Trial Outcomes & Findings for Ibudilast for the Treatment of Alcohol Use Disorder (NCT NCT03594435)

Last Updated: 2024-11-27

Results Overview

Heavy drinking days defined as 5+ drinks for men and 4+ for women. Reported outcome measures are proportions of heavy drinking days.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

102 participants

Primary outcome timeframe

12 week-treatment period

Results posted on

2024-11-27

Participant Flow

Participants were recruited via online and print advertisements, local bus campaigns, and targeted recruitment through a laboratory database of previous study participants who agreed to be contacted for further studies.

A stratified randomization list was developed by a statistician and was based on gender, drinking status (moderate drinking defined as ≥ 14 drinks/week for men and ≥ 7 drinks/week for women versus heavy drinking defined as ≥ 28 drinks/week for men and ≥ 21 drinks/week for women).

Participant milestones

Participant milestones
Measure	Ibudilast 10mg delayed-release capsules, target dose 50mg twice daily (5 x 10mg capsules twice daily) for 12 weeks ibudilast: targets neurotrophine signaling and neuroimmune function	Placebo Oral Capsule matched to experimental drug Placebo oral capsule: matched to active drug, ibudilast
Overall Study STARTED	53	49
Overall Study COMPLETED	48	41
Overall Study NOT COMPLETED	5	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ibudilast for the Treatment of Alcohol Use Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ibudilast n=53 Participants 10mg delayed-release capsules, target dose 50mg twice daily (5 x 10mg capsules twice daily) for 12 weeks. ibudilast: targets neurotrophin signaling and neuroimmune function	Placebo Oral Capsule n=49 Participants matched to experimental drug Placebo oral capsule: matched to active drug, ibudilast	Total n=102 Participants Total of all reporting groups
Age, Continuous	42.74 years STANDARD_DEVIATION 10.01 • n=5 Participants	45.92 years STANDARD_DEVIATION 11.49 • n=7 Participants	44.26 years STANDARD_DEVIATION 10.81 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	20 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	29 Participants n=7 Participants	61 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	33 Participants n=7 Participants	70 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	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants	27 Participants n=7 Participants	52 Participants n=5 Participants
Race (NIH/OMB) More than one race	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	53 participants n=5 Participants	49 participants n=7 Participants	102 participants n=5 Participants
Drinks per drinking day	7.57 drinks per drinking day STANDARD_DEVIATION 4.30 • n=5 Participants	7.52 drinks per drinking day STANDARD_DEVIATION 3.36 • n=7 Participants	7.54 drinks per drinking day STANDARD_DEVIATION 5.36 • n=5 Participants
Percent heavy drinking days	67.5 percent heavy drinking days STANDARD_DEVIATION 34.55 • n=5 Participants	65.7 percent heavy drinking days STANDARD_DEVIATION 34.89 • n=7 Participants	66.6 percent heavy drinking days STANDARD_DEVIATION 34.55 • n=5 Participants
Number of drinking days	22.42 drinking days STANDARD_DEVIATION 7.46 • n=5 Participants	22.71 drinking days STANDARD_DEVIATION 7.41 • n=7 Participants	22.56 drinking days STANDARD_DEVIATION 7.40 • n=5 Participants
Positive THC screen	23 Participants n=5 Participants	11 Participants n=7 Participants	34 Participants n=5 Participants
Mild Cannabis Use Disorder	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Any cigarette use	18 Participants n=5 Participants	17 Participants n=7 Participants	35 Participants n=5 Participants
Smokes cigarettes	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Penn Alcohol Craving Scale Total	13.83 units on a scale STANDARD_DEVIATION 5.85 • n=5 Participants	13.73 units on a scale STANDARD_DEVIATION 6.56 • n=7 Participants	13.78 units on a scale STANDARD_DEVIATION 6.17 • n=5 Participants
Structured Clinical Interview Alcohol Use Disorder symptom count	7.15 units on a scale STANDARD_DEVIATION 2.05 • n=5 Participants	6.27 units on a scale STANDARD_DEVIATION 1.69 • n=7 Participants	6.73 units on a scale STANDARD_DEVIATION 1.93 • n=5 Participants
Alcohol Use Disorders Identification Test	21.23 units on a scale STANDARD_DEVIATION 8.24 • n=5 Participants	19.16 units on a scale STANDARD_DEVIATION 6.14 • n=7 Participants	20.24 units on a scale STANDARD_DEVIATION 7.35 • n=5 Participants
Relief/Habit Drinking	27 Participants n=5 Participants	25 Participants n=7 Participants	52 Participants n=5 Participants
Current Depression	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Beck's Depression Inventory-II Total	11.98 units on a scale STANDARD_DEVIATION 8.55 • n=5 Participants	10.73 units on a scale STANDARD_DEVIATION 7.13 • n=7 Participants	11.38 units on a scale STANDARD_DEVIATION 7.89 • n=5 Participants
Beck's Anxiety Inventory Total	8.53 units on a scale STANDARD_DEVIATION 7.87 • n=5 Participants	6.94 units on a scale STANDARD_DEVIATION 7.08 • n=7 Participants	7.76 units on a scale STANDARD_DEVIATION 7.51 • n=5 Participants
Insomnia Severity Index Total	9 units on a scale STANDARD_DEVIATION 6.29 • n=5 Participants	7.98 units on a scale STANDARD_DEVIATION 5.23 • n=7 Participants	8.51 units on a scale STANDARD_DEVIATION 5.80 • n=5 Participants

PRIMARY outcome

Timeframe: 12 week-treatment period

Heavy drinking days defined as 5+ drinks for men and 4+ for women. Reported outcome measures are proportions of heavy drinking days.

Outcome measures

Outcome measures
Measure	Ibudilast n=53 Participants 10mg delayed-release capsules, target dose 50mg twice daily (5 x 10mg capsules twice daily) for 12 weeks ibudilast: targets neurotrophin signaling and neuroimmune function	Placebo Oral Capsule n=49 Participants matched to experimental drug Placebo oral capsule: matched to active drug, ibudilast
Percent Heavy Drinking Days Randomization	67.4777 percent of heavy drinking days Standard Deviation 34.54664	65.65447 percent of heavy drinking days Standard Deviation 34.89305
Percent Heavy Drinking Days Week 2 Follow-up	53.88376 percent of heavy drinking days Standard Deviation 38.62032	42.96028 percent of heavy drinking days Standard Deviation 42.12516
Percent Heavy Drinking Days Week 4 Follow-up	48.57848 percent of heavy drinking days Standard Deviation 40.24403	43.54836 percent of heavy drinking days Standard Deviation 42.40074
Percent Heavy Drinking Days Week 6 Follow-up	40.13970 percent of heavy drinking days Standard Deviation 41.51441	45.83959 percent of heavy drinking days Standard Deviation 39.41569
Percent Heavy Drinking Days Week 8 Follow-up	47.88029 percent of heavy drinking days Standard Deviation 40.47520	35.80680 percent of heavy drinking days Standard Deviation 40.36051
Percent Heavy Drinking Days Week 10 Follow-up	43.36704 percent of heavy drinking days Standard Deviation 40.82088	37.54797 percent of heavy drinking days Standard Deviation 40.80282
Percent Heavy Drinking Days Week 12 Follow-up	34.96705 percent of heavy drinking days Standard Deviation 38.75223	35.33841 percent of heavy drinking days Standard Deviation 40.07343

SECONDARY outcome

Timeframe: 12-week treatment period

Secondary alcohol consumption endpoint. Outcome measure reported is the proportion of drinks per day. Drinks per day across the trial. Randomization is the first day of study intervention after study eligibility was determined.

Outcome measures

Outcome measures
Measure	Ibudilast n=53 Participants 10mg delayed-release capsules, target dose 50mg twice daily (5 x 10mg capsules twice daily) for 12 weeks ibudilast: targets neurotrophin signaling and neuroimmune function	Placebo Oral Capsule n=49 Participants matched to experimental drug Placebo oral capsule: matched to active drug, ibudilast
Drinks Per Day Randomization	5.5569643 Drinking per day Standard Deviation 3.8825400	5.0916392 Drinking per day Standard Deviation 3.2844504
Drinks Per Day Week 2 Follow-up	2.9712639 Drinking per day Standard Deviation 2.6163298	2.5307298 Drinking per day Standard Deviation 2.5759514
Drinks Per Day Week 4 Follow-up	2.9416414 Drinking per day Standard Deviation 3.0687885	2.7376672 Drinking per day Standard Deviation 2.2163207
Drinks Per Day Week 6 Follow-up	2.9004471 Drinking per day Standard Deviation 3.1327782	2.4886257 Drinking per day Standard Deviation 1.9787647
Drinks Per Day Week 8 Follow-up	2.5295239 Drinking per day Standard Deviation 2.0967361	1.9764896 Drinking per day Standard Deviation 2.0375665
Drinks Per Day Week 10 Follow-up	2.3335342 Drinking per day Standard Deviation 2.2920357	1.9942146 Drinking per day Standard Deviation 1.9999379
Drinks Per Day Week 12 Follow-up	2.2639331 Drinking per day Standard Deviation 2.2143404	1.9131006 Drinking per day Standard Deviation 2.0874590

SECONDARY outcome

Timeframe: 12-week treatment period

Secondary alcohol consumption endpoint. Drinks per drinking day is defined as how many drinks an individual consumed on a day they reported drinking alcohol.

Outcome measures

Outcome measures
Measure	Ibudilast n=53 Participants 10mg delayed-release capsules, target dose 50mg twice daily (5 x 10mg capsules twice daily) for 12 weeks ibudilast: targets neurotrophin signaling and neuroimmune function	Placebo Oral Capsule n=49 Participants matched to experimental drug Placebo oral capsule: matched to active drug, ibudilast
Drinks Per Drinking Day Randomization	7.5702563 drinks per drinking day Standard Deviation 4.3026834	7.5157381 drinks per drinking day Standard Deviation 6.3591036
Drinks Per Drinking Day Week 2 Follow-up	6.0380129 drinks per drinking day Standard Deviation 4.2269696	4.6825232 drinks per drinking day Standard Deviation 3.6986878
Drinks Per Drinking Day Week 4 Follow-up	5.1232947 drinks per drinking day Standard Deviation 3.6194523	4.8648040 drinks per drinking day Standard Deviation 4.2417622
Drinks Per Drinking Day Week 6 Follow-up	4.8955457 drinks per drinking day Standard Deviation 3.9859161	4.4555121 drinks per drinking day Standard Deviation 3.1474673
Drinks Per Drinking Day Week 8 Follow-up	4.9961214 drinks per drinking day Standard Deviation 3.4733168	3.4954873 drinks per drinking day Standard Deviation 2.7084074
Drinks Per Drinking Day Week 10 Follow-up	4.6825531 drinks per drinking day Standard Deviation 4.1278832	3.3946192 drinks per drinking day Standard Deviation 2.5414040
Drinks Per Drinking Day Week 12 Follow-up	4.1250715 drinks per drinking day Standard Deviation 3.1777328	3.4113607 drinks per drinking day Standard Deviation 2.4958175

SECONDARY outcome

Timeframe: 12-week treatment period

Secondary alcohol consumption endpoint. Outcome measure reported is the proportion of percent days abstinent.

Outcome measures

Outcome measures
Measure	Ibudilast n=53 Participants 10mg delayed-release capsules, target dose 50mg twice daily (5 x 10mg capsules twice daily) for 12 weeks ibudilast: targets neurotrophin signaling and neuroimmune function	Placebo Oral Capsule n=49 Participants matched to experimental drug Placebo oral capsule: matched to active drug, ibudilast
Percent Days Abstinent Randomization	25.28269 percent days abstinent. Standard Deviation 24.86230	24.28538 percent days abstinent. Standard Deviation 24.71130
Percent Days Abstinent Week 2 Follow-up	52.10013 percent days abstinent. Standard Deviation 31.53534	51.24152 percent days abstinent. Standard Deviation 36.33756
Percent Days Abstinent Week 4 Follow-up	53.49783 percent days abstinent. Standard Deviation 33.79115	46.76799 percent days abstinent. Standard Deviation 35.31845
Percent Days Abstinent Week 6 Follow-up	50.14506 percent days abstinent. Standard Deviation 34.61062	49.30242 percent days abstinent. Standard Deviation 36.06276
Percent Days Abstinent Week 8 Follow-up	49.85351 percent days abstinent. Standard Deviation 35.34000	54.99929 percent days abstinent. Standard Deviation 38.86134
Percent Days Abstinent Week 10 Follow-up	56.10048 percent days abstinent. Standard Deviation 34.49246	54.35469 percent days abstinent. Standard Deviation 37.55533
Percent Days Abstinent Week 12 Follow-up	54.86251 percent days abstinent. Standard Deviation 34.42088	55.35643 percent days abstinent. Standard Deviation 38.60974

Adverse Events

Ibudilast

Serious events: 1 serious events

Other events: 36 other events

Deaths: 0 deaths

Placebo Oral Capsule

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ibudilast n=53 participants at risk 10mg delayed-release capsules, target dose 50mg twice daily (5 x 10mg capsules twice daily) for 12 weeks Ibudilast: targets neurotrophin signaling and neuroimmune function	Placebo Oral Capsule n=49 participants at risk matched to experimental drug Placebo oral capsule: matched to active drug, ibudilast
General disorders Left Upper Quadrant Abdominal Pain	0.00% 0/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	2.0% 1/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Injury, poisoning and procedural complications Left Ankle Open Fracture	1.9% 1/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	0.00% 0/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Blood and lymphatic system disorders Subdural Hematoma	1.9% 1/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	0.00% 0/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.

Other adverse events

Additional Information

Dr. Lara Ray

University of California Los Angeles

Phone: 310-206-6756

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ibudilast n=53 participants at risk 10mg delayed-release capsules, target dose 50mg twice daily (5 x 10mg capsules twice daily) for 12 weeks Ibudilast: targets neurotrophin signaling and neuroimmune function	Placebo Oral Capsule n=49 participants at risk matched to experimental drug Placebo oral capsule: matched to active drug, ibudilast
General disorders Insomnia	7.5% 4/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	6.1% 3/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Psychiatric disorders Anxiety	7.5% 4/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	8.2% 4/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Gastrointestinal disorders Diarrhea	7.5% 4/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	4.1% 2/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Gastrointestinal disorders Vomiting	9.4% 5/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	6.1% 3/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
General disorders Headache	15.1% 8/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	16.3% 8/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
General disorders Flu like symptoms	7.5% 4/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	8.2% 4/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
General disorders Body pain	15.1% 8/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	12.2% 6/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Gastrointestinal disorders Nausea	15.1% 8/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	16.3% 8/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
General disorders Fatigue	7.5% 4/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	2.0% 1/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
General disorders Dizziness	3.8% 2/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	0.00% 0/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Gastrointestinal disorders Dyspepsia	5.7% 3/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	4.1% 2/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Psychiatric disorders Depression	3.8% 2/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	4.1% 2/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Reproductive system and breast disorders Libido	0.00% 0/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	2.0% 1/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Gastrointestinal disorders Gut pain	5.7% 3/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	8.2% 4/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Skin and subcutaneous tissue disorders Skin discoloration	0.00% 0/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	2.0% 1/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Respiratory, thoracic and mediastinal disorders Dysmenorrhea	1.9% 1/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	2.0% 1/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Skin and subcutaneous tissue disorders Rash	0.00% 0/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	6.1% 3/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
General disorders Sweating	1.9% 1/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	4.1% 2/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
General disorders Flushing	1.9% 1/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	0.00% 0/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Blood and lymphatic system disorders Hypertension	1.9% 1/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	0.00% 0/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Cardiac disorders Abnormal EKG	1.9% 1/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	0.00% 0/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Blood and lymphatic system disorders Anemia	1.9% 1/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	0.00% 0/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
Eye disorders Blurry vision	1.9% 1/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	4.1% 2/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.
General disorders Pain and discomfort	20.8% 11/53 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.	18.4% 9/49 • Adverse event data was collected for each participant between randomization to Week 12 visit (final day of study). The study physician (Dr. Miotto) called every participant at the end of the first week on the study medication to discuss any adverse events. Adverse events were also collected at each monthly visit and the study physician was notified of any reported adverse events.