Tuberous Sclerosis Complex
Conditions
Keywords
Tuberous Sclerosis Complex, Autism, Neurocognition, RAD001, Everolimus, Afinitor, TSC
Brief summary
Tuberous Sclerosis Complex (TSC) is a multi-system disease, usually presenting with seizures, mental retardation and autism, and exhibiting a high variability in clinical findings both among and within families. Investigators are doing research in order to identify possible neurocognitive benefits from treatment with RAD001 or placebo for a six month period. There may also be potential for improvements in seizure frequency, sleep and autistic behaviors. We hope this trial will lead to a better understanding of TSC and to new forms of treatment, to benefit children and adults with TSC in the future. Individuals diagnosed with TSC will be asked to participate in this study if they are between the ages of 6 and 21 years of age and have an IQ of greater than or equal to 60. Both males and females will be asked to participate. Additionally, to be eligible for study participation, individuals must have been on the same seizure medication(s), if applicable, for at least 6 months. Individuals must also be able to participate in neuropsychological testing and meet certain medical criteria. They will need to sign an informed consent. If enrolled in the study, participants will have a number of screening tests to help determine if they are eligible for participation in the clinical trial. If eligible for the treatment phase of the trial, they will be asked to take either the study drug or a placebo (pill with no medicine), which is determined by chance. The study involves about 9 visits, 3 of which can be done locally, over a six month period, as well as follow-up calls with our research nurse. Study visits will vary in length. Screening, three month and six month visits may last up to 8 hours, while all other visits will be less than 2 hours. The study visits include blood draws, laboratory tests and neuropsychological assessments. There is no fee to participate in this study. The study drug will be provided at no charge during the study. After all study data has been analyzed, families will be informed of the overall results. Treatment on this study may or may not improve a child's learning skills (neurocognition). Future patients may benefit from what is learned.
Detailed description
This is a signal-seeking Phase II randomized, placebo-controlled trial of RAD001 in children and young adults with TSC with neurocognition as the primary outcome and autism spectrum disorder as a secondary outcome. Specific Aims /Objectives Primary objective * To evaluate the efficacy of RAD001 on neurocognition in patients with TSC compared to placebo as measured by well-validated, standardized, direct and indirect neurocognitive tools. * To evaluate the safety of RAD001 compared with placebo in patients with TSC focusing on NCI CTCAE Grade 3 and 4 adverse events, serious adverse events, and Grade 3 and 4 laboratory toxicities. Secondary objectives * Comparison of absolute change from baseline in frequency of epileptiform events as recorded on seizure diaries between patients taking RAD001 vs. placebo * Comparison of sleep disturbances between patients taking RAD001 vs. placebo, measured by the Pediatric Sleep Questionnaire (PSQ) and sleep logs * Comparison of autism spectrum disorders features between patients taking RAD001 vs. placebo, measured by ADOS and SRS * Comparison of academic skills between patients taking RAD001 vs. placebo, measured by WRAT4 * Comparison of behavioral problems between patients taking RAD001 vs placebo, measured by behavioral rating scales (BRIEF, BASC, SDQ, CHQ and SRS)
Interventions
DRUGRAD001
RAD001 is formulated as tablets of 5.0 mg strength, blister-packed under aluminum foil in units of 10 tablets and dosed on a regular basis. RAD001 tablets should be opened only at the time of administration as drug is both hygroscopic and light-sensitive. Patients will be instructed to take 4.5 mg/m2 of RAD001 orally with a glass of water at regular intervals at the same time in the morning after a light, nonfat breakfast.
DRUGPlacebo
Matching placebo will be provided as a matching tablet and will also be blister packed under aluminum foil in units of 10. Matching placebo tablets should be opened only at the time of administration as drug is both hygroscopic and light-sensitive. Patients will be instructed to take 4.5 mg/m2 of the matching placebo orally with a glass of water at regular intervals at the same time in the morning after a light, nonfat breakfast.
Sponsors
Tuberous Sclerosis Alliance
Autism Speaks
Novartis Pharmaceuticals
Seizure Tracker LLC
Mustafa Sahin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients ages 6 to 21 years of age. 2. IQ ≥60. 3. Ability to participate in direct neuropsychological and developmental testing. 4. English as primary language. 5. Diagnosis of tuberous sclerosis complex confirmed by genetic testing and/or clinically definite diagnosis of tuberous sclerosis complex according to the modified Gomez criteria and an IQ\>60. 6. Stable anti-epileptic drugs (no changes in medications except dose for \>6 months). 7. Adequate renal function. The GFR would be greater than 50 ml/min.m2 as determined by the Schwartz Formula for children and MDRD for adults: http://www.nkdep.nih.gov/professionals/gfr\_calculators/index.htm 8. If female and of child bearing potential, documentation of negative pregnancy test prior to enrollment. Sexually active pre-menopausal female patients (and female partners of male patients) must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study. Abstinence will be considered an adequate contraceptive measure. 9. INR ≤1.5 (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for \>2 weeks at time of randomization.) 10. Adequate liver function as shown by: * serum bilirubin ≤ 1.5 x ULN * ALT and AST ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases) 11. Written informed consent according to local guidelines.
Exclusion criteria
1. Change of one or more antiepileptic medication in the past 6 months. 2. Prior exposure to the systemic use of an mTOR inhibitor. 3. Exposure to any investigational agent in the 30 days prior to randomization. 4. Neurosurgery within 6 months. 5. Known impaired lung function (e.g.FEV1 or DLCO \<70% of predicted), if not resolved or if resolved within past 24 months. 6. Significant hematological or hepatic abnormality (i.e. transaminase levels \> 2.5 x ULN or serum bilirubin \> 1.5 x ULN, hemoglobin \< 9 g/dL, platelets \< 80,000/ mm3, absolute neutrophil count \< 1,000/mm3). 7. Serum creatinine \> 1.5 x ULN. 8. Uncontrolled hyperlipidemia: Fasting serum cholesterol \> 300 mg/dL OR \> 7.75 mmol/L AND Fasting triglycerides \> 2.5 x ULN. 9. Uncontrolled diabetes mellitus as defined by fasting serum glucose \> 1.5 x ULN. 10. Patients with bleeding diathesis or on oral anti-vitamin K medication (except low dose warfarin). 11. Patients with known history of HIV seropositivity. 12. Pregnancy or breast feeding. 13. Active infection at date of randomization. 14. Prior history of organ transplant. 15. Recent surgery (involving entry into a body cavity or requiring sutures) within the 4 weeks prior to randomization. 16. Inability to attend scheduled clinic visits. 17. History of malignancy in the past two years, other than squamous or basal cell skin cancer. 18. Patients should not receive immunization with attenuated live vaccines within one month of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines. 19. Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C). Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV DNA and HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection. 20. Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed. 21. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: * symptomatic congestive heart failure of New York heart Association Class III or IV * unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease 22. Patients who have received an IQ score under 60 in the six months prior to the study screening visit will be deemed ineligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the Safety of RAD001 on Neurocognition in Patients With TSC Compared With Placebo in Patients With TSC. | 6 months | Evaluation of the safety of RAD001 compared with placebo in patients with TSC focusing on NCI CTCAE Grade 3 and 4 adverse events, serious adverse events, and Grade 3 and 4 laboratory toxicities. |
| Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | 6 months | Baseline and 6 month Timepoint scores are reported for the following primary outcome measures: 1. Peabody Picture Vocabulary Test 4 (PPVT-4; Receptive Language Measure). Scores reported as (mean, SD). Range=40-160, higher scores are better. 2. Expressive Vocabulary Test 2 (EVT-2; Expressive Language Measure). Scores reported as (mean, SD). Range=40-160, higher scores are better. 3. Wide Range Assessment of Memory and Learning 2 (WRAML2; Measure of Verbal Memory and Attention ). Scores reported as (mean, SD). Range=1-19, higher scores are better. 4. Vineland Adaptive Behavior Scales-II (VABS-II; Measure of Adaptive Behavior). Scores reported as (mean, SD). Range = 40-160, higher scores are better. 5. Purdue Pegboard Test (Measure of Fine Motor Speed and Coordination). Scores reported as (mean, SD). Range = 40-160, higher scores are better. |
| Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | 6 months | Scores are reported for baseline and 6 month timepoints on the Cambridge Neuropsychological Test Automated Battery (CANTAB) subscales below. For all subscales, scores are reported as the mean difference between the study subjects and a normative population matched for age, gender and IQ (e.g., subject subscale score - mean of matched normative group = reported score). Higher scores represent a better outcome. 1. Spatial Span (SSP) (spatial memory span) Range: -3 to 3 2. Spatial Working Memory (working memory) Range: -3 to 3 3. Pattern Recognition Memory (PRM) (visual pattern recognition memory) Range: -3 to 3 4. Spatial Recognition Memory (SRM) (spatial recognition memory) Range: -4 to 4 5. Rapid Visual Information Processing (RVIP) (sustained attention) Range: -4 to 4 6. Stockings of Cambridge (SOC) (spatial planning) Range: -4 to 4 7. Intra-Extra Dimensional Set Shift (IDED) (cognitive flexibility) Range: -5 to 5 8. Reaction Time (processing speed) Range: -5 to 5 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Academic Skills Between Patients Taking RAD001 vs. Placebo | 6 months | Scores are reported for Baseline and 6 Month Timepoints. The secondary outcome measure was the Wide Range Achievement Test 4 (WRAT4), which was used to assess academic skills. The Reading and Math subtests were used. Standard scores are reported which have a mean of 100 and a standard deviation of 15 (range=40-160 where higher is better). |
| Comparison of Absolute Change From Baseline in Frequency of Epileptiform Events Between Patients Taking RAD001 vs. Placebo | 6 months | Comparison of absolute change from baseline in frequency of epileptiform events as recorded on seizure diaries between patients taking RAD001 vs. placebo |
| Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | 6 months | Scores for Baseline and 6 Month Timepoints are reported for the following secondary outcome measures: 1. Behavior Rating Inventory of Executive Function (BRIEF) (Measure of executive functions) T-scores are reported, with a mean of 50 and a standard deviation of 10. The range is 30-100 with higher scores indicating a worse outcome. 2. Behavioral Assessment System for Children (BASC) (Measure of emotional and behavioral problems) T-scores are reported (mean of 50, SD of 10). The range is 30-100 with higher scores indicating a worse outcome. Conversely, on the Adaptive Skills subscale of the BASC, lower scores indicate a poorer outcome. 3. Strengths and Difficulties Questionnaire (SDQ). Includes questions related to emotional symptoms, conduct problems, inattention/hyperactivity, peer relationship problems and prosocial behavior. Responses to these items are summed to comprise a Total Difficulties Score, which ranges from 0-40, with lower scores indicating a better outcome |
| Comparison of Sleep Disturbances Between Patients Taking RAD001 vs. Placebo | 6 months | Comparison of sleep disturbances between patients taking RAD001 vs. placebo, measured by the Pediatric Sleep Questionnaire (PSQ) and sleep logs |
| Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | 6 months | Scores for the Baseline and 6 Month Timepoints are reported. The secondary outcome measure was the Social Responsiveness Scale (SRS). Standard scores are reported with a mean of 100 and standard deviation of 15. The range is 40-160 with higher scores indicating a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RAD001 RAD001 is formulated as tablets of 5.0 mg strength, blister-packed under aluminum foil in units of 10 tablets and dosed on a regular basis.
RAD001: RAD001 is formulated as tablets of 5.0 mg strength, blister-packed under aluminum foil in units of 10 tablets and dosed on a regular basis. RAD001 tablets should be opened only at the time of administration as drug is both hygroscopic and light-sensitive.
Patients will be instructed to take 4.5 mg/m2 of RAD001 orally with a glass of water at regular intervals at the same time (delete: each day) in the morning after a light, nonfat breakfast. | 32 |
| Placebo Matching placebo will be provided as a matching tablet and will also be blister packed under aluminum foil in units of 10.
Placebo: Matching placebo will be provided as a matching tablet and will also be blister packed under aluminum foil in units of 10. Matching placebo tablets should be opened only at the time of administration as drug is both hygroscopic and light-sensitive.
Patients will be instructed to take 4.5 mg/m2 of the matching placebo orally with a glass of water at regular intervals at the same time (delete: each day) in the morning after a light, nonfat breakfast. | 15 |
| Total | 47 |
Baseline characteristics
| Characteristic | RAD001 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 13.25 years STANDARD_DEVIATION 5.06 | 11.47 years STANDARD_DEVIATION 5.3 | 12.68 years STANDARD_DEVIATION 5.15 |
| Sex: Female, Male Female | 16 Participants | 7 Participants | 23 Participants |
| Sex: Female, Male Male | 16 Participants | 8 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 32 | 10 / 15 |
| serious Total, serious adverse events | 3 / 32 | 0 / 15 |
Outcome results
Primary
Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo.
Scores are reported for baseline and 6 month timepoints on the Cambridge Neuropsychological Test Automated Battery (CANTAB) subscales below. For all subscales, scores are reported as the mean difference between the study subjects and a normative population matched for age, gender and IQ (e.g., subject subscale score - mean of matched normative group = reported score). Higher scores represent a better outcome. 1. Spatial Span (SSP) (spatial memory span) Range: -3 to 3 2. Spatial Working Memory (working memory) Range: -3 to 3 3. Pattern Recognition Memory (PRM) (visual pattern recognition memory) Range: -3 to 3 4. Spatial Recognition Memory (SRM) (spatial recognition memory) Range: -4 to 4 5. Rapid Visual Information Processing (RVIP) (sustained attention) Range: -4 to 4 6. Stockings of Cambridge (SOC) (spatial planning) Range: -4 to 4 7. Intra-Extra Dimensional Set Shift (IDED) (cognitive flexibility) Range: -5 to 5 8. Reaction Time (processing speed) Range: -5 to 5
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Pattern Recognition Memory | -1.48 units on a scale | Standard Deviation 1.9 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Spatial Recognition Memory | -2.33 units on a scale | Standard Deviation 1.4 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Spatial Span | -1.32 units on a scale | Standard Deviation 1.18 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Spatial Working Memory | -.66 units on a scale | Standard Deviation 0.79 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Reaction Time | -2.24 units on a scale | Standard Deviation 3.63 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Rapid Visual Processing | -.96 units on a scale | Standard Deviation 2.59 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Stockings of Cambridge | -1.38 units on a scale | Standard Deviation 1.32 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB IDED | -1.02 units on a scale | Standard Deviation 1.65 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Rapid Visual Processing | -1.41 units on a scale | Standard Deviation 2.8 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Reaction Time | -1.15 units on a scale | Standard Deviation 2.22 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Spatial Recognition Memory | -2.24 units on a scale | Standard Deviation 1.33 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB IDED | -1.48 units on a scale | Standard Deviation 2.05 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Stockings of Cambridge | -1.89 units on a scale | Standard Deviation 1.47 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Spatial Working Memory | -.67 units on a scale | Standard Deviation 1.57 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Spatial Span | -1.02 units on a scale | Standard Deviation 1.2 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Pattern Recognition Memory | -1.23 units on a scale | Standard Deviation 2.11 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Stockings of Cambridge | -.58 units on a scale | Standard Deviation 1.11 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Spatial Span | -1.29 units on a scale | Standard Deviation 1.41 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Spatial Working Memory | -.73 units on a scale | Standard Deviation 0.97 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Reaction Time | -.88 units on a scale | Standard Deviation 1.38 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Rapid Visual Processing | -.97 units on a scale | Standard Deviation 2.71 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB IDED | -1.05 units on a scale | Standard Deviation 1.64 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Pattern Recognition Memory | -.91 units on a scale | Standard Deviation 1.6 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Spatial Recognition Memory | -2.62 units on a scale | Standard Deviation 1.58 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Spatial Span | -1.32 units on a scale | Standard Deviation 1.37 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Spatial Working Memory | -.27 units on a scale | Standard Deviation 2.87 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Spatial Recognition Memory | -2.19 units on a scale | Standard Deviation 1.56 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Pattern Recognition Memory | -1.09 units on a scale | Standard Deviation 1.79 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Reaction Time | -2.91 units on a scale | Standard Deviation 3.84 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB IDED | -2.24 units on a scale | Standard Deviation 3.32 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Stockings of Cambridge | -1.84 units on a scale | Standard Deviation 1.32 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition (Cambridge Neuropsychological Test Automated Battery) in Patients With TSC Compared With Placebo. | CANTAB Rapid Visual Processing | -1.2 units on a scale | Standard Deviation 2.15 |
Primary
Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo.
Baseline and 6 month Timepoint scores are reported for the following primary outcome measures: 1. Peabody Picture Vocabulary Test 4 (PPVT-4; Receptive Language Measure). Scores reported as (mean, SD). Range=40-160, higher scores are better. 2. Expressive Vocabulary Test 2 (EVT-2; Expressive Language Measure). Scores reported as (mean, SD). Range=40-160, higher scores are better. 3. Wide Range Assessment of Memory and Learning 2 (WRAML2; Measure of Verbal Memory and Attention ). Scores reported as (mean, SD). Range=1-19, higher scores are better. 4. Vineland Adaptive Behavior Scales-II (VABS-II; Measure of Adaptive Behavior). Scores reported as (mean, SD). Range = 40-160, higher scores are better. 5. Purdue Pegboard Test (Measure of Fine Motor Speed and Coordination). Scores reported as (mean, SD). Range = 40-160, higher scores are better.
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | PPVT4 (Receptive Language) | 86.00 units on a scale | Standard Deviation 17.78 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | WRAML2 Verbal Recall | 7.07 units on a scale | Standard Deviation 2.94 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Daily Living Skills | 78.80 units on a scale | Standard Deviation 19.5 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | EVT2 (Expressive Language) | 85.47 units on a scale | Standard Deviation 12.22 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Socialization | 79.07 units on a scale | Standard Deviation 19.67 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Adaptive Behavior Composite | 78.79 units on a scale | Standard Deviation 19.69 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | WRAML2 Verbal Learning | 8.00 units on a scale | Standard Deviation 2 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | Pegboard, Non-Dominant Hand | 105.27 units on a scale | Standard Deviation 37.1 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | Pegboard, Dominant Hand | 101.33 units on a scale | Standard Deviation 54.27 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Communication | 81.27 units on a scale | Standard Deviation 21.87 |
| RAD001 | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Motor Skills | 89.87 units on a scale | Standard Deviation 18.26 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Communication | 73.68 units on a scale | Standard Deviation 15.45 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Motor Skills | 78.83 units on a scale | Standard Deviation 21.68 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Socialization | 74.10 units on a scale | Standard Deviation 15.46 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Daily Living Skills | 74.68 units on a scale | Standard Deviation 15.69 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | WRAML2 Verbal Learning | 7.14 units on a scale | Standard Deviation 3.16 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | Pegboard, Non-Dominant Hand | 119.30 units on a scale | Standard Deviation 44.19 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | WRAML2 Verbal Recall | 7.52 units on a scale | Standard Deviation 2.53 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | Pegboard, Dominant Hand | 103.06 units on a scale | Standard Deviation 41.18 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Adaptive Behavior Composite | 72.06 units on a scale | Standard Deviation 13.9 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | EVT2 (Expressive Language) | 90.00 units on a scale | Standard Deviation 21.15 |
| Placebo | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | PPVT4 (Receptive Language) | 81.06 units on a scale | Standard Deviation 23.96 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | Pegboard, Dominant Hand | 89.83 units on a scale | Standard Deviation 24.99 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | PPVT4 (Receptive Language) | 88.54 units on a scale | Standard Deviation 17.21 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | EVT2 (Expressive Language) | 89.15 units on a scale | Standard Deviation 16.08 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | WRAML2 Verbal Learning | 8.46 units on a scale | Standard Deviation 2.44 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | WRAML2 Verbal Recall | 8.23 units on a scale | Standard Deviation 3.49 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Adaptive Behavior Composite | 79.00 units on a scale | Standard Deviation 15.26 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Communication | 81.77 units on a scale | Standard Deviation 16.66 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Socialization | 80.38 units on a scale | Standard Deviation 17.78 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Daily Living Skills | 81.69 units on a scale | Standard Deviation 14.74 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Motor Skills | 92.69 units on a scale | Standard Deviation 18.65 |
| Placebo - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | Pegboard, Non-Dominant Hand | 92.15 units on a scale | Standard Deviation 34.26 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Communication | 76.79 units on a scale | Standard Deviation 14.76 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | Pegboard, Non-Dominant Hand | 112.78 units on a scale | Standard Deviation 50.89 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Motor Skills | 87.79 units on a scale | Standard Deviation 18.12 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Adaptive Behavior Composite | 74.72 units on a scale | Standard Deviation 14.57 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | WRAML2 Verbal Recall | 8.08 units on a scale | Standard Deviation 2.77 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | WRAML2 Verbal Learning | 7.85 units on a scale | Standard Deviation 2.92 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | Pegboard, Dominant Hand | 97.25 units on a scale | Standard Deviation 39.02 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | EVT2 (Expressive Language) | 82.55 units on a scale | Standard Deviation 21.22 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | PPVT4 (Receptive Language) | 82.5 units on a scale | Standard Deviation 22.32 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Daily Living Skills | 76.41 units on a scale | Standard Deviation 17.37 |
| RAD001 - 6 Months | Evaluation of the Efficacy of RAD001 on Neurocognition in Patients With TSC Compared With Placebo. | VABS2 Socialization | 76.86 units on a scale | Standard Deviation 16.4 |
Primary
Evaluation of the Safety of RAD001 on Neurocognition in Patients With TSC Compared With Placebo in Patients With TSC.
Evaluation of the safety of RAD001 compared with placebo in patients with TSC focusing on NCI CTCAE Grade 3 and 4 adverse events, serious adverse events, and Grade 3 and 4 laboratory toxicities.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RAD001 | Evaluation of the Safety of RAD001 on Neurocognition in Patients With TSC Compared With Placebo in Patients With TSC. | 325 Adverse Events |
| Placebo | Evaluation of the Safety of RAD001 on Neurocognition in Patients With TSC Compared With Placebo in Patients With TSC. | 147 Adverse Events |
Secondary
Comparison of Absolute Change From Baseline in Frequency of Epileptiform Events Between Patients Taking RAD001 vs. Placebo
Comparison of absolute change from baseline in frequency of epileptiform events as recorded on seizure diaries between patients taking RAD001 vs. placebo
Time frame: 6 months
Population: Data was not collected reliably and therefore was not analyzed.
Secondary
Comparison of Academic Skills Between Patients Taking RAD001 vs. Placebo
Scores are reported for Baseline and 6 Month Timepoints. The secondary outcome measure was the Wide Range Achievement Test 4 (WRAT4), which was used to assess academic skills. The Reading and Math subtests were used. Standard scores are reported which have a mean of 100 and a standard deviation of 15 (range=40-160 where higher is better).
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAD001 | Comparison of Academic Skills Between Patients Taking RAD001 vs. Placebo | Word Reading (WRAT 4) | 86.80 units on a scale | Standard Deviation 16.79 |
| RAD001 | Comparison of Academic Skills Between Patients Taking RAD001 vs. Placebo | Math Computation (WRAT 4) | 76.00 units on a scale | Standard Deviation 15.64 |
| Placebo | Comparison of Academic Skills Between Patients Taking RAD001 vs. Placebo | Math Computation (WRAT 4) | 74.60 units on a scale | Standard Deviation 17.99 |
| Placebo | Comparison of Academic Skills Between Patients Taking RAD001 vs. Placebo | Word Reading (WRAT 4) | 84.28 units on a scale | Standard Deviation 20.07 |
| Placebo - 6 Months | Comparison of Academic Skills Between Patients Taking RAD001 vs. Placebo | Math Computation (WRAT 4) | 77.31 units on a scale | Standard Deviation 16.93 |
| Placebo - 6 Months | Comparison of Academic Skills Between Patients Taking RAD001 vs. Placebo | Word Reading (WRAT 4) | 91.15 units on a scale | Standard Deviation 20.76 |
| RAD001 - 6 Months | Comparison of Academic Skills Between Patients Taking RAD001 vs. Placebo | Math Computation (WRAT 4) | 73.81 units on a scale | Standard Deviation 16.01 |
| RAD001 - 6 Months | Comparison of Academic Skills Between Patients Taking RAD001 vs. Placebo | Word Reading (WRAT 4) | 84.45 units on a scale | Standard Deviation 20.45 |
Secondary
Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo
Scores for the Baseline and 6 Month Timepoints are reported. The secondary outcome measure was the Social Responsiveness Scale (SRS). Standard scores are reported with a mean of 100 and standard deviation of 15. The range is 40-160 with higher scores indicating a better outcome.
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAD001 | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Responsiveness (range 40(worse) -160) | 77.14 units on a scale (SRS) | Standard Deviation 17.5 |
| RAD001 | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Awareness | 67.40 units on a scale (SRS) | Standard Deviation 14.69 |
| RAD001 | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Cognition | 76.43 units on a scale (SRS) | Standard Deviation 19.59 |
| RAD001 | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Communication | 74.36 units on a scale (SRS) | Standard Deviation 16.75 |
| RAD001 | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Motivation | 69.80 units on a scale (SRS) | Standard Deviation 16.6 |
| RAD001 | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Autism Mannerisms | 76.71 units on a scale (SRS) | Standard Deviation 17.32 |
| Placebo | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Autism Mannerisms | 80.03 units on a scale (SRS) | Standard Deviation 20.24 |
| Placebo | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Communication | 72.23 units on a scale (SRS) | Standard Deviation 17.18 |
| Placebo | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Responsiveness (range 40(worse) -160) | 76.43 units on a scale (SRS) | Standard Deviation 18.62 |
| Placebo | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Cognition | 75.70 units on a scale (SRS) | Standard Deviation 18.77 |
| Placebo | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Awareness | 62.90 units on a scale (SRS) | Standard Deviation 15.32 |
| Placebo | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Motivation | 69.60 units on a scale (SRS) | Standard Deviation 14.76 |
| Placebo - 6 Months | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Awareness | 67.38 units on a scale (SRS) | Standard Deviation 15.51 |
| Placebo - 6 Months | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Cognition | 81.15 units on a scale (SRS) | Standard Deviation 18.86 |
| Placebo - 6 Months | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Communication | 76.85 units on a scale (SRS) | Standard Deviation 21.55 |
| Placebo - 6 Months | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Autism Mannerisms | 79.77 units on a scale (SRS) | Standard Deviation 24.5 |
| Placebo - 6 Months | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Motivation | 72.77 units on a scale (SRS) | Standard Deviation 20.77 |
| Placebo - 6 Months | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Responsiveness (range 40(worse) -160) | 80.62 units on a scale (SRS) | Standard Deviation 22.83 |
| RAD001 - 6 Months | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Motivation | 67.24 units on a scale (SRS) | Standard Deviation 16.37 |
| RAD001 - 6 Months | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Autism Mannerisms | 78.66 units on a scale (SRS) | Standard Deviation 20.16 |
| RAD001 - 6 Months | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Awareness | 64.86 units on a scale (SRS) | Standard Deviation 17.19 |
| RAD001 - 6 Months | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Communication | 71.69 units on a scale (SRS) | Standard Deviation 17.98 |
| RAD001 - 6 Months | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Responsiveness (range 40(worse) -160) | 75.69 units on a scale (SRS) | Standard Deviation 19.27 |
| RAD001 - 6 Months | Comparison of Autism Spectrum Disorders Features Between Patients Taking RAD001 vs. Placebo | SRS Social Cognition | 76.17 units on a scale (SRS) | Standard Deviation 18.98 |
Secondary
Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo
Scores for Baseline and 6 Month Timepoints are reported for the following secondary outcome measures: 1. Behavior Rating Inventory of Executive Function (BRIEF) (Measure of executive functions) T-scores are reported, with a mean of 50 and a standard deviation of 10. The range is 30-100 with higher scores indicating a worse outcome. 2. Behavioral Assessment System for Children (BASC) (Measure of emotional and behavioral problems) T-scores are reported (mean of 50, SD of 10). The range is 30-100 with higher scores indicating a worse outcome. Conversely, on the Adaptive Skills subscale of the BASC, lower scores indicate a poorer outcome. 3. Strengths and Difficulties Questionnaire (SDQ). Includes questions related to emotional symptoms, conduct problems, inattention/hyperactivity, peer relationship problems and prosocial behavior. Responses to these items are summed to comprise a Total Difficulties Score, which ranges from 0-40, with lower scores indicating a better outcome
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAD001 | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BRIEF Global Executive Composite | 70.50 units on a scale | Standard Deviation 15.13 |
| RAD001 | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BRIEF Behavioral Regulation Index | 70.93 units on a scale | Standard Deviation 16.89 |
| RAD001 | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BRIEF Metacognition Index | 68.07 units on a scale | Standard Deviation 14.52 |
| RAD001 | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Behavioral Symptoms Index | 62.29 units on a scale | Standard Deviation 12.61 |
| RAD001 | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Externalizing Problems | 57.36 units on a scale | Standard Deviation 15.58 |
| RAD001 | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Internalizing Problems | 58.43 units on a scale | Standard Deviation 18.34 |
| RAD001 | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Adaptive Skills | 38.79 units on a scale | Standard Deviation 13.16 |
| RAD001 | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | SDQ Total Difficulties Scale | 16.00 units on a scale | Standard Deviation 6.93 |
| Placebo | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Internalizing Problems | 51.55 units on a scale | Standard Deviation 12.09 |
| Placebo | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Externalizing Problems | 53.24 units on a scale | Standard Deviation 9.85 |
| Placebo | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BRIEF Behavioral Regulation Index | 66.53 units on a scale | Standard Deviation 14.5 |
| Placebo | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | SDQ Total Difficulties Scale | 15.46 units on a scale | Standard Deviation 5.61 |
| Placebo | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Adaptive Skills | 36.72 units on a scale | Standard Deviation 10.22 |
| Placebo | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Behavioral Symptoms Index | 58.97 units on a scale | Standard Deviation 10.87 |
| Placebo | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BRIEF Metacognition Index | 68.93 units on a scale | Standard Deviation 12.12 |
| Placebo | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BRIEF Global Executive Composite | 69.48 units on a scale | Standard Deviation 12.98 |
| Placebo - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Adaptive Skills | 42.08 units on a scale | Standard Deviation 13.27 |
| Placebo - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BRIEF Metacognition Index | 61.83 units on a scale | Standard Deviation 12.97 |
| Placebo - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Behavioral Symptoms Index | 57.54 units on a scale | Standard Deviation 10.02 |
| Placebo - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Externalizing Problems | 52.62 units on a scale | Standard Deviation 9.26 |
| Placebo - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Internalizing Problems | 56.00 units on a scale | Standard Deviation 19.37 |
| Placebo - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | SDQ Total Difficulties Scale | 14.42 units on a scale | Standard Deviation 5.09 |
| Placebo - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BRIEF Global Executive Composite | 62.25 units on a scale | Standard Deviation 12.53 |
| Placebo - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BRIEF Behavioral Regulation Index | 60.83 units on a scale | Standard Deviation 12.41 |
| RAD001 - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BRIEF Metacognition Index | 64.57 units on a scale | Standard Deviation 10.65 |
| RAD001 - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Behavioral Symptoms Index | 55.41 units on a scale | Standard Deviation 11.26 |
| RAD001 - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BRIEF Behavioral Regulation Index | 62.57 units on a scale | Standard Deviation 12 |
| RAD001 - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BRIEF Global Executive Composite | 64.68 units on a scale | Standard Deviation 10.88 |
| RAD001 - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Externalizing Problems | 52.34 units on a scale | Standard Deviation 8.59 |
| RAD001 - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | SDQ Total Difficulties Scale | 13.20 units on a scale | Standard Deviation 5.9 |
| RAD001 - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Adaptive Skills | 40.00 units on a scale | Standard Deviation 12.02 |
| RAD001 - 6 Months | Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo | BASC2 Internalizing Problems | 51.45 units on a scale | Standard Deviation 14.42 |
Secondary
Comparison of Sleep Disturbances Between Patients Taking RAD001 vs. Placebo
Comparison of sleep disturbances between patients taking RAD001 vs. placebo, measured by the Pediatric Sleep Questionnaire (PSQ) and sleep logs
Time frame: 6 months
Population: Data was not collected reliably and therefore was not analyzed.