Huntington Disease
Conditions
Keywords
Huntington Disease
Brief summary
The purpose of this study is to determine if ACR16 is effective and safe in the symptomatic treatment of Huntington's Disease.
Interventions
DRUGACR16
ACR16 will be administered per dose and schedule specified in the arm description.
OTHERPlacebo
Placebo matching to ACR16 will be administered per schedule specified in the arm description.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to provide written Informed Consent prior to any study related procedure, including consent to genotyping of the CYP2D6 gene. * Clinical features of HD, and a positive family history and/or the presence of ≥ 36 CAG repeats in the Huntington gene. * Male or female age ≥ 30 years. * Willing and able to take oral medication and to comply with the study specific procedures. * Ambulatory, being able to travel to the assessment center, and judged by the Investigator as likely to be able to continue to travel for the duration of the study. * Availability of a caregiver or family member to accompany the participant to two visits. * A sum of ≥ 10 points on the mMS at the screening visit. * For participants taking allowed antidepressants or other psychotropic medication , the dosing of medication must have been kept constant for at least 6 weeks before baseline visit.
Exclusion criteria
* Treatment with any antipsychotic medication (neuroleptics) within 8 weeks of baseline visit, or at any time point during the study period. * Use of tetrabenazine within 12 weeks of baseline visit, or at any time during the study period. * Treatment with any investigational product within 4 weeks of baseline visit. * Use of tricyclic antidepressants or class I antiarrhythmics within 6 weeks of baseline visit, or at any time during the study period. * Use of concomitant medication that may lower the seizure threshold within 6 weeks of baseline visit, or at any time during the study period . * Use of metoclopramide within 12 weeks of baseline visit, or at any time during the study period. * Participants currently receiving deep brain stimulation (DBS). * Participants with a history of surgical procedures aiming to improve the symptoms of Huntington disease, such as neural transplantations, lesions of the central nervous system, infusions of neurotrophic agents or previous attempts of deep brain stimulation. * Participants previously randomized into this study. * A prolonged QTc interval at Screening Visit (defined as a QTc interval of \> 450 milliseconds \[msec\] for males or \> 470 msec for females), or other clinically significant heart conditions as judged by the investigator. * Creatinine clearance \<40 milliliters (mL)/minute (min) as measured at the screening visit. * Any clinically significant, abnormal, baseline laboratory result which in the opinion of the Investigator, affects the participant' suitability for the study or puts the participant at risk if he/she enters the study. * Clinically significant hepatic or renal impairment. * Participants with a known history of epilepsy or a history of febrile seizure(s) or seizure(s) of unknown cause. * Severe intercurrent illness, which, in the opinion of the Investigator, may put the participant at risk when participating in the trial or may influence the results of the trial or affect the subjects' ability to take part in the trial. * Alcohol and/or drug abuse as defined by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM IV-TR) criteria for Substance Abuse - this includes the illicit use of cannabis within the last 12 months prior to Screening Visit * Participants with suicidal ideation as defined as a positive score on criteria for major depressive episode, item A9 on the DSM -IV-TR criteria for a Major Depressive Episode * Females who are pregnant or lactating or who intend to become pregnant during the study period. * Females who are of child bearing potential and not taking adequate contraceptive precautions are excluded from the trial. (Females of childbearing potential taking acceptable contraceptive precautions can be included) * Known allergy to any ingredients of the trial medication or placebo * Any previous participation in a clinical study with ACR16.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Modified Motor Score (mMS) (Sum of Score of Items 4-10 and 13-15 of the UHDRS Motor Assessments) at Week 12 | Baseline, Week 12 | 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 included 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 were rated on a scale of 0 (normal) to 4 (marked impairment). Total score ranged from 0 to 52, with higher scores indicating more severe motor impairment. The last observation carried forward (LOCF) method was used to generate an mMS score for each participant for Week 12 assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Week 12 | The CGI-C was 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. |
| Change From Baseline in Stroop Word Reading Test | Baseline, Week 12 | 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. |
| Change From Baseline in Total Motor Score (TMS) | Basline, Week 12 | The UHDRS Motor Assessment comprises 31 responses from the 15 items, where each response is rated on a 5-point scale from 0 (normal) to 4 (maximally abnormal). The Total Motor Score (TMS) is the sum of all the 31 responses with higher scores indicating more severe motor impairment than lower scores. |
| Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score | Baseline, Week 12 | 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 0-42. Lower change from baseline scores indicate improvement. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Baseline up to Week 14 | 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 adverse events that began after ACR16/placebo administration. 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'. |
| Change From Baseline in Total UHDRS Behavioral Assessment Score | Baseline, Week 12 | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a placebo capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), placebo capsule was taken twice daily (BID) as 2 separate doses. | 58 |
| ACR16 10 mg BID Participants received ACR16 10 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 10 mg capsule was taken twice daily (BID) as 2 separate doses (total dose: 20 mg). | 55 |
| ACR16 22.5 mg BID Participants received ACR16 22.5 mg capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 22.5 mg capsule was taken twice daily (BID) as 2 separate doses (total dose: 45 mg). | 55 |
| ACR16 45 mg BID Participants received ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 45 mg capsule was taken twice daily (BID) as 2 separate doses (total dose: 90 mg). | 58 |
| Total | 226 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 | 0 |
| Overall Study | Did not tolerate study drug | 0 | 0 | 0 | 1 |
| Overall Study | Investigator decision | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Other than specified | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | ACR16 10 mg BID | ACR16 22.5 mg BID | ACR16 45 mg BID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 49.9 years STANDARD_DEVIATION 10.6 | 54.0 years STANDARD_DEVIATION 10.8 | 50.0 years STANDARD_DEVIATION 10.5 | 50.3 years STANDARD_DEVIATION 9.7 | 51.0 years STANDARD_DEVIATION 10.5 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized More than 1 Race | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 56 Participants | 52 Participants | 52 Participants | 54 Participants | 214 Participants |
| Sex: Female, Male Female | 33 Participants | 32 Participants | 27 Participants | 28 Participants | 120 Participants |
| Sex: Female, Male Male | 25 Participants | 23 Participants | 28 Participants | 30 Participants | 106 Participants |
| Unified Huntington's Disease Rating Scale (UHDRS) Modified Motor Score (mMS) | 17.19 units on a scale STANDARD_DEVIATION 6.49 | 16.96 units on a scale STANDARD_DEVIATION 6.18 | 14.18 units on a scale STANDARD_DEVIATION 5.03 | 16.22 units on a scale STANDARD_DEVIATION 6.39 | 16.15 units on a scale STANDARD_DEVIATION 6.13 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 58 | 18 / 56 | 16 / 55 | 30 / 58 |
| serious Total, serious adverse events | 1 / 58 | 0 / 56 | 2 / 55 | 3 / 58 |
Outcome results
Primary
Change From Baseline in Modified Motor Score (mMS) (Sum of Score of Items 4-10 and 13-15 of the UHDRS Motor Assessments) at Week 12
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 included 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 were rated on a scale of 0 (normal) to 4 (marked impairment). Total score ranged from 0 to 52, with higher scores indicating more severe motor impairment. The last observation carried forward (LOCF) method was used to generate an mMS score for each participant for Week 12 assessment.
Time frame: Baseline, Week 12
Population: The Full Analysis Set (FAS) was defined as 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Modified Motor Score (mMS) (Sum of Score of Items 4-10 and 13-15 of the UHDRS Motor Assessments) at Week 12 | -1.40 units on a scale | Standard Deviation 3.72 |
| ACR16 10 mg BID | Change From Baseline in Modified Motor Score (mMS) (Sum of Score of Items 4-10 and 13-15 of the UHDRS Motor Assessments) at Week 12 | -1.30 units on a scale | Standard Deviation 3.33 |
| ACR16 22.5 mg BID | Change From Baseline in Modified Motor Score (mMS) (Sum of Score of Items 4-10 and 13-15 of the UHDRS Motor Assessments) at Week 12 | -2.49 units on a scale | Standard Deviation 3.37 |
| ACR16 45 mg BID | Change From Baseline in Modified Motor Score (mMS) (Sum of Score of Items 4-10 and 13-15 of the UHDRS Motor Assessments) at Week 12 | -2.32 units on a scale | Standard Deviation 3.72 |
Comparison: The ANCOVA model included a term for treatment, as well as covariates for baseline mMS, and age at entry to the study.p-value: 0.07895% CI: [-2.47, 0.13]ANCOVA
Comparison: The ANCOVA model included a term for treatment, as well as covariates for baseline mMS, and age at entry to the study.p-value: 0.08495% CI: [-2.53, 0.16]ANCOVA
Comparison: The ANCOVA model included a term for treatment, as well as covariates for baseline mMS, and age at entry to the study.p-value: 0.98295% CI: [-1.35, 1.32]ANCOVA
Secondary
Change From Baseline in Stroop Word Reading Test
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.
Time frame: Baseline, Week 12
Population: The FAS was defined as 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Stroop Word Reading Test | 2.5 correct responses | Standard Deviation 13 |
| ACR16 10 mg BID | Change From Baseline in Stroop Word Reading Test | 3.7 correct responses | Standard Deviation 10.6 |
| ACR16 22.5 mg BID | Change From Baseline in Stroop Word Reading Test | -0.0 correct responses | Standard Deviation 12.7 |
| ACR16 45 mg BID | Change From Baseline in Stroop Word Reading Test | 2.8 correct responses | Standard Deviation 10.5 |
Secondary
Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score
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 0-42. Lower change from baseline scores indicate improvement.
Time frame: Baseline, Week 12
Population: The FAS was defined as 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score | -1.04 Units on a scale | Standard Deviation 3.67 |
| ACR16 10 mg BID | Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score | -1.24 Units on a scale | Standard Deviation 4.57 |
| ACR16 22.5 mg BID | Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score | -0.95 Units on a scale | Standard Deviation 4.68 |
| ACR16 45 mg BID | Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score | -2.10 Units on a scale | Standard Deviation 5.68 |
Secondary
Change From Baseline in Total Motor Score (TMS)
The UHDRS Motor Assessment comprises 31 responses from the 15 items, where each response is rated on a 5-point scale from 0 (normal) to 4 (maximally abnormal). The Total Motor Score (TMS) is the sum of all the 31 responses with higher scores indicating more severe motor impairment than lower scores.
Time frame: Basline, Week 12
Population: The FAS was defined as 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Total Motor Score (TMS) | -2.09 Units on a scale | Standard Deviation 8.31 |
| ACR16 10 mg BID | Change From Baseline in Total Motor Score (TMS) | -1.92 Units on a scale | Standard Deviation 6.07 |
| ACR16 22.5 mg BID | Change From Baseline in Total Motor Score (TMS) | -3.30 Units on a scale | Standard Deviation 6.91 |
| ACR16 45 mg BID | Change From Baseline in Total Motor Score (TMS) | -4.61 Units on a scale | Standard Deviation 7.21 |
Secondary
Change From Baseline in Total UHDRS Behavioral Assessment Score
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.
Time frame: Baseline, Week 12
Population: The FAS was defined as 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Total UHDRS Behavioral Assessment Score | -3.56 Units on a scale | Standard Deviation 8.51 |
| ACR16 10 mg BID | Change From Baseline in Total UHDRS Behavioral Assessment Score | -3.24 Units on a scale | Standard Deviation 11.24 |
| ACR16 22.5 mg BID | Change From Baseline in Total UHDRS Behavioral Assessment Score | -3.45 Units on a scale | Standard Deviation 10.1 |
| ACR16 45 mg BID | Change From Baseline in Total UHDRS Behavioral Assessment Score | -6.19 Units on a scale | Standard Deviation 10.17 |
Secondary
Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale
The CGI-C was 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.
Time frame: Week 12
Population: The FAS was defined as 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.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Very much improved | 0 Participants |
| Placebo | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | No change | 24 Participants |
| Placebo | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Minimally worse | 4 Participants |
| Placebo | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Very much worse | 0 Participants |
| Placebo | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Minimally improved | 20 Participants |
| Placebo | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Much improved | 8 Participants |
| Placebo | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Not assessed | 0 Participants |
| Placebo | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Much worse | 1 Participants |
| ACR16 10 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Not assessed | 1 Participants |
| ACR16 10 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Very much improved | 1 Participants |
| ACR16 10 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Minimally improved | 14 Participants |
| ACR16 10 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Minimally worse | 4 Participants |
| ACR16 10 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Much improved | 3 Participants |
| ACR16 10 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | No change | 31 Participants |
| ACR16 10 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Very much worse | 0 Participants |
| ACR16 10 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Much worse | 1 Participants |
| ACR16 22.5 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Minimally worse | 5 Participants |
| ACR16 22.5 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Much worse | 0 Participants |
| ACR16 22.5 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Very much worse | 0 Participants |
| ACR16 22.5 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Minimally improved | 17 Participants |
| ACR16 22.5 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | No change | 22 Participants |
| ACR16 22.5 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Much improved | 8 Participants |
| ACR16 22.5 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Not assessed | 1 Participants |
| ACR16 22.5 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Very much improved | 2 Participants |
| ACR16 45 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Very much worse | 0 Participants |
| ACR16 45 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Much improved | 4 Participants |
| ACR16 45 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Minimally improved | 21 Participants |
| ACR16 45 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | No change | 25 Participants |
| ACR16 45 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Minimally worse | 1 Participants |
| ACR16 45 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Not assessed | 2 Participants |
| ACR16 45 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Much worse | 1 Participants |
| ACR16 45 mg BID | Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale | Very much improved | 4 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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 adverse events that began after ACR16/placebo administration. 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'.
Time frame: Baseline up to Week 14
Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 33 Participants |
| ACR16 10 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 30 Participants |
| ACR16 22.5 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 25 Participants |
| ACR16 45 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 40 Participants |