Phelan-McDermid Syndrome
Conditions
Keywords
Phelan-McDermid Syndrome
Brief summary
A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy in children and adolescents with Phelan-McDermid Syndrome.
Detailed description
The primary purpose of this study is to investigate the safety, tolerability and pharmacokinetics of treatment with NNZ-2591 oral solution in children and adolescents with Phelan-McDermid Syndrome. The secondary purpose is to investigate measures of efficacy. Subjects will receive treatment with NNZ-2591 oral solution (50 mg/mL) doses for a total of 13 weeks.
Interventions
DRUGNNZ-2591
NNZ-2591 oral solution (50mg/mL) to be administered twice daily dose for 13 weeks.
Sponsors
Neuren Pharmaceuticals Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
1. Clinical diagnosis of PMS with a documented disease-causing genetic abnormality of SHANK3. 2. Males or females aged 3-12 years. 3. Body weight of 12 kg or higher at Screening. 4. Subjects with a Clinical Global Impression - Severity (CGI-S) score of 4 or greater at the Screening visit. 5. Not actively undergoing regression or loss of skills, defined as no persistent loss of previously acquired developmental skills for a period within 3 months of the Screening visit 6. Each subject must be able to swallow the study medication provided as a liquid solution. 7. Caregiver(s) must have sufficient English language skills.
Exclusion criteria
1. Body weight \< 12kg at screening 2. Clinically significant abnormalities in safety laboratory tests and vital signs at Screening. 3. Abnormal QTcF interval or prolongation at Screening. 4. Any other clinically significant finding on ECG at the Screening visit. 5. Positive for severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) and previous COVID 19 infection with last 12 months that required hospitalization 6. Unstable or changes Psychotropic treatment 2 weeks prior to screening . 7. Excluded concomitant treatments. 8. Actively undergoing regression or loss of skills. 9. Unstable seizure profile. 10. Current clinically significant renal conditions and abnormalities 11. Current clinically significant cardiovascular, renal, hepatic, gastrointestinal, respiratory, endocrine disease, or clinically significant organ impairment. 12. Current clinically significant hypo or hyperthyroidism, Type 1 or Type 2 diabetes mellitus requiring insulin (whether well controlled or uncontrolled), or uncontrolled Type 1 or Type 2 diabetes. 13. Has planned surgery during the study. 14. History of, or current, cerebrovascular disease or brain trauma. 15. History of, or current catatonia or catatonia-like symptoms. 16. History of, or current, malignancy. 17. Current major or persistent depressive disorder (including bipolar depression). 18. Significant, uncorrected visual or uncorrected hearing impairment. 19. Allergy to strawberry. 20. Positive pregnancy test 21. Subject is judged by the Investigator or Medical Monitor to be inappropriate for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | 13 weeks | To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591. |
| Pharmacokinetic - Mean AUC24 | Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13. | Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model. |
| Pharmacokinetic - t1/2 | Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13. | Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Top 3 Concerns | Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall improvement score. | Caregiver Top 3 Concerns - Total Concerns Severity: Change from baseline. The range of scores was (0-30) for total concerns, with higher scores being worse |
| MB-CDI | Change from baseline (visit 3, week 0) to visit 13/EOT (week 16). | MacArthur-Bates Communicative Development Inventory (MB-CDI) - change from baseline. Range of scores was (0-792) with higher scores being better. |
| ORCA | Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in Total Score. | Observer-Reported Communication Ability (ORCA) - Change from baseline in Total Score. Range of Scores was (25.8-83.8) with higher scores being better |
| ABC-2 | Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score. | Aberrant Behavior Checklist-2 (ABC-2) - Total score: Change from baseline. Range of scores was (0-174) with higher scores being worse |
| CSHQ | Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score. | Child Sleep Habits Questionnaire (CSHQ) - Change from baseline in Total Score. Range of scores was (33-99) with higher scores being worse. |
| CGI-I | CGI-I was assessed at Weeks 6, 13/EOT & 15. Overall improvement scores relate to Week 13/EOT visit. | Phelan-McDermid Syndrome-specific Clinical Global Impression of Improvement Scale (CGI-I) - Overall Improvement Score on a 7 point Likert scale (1-7) where lower scores are better. |
| VABS-3 | Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in composite standard score. | Vineland Adaptive Behavior Scales-3, Change from baseline in Composite Standard Score. Range of scores was (20-140) with higher scores being better. |
| QL-Disability | Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall score score. | Quality of Life Inventory-Disability (QL-Disability) Overall Score - change from baseline. Range of scores was (0-100) with higher scores being better. |
| ICND | Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall quality of life rating score. | Impact of Childhood Neurological Disability (ICND) - Change from baseline in overall quality of life rating. Range of (1- 6) for quality of life rating, with higher scores indicating greater impact. |
| PMS-DSRS | Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall severity score. | PMS Clinician Domain Specific Rating Scale - Change from baseline in overall severity score. Range of Scores Was (0-20) With Higher Scores Being Worse. |
| Behavior Problems Inventory - Short Form | Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score. | Total Frequency Score - Change from Baseline. Range of scores was (0-4) for each of 30 behaviors, total range (0-120), with lower scores being better. |
| GIHQ | Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score. | Gastrointestinal Health Questionnaire (GIHQ) - Total Frequency Score: Change from Baseline. Range of scores was (0-212) with higher scores being worse. |
| CIC | CIC was assessed at Week13/EOT | Caregiver Impression of Improvement: Measured on a 7 point Likert scale (1-7) where lower scores are better. |
| CGI-S | Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT). | Phelan-McDermid syndrome-specific Clinical Global Impression Scale-Severity (CGI-S) -Change from baseline on Overall Score. Based on a 7 point Likert scale (1-7) where a lower score is better. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited based on physician referral at 4 academic medical centers between August 2022 and June 2023. The first participant entered screening on 08 August 2022, and the last participant entered screening on 22 June 2023. Of 23 consented participants, 18 met eligibility criteria and were enrolled into the study. Enrolled participants received NNZ2591 12 mg/kg by liquid oral dose twice daily
Pre-assignment details
Following consent, participants underwent 4 weeks of screening for eligibility. If successful, participants were enrolled and commenced open-label active treatment.
Participants by arm
| Arm | Count |
|---|---|
| NNZ-2591 All enrolled participants | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Screening | Failed Screening | 5 |
| Treatment and Follow Up | Adverse Event | 3 |
Baseline characteristics
| Characteristic | NNZ-2591 |
|---|---|
| Age, Continuous | 8.6 years STANDARD_DEVIATION 2.7 |
| Autism Mental Status Exam | 7.8 score on a scale STANDARD_DEVIATION 2.05 |
| BMI (kg/m^2) | 17.4 kg/m^2 STANDARD_DEVIATION 3.48 |
| Height (cm) | 130.6 cm STANDARD_DEVIATION 15.15 |
| History of regression No | 7 Participants |
| History of regression Yes | 11 Participants |
| Mullen Scales of Early Learning Non-Verbal Developmental Quotient Score | 15.7 score on a scale STANDARD_DEVIATION 7.25 |
| PMS Genotype Interstitial Deletion | 1 Participants |
| PMS Genotype Other | 1 Participants |
| PMS Genotype Ring 22 | 0 Participants |
| PMS Genotype SHANK 3 variant/mutation | 6 Participants |
| PMS Genotype Terminal Deletion - Class I | 7 Participants |
| PMS Genotype Terminal Deletion - Class II | 3 Participants |
| PMS Genotype Unbalanced Translocation | 0 Participants |
| Presence of co-morbid psychiatric disorders Attention Deficit Disorder | 5 participants |
| Presence of co-morbid psychiatric disorders Autism Spectrum Disorder (ASD) | 14 participants |
| Presence of co-morbid psychiatric disorders BiPolar Disorders | 0 participants |
| Presence of co-morbid psychiatric disorders Obsessive Compulsive Disorder | 0 participants |
| Presence of co-morbid psychiatric disorders Other | 1 participants |
| Race/Ethnicity, Customized Ethnicity : Hispanic or Latino | 3 Participants |
| Race/Ethnicity, Customized Ethnicity : Not Hispanic or Latino | 15 Participants |
| Race/Ethnicity, Customized Race : American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Race : Asian | 0 Participants |
| Race/Ethnicity, Customized Race : Black or African American | 1 Participants |
| Race/Ethnicity, Customized Race : Multi Racial | 1 Participants |
| Race/Ethnicity, Customized Race : Native Hawaiian or other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Race : Other | 0 Participants |
| Race/Ethnicity, Customized Race : White | 16 Participants |
| Seizure Characteristics at baseline Automatic repeated movements | 0 participants |
| Seizure Characteristics at baseline Change in awareness | 2 participants |
| Seizure Characteristics at baseline Common triggers | 0 participants |
| Seizure Characteristics at baseline Falls if sitting or standing | 0 participants |
| Seizure Characteristics at baseline Head drops | 1 participants |
| Seizure Characteristics at baseline Loss of ability to communicate | 2 participants |
| Seizure Characteristics at baseline Loss of urine or bowel control | 0 participants |
| Seizure Characteristics at baseline Muscle stiffness | 1 participants |
| Seizure Characteristics at baseline Muscle twitch | 1 participants |
| Seizure Characteristics at baseline Other | 1 participants |
| Seizure Characteristics at baseline Rhythmic jerking muscle | 2 participants |
| Seizure Characteristics at baseline Warning before seizure occurred | 0 participants |
| Seizure Types Absence/Atypical Absence | 0 Participants |
| Seizure Types Atonic | 1 Participants |
| Seizure Types Clonic | 0 Participants |
| Seizure Types Complex Partial | 1 Participants |
| Seizure Types Myoclonic | 0 Participants |
| Seizure Types Not Actual Seizure/Spells | 0 Participants |
| Seizure Types Other | 1 Participants |
| Seizure Types Simple Partial | 0 Participants |
| Seizure Types Tonic | 1 Participants |
| Seizure Types Tonic-Clonic | 1 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 12 Participants |
| Stanford-Binet Intelligence Scale (NVIQ) Standard Score | 47.7 score on a scale STANDARD_DEVIATION 5.39 |
| Stanford-Binet Intelligence Scale (NVIQ) z deviation score | 40.9 score on a scale STANDARD_DEVIATION 17.2 |
| Weight (kg) | 30.4 kg STANDARD_DEVIATION 10.75 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 17 / 18 |
| serious Total, serious adverse events | 1 / 18 |
Outcome results
Primary
Pharmacokinetic - Mean AUC24
Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.
Time frame: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.
Population: PK Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Pharmacokinetic - Mean AUC24 | 411 µg.h/mL | Standard Deviation 116 |
Primary
Pharmacokinetic - t1/2
Approximately nine sparse pharmacokinetic (PK) samples were collected from each participant under steady-state conditions. These samples were taken at pre-dose, 1-3 hours post-dose, and/or 4-7 hours post-dose during Weeks 2, 6, and 13. The individual pharmacokinetic parameters for NNZ-2591, including half-life (t1/2) and area under the curve over 24 hours (AUC24), were derived using subject-level concentration-time profiles from the study population model.
Time frame: Pre-dose, 1-3 h post-dose and/or 4-7 h post-dose at Weeks 2, 6 and 13.
Population: All participants enrolled in this study who receive the study drug through to the morning dose of Week 2 (Visit 5) as a minimum, and who undergo PK sample collection at least one of the specified post-dose time point(s).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Pharmacokinetic - t1/2 | 8.02 hours | Standard Deviation 2.33 |
Primary
Safety and Tolerability
To examine the incidence, severity and frequency of adverse events (AEs), including serious adverse events (SAEs) during treatment with NNZ-2591.
Time frame: 13 weeks
Population: Intention to treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NNZ-2591 | Safety and Tolerability | Participants with mild TEAE | 11 Participants |
| NNZ-2591 | Safety and Tolerability | Participants with moderate TEAE | 5 Participants |
| NNZ-2591 | Safety and Tolerability | Participants with any AE | 17 Participants |
| NNZ-2591 | Safety and Tolerability | Participants with TEAE | 17 Participants |
| NNZ-2591 | Safety and Tolerability | Participants with Serious TEAE | 1 Participants |
| NNZ-2591 | Safety and Tolerability | Participants who discontinued due to TEAE | 3 Participants |
| NNZ-2591 | Safety and Tolerability | Participants with severe TEAE | 1 Participants |
Secondary
ABC-2
Aberrant Behavior Checklist-2 (ABC-2) - Total score: Change from baseline. Range of scores was (0-174) with higher scores being worse
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | ABC-2 | -17.2 score on a scale | Standard Deviation 19.65 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: 0.0013Wilcoxon Signed rank
Secondary
Behavior Problems Inventory - Short Form
Total Frequency Score - Change from Baseline. Range of scores was (0-4) for each of 30 behaviors, total range (0-120), with lower scores being better.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Behavior Problems Inventory - Short Form | -5.1 score on a scale | Standard Deviation 9.41 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: 0.0326Wilcoxon Signed rank
Secondary
CGI-I
Phelan-McDermid Syndrome-specific Clinical Global Impression of Improvement Scale (CGI-I) - Overall Improvement Score on a 7 point Likert scale (1-7) where lower scores are better.
Time frame: CGI-I was assessed at Weeks 6, 13/EOT & 15. Overall improvement scores relate to Week 13/EOT visit.
Population: Intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | CGI-I | 2.4 score on a scale | Standard Deviation 0.86 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: <0.0001Wilcoxon Signed rank
Secondary
CGI-S
Phelan-McDermid syndrome-specific Clinical Global Impression Scale-Severity (CGI-S) -Change from baseline on Overall Score. Based on a 7 point Likert scale (1-7) where a lower score is better.
Time frame: Change in score assessed from baseline (visit 3, week 0) to visit 16 (week 13/EOT).
Population: Intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | CGI-S | -0.4 score on a scale | Standard Deviation 0.5 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: 0.0156Wilcoxon Signed rank
Secondary
CIC
Caregiver Impression of Improvement: Measured on a 7 point Likert scale (1-7) where lower scores are better.
Time frame: CIC was assessed at Week13/EOT
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | CIC | 2.7 score on a scale | Standard Deviation 1.02 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: 0.0003Wilcoxon Signed rank
Secondary
CSHQ
Child Sleep Habits Questionnaire (CSHQ) - Change from baseline in Total Score. Range of scores was (33-99) with higher scores being worse.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total score.
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | CSHQ | -3.6 score on a scale | Standard Deviation 5.68 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: 0.0191Wilcoxon Signed rank
Secondary
GIHQ
Gastrointestinal Health Questionnaire (GIHQ) - Total Frequency Score: Change from Baseline. Range of scores was (0-212) with higher scores being worse.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in total frequency score.
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | GIHQ | -9.6 score on a scale | Standard Deviation 10.8 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: 0.0013Wilcoxon Signed rank
Secondary
ICND
Impact of Childhood Neurological Disability (ICND) - Change from baseline in overall quality of life rating. Range of (1- 6) for quality of life rating, with higher scores indicating greater impact.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall quality of life rating score.
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | ICND | 0.3 score on a scale | Standard Deviation 0.69 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: 0.1094Wilcoxon Signed rank
Secondary
MB-CDI
MacArthur-Bates Communicative Development Inventory (MB-CDI) - change from baseline. Range of scores was (0-792) with higher scores being better.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16).
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | MB-CDI | 12.3 score on a scale | Standard Deviation 35.19 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participants.p-value: 0.0647Wilcoxon Signed rank
Secondary
ORCA
Observer-Reported Communication Ability (ORCA) - Change from baseline in Total Score. Range of Scores was (25.8-83.8) with higher scores being better
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in Total Score.
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | ORCA | 1.9 score on a scale | Standard Deviation 4.22 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: 0.0984Wilcoxon Signed rank
Secondary
PMS-DSRS
PMS Clinician Domain Specific Rating Scale - Change from baseline in overall severity score. Range of Scores Was (0-20) With Higher Scores Being Worse.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall severity score.
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | PMS-DSRS | -0.9 score on a scale | Standard Deviation 1.69 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: 0.0156Wilcoxon Signed rank
Secondary
QL-Disability
Quality of Life Inventory-Disability (QL-Disability) Overall Score - change from baseline. Range of scores was (0-100) with higher scores being better.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall score score.
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | QL-Disability | 6.1 score on a scale | Standard Deviation 8.91 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: 0.0066Wilcoxon Signed rank
Secondary
Top 3 Concerns
Caregiver Top 3 Concerns - Total Concerns Severity: Change from baseline. The range of scores was (0-30) for total concerns, with higher scores being worse
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in overall improvement score.
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | Top 3 Concerns | -5.9 score on a scale | Standard Deviation 5.86 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: 0.0005Wilcoxon Signed rank
Secondary
VABS-3
Vineland Adaptive Behavior Scales-3, Change from baseline in Composite Standard Score. Range of scores was (20-140) with higher scores being better.
Time frame: Change from baseline (visit 3, week 0) to visit 13/EOT (week 16) in composite standard score.
Population: Intention to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NNZ-2591 | VABS-3 | 2.8 score on a scale | Standard Deviation 7.82 |
Comparison: Efficacy endpoints were analyzed using a Wilcoxon signed rank test on the paired participant data from baseline to EOT (Visit 16), when applicable. Baseline values were based on the average non-missing values of visits 1, 2, and 3 for assessments collected at more than one visit during the Screening/Baseline period. Descriptive statistics were used to summarize the data. For total scores, waterfall plots, and histograms were created at the EOT visit with plots for all participantsp-value: 0.171Wilcoxon Signed rank