Trial Outcomes & Findings for A Study of Treatment With Pridopidine (ACR16) in Participants With Huntington's Disease (NCT NCT00665223)

Last Updated: 2023-08-29

Results Overview

The mMS is a subscale of the UHDRS total motor score and comprises 13 responses from the 10 items, 4-10 and 13-15, from the UHDRS motor assessment. The items for mMS include dysarthria, tongue protrusion, finger taps (right and left), pronate/supinate hands (right and left), luria - first-hand-palm sequencing, arms rigidity (right and left), body bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these items are rated on a scale of 0 (normal) to 4 (marked impairment). Total score ranges from 0 to 52, with higher scores indicating more severe motor impairment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

437 participants

Primary outcome timeframe

Baseline, Week 26

Results posted on

2023-08-29

Participant Flow

Participants that completed the randomized phase to week 26 on-treatment were given the option to continue treatment in the open-label phase.

Participant milestones

Participant milestones
Measure	Placebo/ACR16 90 mg Randomized phase: Participants received a placebo capsule matched to ACR16 once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), placebo capsule was taken twice daily as 2 separate doses. Open-label phase: Participants received ACR16 45 milligrams (mg) capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 45 mg/90 mg Randomized phase: Participants received ACR16 45 mg capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule were taken as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 90 mg/90 mg Randomized Phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg). Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).
Randomized Phase (26 Weeks) STARTED	144	148	145
Randomized Phase (26 Weeks) Received at Least 1 Dose of Study Drug	144	148	145
Randomized Phase (26 Weeks) COMPLETED	126	136	124
Randomized Phase (26 Weeks) NOT COMPLETED	18	12	21
Open-Label Period (26 Weeks) STARTED	113	125	115
Open-Label Period (26 Weeks) COMPLETED	97	108	100
Open-Label Period (26 Weeks) NOT COMPLETED	16	17	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/ACR16 90 mg Randomized phase: Participants received a placebo capsule matched to ACR16 once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), placebo capsule was taken twice daily as 2 separate doses. Open-label phase: Participants received ACR16 45 milligrams (mg) capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 45 mg/90 mg Randomized phase: Participants received ACR16 45 mg capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule were taken as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 90 mg/90 mg Randomized Phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg). Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).
Randomized Phase (26 Weeks) Adverse Event	13	9	15
Randomized Phase (26 Weeks) Death	0	0	1
Randomized Phase (26 Weeks) Withdrawal by Subject	5	2	3
Randomized Phase (26 Weeks) Protocol Violation	0	1	1
Randomized Phase (26 Weeks) Other than specified	0	0	1
Open-Label Period (26 Weeks) Adverse Event	8	11	7
Open-Label Period (26 Weeks) Death	0	1	0
Open-Label Period (26 Weeks) Lost to Follow-up	3	1	2
Open-Label Period (26 Weeks) Withdrawal by Subject	5	3	4
Open-Label Period (26 Weeks) Protocol Violation	0	1	0
Open-Label Period (26 Weeks) Other than specified	0	0	2

Baseline Characteristics

A Study of Treatment With Pridopidine (ACR16) in Participants With Huntington's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/ACR16 90 mg n=144 Participants Randomized-phase: Participants received a placebo capsule matched to ACR16 once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), placebo capsule was taken twice daily as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 45 mg/90 mg n=148 Participants Randomized phase: Participants received ACR16 45 mg capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule were taken as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 90 mg/90 mg n=145 Participants Randomized Phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg). Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	Total n=437 Participants Total of all reporting groups
Age, Continuous	49.1 years STANDARD_DEVIATION 9.6 • n=5 Participants	51.0 years STANDARD_DEVIATION 10.7 • n=7 Participants	51.8 years STANDARD_DEVIATION 11.1 • n=5 Participants	50.6 years STANDARD_DEVIATION 10.5 • n=4 Participants
Sex: Female, Male Female	76 Participants n=5 Participants	82 Participants n=7 Participants	64 Participants n=5 Participants	222 Participants n=4 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	66 Participants n=7 Participants	81 Participants n=5 Participants	215 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Race · Caucasian	144 Participants n=5 Participants	145 Participants n=7 Participants	145 Participants n=5 Participants	434 Participants n=4 Participants
Unified Huntington's Disease Rating Scale (UHDRS) Modified Motor Score (mMS)	19.43 units on a scale STANDARD_DEVIATION 8.28 • n=5 Participants	18.38 units on a scale STANDARD_DEVIATION 6.76 • n=7 Participants	18.57 units on a scale STANDARD_DEVIATION 6.90 • n=5 Participants	18.79 units on a scale STANDARD_DEVIATION 7.34 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug and had undergone at least 1 clinical assessment post randomization. Here, 'Overall number of participants analyzed signifies participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo/ACR16 90 mg n=138 Participants Randomized phase: Participants received a placebo capsule matched to ACR16 once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), placebo capsule was taken twice daily as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 45 mg/90 mg n=146 Participants Randomized phase: Participants received ACR16 45 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule were taken as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 90 mg/90 mg n=139 Participants Randomized phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg). Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).
Change From Baseline in Modified Motor Score (mMS) (Sum of Score of Items 4-10 and 13-15 of the Unified Huntington's Disease Rating Scale [UHDRS] Motor Assessments) at Week 26	0.27 units on a scale Standard Deviation 4.43	-0.23 units on a scale Standard Deviation 4.12	-0.94 units on a scale Standard Deviation 3.87

SECONDARY outcome

Timeframe: Week 26

Population: FAS included all randomized participants who received at least 1 dose of study drug and had undergone at least 1 clinical assessment post randomization. Here, 'Overall number of participants analyzed signifies participants evaluable for this outcome measure.

The UHDRS Functional Assessment considers 25 items associated with functional problems. The participant scores 1 point for every item to which they respond positively (zero points for negative responses). Total score ranges from 0 (worst) to 25 (best). Higher scores indicate better functional ability.

Outcome measures

Outcome measures
Measure	Placebo/ACR16 90 mg n=139 Participants Randomized phase: Participants received a placebo capsule matched to ACR16 once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), placebo capsule was taken twice daily as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 45 mg/90 mg n=146 Participants Randomized phase: Participants received ACR16 45 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule were taken as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 90 mg/90 mg n=139 Participants Randomized phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg). Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).
The UHDRS Functional Assessment at Week 26	16.81 Units on a Scale Standard Deviation 6.20	17.50 Units on a Scale Standard Deviation 5.73	17.48 Units on a Scale Standard Deviation 5.43

SECONDARY outcome

Timeframe: Week 26

Global improvement is rated by the investigator on a 7-point scale as: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; and 7 = Very much worse.

Outcome measures

Outcome measures
Measure	Placebo/ACR16 90 mg n=139 Participants Randomized phase: Participants received a placebo capsule matched to ACR16 once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), placebo capsule was taken twice daily as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 45 mg/90 mg n=146 Participants Randomized phase: Participants received ACR16 45 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule were taken as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 90 mg/90 mg n=140 Participants Randomized phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg). Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).
Number of Participants With Clinical Global Impression - Improvement (CGI-I) Score Much worse	7 Participants	9 Participants	2 Participants
Number of Participants With Clinical Global Impression - Improvement (CGI-I) Score Very much improved	1 Participants	1 Participants	1 Participants
Number of Participants With Clinical Global Impression - Improvement (CGI-I) Score Much improved	8 Participants	8 Participants	7 Participants
Number of Participants With Clinical Global Impression - Improvement (CGI-I) Score Minimally improved	30 Participants	32 Participants	33 Participants
Number of Participants With Clinical Global Impression - Improvement (CGI-I) Score No change	55 Participants	59 Participants	50 Participants
Number of Participants With Clinical Global Impression - Improvement (CGI-I) Score Minimally worse	38 Participants	37 Participants	46 Participants
Number of Participants With Clinical Global Impression - Improvement (CGI-I) Score Very much worse	0 Participants	0 Participants	0 Participants
Number of Participants With Clinical Global Impression - Improvement (CGI-I) Score Missing	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline, Week 26

The Stroop test measures the ability to concentrate and ward off distractions. The test consists of three items: (i) colour naming; (ii) word reading; (iii) interference. The word reading test requires participants to read colour words written in black and each response is scored as the number of correct answers made in 45 seconds. Higher scores indicate less severe disease, and an increase in score represents an improvement.

Outcome measures

Outcome measures
Measure	Placebo/ACR16 90 mg n=135 Participants Randomized phase: Participants received a placebo capsule matched to ACR16 once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), placebo capsule was taken twice daily as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 45 mg/90 mg n=140 Participants Randomized phase: Participants received ACR16 45 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule were taken as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 90 mg/90 mg n=136 Participants Randomized phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg). Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).
Change From Baseline in Stroop Word Reading Test at Week 26	-1.3 correct responses Standard Deviation 11.9	-1.1 correct responses Standard Deviation 10.3	-0.8 correct responses Standard Deviation 11.7

SECONDARY outcome

Timeframe: Baseline, Week 26

The total behavioral assessment score is the sum of the 11 products (depressed mood, apathy, low self-esteem/guilt, compulsive behavior, anxiety, irritable behavior, perseverative/obsessive thinking, disruptive/aggressive behavior, suicidal thoughts, delusions, and hallucinations) of frequency and severity symptom scores and excluded the 3 yes/no questions relating to confusion, dementia, and depression. Frequency is rated on a scale of 0 (never or almost never) to 4 (very frequently, most of the time). Severity is rated on a scale of 0 (no evidence) to 4 (severe). Total behavior score ranges from 0 (no impairment) to 88 (severe impairment), with higher scores indicating greater behavioral impairments.

Outcome measures

Outcome measures
Measure	Placebo/ACR16 90 mg n=139 Participants Randomized phase: Participants received a placebo capsule matched to ACR16 once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), placebo capsule was taken twice daily as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 45 mg/90 mg n=146 Participants Randomized phase: Participants received ACR16 45 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule were taken as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 90 mg/90 mg n=139 Participants Randomized phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg). Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).
Change From Baseline in Total UHDRS Behavioral Assessment Score at Week 26	0.12 units on a scale Standard Deviation 13.51	-0.41 units on a scale Standard Deviation 16.78	-2.22 units on a scale Standard Deviation 10.84

SECONDARY outcome

Timeframe: Baseline, Week 26

HADS is a self-administered instrument reliable for detecting states of depression and anxiety. It includes 2 subscales: Hospital Anxiety and Depression Scale - anxiety (HADS-A) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); Hospital Anxiety and Depression Scale - depression (HADS-D) assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale is comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score ranges from 0 to 21 for each subscale where higher scores indicate greater severity of anxiety and depression symptoms. The total HADS score was a composite score summed of all 14 items for a total range of 0 to 42. Lower change from baseline scores indicate improvement.

Outcome measures

Outcome measures
Measure	Placebo/ACR16 90 mg n=133 Participants Randomized phase: Participants received a placebo capsule matched to ACR16 once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), placebo capsule was taken twice daily as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 45 mg/90 mg n=142 Participants Randomized phase: Participants received ACR16 45 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule were taken as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 90 mg/90 mg n=138 Participants Randomized phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg). Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).
Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 26	-0.10 units on a scale Standard Deviation 6.04	-0.73 units on a scale Standard Deviation 6.78	0.13 units on a scale Standard Deviation 6.00

SECONDARY outcome

Timeframe: Baseline up to Week 30

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

An adverse event (AE) was defined as any change from the participant's baseline (pre-treatment) condition, other than improvement, that did not necessarily have causal relationship with the study drug. TEAEs were defined as AEs that began after ACR16/placebo administration through week 26 or up to week 30 for participants not continuing in the open-label period. AEs included both serious adverse events (SAEs) and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

Outcome measures

Outcome measures
Measure	Placebo/ACR16 90 mg n=144 Participants Randomized phase: Participants received a placebo capsule matched to ACR16 once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), placebo capsule was taken twice daily as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 45 mg/90 mg n=148 Participants Randomized phase: Participants received ACR16 45 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule were taken as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 90 mg/90 mg n=145 Participants Randomized phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg). Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).
Randomized Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	92 Participants	91 Participants	99 Participants

SECONDARY outcome

Timeframe: Week 26 up to Week 56

Population: Open-label analysis set (OLAS) included the subset of participants who completed the randomized phase on study treatment and who consented to enter the open-label follow-up phase.

An AE was defined as any change from the participant's baseline (pre-treatment) condition, other than improvement, that did not necessarily have causal relationship with the study drug. TEAEs were defined as adverse events that began after ACR16/placebo administration through Week 56. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

Outcome measures

Outcome measures
Measure	Placebo/ACR16 90 mg n=113 Participants Randomized phase: Participants received a placebo capsule matched to ACR16 once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), placebo capsule was taken twice daily as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 45 mg/90 mg n=125 Participants Randomized phase: Participants received ACR16 45 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule were taken as 2 separate doses. Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).	ACR16 90 mg/90 mg n=115 Participants Randomized phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg). Open-label phase: Participants received ACR16 45 mg capsule once daily for the first 4 weeks (Weeks 26 to 30). After 4 weeks (Weeks 31 to 52), ACR16 45 mg capsule was taken twice daily as 2 separate doses (total dose: 90 mg).
Open-label Phase: Number of Participants With TEAEs	90 Participants	101 Participants	95 Participants

Adverse Events

Randomized Phase: Placebo

Serious events: 11 serious events

Other events: 54 other events

Deaths: 0 deaths

Randomized Phase: ACR16 45 mg

Serious events: 10 serious events

Other events: 49 other events

Deaths: 0 deaths

Randomized Phase: ACR16 90 mg

Serious events: 9 serious events

Other events: 56 other events

Deaths: 0 deaths

Open Label Phase: Placebo

Serious events: 6 serious events

Other events: 38 other events

Deaths: 0 deaths

Open Label Phase: ACR 16

Serious events: 15 serious events

Other events: 88 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Randomized Phase: Placebo n=144 participants at risk Participants received placebo matched to ACR16 in the randomized phase.	Randomized Phase: ACR16 45 mg n=148 participants at risk Participants received ACR16 45 mg in the randomized phase.	Randomized Phase: ACR16 90 mg n=145 participants at risk Participants received ACR16 90 mg in the randomized phase.	Open Label Phase: Placebo n=113 participants at risk Participants who received placebo during the randomized phase and received ACR16 90 mg in the open label phase.	Open Label Phase: ACR 16 n=240 participants at risk Participants who received ACR16 45 mg or 90 mg in the randomized phase and received ACR16 90 mg in the open label phase.
Gastrointestinal disorders ANAL SPASM	0.69% 1/144 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Gastrointestinal disorders CONSTIPATION	0.69% 1/144 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Gastrointestinal disorders DYSPHAGIA	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.69% 1/145 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Gastrointestinal disorders ILEUS	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.69% 1/145 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Gastrointestinal disorders NAUSEA	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
General disorders ASTHENIA	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
General disorders DISEASE PROGRESSION	0.69% 1/144 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.88% 1/113 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Infections and infestations ABSCESS	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Infections and infestations ERYSIPELAS	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.69% 1/145 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Infections and infestations PNEUMONIA	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.69% 1/145 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Infections and infestations URINARY TRACT INFECTION	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Infections and infestations UROSEPSIS	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Injury, poisoning and procedural complications ALCOHOL POISONING	0.69% 1/144 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Injury, poisoning and procedural complications FALL	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Injury, poisoning and procedural complications RESPIRATORY FUME INHALATION DISORDER	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.69% 1/145 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Injury, poisoning and procedural complications SPINAL COMPRESSION FRACTURE	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.69% 1/145 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Investigations ELECTROCARDIOGRAM QT PROLONGED	0.69% 1/144 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Investigations WEIGHT DECREASED	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Metabolism and nutrition disorders HYPOGLYCAEMIA	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.69% 1/145 • Number of events 2 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Metabolism and nutrition disorders MALNUTRITION	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Musculoskeletal and connective tissue disorders NECK PAIN	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	0.69% 1/144 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) OVARIAN EPITHELIAL CANCER	0.69% 1/144 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Nervous system disorders DIZZINESS	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Nervous system disorders SUBARACHNOID HAEMORRHAGE	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.69% 1/145 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Nervous system disorders SYNCOPE	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Psychiatric disorders AGGRESSION	0.69% 1/144 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Psychiatric disorders AGITATION	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.69% 1/145 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.88% 1/113 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.83% 2/240 • Number of events 2 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Psychiatric disorders COMPLETED SUICIDE	0.69% 1/144 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Psychiatric disorders DEPRESSION	0.69% 1/144 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Psychiatric disorders SUICIDAL IDEATION	0.69% 1/144 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Psychiatric disorders SUICIDE ATTEMPT	0.69% 1/144 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	1.4% 2/145 • Number of events 2 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Renal and urinary disorders RENAL FAILURE ACUTE	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Renal and urinary disorders URINARY TRACT OBSTRUCTION	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Reproductive system and breast disorders MENORRHAGIA	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Respiratory, thoracic and mediastinal disorders CHOKING	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.69% 1/145 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Respiratory, thoracic and mediastinal disorders PNEUMONIA ASPIRATION	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.69% 1/145 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Skin and subcutaneous tissue disorders NEURODERMATITIS	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.68% 1/148 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Congenital, familial and genetic disorders HUNTINGTON'S CHOREA	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
General disorders CHEST PAIN	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Hepatobiliary disorders CHOLANGITIS	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Infections and infestations GASTROENTERITIS	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.88% 1/113 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Infections and infestations HELICOBACTER GASTRITIS	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Injury, poisoning and procedural complications HEAD INJURY	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.88% 1/113 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Injury, poisoning and procedural complications INTENTIONAL OVERDOSE	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Injury, poisoning and procedural complications LOWER LIMB FRACTURE	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Injury, poisoning and procedural complications OVERDOSE	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Investigations GLASGOW COMA SCALE ABNORMAL	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Investigations LIVER FUNCTION TEST ABNORMAL	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Musculoskeletal and connective tissue disorders DUPUYTREN'S CONTRACTURE	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BREAST CANCER	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.88% 1/113 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/240 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MALIGNANT MELANOMA	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Psychiatric disorders ABNORMAL BEHAVIOUR	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Psychiatric disorders MAJOR DEPRESSION	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.88% 1/113 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Psychiatric disorders PSYCHOTIC DISORDER	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Eye disorders ENTROPION	0.00% 0/144 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/148 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/145 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.00% 0/113 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	0.42% 1/240 • Number of events 1 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.

Other adverse events

Other adverse events
Measure	Randomized Phase: Placebo n=144 participants at risk Participants received placebo matched to ACR16 in the randomized phase.	Randomized Phase: ACR16 45 mg n=148 participants at risk Participants received ACR16 45 mg in the randomized phase.	Randomized Phase: ACR16 90 mg n=145 participants at risk Participants received ACR16 90 mg in the randomized phase.	Open Label Phase: Placebo n=113 participants at risk Participants who received placebo during the randomized phase and received ACR16 90 mg in the open label phase.	Open Label Phase: ACR 16 n=240 participants at risk Participants who received ACR16 45 mg or 90 mg in the randomized phase and received ACR16 90 mg in the open label phase.
Congenital, familial and genetic disorders HUNTINGTON'S CHOREA	6.2% 9/144 • Number of events 10 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	4.7% 7/148 • Number of events 7 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	6.9% 10/145 • Number of events 10 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	6.2% 7/113 • Number of events 7 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	12.1% 29/240 • Number of events 32 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Gastrointestinal disorders DIARRHOEA	4.9% 7/144 • Number of events 8 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	6.8% 10/148 • Number of events 11 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	6.2% 9/145 • Number of events 10 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	2.7% 3/113 • Number of events 3 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	3.3% 8/240 • Number of events 9 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Gastrointestinal disorders NAUSEA	6.2% 9/144 • Number of events 13 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	6.1% 9/148 • Number of events 11 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	3.4% 5/145 • Number of events 5 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	1.8% 2/113 • Number of events 2 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	2.1% 5/240 • Number of events 5 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
General disorders FATIGUE	6.2% 9/144 • Number of events 10 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	4.7% 7/148 • Number of events 8 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	2.8% 4/145 • Number of events 5 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	3.5% 4/113 • Number of events 4 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	2.5% 6/240 • Number of events 6 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Infections and infestations NASOPHARYNGITIS	4.2% 6/144 • Number of events 6 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	6.1% 9/148 • Number of events 11 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	6.9% 10/145 • Number of events 10 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	4.4% 5/113 • Number of events 6 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	3.8% 9/240 • Number of events 10 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Injury, poisoning and procedural complications FALL	8.3% 12/144 • Number of events 17 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	4.7% 7/148 • Number of events 10 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	10.3% 15/145 • Number of events 19 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	12.4% 14/113 • Number of events 14 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	10.0% 24/240 • Number of events 30 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Nervous system disorders DIZZINESS	4.2% 6/144 • Number of events 6 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	6.8% 10/148 • Number of events 10 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	5.5% 8/145 • Number of events 18 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	3.5% 4/113 • Number of events 4 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	2.5% 6/240 • Number of events 7 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Nervous system disorders HEADACHE	2.8% 4/144 • Number of events 5 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	2.7% 4/148 • Number of events 4 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	5.5% 8/145 • Number of events 8 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	3.5% 4/113 • Number of events 4 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	1.7% 4/240 • Number of events 4 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Psychiatric disorders DEPRESSION	5.6% 8/144 • Number of events 8 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	4.1% 6/148 • Number of events 6 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	4.1% 6/145 • Number of events 6 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	3.5% 4/113 • Number of events 4 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	4.6% 11/240 • Number of events 11 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
Psychiatric disorders INSOMNIA	3.5% 5/144 • Number of events 5 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	3.4% 5/148 • Number of events 5 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	6.2% 9/145 • Number of events 11 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	2.7% 3/113 • Number of events 4 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	3.3% 8/240 • Number of events 8 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.
General disorders IRRITABILITY	4.2% 6/144 • Number of events 6 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	2.0% 3/148 • Number of events 3 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	4.1% 6/145 • Number of events 6 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	5.3% 6/113 • Number of events 7 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.	3.8% 9/240 • Number of events 9 • Baseline up to Week 56 Safety set included all randomized participants who received at least 1 dose of study drug. The Open-label analysis set included participants who completed the randomized phase (RP) and entered the open-label phase (OLP). AEs were analyzed in the OLP for participants who received ACR16 in the RP and then received ACR16 90 mg in the OLP as one group combined per planned analysis. Participants who received placebo in the RP and received ACR16 90 mg in OLP were analyzed as a separate OL group.

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 30 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.
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