain	1.2% 1/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Psychiatric disorders Agitation	0.00% 0/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	1.3% 1/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Immune system disorders Allergic Reaction	0.00% 0/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	1.3% 1/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Psychiatric disorders Anxiety	1.2% 1/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Nervous system disorders Concentration Impairment	0.00% 0/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	2.6% 2/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Psychiatric disorders Depression	0.00% 0/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	1.3% 1/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Psychiatric disorders Drug Withdrawal	0.00% 0/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	1.3% 1/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Nervous system disorders Dysgeusia	0.00% 0/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	1.3% 1/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Psychiatric disorders Insomnia	0.00% 0/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	1.3% 1/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Nervous system disorders Intracranial Hemorrhage	1.2% 1/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Gastrointestinal disorders Nausea	1.2% 1/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	1.3% 1/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms Benign, Malignant And Unspecified Incl Cysts And Polyps - Other	1.2% 1/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	1.3% 1/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Infections and infestations Sepsis	0.00% 0/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	1.3% 1/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Surgical and medical procedures Surgical And Medical Procedures - Other	2.4% 2/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	2.7% 2/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Gastrointestinal disorders Toothache	0.00% 0/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	1.3% 1/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).
Musculoskeletal and connective tissue disorders Arthritis	1.2% 1/84 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/75 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).	0.00% 0/77 • Adverse Events data were collected at all study visits (18 weeks), plus 30-day follow-up. Adverse events reporting followed the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US Department of Health and Human Services, 2017).