Fragile X Syndrome
Conditions
Brief summary
The purpose of this study is to assess the safety, tolerability and efficacy of Ergoloid mesylates (EM) and 5-hydroxytryptophan (5-HTP) and the combination (EM + 5-HTP) compared to placebo in males aged 18-45 years old with Fragile X Syndrome.
Detailed description
This single-center, Phase 2, single-blind, 4-period sequential study will enroll 15 males Fragile X Syndrome, ages 18-45 years old. The study will begin with a Screening period of up to 28 days. During screening, participants and their parent/legal authorized guardian, if indicated, will review and sign an Informed Consent/Assent form prior to any study procedures being performed. Following confirmation of a prior diagnosis for Fragile X, information will be collected to further assess their eligibility. Participants who meet entry criteria and agree to participate will proceed to a Baseline visit. At the Baseline visit (Period 1/Day 1), cognitive, behavioral, ERP and eye tracking assessments will be performed to assess current functioning. The Baseline visit will be followed by four 4-week single-blind treatment periods. During treatment periods, participants will be placed on a different treatment regimen every 4 weeks (listed below). Throughout all 4 periods, participants will take two identical capsules three times a day. If only taking one study drug, they will take one placebo pill with the drug at each dose, and in period 4, they will take two placebo pills at each dose. * Period 1: Ergoloid mesylates (EM) 1 mg three times per day for 4 weeks * Period 2: Ergoloid mesylates (EM) 1 mg TID and 5-hydroxytryptophan (5-HTP) 100 mg three times per day for 4 weeks * Period 3: 5-hydroxytryptophan (5-HTP) 100 mg three times per day for 4 weeks * Period 4: Placebo three times per day for 4 weeks Participants will return to the clinic at the end of each treatment period at weeks 4, 8, 12, and 16 and cognitive and behavioral evaluations will be repeated at these clinic visits. Safety and tolerability assessments will include adverse event monitoring, vital signs, blood chemistry and hematology, and urinalysis. Additionally, participants will be monitored for adverse events via a telephone call at the end of Week 1 of each Period, and one week following completion of Period 4 or following early discontinuation. Total study participation will last up to 21 weeks.
Interventions
5-HTP will be over-encapsulated in identical size 00 capsules. During the 5-HTP Treatment Period (Period 3) and 5-HTP/EM Treatment Period (Period 2), subjects will take 1 capsule of 5-HTP 3 times per day.
DRUGErgoloid Mesylates
Ergoloid mesylates 1 mg will be mixed with methyl cellulose and placed in a size 00 capsule. During the EM Treatment Period (Period 1) and 5-HTP/EM Treatment Period (Period 2), subjects will take 1 capsule of EM 3 times per day.
DRUGMatching placebo for Ergoloid mesylates
Matching placebo for Ergoloid mesylates will be ascorbic acid powder in identical size 00 capsules. During the 5-HTP Treatment Period (Period 3) and Placebo Treatment Period (Period 4), subjects will take 1 capsule of matching placebo for EM 3 times per day.
DRUGMatching placebo for 5-Hydroxytryptophan
Matching placebo for 5-Hydroxytryptophan will be ascorbic acid powder in identical size 00 capsules. During the EM Treatment Period (Period 2) and Placebo Treatment Period (Period 4), subjects will take 1 capsule of matching placebo for 5-HTP 3 times per day.
Sponsors
FRAXA Research Foundation
Purposeful IKE
Elizabeth Berry-Kravis
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
This is a single-blind study, meaning the participant and his family/caregivers will not know what drug or combination the participant is receiving during each time period. The investigator and study coordinator will know what drug the participant is taking. The remainder of the study team performing assessments such as the Vineland, eye tracking, ERP, Toolbox, and the KiTAP will not know the type of treatment the patient is on when testing is done.
Intervention model description
This study will use a single-blind, 4-period sequential design. Fifteen participants with Fragile X Syndrome ages 18-45 years will enter a Screening period of up to 28 days followed by four 4 week single-blind treatment periods (summarized below). * Period 1: Ergoloid mesylates 1 mg and matching placebo for 5-Hydroxytryptophan 100 mg, taken three times per day * Period 2: Ergoloid mesylates 1 mg and 5-Hydroxytryptophan 100 mg, taken three times per day * Period 3: 5-Hydroxytryptophan 100 mg and matching placebo for Ergoloid mesylates 1mg, taken three times per day * Period 4: Matching placebo for Ergoloid mesylates 1mg and matching placebo for 5- Hydroxytryptophan 100mg, taken three times per day
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Male aged 18 to 45 years, inclusive. 2. Participant has Fragile X Syndrome with a molecular genetic confirmation of the full Fragile X Mental Retardation (FMR1) mutation (≥200 CGG repeats). 3. Current treatment with no more than 3 prescribed psychotropic medications. Anti-epileptic medications are permitted and are not counted as psychotropic medications if they are used for treatment of seizures. Anti-epileptics for other indications, such as the treatment of mood disorders, count towards the limit of permitted medications. 4. Permitted concomitant psychotropic medications must be at a stable dose and dosing regimen for at least 2 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication. 5. Anti-epileptic medications must be at a stable dose and dosing regimen for 12 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication. 6. Participants with a history of seizure disorder who are currently receiving treatment with anti-epileptics must have been seizure-free for 3 months preceding screening, or must be seizure-free for 3 years if not currently receiving anti-epileptics. 7. Behavioral and therapy treatments/interventions must be stable for 4 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication, and throughout the study. Minor changes in hours or times of therapy that are not considered clinically significant will not be exclusionary. Changes in therapies provided through a school program, due to school vacations, are allowed. 8. Participant must be willing to practice barrier methods of contraception while on study, if sexually active. Abstinence is also considered a reasonable form of birth control in this study population. 9. Participant has a parent, legal authorized guardian or consistent caregiver. 10. Participant and caregiver are able to attend the clinic regularly and reliably. 11. Participant is able to swallow capsules. 12. For participants who are not their own legal guardian, participant's parent/legal authorized guardian is able to understand and sign an informed consent form to participate in the study. 13. If participant is his own legal guardian, he can understand and sign informed consent to participate in the study. 14. If participant is not their own legal guardian, the participant provides assent for participation in the study, if the participant has the cognitive ability to provide assent.
Exclusion criteria
1. History of, or current cardiovascular, renal, hepatic, respiratory, gastrointestinal, psychiatric, neurologic, cerebrovascular, or other systemic disease that would place the participant at risk or potentially interfere with the interpretation of the safety, tolerability, or efficacy of the study medication. Common diseases such as mild hypertension, well-controlled type 2 diabetes mellitus (hemoglobin A1C \[Hgb A1C\] \<6.5%), etc. are allowed per the investigator's judgment as long as they are stable and controlled by medical therapy that is constant for at least 4 weeks before randomization. 2. Clinically significant abnormalities, in the investigator's judgment, in safety laboratory tests, vital signs, as measured during Screening. 3. History of substance abuse within the past year, according to investigator assessment. 4. Use of CYP3A4 inhibitors, beta-blockers, MAO inhibitors or triptans at any time during participation in the study. 5. Significant hearing or visual impairment that may affect the participant's ability to complete the test procedures. 6. Concurrent major psychiatric condition (e.g., Major Depressive Disorder, Schizophrenia or Bipolar Disorder) as diagnosed by the investigator. Participants with additional diagnosis of Autism Spectrum Disorder or Anxiety Disorder will be allowed as these are characteristics of FXS. 7. Participant has active diseases that would interfere with participation, such as acquired immunodeficiency disorder, hepatitis C, hepatitis B, or tuberculosis. 8. Participant is planning to commence psychotherapy or cognitive behavior therapy (CBT) during the period of the study or had begun psychotherapy or CBT within 4 weeks prior to Screening. 9. Participant has participated in another clinical trial within the 30 days preceding Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability - Number of Treatment-Emergent Adverse Events | Baseline through Week 17 | Adverse Events (AEs), including clinically meaningful laboratory abnormalities and significant behavioral changes will be recorded from the time of the subject's first dose of study drug to the end of the study (Week 17) or longer if needed. Adverse events will be assessed at each visit as well as during each phone call and will be tabulated for each treatment period. |
| Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Baseline through Week 17 | Adverse Events (AEs), including clinically meaningful laboratory abnormalities and significant behavioral changes will be tabulated for each treatment period. The Investigator is responsible for assessing the severity (intensity) of each adverse event as mild, moderate, or severe according to the following definitions: Mild - An event that is easily tolerated and generally not interfering with normal daily activities. Moderate - An event that is sufficiently discomforting to interfere with normal daily activities. Severe - An event that is incapacitating with inability to work or perform normal daily activities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Number of Errors on KiTAP Executive Battery Distractibility Subtest | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The distractibility subtest measures how easily the subject is distracted by extraneous stimuli. This subtest requires subjects to tap a button when a target stimulus appears on the screen while ignoring distracters that appear shortly before the stimulus. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean number of correct responses and errors were recorded, and change from baseline was calculated. For the distractability subtest, a higher mean number of correct responses and lower mean number of errors over the 3 minutes indicates better performance. |
| Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Flexibility Subtest | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The flexibility subtest measures the subject's ability to be flexible about shifting from one response type to another. This subtest is 2 minutes long and requires subjects to alternate between identifying blue and green dragons which seem on random sides of the screen by tapping one of two buttons. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean number of correct responses and errors were recorded and change from baseline was calculated. For the flexibility subtest, a higher mean number of correct responses and lower mean number of errors indicates better performance. |
| Change From Baseline in Total Number of Errors on KiTAP Executive Battery Flexibility Subtest | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The flexibility subtest measures the subject's ability to be flexible about shifting from one response type to another. This subtest is 2 minutes long and requires subjects to alternate between identifying blue and green dragons which seem on random sides of the screen by tapping one of two buttons. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean number of correct responses and errors were recorded and change from baseline was calculated. For the flexibility subtest, a higher mean number of correct responses and lower mean number of errors indicates better performance. |
| Change From Baseline in Total Number of Correct Responses on KiTAP Test of Attentional Performance Go-NoGo Subtest | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The Go-NoGo subtest measures a subject's impulsivity by requiring subjects to tap a button when the target stimulus is presented, while refraining from hitting the button for the non-target stimulus. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). This subtest takes place over 2 minutes 30 seconds. Mean number of correct responses and errors were recorded, and change from baseline was calculated. For the Go-NoGo subtest, a higher mean number of correct responses and a lower mean number of errors indicates better performance. |
| Change From Baseline in Total Number of Errors on KiTAP Test of Attentional Performance Go-NoGo Subtest | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The Go-NoGo subtest measures a subject's impulsivity by requiring subjects to tap a button when the target stimulus is presented, while refraining from hitting the button for the non-target stimulus. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). This subtest takes place over 2 minutes 30 seconds. Mean number of correct responses and errors were recorded, and change from baseline was calculated. For the Go-NoGo subtest, a higher mean number of correct responses and a lower mean number of errors indicates better performance. |
| Change From Baseline in Clinical Global Impression Severity Scale Overall Score | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | The Clinical Global Impression-Severity (CGI-S) is a global measure to provide a clinical judgment of a participant's overall condition based on a trained clinician's assessment of cognition, behavior and activities of daily living. The clinician compares the subject with individuals of the same age and sex. The assessment of severity is with a 7-point scale: 1, not ill; 2, very mild; 3, mild; 4, moderate; 5, marked; 6, severe; 7, extremely severe. A net decrease in severity score over time indicates a positive outcome. |
| Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | This assessment is a parent/caregiver-rated scale with six subscales to assess irritability, stereotypes, lethargy, hyperactivity, inappropriate speech, and social avoidance, using ABC-FX factoring system. The ABC was was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean score for each subscale was measured and change from baseline was calculated. Lower mean scores on each subscale indicate fewer aberrant behaviors (better functioning).The range of possible scores on each subscale are irritability (0-54), lethargy (0-39), stereotypes (0-18), hyperactivity (0-30), inappropriate speech (0-12), and social avoidance (0-12). |
| Change From Baseline in KiTAP Executive Battery - Alertness Subscore (Reaction Time) | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The alertness subtest requires subjects to tap a button every time a stimulus appears on the screen. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean reaction time was measured over 90 seconds and change from baseline was calculated. A lower reaction time (net decrease in reaction time) indicates better performance. |
| Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | VABS-3 is a clinician-administered standardized interview. For this study, we collected data in domains of communication (receptive & written language), daily living skills (domestic & community skills), & socialization (interpersonal relationships, play & leisure time, & coping abilities). This assessment was administered at Baseline as well as at Week 4, Week 8, Week 12, and Week 16 (end of each treatment period). Mean growth scale value (GSV) for each subdomain was recorded at each time point and change from baseline was calculated. The possible GSVs for each subdomain are receptive (10-162), written (10-163), domestic (10-110), community (10-136), interpersonal (10-152), play and leisure (10-164), & coping skills (10-120). Higher GSVs for each subdomain indicate better functioning. |
| Change From Baseline in NIH Toolbox Cognitive Battery for Intellectual Disabilities (NIH-TCB) Total Cognition Score | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | The NIH-TCB is a battery of extensively validated computer-administered cognitive tests. The NIH-TCB includes 7 evaluations measuring cognitive flexibility, inhibition & visual attention, episodic memory, immediate recall & sequencing of different visually & orally presented stimuli, processing speed, recognition of letters and words, & receptive vocabulary. This assessment was administered at Baseline as well as at Week 4, Week 8, Week 12, and Week 16 (end of each treatment period). This battery produces fluid and crystallized cognition composite scores. The Total Cognition Composite Score is found by converting raw fluid and crystallized scores to standard scores, averaging these two scores, then deriving standard scores based on this new distribution. Scores range from 0-140. The normative mean of the uncorrected standard score is 100 and the standard deviation is 15. A higher mean total cognition composite score indicates better performance. |
| Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | IIn an attempt to measure the level of behavioral difficulty experienced by the parent/caregiver with respect to the child with FXS, the VAS allows parents to mark on a visual line measuring 10 cm with one side marked worst behavior and the other side marked best behavior. The caregiver rated the participant's behavior with respect to three domains: daily functioning, anxiety/irritability and language. Distances closer to 10 cm are considered worse behavior and distances closer to 0 cm are considered better behavior. Average distance of the mark was recorded for each domain at Baseline then again at Week 4, Week 8, Week 12, and Week 16 (end of each treatment period). Change from baseline was calculated for each domain. Lower scores indicate a better outcome (closer distance to best behavior side). |
| Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal) | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | Event-Related Potentials (ERPs) enable extraction of neural responses associated with specific sensory, cognitive, or motor events from an overall EEG. Gamma 1 and gamma 2 waves were measured for various parts of the brain at a resting state. ERP was performed at Baseline as well as at Week 4, Week 8, Week 12, Week 16 (at the end of each treatment period). Mean power of gamma 1 and gamma 2 bands, measured by frontal EEG leads, was recorded for each time point and change from baseline was calculated. FXS patients have typically been found to exhibit greater gamma frequency band power than typically developing controls, which may be related to social and sensory processing difficulties. Therefore, lower gamma band power would indicate better functioning. |
| Event-Related Potentials (ERP) Components in Response to Standard Tones | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | Event-Related Potentials (ERPs) enable extraction of neural responses associated with specific sensory, cognitive, or motor events from an overall EEG. Auditory stimuli are presented and EEG events are assessed in relation to timing of the stimuli. ERP was performed at Baseline as well as at week Week 4, Week 8, Week 12, Week 16 (end of each treatment period). The area under the curve was measured for different components of the ERP including P1 and P2 (positive components) and N1 and N2 (negative components). The average area under the curve was recorded for each component at each time point and change from baseline was calculated. Individuals with FXS are thought to have excessive ERP response, so a decrease in area under each curve compared to baseline would indicate a favorable outcome. |
| Event-Related Potentials - Frontal Alpha Asymmetry at Resting State | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | Event-Related Potentials (ERPs) enable extraction of neural responses associated with specific sensory, cognitive, or motor events from an overall EEG. EEG data was collected when the subject was in a resting state. Frontal alpha asymmetry measures differences in alpha activity level of the right and left hemisphere of the frontal lobe of the brain. ERP was performed at Baseline as well as at Week 4, Week 8, Week 12, Week 16 (end of each treatment period). Mean alpha asymmetry at resting state was recorded and change from baseline was calculated for each time point. Higher alpha asymmetry scores indicate greater alpha power in the right hemisphere, which corresponds to increased neural activity of the left hemisphere. High activity of the left frontal lobe is hypothesized to correspond with approach behaviors, and high activity of the right frontal lobe is thought to correspond to withdrawal behaviors. In this study, higher alpha asymmetry scores indicate a better outcome. |
| Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | The ADAMS is a parent/caregiver rated scale with five subscores to assess manic/hyperactive behavior, depressed mood, social avoidance, general anxiety, and obsessive/compulsive behavior. The ADAMs was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean score for each subscale was recorded, and change from baseline was calculated for each subscore. The range of possible scores for each subscale is 0-21. Lower mean scores on each subscale indicate better functioning. |
| Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Distractibility Subtest | Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment) | The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The distractibility subtest measures how easily the subject is distracted by extraneous stimuli. This subtest requires subjects to tap a button when a target stimulus appears on the screen while ignoring distracters that appear shortly before the stimulus. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean number of correct responses and errors were recorded, and change from baseline was calculated. For the distractability subtest, a higher mean number of correct responses and lower mean number of errors over the 3 minutes indicates better performance. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adult Males With Fragile X Syndrome Fifteen participants with Fragile X syndrome ages 18-45 years old will be enrolled in this single-blind study. Eligible participants will be started on EM for 4 weeks in Treatment Period 1, then will take EM and 5-HTP for 4 weeks in Treatment Period 2, then, 5-HTP for 4 weeks in Treatment Period 3, then placebo for 4 weeks in Treatment Period 4. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Adult Males With Fragile X Syndrome |
|---|---|
| Aberrant Behavior Checklist (ABC) Subscores Hyperactivity Subscale | 4.733333333 scores on a scale |
| Aberrant Behavior Checklist (ABC) Subscores Inappropriate Speech Subscale | 4.4 scores on a scale |
| Aberrant Behavior Checklist (ABC) Subscores Irritability Subscale | 6.666666667 scores on a scale |
| Aberrant Behavior Checklist (ABC) Subscores Lethargy Subscale | 4.8 scores on a scale |
| Aberrant Behavior Checklist (ABC) Subscores Social Avoidance Subscale | 4.133333333 scores on a scale |
| Aberrant Behavior Checklist (ABC) Subscores Stereotypes Subscale | 2.666666667 scores on a scale |
| Age, Continuous | 31 years STANDARD_DEVIATION 7.7 |
| Anxiety, Depression, and Mood Scale (ADAMS) Subscores Depressed Mood Subscore | 3.2 scores on a scale |
| Anxiety, Depression, and Mood Scale (ADAMS) Subscores General Anxiety Subscore | 6.666666667 scores on a scale |
| Anxiety, Depression, and Mood Scale (ADAMS) Subscores Manic/Hyperactive Behavior Subscore | 5.333333333 scores on a scale |
| Anxiety, Depression, and Mood Scale (ADAMS) Subscores Obsessive/Compulsive Behavior Subscore | 1.866666667 scores on a scale |
| Anxiety, Depression, and Mood Scale (ADAMS) Subscores Social Avoidance Subscore | 8 scores on a scale |
| Clinical Global Impression - Severity (CGI-S) Scale Overall Score Extremely Severe | 0 Participants |
| Clinical Global Impression - Severity (CGI-S) Scale Overall Score Marked | 5 Participants |
| Clinical Global Impression - Severity (CGI-S) Scale Overall Score Mild | 2 Participants |
| Clinical Global Impression - Severity (CGI-S) Scale Overall Score Moderate | 8 Participants |
| Clinical Global Impression - Severity (CGI-S) Scale Overall Score Not Ill | 0 Participants |
| Clinical Global Impression - Severity (CGI-S) Scale Overall Score Severe | 0 Participants |
| Clinical Global Impression - Severity (CGI-S) Scale Overall Score Very Mild | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Event-Related Potential (ERP) Components in Response to Standard Tones N1 Component | 0.0164247 μV*seconds STANDARD_DEVIATION 0.022616337 |
| Event-Related Potential (ERP) Components in Response to Standard Tones N2 Component | 0.0360871 μV*seconds STANDARD_DEVIATION 0.041661709 |
| Event-Related Potential (ERP) Components in Response to Standard Tones P1 Component | 0.01171 μV*seconds STANDARD_DEVIATION 0.010617538 |
| Event-Related Potential (ERP) Components in Response to Standard Tones P2 Component | 0.0345626 μV*seconds STANDARD_DEVIATION 0.032675507 |
| Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal) Gamma 1 (30-55 Hz) Absolute Power | 0.047656355 V^2/Hz STANDARD_DEVIATION 0.018258564 |
| Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal) Gamma 2 (65-80 Hz) Absolute Power | 0.026220458 V^2/Hz STANDARD_DEVIATION 0.011025469 |
| Event-Related Potentials - Frontal Alpha Asymmetry at Resting State | -0.049005225 unitless STANDARD_DEVIATION 0.326769814 |
| KiTAP Executive Battery - Alertness Subscore (Reaction Time) | 482.7857143 milliseconds |
| KiTAP Executive Battery Distractibility Subtest - Total Number of Correct Responses | 11.78 Correct Responses |
| KiTAP Executive Battery Distractibility Subtest - Total Number of Errors | 6.214285714 Errors |
| KiTAP Executive Battery Flexibility Subtest - Total Number of Correct Responses | 14.64 Correct Responses |
| KiTAP Executive Battery Flexibility Subtest - Total Number of Errors | 12.29 Errors |
| KiTAP Test of Attentional Performance Go-NoGo Subtest - Total Number of Correct Responses | 14.86 Correct Responses |
| KiTAP Test of Attentional Performance Go-NoGo Subtest - Total Number of Errors | 9.57 Errors |
| NIH Toolbox Cognitive Battery for Intellectual Disabilities (NIH-TCB) Total Cognition Score | 57.3 score on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 15 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 15 Participants |
| Vineland-3 Adaptive Behavior Scale (VABS-3) - Subdomain Growth Scale Values Daily Living Skills - Community Subdomain | 67.35714286 score on a scale |
| Vineland-3 Adaptive Behavior Scale (VABS-3) - Subdomain Growth Scale Values Daily Living Skills - Domestic Subdomain | 60.92857143 score on a scale |
| Vineland-3 Adaptive Behavior Scale (VABS-3) - Subdomain Growth Scale Values Receptive Communication Subdomain | 126.5 score on a scale |
| Vineland-3 Adaptive Behavior Scale (VABS-3) - Subdomain Growth Scale Values Social - Coping Skills Subdomain | 69.5 score on a scale |
| Vineland-3 Adaptive Behavior Scale (VABS-3) - Subdomain Growth Scale Values Social - Interpersonal Relationships Subdomain | 101.7857143 score on a scale |
| Vineland-3 Adaptive Behavior Scale (VABS-3) - Subdomain Growth Scale Values Social - Play and Leisure Subdomain | 105.9230769 score on a scale |
| Vineland-3 Adaptive Behavior Scale (VABS-3) - Subdomain Growth Scale Values Written Communication Subdomain | 91 score on a scale |
| Visual Analog Scale (VAS) Assessment Domain Scores Anxiety or Irritability Issues | 5.426666667 score on a scale |
| Visual Analog Scale (VAS) Assessment Domain Scores Daily Function Issues | 6.11 score on a scale |
| Visual Analog Scale (VAS) Assessment Domain Scores Target Language Issues | 5.241333333 score on a scale |
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 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 1 / 15 | 3 / 15 | 2 / 15 | 1 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Safety and Tolerability - Number of Treatment-Emergent Adverse Events
Adverse Events (AEs), including clinically meaningful laboratory abnormalities and significant behavioral changes will be recorded from the time of the subject's first dose of study drug to the end of the study (Week 17) or longer if needed. Adverse events will be assessed at each visit as well as during each phone call and will be tabulated for each treatment period.
Time frame: Baseline through Week 17
Population: The Safety population will include all participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ergoloid Mesylates (EM) | Safety and Tolerability - Number of Treatment-Emergent Adverse Events | 2 Number of Adverse Events |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Safety and Tolerability - Number of Treatment-Emergent Adverse Events | 1 Number of Adverse Events |
| 5-hydroxytryptophan (5-HTP) | Safety and Tolerability - Number of Treatment-Emergent Adverse Events | 1 Number of Adverse Events |
| Placebo | Safety and Tolerability - Number of Treatment-Emergent Adverse Events | 3 Number of Adverse Events |
Primary
Safety and Tolerability - Severity of Treatment Emergent Adverse Events
Adverse Events (AEs), including clinically meaningful laboratory abnormalities and significant behavioral changes will be tabulated for each treatment period. The Investigator is responsible for assessing the severity (intensity) of each adverse event as mild, moderate, or severe according to the following definitions: Mild - An event that is easily tolerated and generally not interfering with normal daily activities. Moderate - An event that is sufficiently discomforting to interfere with normal daily activities. Severe - An event that is incapacitating with inability to work or perform normal daily activities.
Time frame: Baseline through Week 17
Population: The Safety population will include all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ergoloid Mesylates (EM) | Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Mild | 2 Number of Adverse Events |
| Ergoloid Mesylates (EM) | Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Severe | 0 Number of Adverse Events |
| Ergoloid Mesylates (EM) | Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Moderate | 0 Number of Adverse Events |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Moderate | 0 Number of Adverse Events |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Severe | 0 Number of Adverse Events |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Mild | 1 Number of Adverse Events |
| 5-hydroxytryptophan (5-HTP) | Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Mild | 1 Number of Adverse Events |
| 5-hydroxytryptophan (5-HTP) | Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Moderate | 0 Number of Adverse Events |
| 5-hydroxytryptophan (5-HTP) | Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Severe | 0 Number of Adverse Events |
| Placebo | Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Severe | 0 Number of Adverse Events |
| Placebo | Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Mild | 2 Number of Adverse Events |
| Placebo | Safety and Tolerability - Severity of Treatment Emergent Adverse Events | Moderate | 1 Number of Adverse Events |
Secondary
Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores
This assessment is a parent/caregiver-rated scale with six subscales to assess irritability, stereotypes, lethargy, hyperactivity, inappropriate speech, and social avoidance, using ABC-FX factoring system. The ABC was was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean score for each subscale was measured and change from baseline was calculated. Lower mean scores on each subscale indicate fewer aberrant behaviors (better functioning).The range of possible scores on each subscale are irritability (0-54), lethargy (0-39), stereotypes (0-18), hyperactivity (0-30), inappropriate speech (0-12), and social avoidance (0-12).
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Irritability Subscale | -2.59088 score on a scale | Standard Error 0.9919 |
| Ergoloid Mesylates (EM) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Lethargy Subscale | -0.86667 score on a scale | Standard Error 0.8081 |
| Ergoloid Mesylates (EM) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Stereotypes Subscale | -0.73333 score on a scale | Standard Error 0.5678 |
| Ergoloid Mesylates (EM) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Hyperactivity Subscale | -0.6 score on a scale | Standard Error 0.5241 |
| Ergoloid Mesylates (EM) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Inappropriate Speech Subscale | -0.53333 score on a scale | Standard Error 0.3355 |
| Ergoloid Mesylates (EM) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Social Avoidance Subscale | -0.73333 score on a scale | Standard Error 0.3362 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Social Avoidance Subscale | -0.64283 score on a scale | Standard Error 0.352 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Hyperactivity Subscale | -1.31738 score on a scale | Standard Error 0.5355 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Irritability Subscale | -2.36774 score on a scale | Standard Error 0.9919 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Stereotypes Subscale | -0.82132 score on a scale | Standard Error 0.5801 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Lethargy Subscale | -0.34695 score on a scale | Standard Error 0.8258 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Inappropriate Speech Subscale | -0.9934 score on a scale | Standard Error 0.3429 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Lethargy Subscale | -0.79147 score on a scale | Standard Error 0.8258 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Stereotypes Subscale | -1.06667 score on a scale | Standard Error 0.5678 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Hyperactivity Subscale | -1.46667 score on a scale | Standard Error 0.5241 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Social Avoidance Subscale | -0.50848 score on a scale | Standard Error 0.3436 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Inappropriate Speech Subscale | -1.46667 score on a scale | Standard Error 0.3355 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Irritability Subscale | -2.53333 score on a scale | Standard Error 0.9706 |
| Placebo | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Inappropriate Speech Subscale | -1.46667 score on a scale | Standard Error 0.3355 |
| Placebo | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Social Avoidance Subscale | -0.4 score on a scale | Standard Error 0.3362 |
| Placebo | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Lethargy Subscale | -1.8 score on a scale | Standard Error 0.8081 |
| Placebo | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Hyperactivity Subscale | -1.4 score on a scale | Standard Error 0.5241 |
| Placebo | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Irritability Subscale | -2.13333 score on a scale | Standard Error 0.9706 |
| Placebo | Change From Baseline in Aberrant Behavior Checklist (ABC) Subscores | Stereotypes Subscale | -0.8 score on a scale | Standard Error 0.5678 |
Secondary
Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores
The ADAMS is a parent/caregiver rated scale with five subscores to assess manic/hyperactive behavior, depressed mood, social avoidance, general anxiety, and obsessive/compulsive behavior. The ADAMs was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean score for each subscale was recorded, and change from baseline was calculated for each subscore. The range of possible scores for each subscale is 0-21. Lower mean scores on each subscale indicate better functioning.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Social Avoidance Total Score | -1.733333 score on a scale | Standard Error 0.6911 |
| Ergoloid Mesylates (EM) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Depressed Mood Total Score | -1.13333 score on a scale | Standard Error 0.6433 |
| Ergoloid Mesylates (EM) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Manic/Hyperactive Behavior Total Score | -1.4 score on a scale | Standard Error 0.4076 |
| Ergoloid Mesylates (EM) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | General Anxiety Total Score | -1.533333 score on a scale | Standard Error 0.677 |
| Ergoloid Mesylates (EM) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Obsessive/Compulsive Behavior Total Score | -0.13333333 score on a scale | Standard Error 0.3792 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Social Avoidance Total Score | -1.333333 score on a scale | Standard Error 0.6911 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Manic/Hyperactive Behavior Total Score | -1.7333 score on a scale | Standard Error 0.4076 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Depressed Mood Total Score | -0.06667 score on a scale | Standard Error 0.6433 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | General Anxiety Total Score | -1.8 score on a scale | Standard Error 0.677 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Obsessive/Compulsive Behavior Total Score | 0.06666667 score on a scale | Standard Error 0.3792 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Social Avoidance Total Score | -2.666667 score on a scale | Standard Error 0.6911 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Manic/Hyperactive Behavior Total Score | -2.26667 score on a scale | Standard Error 0.4076 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Obsessive/Compulsive Behavior Total Score | -0.2 score on a scale | Standard Error 0.3792 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Depressed Mood Total Score | -1.13333333 score on a scale | Standard Error 0.6433 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | General Anxiety Total Score | -2.946642 score on a scale | Standard Error 0.677 |
| Placebo | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Depressed Mood Total Score | -1.6 score on a scale | Standard Error 0.6433 |
| Placebo | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Social Avoidance Total Score | -1.866667 score on a scale | Standard Error 0.6911 |
| Placebo | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | General Anxiety Total Score | -2.266667 score on a scale | Standard Error 0.677 |
| Placebo | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Obsessive/Compulsive Behavior Total Score | -0.4 score on a scale | Standard Error 0.3792 |
| Placebo | Change From Baseline in Anxiety, Depression, and Mood Scale (ADAMS) Subscores | Manic/Hyperactive Behavior Total Score | -1.8 score on a scale | Standard Error 0.4076 |
Secondary
Change From Baseline in Clinical Global Impression Severity Scale Overall Score
The Clinical Global Impression-Severity (CGI-S) is a global measure to provide a clinical judgment of a participant's overall condition based on a trained clinician's assessment of cognition, behavior and activities of daily living. The clinician compares the subject with individuals of the same age and sex. The assessment of severity is with a 7-point scale: 1, not ill; 2, very mild; 3, mild; 4, moderate; 5, marked; 6, severe; 7, extremely severe. A net decrease in severity score over time indicates a positive outcome.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline in Clinical Global Impression Severity Scale Overall Score | -0.06667 scores on a scale | Standard Error 0.0805 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Clinical Global Impression Severity Scale Overall Score | -0.06667 scores on a scale | Standard Error 0.0805 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Clinical Global Impression Severity Scale Overall Score | -0.06667 scores on a scale | Standard Error 0.0805 |
| Placebo | Change From Baseline in Clinical Global Impression Severity Scale Overall Score | -0.06667 scores on a scale | Standard Error 0.0805 |
Secondary
Change From Baseline in KiTAP Executive Battery - Alertness Subscore (Reaction Time)
The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The alertness subtest requires subjects to tap a button every time a stimulus appears on the screen. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean reaction time was measured over 90 seconds and change from baseline was calculated. A lower reaction time (net decrease in reaction time) indicates better performance.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline in KiTAP Executive Battery - Alertness Subscore (Reaction Time) | -78.2678 milliseconds | Standard Error 107.4594 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in KiTAP Executive Battery - Alertness Subscore (Reaction Time) | -0.52675 milliseconds | Standard Error 107.4594 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in KiTAP Executive Battery - Alertness Subscore (Reaction Time) | 14.3989 milliseconds | Standard Error 109.7533 |
| Placebo | Change From Baseline in KiTAP Executive Battery - Alertness Subscore (Reaction Time) | 31.48097 milliseconds | Standard Error 109.7533 |
Secondary
Change From Baseline in NIH Toolbox Cognitive Battery for Intellectual Disabilities (NIH-TCB) Total Cognition Score
The NIH-TCB is a battery of extensively validated computer-administered cognitive tests. The NIH-TCB includes 7 evaluations measuring cognitive flexibility, inhibition & visual attention, episodic memory, immediate recall & sequencing of different visually & orally presented stimuli, processing speed, recognition of letters and words, & receptive vocabulary. This assessment was administered at Baseline as well as at Week 4, Week 8, Week 12, and Week 16 (end of each treatment period). This battery produces fluid and crystallized cognition composite scores. The Total Cognition Composite Score is found by converting raw fluid and crystallized scores to standard scores, averaging these two scores, then deriving standard scores based on this new distribution. Scores range from 0-140. The normative mean of the uncorrected standard score is 100 and the standard deviation is 15. A higher mean total cognition composite score indicates better performance.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which includes all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline in NIH Toolbox Cognitive Battery for Intellectual Disabilities (NIH-TCB) Total Cognition Score | 2.10074 scores on a scale | Standard Error 4.547 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in NIH Toolbox Cognitive Battery for Intellectual Disabilities (NIH-TCB) Total Cognition Score | -9.156292 scores on a scale | Standard Error 6.9968 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in NIH Toolbox Cognitive Battery for Intellectual Disabilities (NIH-TCB) Total Cognition Score | -4.734578 scores on a scale | Standard Error 5.0309 |
| Placebo | Change From Baseline in NIH Toolbox Cognitive Battery for Intellectual Disabilities (NIH-TCB) Total Cognition Score | -2.531407 scores on a scale | Standard Error 4.1965 |
Secondary
Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Distractibility Subtest
The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The distractibility subtest measures how easily the subject is distracted by extraneous stimuli. This subtest requires subjects to tap a button when a target stimulus appears on the screen while ignoring distracters that appear shortly before the stimulus. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean number of correct responses and errors were recorded, and change from baseline was calculated. For the distractability subtest, a higher mean number of correct responses and lower mean number of errors over the 3 minutes indicates better performance.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which includes all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Distractibility Subtest | 2.142857 Correct Responses | Standard Error 2.9003 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Distractibility Subtest | -3.1705358 Correct Responses | Standard Error 2.9201 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Distractibility Subtest | 0.8607271 Correct Responses | Standard Error 2.9201 |
| Placebo | Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Distractibility Subtest | -4.0571867 Correct Responses | Standard Error 2.9201 |
Secondary
Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Flexibility Subtest
The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The flexibility subtest measures the subject's ability to be flexible about shifting from one response type to another. This subtest is 2 minutes long and requires subjects to alternate between identifying blue and green dragons which seem on random sides of the screen by tapping one of two buttons. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean number of correct responses and errors were recorded and change from baseline was calculated. For the flexibility subtest, a higher mean number of correct responses and lower mean number of errors indicates better performance.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Flexibility Subtest | -1.928571 Correct Responses | Standard Error 1.1029 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Flexibility Subtest | -1.452112 Correct Responses | Standard Error 1.1124 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Flexibility Subtest | -3.340254 Correct Responses | Standard Error 1.1124 |
| Placebo | Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Flexibility Subtest | -1.237821 Correct Responses | Standard Error 1.1124 |
Secondary
Change From Baseline in Total Number of Correct Responses on KiTAP Test of Attentional Performance Go-NoGo Subtest
The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The Go-NoGo subtest measures a subject's impulsivity by requiring subjects to tap a button when the target stimulus is presented, while refraining from hitting the button for the non-target stimulus. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). This subtest takes place over 2 minutes 30 seconds. Mean number of correct responses and errors were recorded, and change from baseline was calculated. For the Go-NoGo subtest, a higher mean number of correct responses and a lower mean number of errors indicates better performance.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: The primary efficacy population will be the intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline in Total Number of Correct Responses on KiTAP Test of Attentional Performance Go-NoGo Subtest | 0.3966214 Correct Responses | Standard Error 1.5644 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Total Number of Correct Responses on KiTAP Test of Attentional Performance Go-NoGo Subtest | 1.8198629 Correct Responses | Standard Error 1.5962 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Total Number of Correct Responses on KiTAP Test of Attentional Performance Go-NoGo Subtest | 0.4632881 Correct Responses | Standard Error 1.5644 |
| Placebo | Change From Baseline in Total Number of Correct Responses on KiTAP Test of Attentional Performance Go-NoGo Subtest | -1.1383753 Correct Responses | Standard Error 1.5962 |
Secondary
Change From Baseline in Total Number of Errors on KiTAP Executive Battery Distractibility Subtest
The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The distractibility subtest measures how easily the subject is distracted by extraneous stimuli. This subtest requires subjects to tap a button when a target stimulus appears on the screen while ignoring distracters that appear shortly before the stimulus. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean number of correct responses and errors were recorded, and change from baseline was calculated. For the distractability subtest, a higher mean number of correct responses and lower mean number of errors over the 3 minutes indicates better performance.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which includes all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline in Total Number of Errors on KiTAP Executive Battery Distractibility Subtest | 2.64285 Errors | Standard Error 2.7233 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Total Number of Errors on KiTAP Executive Battery Distractibility Subtest | 0.53599 Errors | Standard Error 2.8155 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Total Number of Errors on KiTAP Executive Battery Distractibility Subtest | 0.79141 Errors | Standard Error 2.8155 |
| Placebo | Change From Baseline in Total Number of Errors on KiTAP Executive Battery Distractibility Subtest | -1.9874 Errors | Standard Error 2.7474 |
Secondary
Change From Baseline in Total Number of Errors on KiTAP Executive Battery Flexibility Subtest
The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The flexibility subtest measures the subject's ability to be flexible about shifting from one response type to another. This subtest is 2 minutes long and requires subjects to alternate between identifying blue and green dragons which seem on random sides of the screen by tapping one of two buttons. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). Mean number of correct responses and errors were recorded and change from baseline was calculated. For the flexibility subtest, a higher mean number of correct responses and lower mean number of errors indicates better performance.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline in Total Number of Errors on KiTAP Executive Battery Flexibility Subtest | 1.5 Errors | Standard Error 0.712 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Total Number of Errors on KiTAP Executive Battery Flexibility Subtest | 1.93979 Errors | Standard Error 0.7178 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Total Number of Errors on KiTAP Executive Battery Flexibility Subtest | 2.05569 Errors | Standard Error 0.7178 |
| Placebo | Change From Baseline in Total Number of Errors on KiTAP Executive Battery Flexibility Subtest | 1.56290 Errors | Standard Error 0.7178 |
Secondary
Change From Baseline in Total Number of Errors on KiTAP Test of Attentional Performance Go-NoGo Subtest
The KiTAP is a computerized executive function battery that consists of eight nonverbal subtests measuring different basal as well as higher-order components of attention and executive functioning. The Go-NoGo subtest measures a subject's impulsivity by requiring subjects to tap a button when the target stimulus is presented, while refraining from hitting the button for the non-target stimulus. KiTAP was completed at Baseline as well as Week 4, Week 8, Week 12, and Week 16 (the end of each treatment period). This subtest takes place over 2 minutes 30 seconds. Mean number of correct responses and errors were recorded, and change from baseline was calculated. For the Go-NoGo subtest, a higher mean number of correct responses and a lower mean number of errors indicates better performance.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: The primary efficacy population will be the intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline in Total Number of Errors on KiTAP Test of Attentional Performance Go-NoGo Subtest | -0.1177 Errors | Standard Error 1.5019 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Total Number of Errors on KiTAP Test of Attentional Performance Go-NoGo Subtest | 0.55828 Errors | Standard Error 1.5335 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Total Number of Errors on KiTAP Test of Attentional Performance Go-NoGo Subtest | 0.28221 Errors | Standard Error 1.5019 |
| Placebo | Change From Baseline in Total Number of Errors on KiTAP Test of Attentional Performance Go-NoGo Subtest | 0.73542 Errors | Standard Error 1.5335 |
Secondary
Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores
IIn an attempt to measure the level of behavioral difficulty experienced by the parent/caregiver with respect to the child with FXS, the VAS allows parents to mark on a visual line measuring 10 cm with one side marked worst behavior and the other side marked best behavior. The caregiver rated the participant's behavior with respect to three domains: daily functioning, anxiety/irritability and language. Distances closer to 10 cm are considered worse behavior and distances closer to 0 cm are considered better behavior. Average distance of the mark was recorded for each domain at Baseline then again at Week 4, Week 8, Week 12, and Week 16 (end of each treatment period). Change from baseline was calculated for each domain. Lower scores indicate a better outcome (closer distance to best behavior side).
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Target Language Issues | 0.9786667 score on a scale | Standard Error 0.5869 |
| Ergoloid Mesylates (EM) | Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Anxiety or Irritability Issues | 0.2533333 score on a scale | Standard Error 0.6165 |
| Ergoloid Mesylates (EM) | Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Daily Function Issues | 0.6833333 score on a scale | Standard Error 0.5763 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Target Language Issues | 0.9786667 score on a scale | Standard Error 0.5869 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Anxiety or Irritability Issues | 1.1233333 score on a scale | Standard Error 0.6165 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Daily Function Issues | 0.8433333 score on a scale | Standard Error 0.5763 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Daily Function Issues | 0.6566667 score on a scale | Standard Error 0.5763 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Target Language Issues | 0.712 score on a scale | Standard Error 0.5869 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Anxiety or Irritability Issues | 0.6433333 score on a scale | Standard Error 0.6165 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Target Language Issues | 0.5253333 score on a scale | Standard Error 0.5869 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Anxiety or Irritability Issues | -0.2933333 score on a scale | Standard Error 0.6165 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) Assessment Domain Scores | Daily Function Issues | 0.93 score on a scale | Standard Error 0.5763 |
Secondary
Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values
VABS-3 is a clinician-administered standardized interview. For this study, we collected data in domains of communication (receptive & written language), daily living skills (domestic & community skills), & socialization (interpersonal relationships, play & leisure time, & coping abilities). This assessment was administered at Baseline as well as at Week 4, Week 8, Week 12, and Week 16 (end of each treatment period). Mean growth scale value (GSV) for each subdomain was recorded at each time point and change from baseline was calculated. The possible GSVs for each subdomain are receptive (10-162), written (10-163), domestic (10-110), community (10-136), interpersonal (10-152), play and leisure (10-164), & coping skills (10-120). Higher GSVs for each subdomain indicate better functioning.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ergoloid Mesylates (EM) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Receptive Communication Subdomain | 0.3603766 score on a scale | Standard Error 3.0827 |
| Ergoloid Mesylates (EM) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Daily Living Skills - Domestic Subdomain | -1.940166 score on a scale | Standard Error 2.46 |
| Ergoloid Mesylates (EM) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Daily Living Skills - Community Subdomain | 2.2145 score on a scale | Standard Error 1.9946 |
| Ergoloid Mesylates (EM) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Social - Play and Leisure Subdomain | -10.989137 score on a scale | Standard Error 6.4126 |
| Ergoloid Mesylates (EM) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Social - Coping Skills Subdomain | 1.460214 score on a scale | Standard Error 2.8857 |
| Ergoloid Mesylates (EM) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Social - Interpersonal Relationships Subdomain | 6.01876 score on a scale | Standard Error 2.346 |
| Ergoloid Mesylates (EM) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Written Communication Subdomain | 3.926537 score on a scale | Standard Error 2.603 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Daily Living Skills - Domestic Subdomain | 1.421966 score on a scale | Standard Error 2.3207 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Receptive Communication Subdomain | 4.4457568 score on a scale | Standard Error 2.9079 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Written Communication Subdomain | 3.915339 score on a scale | Standard Error 2.4556 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Daily Living Skills - Community Subdomain | 3.437951 score on a scale | Standard Error 1.8816 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Social - Interpersonal Relationships Subdomain | 6.042022 score on a scale | Standard Error 2.2132 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Social - Play and Leisure Subdomain | -3.47187 score on a scale | Standard Error 6.0588 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Social - Coping Skills Subdomain | 2.756048 score on a scale | Standard Error 2.7214 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Written Communication Subdomain | 5.287075 score on a scale | Standard Error 2.2088 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Daily Living Skills - Domestic Subdomain | 5.013375 score on a scale | Standard Error 2.0873 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Social - Interpersonal Relationships Subdomain | 6.664025 score on a scale | Standard Error 1.9898 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Social - Coping Skills Subdomain | 2.077872 score on a scale | Standard Error 2.4548 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Social - Play and Leisure Subdomain | -1.203629 score on a scale | Standard Error 5.5469 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Receptive Communication Subdomain | 3.9678919 score on a scale | Standard Error 2.6167 |
| 5-hydroxytryptophan (5-HTP) | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Daily Living Skills - Community Subdomain | 2.733986 score on a scale | Standard Error 1.6921 |
| Placebo | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Written Communication Subdomain | 5.051526 score on a scale | Standard Error 2.3123 |
| Placebo | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Daily Living Skills - Community Subdomain | 4.313574 score on a scale | Standard Error 1.7715 |
| Placebo | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Daily Living Skills - Domestic Subdomain | 5.501518 score on a scale | Standard Error 2.1852 |
| Placebo | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Receptive Communication Subdomain | 5.2990546 score on a scale | Standard Error 2.7389 |
| Placebo | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Social - Coping Skills Subdomain | 7.090882 score on a scale | Standard Error 2.5673 |
| Placebo | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Social - Play and Leisure Subdomain | 5.592143 score on a scale | Standard Error 5.8006 |
| Placebo | Change From Baseline on Vineland-3 Adaptive Behavior Scale - Subdomain Growth Scale Values | Social - Interpersonal Relationships Subdomain | 5.801988 score on a scale | Standard Error 2.0834 |
Secondary
Event-Related Potentials (ERP) Components in Response to Standard Tones
Event-Related Potentials (ERPs) enable extraction of neural responses associated with specific sensory, cognitive, or motor events from an overall EEG. Auditory stimuli are presented and EEG events are assessed in relation to timing of the stimuli. ERP was performed at Baseline as well as at week Week 4, Week 8, Week 12, Week 16 (end of each treatment period). The area under the curve was measured for different components of the ERP including P1 and P2 (positive components) and N1 and N2 (negative components). The average area under the curve was recorded for each component at each time point and change from baseline was calculated. Individuals with FXS are thought to have excessive ERP response, so a decrease in area under each curve compared to baseline would indicate a favorable outcome.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ergoloid Mesylates (EM) | Event-Related Potentials (ERP) Components in Response to Standard Tones | P1 Component | 0.009766667 μV*seconds | Standard Error 0.001838821 |
| Ergoloid Mesylates (EM) | Event-Related Potentials (ERP) Components in Response to Standard Tones | P2 Component | 0.041122167 μV*seconds | Standard Error 0.007281467 |
| Ergoloid Mesylates (EM) | Event-Related Potentials (ERP) Components in Response to Standard Tones | N1 Component | 0.025633667 μV*seconds | Standard Error 0.006968832 |
| Ergoloid Mesylates (EM) | Event-Related Potentials (ERP) Components in Response to Standard Tones | N2 Component | 0.033444167 μV*seconds | Standard Error 0.009811161 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Event-Related Potentials (ERP) Components in Response to Standard Tones | P2 Component | 0.031379615 μV*seconds | Standard Error 0.009411693 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Event-Related Potentials (ERP) Components in Response to Standard Tones | N1 Component | 0.029363077 μV*seconds | Standard Error 0.006649054 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Event-Related Potentials (ERP) Components in Response to Standard Tones | N2 Component | 0.038742385 μV*seconds | Standard Error 0.01309467 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Event-Related Potentials (ERP) Components in Response to Standard Tones | P1 Component | 0.010784615 μV*seconds | Standard Error 0.002861501 |
| 5-hydroxytryptophan (5-HTP) | Event-Related Potentials (ERP) Components in Response to Standard Tones | N1 Component | 0.035257182 μV*seconds | Standard Error 0.007841523 |
| 5-hydroxytryptophan (5-HTP) | Event-Related Potentials (ERP) Components in Response to Standard Tones | P2 Component | 0.046629091 μV*seconds | Standard Error 0.009927824 |
| 5-hydroxytryptophan (5-HTP) | Event-Related Potentials (ERP) Components in Response to Standard Tones | N2 Component | 0.028213 μV*seconds | Standard Error 0.012192131 |
| 5-hydroxytryptophan (5-HTP) | Event-Related Potentials (ERP) Components in Response to Standard Tones | P1 Component | 0.012972727 μV*seconds | Standard Error 0.003341777 |
| Placebo | Event-Related Potentials (ERP) Components in Response to Standard Tones | N2 Component | 0.0185623 μV*seconds | Standard Error 0.009189006 |
| Placebo | Event-Related Potentials (ERP) Components in Response to Standard Tones | P2 Component | 0.0558891 μV*seconds | Standard Error 0.014525993 |
| Placebo | Event-Related Potentials (ERP) Components in Response to Standard Tones | P1 Component | 0.00621 μV*seconds | Standard Error 0.001656264 |
| Placebo | Event-Related Potentials (ERP) Components in Response to Standard Tones | N1 Component | 0.0354182 μV*seconds | Standard Error 0.008270948 |
Secondary
Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal)
Event-Related Potentials (ERPs) enable extraction of neural responses associated with specific sensory, cognitive, or motor events from an overall EEG. Gamma 1 and gamma 2 waves were measured for various parts of the brain at a resting state. ERP was performed at Baseline as well as at Week 4, Week 8, Week 12, Week 16 (at the end of each treatment period). Mean power of gamma 1 and gamma 2 bands, measured by frontal EEG leads, was recorded for each time point and change from baseline was calculated. FXS patients have typically been found to exhibit greater gamma frequency band power than typically developing controls, which may be related to social and sensory processing difficulties. Therefore, lower gamma band power would indicate better functioning.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ergoloid Mesylates (EM) | Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal) | Gamma 1 (30-55 Hz) Absolute Power | 0.054717778 V^2/Hz | Standard Error 0.009638014 |
| Ergoloid Mesylates (EM) | Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal) | Gamma 2 (65-80 Hz) Absolute Power | 0.027005807 V^2/Hz | Standard Error 0.005267368 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal) | Gamma 2 (65-80 Hz) Absolute Power | 0.025525849 V^2/Hz | Standard Error 0.004251649 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal) | Gamma 1 (30-55 Hz) Absolute Power | 0.051050595 V^2/Hz | Standard Error 0.006690128 |
| 5-hydroxytryptophan (5-HTP) | Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal) | Gamma 1 (30-55 Hz) Absolute Power | 0.061321956 V^2/Hz | Standard Error 0.007923461 |
| 5-hydroxytryptophan (5-HTP) | Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal) | Gamma 2 (65-80 Hz) Absolute Power | 0.031589661 V^2/Hz | Standard Error 0.004834075 |
| Placebo | Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal) | Gamma 1 (30-55 Hz) Absolute Power | 0.050649034 V^2/Hz | Standard Error 0.010533546 |
| Placebo | Event-Related Potentials (ERP) - Gamma Band Absolute Power at Resting State (Frontal) | Gamma 2 (65-80 Hz) Absolute Power | 0.025235128 V^2/Hz | Standard Error 0.004757463 |
Secondary
Event-Related Potentials - Frontal Alpha Asymmetry at Resting State
Event-Related Potentials (ERPs) enable extraction of neural responses associated with specific sensory, cognitive, or motor events from an overall EEG. EEG data was collected when the subject was in a resting state. Frontal alpha asymmetry measures differences in alpha activity level of the right and left hemisphere of the frontal lobe of the brain. ERP was performed at Baseline as well as at Week 4, Week 8, Week 12, Week 16 (end of each treatment period). Mean alpha asymmetry at resting state was recorded and change from baseline was calculated for each time point. Higher alpha asymmetry scores indicate greater alpha power in the right hemisphere, which corresponds to increased neural activity of the left hemisphere. High activity of the left frontal lobe is hypothesized to correspond with approach behaviors, and high activity of the right frontal lobe is thought to correspond to withdrawal behaviors. In this study, higher alpha asymmetry scores indicate a better outcome.
Time frame: Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)
Population: Intent to treat (ITT) efficacy population, which will include all participants who received at least one dose of treatment and returned for at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ergoloid Mesylates (EM) | Event-Related Potentials - Frontal Alpha Asymmetry at Resting State | 0.044133817 unitless | Standard Error 0.085312863 |
| Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP) | Event-Related Potentials - Frontal Alpha Asymmetry at Resting State | -0.048217532 unitless | Standard Error 0.094117681 |
| 5-hydroxytryptophan (5-HTP) | Event-Related Potentials - Frontal Alpha Asymmetry at Resting State | -0.133404775 unitless | Standard Error 0.085879258 |
| Placebo | Event-Related Potentials - Frontal Alpha Asymmetry at Resting State | 0.191055011 unitless | Standard Error 0.106432066 |