Trial Outcomes & Findings for Alternatives for Reducing Tics in Tourette Syndrome (TS): A Study of TEV-50717 (Deutetrabenazine) for the Treatment of Tourette Syndrome in Children and Adolescents (NCT NCT03452943)

Last Updated: 2021-11-09

Results Overview

YGTSS rating scale is a semi-structured clinician rating instrument that provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic tics. YGTSS is composed of 11 items: 5 items for motor tic severity, 5 items for vocal tic severity, and 1 item for impairment. Each item for motor tic severity and vocal is rated on a 6-point scale (0 for none to 5 to severe). MTSS is the sum of the 5 items for motor tic severity and VTSS is the sum of the 5 items for vocal tic severity. TTS is the sum of MTSS and VTSS, ranges from 0 (none/absent) to 50 (severe). Higher scores indicate greater severity/worse outcome. Least square (LS) mean and standard error (SE) was calculated using mixed-model repeated-measures (MMRM) with treatment group, week (5 levels: weeks 2, 4, 6, 9, and 12), and the treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6 to 11 years, 12 to 16 years) as covariates.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

119 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2021-11-09

Participant Flow

A total of 119 participants were randomized in a 1:1 ratio to either TEV-50717 or placebo group.

Participant milestones

Participant milestones
Measure	TEV-50717 Participants received TEV-50717 as oral tablets at a starting dose of 6 milligrams (mg)/day, with the dose titrated weekly for 7 weeks to an optimal level. The target maximum daily dose was determined by body weight and cytochrome P450 2D6 (CYP2D6) impairment status at baseline. Maximum total daily dose for participants greater than or equal to (≥) 40 kilograms (kg) was 48 mg/day (24 mg twice daily \[BID\]), 30 to less than (\<) 40 kg was 42 mg/day (21 mg BID), and 20 to \<30 kg was 30 mg/day (15 mg BID). For those considered CYP2D6 impaired, maximum daily dose for participants ≥40 kg was 36 mg/day, 30 to \<40 kg was 24 mg/day, and 20 to \<30 kg was 18 mg/day. Total daily doses of ≥12 mg/day was divided into a BID administration. Depending on the dose, TEV-50717 tablets and/or placebo tablets were taken to maintain the blind. Participants then received TEV-50717 at the optimal level as maintenance therapy daily for 5 weeks.	Placebo Participants received placebo matched to TEV-50717 BID for a total of 12 weeks.
Titration Period (7 Weeks) STARTED	59	60
Titration Period (7 Weeks) Safety Analysis Set	58	59
Titration Period (7 Weeks) Modified ITT (mITT) Analysis Set	58	59
Titration Period (7 Weeks) COMPLETED	54	56
Titration Period (7 Weeks) NOT COMPLETED	5	4
Maintenance Period (5 Weeks) STARTED	54	56
Maintenance Period (5 Weeks) COMPLETED	51	56
Maintenance Period (5 Weeks) NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	TEV-50717 Participants received TEV-50717 as oral tablets at a starting dose of 6 milligrams (mg)/day, with the dose titrated weekly for 7 weeks to an optimal level. The target maximum daily dose was determined by body weight and cytochrome P450 2D6 (CYP2D6) impairment status at baseline. Maximum total daily dose for participants greater than or equal to (≥) 40 kilograms (kg) was 48 mg/day (24 mg twice daily \[BID\]), 30 to less than (\<) 40 kg was 42 mg/day (21 mg BID), and 20 to \<30 kg was 30 mg/day (15 mg BID). For those considered CYP2D6 impaired, maximum daily dose for participants ≥40 kg was 36 mg/day, 30 to \<40 kg was 24 mg/day, and 20 to \<30 kg was 18 mg/day. Total daily doses of ≥12 mg/day was divided into a BID administration. Depending on the dose, TEV-50717 tablets and/or placebo tablets were taken to maintain the blind. Participants then received TEV-50717 at the optimal level as maintenance therapy daily for 5 weeks.	Placebo Participants received placebo matched to TEV-50717 BID for a total of 12 weeks.
Titration Period (7 Weeks) Adverse Event	1	1
Titration Period (7 Weeks) Protocol Violation	0	1
Titration Period (7 Weeks) Withdrawal by Subject	3	2
Titration Period (7 Weeks) Lost to Follow-up	1	0
Maintenance Period (5 Weeks) Adverse Event	1	0
Maintenance Period (5 Weeks) Withdrawal by Subject	2	0

Baseline Characteristics

Alternatives for Reducing Tics in Tourette Syndrome (TS): A Study of TEV-50717 (Deutetrabenazine) for the Treatment of Tourette Syndrome in Children and Adolescents

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TEV-50717 n=59 Participants Participants received TEV-50717 as oral tablets at a starting dose of 6 mg/day, with the dose titrated weekly for 7 weeks to an optimal level. The target maximum daily dose was determined by body weight and CYP2D6 impairment status at baseline. Maximum total daily dose for participants ≥40 kg was 48 mg/day (24 mg BID), 30 to \<40 kg was 42 mg/day (21 mg BID), and 20 to \<30 kg was 30 mg/day (15 mg BID). For those considered CYP2D6 impaired, maximum daily dose for participants ≥40 kg was 36 mg/day, 30 to \<40 kg was 24 mg/day, and 20 to \<30 kg was 18 mg/day. Total daily doses of ≥12 mg/day was divided into a BID administration. Depending on the dose, TEV-50717 tablets and/or placebo tablets were taken to maintain the blind. Participants then received TEV-50717 at the optimal level as maintenance therapy daily for 5 weeks.	Placebo n=60 Participants Participants received placebo matched to TEV-50717 BID for a total of 12 weeks.	Total n=119 Participants Total of all reporting groups
Age, Continuous	11.5 years STANDARD_DEVIATION 2.52 • n=5 Participants	11.5 years STANDARD_DEVIATION 2.59 • n=7 Participants	11.5 years STANDARD_DEVIATION 2.54 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	51 Participants n=7 Participants	104 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	51 Participants n=5 Participants	50 Participants n=7 Participants	101 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	49 Participants n=5 Participants	53 Participants n=7 Participants	102 Participants n=5 Participants
Race/Ethnicity, Customized Black	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Native American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS)	31.7 units on a scale STANDARD_DEVIATION 5.81 • n=5 Participants	33.0 units on a scale STANDARD_DEVIATION 5.96 • n=7 Participants	32.3 units on a scale STANDARD_DEVIATION 5.89 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline YGTSS assessment.

Outcome measures

Outcome measures
Measure	TEV-50717 n=58 Participants Participants received TEV-50717 as oral tablets at a starting dose of 6 mg/day, with the dose titrated weekly for 7 weeks to an optimal level. The target maximum daily dose was determined by body weight and CYP2D6 impairment status at baseline. Maximum total daily dose for participants ≥40 kg was 48 mg/day (24 mg BID), 30 to \<40 kg was 42 mg/day (21 mg BID), and 20 to \<30 kg was 30 mg/day (15 mg BID). For those considered CYP2D6 impaired, maximum daily dose for participants ≥40 kg was 36 mg/day, 30 to \<40 kg was 24 mg/day, and 20 to \<30 kg was 18 mg/day. Total daily doses of ≥12 mg/day was divided into a BID administration. Depending on the dose, TEV-50717 tablets and/or placebo tablets were taken to maintain the blind. Participants then received TEV-50717 at the optimal level as maintenance therapy daily for 5 weeks.	Placebo n=59 Participants Participants received placebo matched to TEV-50717 BID for a total of 12 weeks.
Change From Baseline in the TTS of the YGTSS at Week 12	-9.1 units on a scale Standard Error 1.28	-8.4 units on a scale Standard Error 1.25

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline YGTSS assessment.

The TS-CGI scale is a 7-point Likert scale that allows the clinician to use all available information to assess the impact of tics on the participant's quality of life. The TS-CGI is rated as follows: 1 (normal or no tics at all), 2 (borderline), 3 (mild), 4 (moderate), 5 (marked), 6 (severe), and 7 (extreme, incapacitating tics). Lower scores indicate better quality of life. LS mean and SE was calculated using MMRM with treatment group, week (5 levels: weeks 2, 4, 6, 9, and 12), and the treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6 to 11 years, 12 to 16 years) as covariates.

Outcome measures

Outcome measures
Measure	TEV-50717 n=58 Participants Participants received TEV-50717 as oral tablets at a starting dose of 6 mg/day, with the dose titrated weekly for 7 weeks to an optimal level. The target maximum daily dose was determined by body weight and CYP2D6 impairment status at baseline. Maximum total daily dose for participants ≥40 kg was 48 mg/day (24 mg BID), 30 to \<40 kg was 42 mg/day (21 mg BID), and 20 to \<30 kg was 30 mg/day (15 mg BID). For those considered CYP2D6 impaired, maximum daily dose for participants ≥40 kg was 36 mg/day, 30 to \<40 kg was 24 mg/day, and 20 to \<30 kg was 18 mg/day. Total daily doses of ≥12 mg/day was divided into a BID administration. Depending on the dose, TEV-50717 tablets and/or placebo tablets were taken to maintain the blind. Participants then received TEV-50717 at the optimal level as maintenance therapy daily for 5 weeks.	Placebo n=59 Participants Participants received placebo matched to TEV-50717 BID for a total of 12 weeks.
Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score at Week 12	-0.7 units on a scale Standard Error 0.13	-0.7 units on a scale Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline YGTSS assessment.

The TS-PGII is a single-item questionnaire that asks the participant to assess the degree of impact due to current tics (How much do your current tics disrupt things in your life?). The TS-PGII uses a 5-point scale, ranging from not at all (1) to very much (5), to assess overall response to therapy.

Outcome measures

Outcome measures
Measure	TEV-50717 n=58 Participants Participants received TEV-50717 as oral tablets at a starting dose of 6 mg/day, with the dose titrated weekly for 7 weeks to an optimal level. The target maximum daily dose was determined by body weight and CYP2D6 impairment status at baseline. Maximum total daily dose for participants ≥40 kg was 48 mg/day (24 mg BID), 30 to \<40 kg was 42 mg/day (21 mg BID), and 20 to \<30 kg was 30 mg/day (15 mg BID). For those considered CYP2D6 impaired, maximum daily dose for participants ≥40 kg was 36 mg/day, 30 to \<40 kg was 24 mg/day, and 20 to \<30 kg was 18 mg/day. Total daily doses of ≥12 mg/day was divided into a BID administration. Depending on the dose, TEV-50717 tablets and/or placebo tablets were taken to maintain the blind. Participants then received TEV-50717 at the optimal level as maintenance therapy daily for 5 weeks.	Placebo n=59 Participants Participants received placebo matched to TEV-50717 BID for a total of 12 weeks.
Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score at Week 12	-0.7 units on a scale Standard Error 0.18	-0.4 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline YGTSS assessment.

C\&A-GTS-QOL is a 27-item questionnaire that asks participant to assess the extent to which their quality of life is impacted by their symptoms. C\&A-GTS-QOL contains 6 subscales (cognitive, coprophenomena, psychological, physical, obsessive-compulsive, and ADL) and uses a 5-point Likert scale ranging from no problem to extreme problem. Following 3 questions from 27-item questionnaire were assessed in ADL C\&A-GTS-QOL subscale: Question 2 (Had difficulty with school or sport activities?), 24 (Felt you needed more help or support from other people?), and 26 (Had difficulty going out with other people?). Total score of ADL subscale ranged from 0 (no problem) to 12 (extreme problem). Lower score indicated better quality of life. LS mean and SE was calculated using MMRM with treatment group, week (5 levels: weeks 2, 4, 6, 9, and 12), and treatment group by week interaction as fixed effects; and baseline TTS, region, and age group at baseline (2 levels: 6-11 years, 12-16 years) as covariates.

Outcome measures

Outcome measures
Measure	TEV-50717 n=58 Participants Participants received TEV-50717 as oral tablets at a starting dose of 6 mg/day, with the dose titrated weekly for 7 weeks to an optimal level. The target maximum daily dose was determined by body weight and CYP2D6 impairment status at baseline. Maximum total daily dose for participants ≥40 kg was 48 mg/day (24 mg BID), 30 to \<40 kg was 42 mg/day (21 mg BID), and 20 to \<30 kg was 30 mg/day (15 mg BID). For those considered CYP2D6 impaired, maximum daily dose for participants ≥40 kg was 36 mg/day, 30 to \<40 kg was 24 mg/day, and 20 to \<30 kg was 18 mg/day. Total daily doses of ≥12 mg/day was divided into a BID administration. Depending on the dose, TEV-50717 tablets and/or placebo tablets were taken to maintain the blind. Participants then received TEV-50717 at the optimal level as maintenance therapy daily for 5 weeks.	Placebo n=59 Participants Participants received placebo matched to TEV-50717 BID for a total of 12 weeks.
Change From Baseline in the Child and Adolescent Gilles de la Tourette Syndrome - Quality of Life (C&A-GTS-QOL) Activities of Daily Living (ADL) Subscale Score at Week 12	-9.9 units on a scale Standard Error 2.37	-8.8 units on a scale Standard Error 2.27

SECONDARY outcome

Timeframe: Baseline (Day 1) to follow-up (Week 14)

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Outcome measures

Outcome measures
Measure	TEV-50717 n=58 Participants Participants received TEV-50717 as oral tablets at a starting dose of 6 mg/day, with the dose titrated weekly for 7 weeks to an optimal level. The target maximum daily dose was determined by body weight and CYP2D6 impairment status at baseline. Maximum total daily dose for participants ≥40 kg was 48 mg/day (24 mg BID), 30 to \<40 kg was 42 mg/day (21 mg BID), and 20 to \<30 kg was 30 mg/day (15 mg BID). For those considered CYP2D6 impaired, maximum daily dose for participants ≥40 kg was 36 mg/day, 30 to \<40 kg was 24 mg/day, and 20 to \<30 kg was 18 mg/day. Total daily doses of ≥12 mg/day was divided into a BID administration. Depending on the dose, TEV-50717 tablets and/or placebo tablets were taken to maintain the blind. Participants then received TEV-50717 at the optimal level as maintenance therapy daily for 5 weeks.	Placebo n=59 Participants Participants received placebo matched to TEV-50717 BID for a total of 12 weeks.
Percentage of Participants With Adverse Events Any AEs	65.5 percentage of participants	55.9 percentage of participants
Percentage of Participants With Adverse Events Treatment-related AEs	50.0 percentage of participants	20.3 percentage of participants
Percentage of Participants With Adverse Events Serious AEs	0 percentage of participants	0 percentage of participants
Percentage of Participants With Adverse Events AEs leading to discontinuation	1.7 percentage of participants	1.7 percentage of participants

Adverse Events

TEV-50717

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products R&D, Inc.

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER

Measure	TEV-50717 n=58 participants at risk Participants received TEV-50717 as oral tablets at a starting dose of 6 mg/day, with the dose titrated weekly for 7 weeks to an optimal level. The target maximum daily dose was determined by body weight and CYP2D6 impairment status at baseline. Maximum total daily dose for participants ≥40 kg was 48 mg/day (24 mg BID), 30 to \<40 kg was 42 mg/day (21 mg BID), and 20 to \<30 kg was 30 mg/day (15 mg BID). For those considered CYP2D6 impaired, maximum daily dose for participants ≥40 kg was 36 mg/day, 30 to \<40 kg was 24 mg/day, and 20 to \<30 kg was 18 mg/day. Total daily doses of ≥12 mg/day was divided into a BID administration. Depending on the dose, TEV-50717 tablets and/or placebo tablets were taken to maintain the blind. Participants then received TEV-50717 at the optimal level as maintenance therapy daily for 5 weeks.	Placebo n=59 participants at risk Participants received placebo matched to TEV-50717 BID for a total of 12 weeks.
Gastrointestinal disorders Abdominal pain	1.7% 1/58 • Number of events 2 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	5.1% 3/59 • Number of events 3 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	6.9% 4/58 • Number of events 4 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/59 • Number of events 1 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	6.9% 4/58 • Number of events 5 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	8.5% 5/59 • Number of events 11 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	5.2% 3/58 • Number of events 3 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	5.1% 3/59 • Number of events 3 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Fatigue	12.1% 7/58 • Number of events 8 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	5.1% 3/59 • Number of events 4 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
General disorders Pyrexia	5.2% 3/58 • Number of events 3 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	3.4% 2/59 • Number of events 2 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	0.00% 0/58 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	11.9% 7/59 • Number of events 9 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
Investigations Weight increased	12.1% 7/58 • Number of events 7 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/59 • Number of events 1 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Increased appetite	5.2% 3/58 • Number of events 3 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/59 • Number of events 1 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Headache	10.3% 6/58 • Number of events 6 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	10.2% 6/59 • Number of events 12 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
Nervous system disorders Somnolence	8.6% 5/58 • Number of events 8 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	1.7% 1/59 • Number of events 1 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
Psychiatric disorders Anxiety	3.4% 2/58 • Number of events 2 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	5.1% 3/59 • Number of events 3 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
Psychiatric disorders Depressed mood	3.4% 2/58 • Number of events 2 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	5.1% 3/59 • Number of events 3 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
Psychiatric disorders Enuresis	6.9% 4/58 • Number of events 6 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	0.00% 0/59 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.
Psychiatric disorders Suicidal ideation	1.7% 1/58 • Number of events 1 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.	5.1% 3/59 • Number of events 3 • Baseline (Day 1) to follow-up (Week 14) Safety analysis set included all participants who received at least 1 dose of study drug.