PTEN Gene Mutation, PTEN Hamartoma Tumor Syndrome
Conditions
Keywords
PTEN, PTEN Gene Mutation, PTEN Hamartoma Tumor Syndrome, Autism, Intellectual Disability, Neurocognition, Afinitor, Everolimus, RAD001
Brief summary
Phosphatase and TENsin homolog (PTEN) gene germline mutations are associated with a spectrum of clinical manifestations characterized by neurocognitive deficits, intellectual disability, autism symptomatology, skin lesions, macrocephaly, hamartomatous overgrowth of tissues, and an increased risk of cancers. Investigators are conducting research to evaluate the potential safety and efficacy of RAD001 (everolimus) in this patient population, and the potential neurocognitive benefits from treatment with RAD001 or placebo for a six month period. The investigators hope this trial will lead to a better understanding of PTEN and to new forms of treatment that may benefit children and adults with PTEN in the future.
Detailed description
This is a signal seeking Phase I/II 6-month, randomized, double-blind placebo-controlled trial of everolimus in individuals, ages 5 to 45 years with a PTEN mutation, with safety and neurocognition as the primary endpoints. Participant's or a legal guardian will need to sign an informed consent prior to enrollment in the study. To determine eligibility participants will undergo a series of screening tests and safety measures. If determined to be eligible for the blinded phase of the study, participants will be randomly assigned to take either the study drug or a placebo (pill with no medicine). The blinded phase of the study involves about eight visits, five of which will occur at the study site, and three of which will be conducted over the phone. These visits will take place over a six month period. Study visits will vary in length. Baseline, three month and six month visits may last up to 8 hours, if optional measures are done, while all other visits will be less than 2 hours. The study visits include blood draws, general health exams, and neuropsychological assessments. The study will also include optional eye-tracking, EEG and auditory evoked potential (AEP) measures, and the collection of microbiome/mycobiome and biomarker blood sample. There is no fee to participate in this study. The study drug will be provided at no charge during the study. After the 6 month treatment phase, individuals who were randomly assigned to take placebo will be offered inclusion in a 6 month open label phase where the study drug will be provided at no charge. The open label phase assessments will be similar to those done in the blinded phase, but patients/families will only need to return to the study site three times during this phase. Participants will receive a developmental assessments report after completing the study. After all study data has been analyzed, patients and families will also be informed of the overall results. Treatment on this study may or may not improve an individual's learning skills (neurocognition) or behavior. We hope that future patients and families will benefit from what is learned by this study. Specific Aims /Objectives Primary objective -To evaluate the safety of everolimus compared with placebo in patients with PTEN mutations focusing on NCI CTCAE Grade 3 and 4 adverse events, serious adverse events, and Grade 3 and 4 laboratory toxicities. Secondary objectives -To evaluate the efficacy of everolimus on neurocognition and behavior in inividuals with PTEN mutations compared to placebo as measured by standardized, direct and indirect neurocognitive tools and behavioral measures.
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 (delete: each day) 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 (delete: each day) in the morning after a light, nonfat breakfast.
Sponsors
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Office of Rare Diseases (ORD)
National Center for Advancing Translational Sciences (NCATS)
Novartis Pharmaceuticals
PTEN Research
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Boston Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
5 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
Double-Blind Inclusion Criteria 1. Male and female outpatients between 5 and 45 years of age (inclusive); 2. Pathogenic PTEN mutation confirmed by clinical genetic testing; 3. Participant must be able to complete one of the following three standardized assessments: Conners' Continuous Performance Tasks (CPT-3-mean reaction time), Stanford Binet (SB-5; working memory), or the Purdue Pegboard Test; 4. Performance below the age-adjusted population mean on at least one of the above standardized measure: attention (CPT-3, mean reaction time), working memory (SB5), or fine motor skills (Purdue Pegboard Test; either dominant hand, non-dominant hand, or both hands); 5. Adequate bone marrow function as shown by: 1. platelets ≥ 80,000/mm3 2. absolute neutrophil count ≥ 1,000/mm3 3. hemoglobin ≥ 9 g/dL 6. Adequate liver function as shown by: 1. Total serum bilirubin \< 1.5 x ULN 2. AST and ALT levels \< 2.5 x ULN 3. INR ≤ 2 7. Adequate renal function: serum creatinine \< 1.5 x ULN, 8. Signed informed consent obtained prior to any screening procedures; 9. Individuals on psychotropic and anti-epileptic medications should maintain a stable dose for at least 2 months prior to the screening visit; 10. Negative serum pregnancy test for females at screening and no plans to become pregnant or conceive a child while participating in the study. The effects of mTOR inhibitors on the developing fetus at the doses used in this study are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study. Estrogen-containing oral contraceptives are not recommended in women enrolled in this study. Abstinence or two effective non-estrogen or barrier methods of contraception (such as condoms + spermicidal foam) must be used; 11. No anticipated changes in the frequency and intensity of existing interventions such as behavioral and developmental treatments, in home services, and speech therapy; 12. No planned changes in school placement; 13. For individuals under 18 or who are otherwise incapable, there must be an available caregiver who can reliably bring subject to clinic visits and provide trustworthy data 14. Able to communicate fluently in English Double-Blind
Exclusion criteria
1. Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of Everolimus (including chemotherapy, radiation therapy, antibody based therapy, etc.); 2. Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus); 3. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus; 4. Uncontrolled diabetes mellitus as defined by HbA1c \>8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary; 5. Patient with uncontrolled hyperlipidemia: fasting serum cholesterol \> 300 mg/dL OR \>7.75 mmol/L AND fasting triglycerides \> 2.5 x ULN. 6. Patients who have any severe and/or uncontrolled medical or psychiatric conditions (see section 4.6 for additional details) 7. Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled corticosteroids are allowed; 8. Known history of or seropositivity for Hepatitis B, Hepatitis C, or HIV; 9. Patients who have received live attenuated vaccines within 1 week of start of Everolimus and during the study. Patient should also avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines; 10. Patients who have a history of another primary malignancy, with the exceptions of: 1. non-melanoma skin cancer, 2. and carcinoma in situ of the cervix, uteri, or breast from which the patient has been disease free for ≥3 years; 11. Planned changes to concomitant medications; 12. Prior or concomitant therapy with known or possible anti-mTOR activity, including rapamycin (sirolimus); 13. Concomitant therapy with strong inhibitor (e.g., cyclosporine and ketoconazole) or inducer of CYP3A; 14. Active infection at time of enrollment; 15. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study; 16. Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing; 17. Pregnant or nursing (lactating) women; 18. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after. Highly effective contraception methods include: a. A combination of any two of the following: i. Use of oral, injected or implanted hormonal non-estrogen containing methods of contraception or; ii. Placement of an intrauterine device (IUD) or intrauterine system (IUS); iii. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository; b. Total abstinence or; c. Male/female sterilization. Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential. 19. Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment 20. Major surgery, radiation therapy, or stereotactic radio-surgery within previous 4 weeks at time of screening 21. Neurosurgery within prior 6 months at time of screening. Open-Label Inclusion Criteria 1. Patients who completed Double-Blind phase of the study and were assigned to the placebo treatment arm; 2. Verbal consent (and assent, as appropriate) obtained prior to any open-label phase study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Through study completion, an average of 6 months | The primary endpoint will be safety as measured by study drop-out rate due to side effects, comparing everolimus vs. placebo. We will also determine the frequency of adverse events by type and severity. This section displays participant dropout rate and for what reason. |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Through study completion, an average of 6 months | The primary endpoint will be safety as measured by study drop-out rate due to side effects, comparing everolimus vs. placebo. We will also determine the frequency of adverse events by type and severity. this section displays the number of participants who experienced an AE and the description of such AEs, pertaining to: 1. Seriousness 2. Grade, 3. Relation to treatment 4. Recovery from AE 5. Category |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fine Motor Skills at 6 Months, Purdue Pegboard | 6 months | Fine motor skills will be evaluated using the Purdue Pegboard sub-tests average of both hands. This outcome evaluates the change from baseline to 6 months. |
| Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | 6 months | Change in global cognitive ability will be measured by Stanford-Binet 5 or Mullen; Full scale, verbal and nonverbal ability (IQ). This outcome evaluates the change from baseline to 6 months. |
| Change at 6 Months in Composite Score | 6 months | Composite score was based on the following: Stanford-Binet Intelligence Scales, 5th Ed (SB-5) non-verbal and verbal working memory standard score; for the SB-5, the minimum score is 40 and the maximum score is 160, where the higher score represents a better outcome. Conners' Continuous Performance Test, 3rd Ed (CPT-3) hit reaction time standard score (reverse coded; standard score generated from T-score); for the CPT-3, the min score is 0 and the max score is 90, where the lower the T-score, the better the outcome. Purdue Pegboard Test (PPT) both hands standard score (generated from T-score); for the PPT, the min score is 20 and the max score is 190, where the higher the T-score, the better the outcome. For the composite score, the higher the score, the better the outcome. The composite score is on the SS metric (M=100, SD=15, min=20, max=180). |
| Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | 6 months | 1. Change in memory measured by Wide Range Assessment of Memory and Learning (WRAML-2) verbal learning core subtest, delayed recall, and recognition scaled scores over 6 months. 2. Change in executive functioning measured by Behavior Rating Inventory of Executive Function (BRIEF-2) global executive composite standard score over 6 months. 3. Change in autism symptoms measured by Social Responsiveness Scale (SRS-2) total standard score and Repetitive Behaviors Scale (RBS-R) total subscale score over 6 months. 4. Change in adaptive behaviors measured by Vineland Adaptive Behavior Scales (VABS-III) adaptive behavior composite standard score over 6 months. 5. Change in other behaviors measured by Child Behavior Checklist (CBCL) total problems standard score and Short Sensory Profile (SSP) total score over 6 months. |
| Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | 6 months | Motor functioning will be measured by the Purdue Pegboard (Pegs): Dominant and non-dominant hand combined standard scores and Developmental Coordination Disorder Questionnaire (DCDQ): Total score. This outcome evaluates the change from baseline to 6 months. |
| Change in Processing Speed at 6 Months, Conner's Continuous Performance Test (CPT)-3 | 6 months | Processing speed will be evaluated using mean reaction time on the Conner's Continuous Performance Test (CPT)-3. This outcome evaluates the change from baseline to 6 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RAD001 RAD001 is formulated as tablets of 5.0 mg or 2.5mg 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 in the morning after a light, nonfat breakfast. | 24 |
| 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 in the morning after a light, nonfat breakfast. | 22 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Investigator decision at baseline given safety concerns related to drug administration compliance | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | RAD001 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 16.5 years STANDARD_DEVIATION 11.3 | 14.7 years STANDARD_DEVIATION 10.9 | 15.6 years STANDARD_DEVIATION 11 |
| Autism spectrum disorder (%) | 25 percentage of participants | 36.3 percentage of participants | 30.4 percentage of participants |
| Autism spectrum disorder (n) | 6 participants | 8 participants | 14 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 20 Participants | 18 Participants | 38 Participants |
| Sex: Female, Male Female | 11 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Male | 13 Participants | 15 Participants | 28 Participants |
| Stanford-Binet Intelligence Scales, Fifth Edition (SB-5): Mean full scale IQ (FSIQ) | 77.8 scores on a scale STANDARD_DEVIATION 20.3 | 75.2 scores on a scale STANDARD_DEVIATION 23.5 | 76.6 scores on a scale STANDARD_DEVIATION 21.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 22 |
| other Total, other adverse events | 21 / 24 | 13 / 22 |
| serious Total, serious adverse events | 3 / 24 | 0 / 22 |
Outcome results
Primary
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants)
The primary endpoint will be safety as measured by study drop-out rate due to side effects, comparing everolimus vs. placebo. We will also determine the frequency of adverse events by type and severity. this section displays the number of participants who experienced an AE and the description of such AEs, pertaining to: 1. Seriousness 2. Grade, 3. Relation to treatment 4. Recovery from AE 5. Category
Time frame: Through study completion, an average of 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Probably not related to treatment (%) | 37.5 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 3 (%) | 16.7 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Non-serious AEs (%) | 87.5 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Definitely not related to treatment (%) | 20.8 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 4 (%) | 0 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Any AE (%) | 87.5 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 5 (%) | 0 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Patients recovered/resolved without sequelae fro AEs (%) | 83.3 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Serious AEs (%) | 12.5 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Patients recovered/resolved with sequelae form AEs (%) | 4.2 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Patients not recovered/not resolved from AEs (%) | 0 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 1 (%) | 75 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Possibly or probably related to treatment (%) | 70.8 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Definitely related to treatment (%) | 12.5 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 2 (%) | 50 percentage of participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Patients recovering/resolving from AEs (%) | 8.3 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 1 (%) | 45.5 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Any AE (%) | 59.1 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Non-serious AEs (%) | 59.1 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Serious AEs (%) | 0 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 2 (%) | 18.2 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 3 (%) | 0 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 4 (%) | 0 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 5 (%) | 0 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Definitely not related to treatment (%) | 27.3 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Probably not related to treatment (%) | 18.2 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Possibly or probably related to treatment (%) | 31.8 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Definitely related to treatment (%) | 0 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Patients not recovered/not resolved from AEs (%) | 4.5 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Patients recovered/resolved with sequelae form AEs (%) | 0 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Patients recovered/resolved without sequelae fro AEs (%) | 59.1 percentage of participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Patients recovering/resolving from AEs (%) | 3 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Non-serious AEs (%) | 73.9 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Possibly or probably related to treatment (%) | 52.2 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 1 (%) | 60.9 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Patients recovering/resolving from AEs (%) | 4.3 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Definitely related to treatment (%) | 6.5 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Serious AEs (%) | 6.5 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Patients recovered/resolved without sequelae fro AEs (%) | 71.7 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 4 (%) | 0 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Patients not recovered/not resolved from AEs (%) | 2.2 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 5 (%) | 0 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 3 (%) | 8.7 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Any AE (%) | 73.9 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Definitely not related to treatment (%) | 23.9 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Grade 2 (%) | 34.8 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Patients recovered/resolved with sequelae form AEs (%) | 2.2 percentage of participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants) | Probably not related to treatment (%) | 28.3 percentage of participants |
Primary
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout
The primary endpoint will be safety as measured by study drop-out rate due to side effects, comparing everolimus vs. placebo. We will also determine the frequency of adverse events by type and severity. This section displays participant dropout rate and for what reason.
Time frame: Through study completion, an average of 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Dropout due to investigator request | 0 Participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Dropout (Total) | 3 Participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Dropout due to other requests | 1 Participants |
| RAD001 | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Dropout due to participant/parent request | 2 Participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Dropout due to investigator request | 1 Participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Dropout due to participant/parent request | 1 Participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Dropout (Total) | 2 Participants |
| Placebo | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Dropout due to other requests | 0 Participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Dropout due to participant/parent request | 3 Participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Dropout (Total) | 5 Participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Dropout due to other requests | 1 Participants |
| Total | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout | Dropout due to investigator request | 1 Participants |
Secondary
Change at 6 Months in Composite Score
Composite score was based on the following: Stanford-Binet Intelligence Scales, 5th Ed (SB-5) non-verbal and verbal working memory standard score; for the SB-5, the minimum score is 40 and the maximum score is 160, where the higher score represents a better outcome. Conners' Continuous Performance Test, 3rd Ed (CPT-3) hit reaction time standard score (reverse coded; standard score generated from T-score); for the CPT-3, the min score is 0 and the max score is 90, where the lower the T-score, the better the outcome. Purdue Pegboard Test (PPT) both hands standard score (generated from T-score); for the PPT, the min score is 20 and the max score is 190, where the higher the T-score, the better the outcome. For the composite score, the higher the score, the better the outcome. The composite score is on the SS metric (M=100, SD=15, min=20, max=180).
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAD001 | Change at 6 Months in Composite Score | 80.34 score on a scale | Standard Deviation 15.23 |
| Placebo | Change at 6 Months in Composite Score | 75.14 score on a scale | Standard Deviation 18.3 |
| Total | Change at 6 Months in Composite Score | 81.60 score on a scale | Standard Deviation 17.17 |
| Placebo - 6 Months | Change at 6 Months in Composite Score | 78.47 score on a scale | Standard Deviation 21.96 |
Secondary
Change in Fine Motor Skills at 6 Months, Purdue Pegboard
Fine motor skills will be evaluated using the Purdue Pegboard sub-tests average of both hands. This outcome evaluates the change from baseline to 6 months.
Time frame: 6 months
Population: Change in fine motor skill scores were obtained from Purdue Pegboard. Fine motor skill scores were generated using standard scores, where a higher score indicates a better result (range 0-100).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAD001 | Change in Fine Motor Skills at 6 Months, Purdue Pegboard | 62.83 score on a scale | Standard Deviation 20.52 |
| Placebo | Change in Fine Motor Skills at 6 Months, Purdue Pegboard | 55.92 score on a scale | Standard Deviation 23.56 |
| Total | Change in Fine Motor Skills at 6 Months, Purdue Pegboard | 67.12 score on a scale | Standard Deviation 20.08 |
| Placebo - 6 Months | Change in Fine Motor Skills at 6 Months, Purdue Pegboard | 61.49 score on a scale | Standard Deviation 33.37 |
Secondary
Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning
Change in global cognitive ability will be measured by Stanford-Binet 5 or Mullen; Full scale, verbal and nonverbal ability (IQ). This outcome evaluates the change from baseline to 6 months.
Time frame: 6 months
Population: Global Cognitive Ability scores were obtained from Stanford Binet 5 or Mullen Scales of Early Learning depending on participant age and testing capability. Global Cognitive Ability subscale scores were converted to standard scores, where a higher score indicates a better result (range 0-100).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAD001 | Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | Full Scale (FSIQ) | 77.83 score on a scale | Standard Deviation 19.85 |
| RAD001 | Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | Nonverbal (NVIQ) | 78.96 score on a scale | Standard Deviation 19.03 |
| RAD001 | Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | Verbal (VIQ) | 78.79 score on a scale | Standard Deviation 19.73 |
| Placebo | Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | Full Scale (FSIQ) | 75.19 score on a scale | Standard Deviation 22.9 |
| Placebo | Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | Nonverbal (NVIQ) | 75.91 score on a scale | Standard Deviation 22.7 |
| Placebo | Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | Verbal (VIQ) | 76.05 score on a scale | Standard Deviation 23.67 |
| Total | Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | Verbal (VIQ) | 78.46 score on a scale | Standard Deviation 18.05 |
| Total | Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | Full Scale (FSIQ) | 79.39 score on a scale | Standard Deviation 17.3 |
| Total | Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | Nonverbal (NVIQ) | 82.31 score on a scale | Standard Deviation 16.25 |
| Placebo - 6 Months | Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | Full Scale (FSIQ) | 74.79 score on a scale | Standard Deviation 25.79 |
| Placebo - 6 Months | Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | Nonverbal (NVIQ) | 73.15 score on a scale | Standard Deviation 22.87 |
| Placebo - 6 Months | Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning | Verbal (VIQ) | 78.71 score on a scale | Standard Deviation 27.07 |
Secondary
Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months
1. Change in memory measured by Wide Range Assessment of Memory and Learning (WRAML-2) verbal learning core subtest, delayed recall, and recognition scaled scores over 6 months. 2. Change in executive functioning measured by Behavior Rating Inventory of Executive Function (BRIEF-2) global executive composite standard score over 6 months. 3. Change in autism symptoms measured by Social Responsiveness Scale (SRS-2) total standard score and Repetitive Behaviors Scale (RBS-R) total subscale score over 6 months. 4. Change in adaptive behaviors measured by Vineland Adaptive Behavior Scales (VABS-III) adaptive behavior composite standard score over 6 months. 5. Change in other behaviors measured by Child Behavior Checklist (CBCL) total problems standard score and Short Sensory Profile (SSP) total score over 6 months.
Time frame: 6 months
Population: WRAML-2 scaled scores (range 1-19, higher = better) BRIEF-2 global executive composite standard score (range 0-100, higher = better) SRS-2 total standard score (range 0-100, higher = better) RBS-R total subscale score (range 0-56, LOWER = better) VABS-III adaptive behavior composite standard score (range 0-100, higher = better) CBCL total problems standard score (range 0-100, higher = better) SSP total score (range 38-190, higher = better)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAD001 | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | VABS-III adaptive behavior composite standard score | 76.96 score on a scale | Standard Deviation 14.44 |
| RAD001 | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | RBS-R total subscale score | 16.44 score on a scale | Standard Deviation 16.83 |
| RAD001 | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | SSP total score | 137.46 score on a scale | Standard Deviation 21.68 |
| RAD001 | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | BRIEF-2 global executive composite standard score | 77.68 score on a scale | Standard Deviation 19.77 |
| RAD001 | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | WRAML-2 verbal learning recognition scaled score | 5.94 score on a scale | Standard Deviation 3.49 |
| RAD001 | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | WRAML-2 verbal learning delayed recall scaled score | 6.73 score on a scale | Standard Deviation 2.02 |
| RAD001 | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | CBCL total problems standard score | 85.90 score on a scale | Standard Deviation 13.82 |
| RAD001 | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | SRS-2 total standard score | 73.12 score on a scale | Standard Deviation 18.23 |
| RAD001 | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | WRAML-2 verbal learning core subtest scaled score | 6.11 score on a scale | Standard Deviation 2.65 |
| Placebo | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | SRS-2 total standard score | 67.52 score on a scale | Standard Deviation 19.6 |
| Placebo | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | VABS-III adaptive behavior composite standard score | 74.41 score on a scale | Standard Deviation 18.21 |
| Placebo | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | RBS-R total subscale score | 23.35 score on a scale | Standard Deviation 19.98 |
| Placebo | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | WRAML-2 verbal learning delayed recall scaled score | 6.57 score on a scale | Standard Deviation 3.4 |
| Placebo | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | WRAML-2 verbal learning core subtest scaled score | 6.90 score on a scale | Standard Deviation 3.36 |
| Placebo | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | WRAML-2 verbal learning recognition scaled score | 5.97 score on a scale | Standard Deviation 3.14 |
| Placebo | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | SSP total score | 128.25 score on a scale | Standard Deviation 26.05 |
| Placebo | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | CBCL total problems standard score | 80.54 score on a scale | Standard Deviation 18.07 |
| Placebo | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | BRIEF-2 global executive composite standard score | 71.18 score on a scale | Standard Deviation 19.35 |
| Total | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | SRS-2 total standard score | 78.91 score on a scale | Standard Deviation 17.75 |
| Total | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | WRAML-2 verbal learning core subtest scaled score | 7.47 score on a scale | Standard Deviation 3.93 |
| Total | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | WRAML-2 verbal learning delayed recall scaled score | 8.13 score on a scale | Standard Deviation 2.98 |
| Total | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | WRAML-2 verbal learning recognition scaled score | 6.74 score on a scale | Standard Deviation 3.96 |
| Total | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | BRIEF-2 global executive composite standard score | 82.61 score on a scale | Standard Deviation 17.43 |
| Total | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | RBS-R total subscale score | 14.42 score on a scale | Standard Deviation 5.86 |
| Total | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | VABS-III adaptive behavior composite standard score | 81.56 score on a scale | Standard Deviation 10.45 |
| Total | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | CBCL total problems standard score | 90.10 score on a scale | Standard Deviation 13.28 |
| Total | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | SSP total score | 143.08 score on a scale | Standard Deviation 16.54 |
| Placebo - 6 Months | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | VABS-III adaptive behavior composite standard score | 74.71 score on a scale | Standard Deviation 15.75 |
| Placebo - 6 Months | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | BRIEF-2 global executive composite standard score | 74.24 score on a scale | Standard Deviation 16.97 |
| Placebo - 6 Months | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | WRAML-2 verbal learning recognition scaled score | 6.42 score on a scale | Standard Deviation 4.22 |
| Placebo - 6 Months | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | SSP total score | 126.52 score on a scale | Standard Deviation 28.09 |
| Placebo - 6 Months | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | CBCL total problems standard score | 81.53 score on a scale | Standard Deviation 14.8 |
| Placebo - 6 Months | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | WRAML-2 verbal learning delayed recall scaled score | 7.72 score on a scale | Standard Deviation 2.99 |
| Placebo - 6 Months | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | RBS-R total subscale score | 19.96 score on a scale | Standard Deviation 16.06 |
| Placebo - 6 Months | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | SRS-2 total standard score | 66.90 score on a scale | Standard Deviation 19.36 |
| Placebo - 6 Months | Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months | WRAML-2 verbal learning core subtest scaled score | 7.22 score on a scale | Standard Deviation 3.76 |
Secondary
Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ)
Motor functioning will be measured by the Purdue Pegboard (Pegs): Dominant and non-dominant hand combined standard scores and Developmental Coordination Disorder Questionnaire (DCDQ): Total score. This outcome evaluates the change from baseline to 6 months.
Time frame: 6 months
Population: Change in motor functioning scores were obtained from Purdue Pegboard Developmental Coordination Disorder Questionnaire (DCDQ). Pegboard motor functioning scores were generated using standard scores, where a higher score indicates a better result (range 0-100). DCDQ motor functioning scores utilize the scale's total score, where higher scores indicate a better result (range 15-75).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAD001 | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (non-dominant hand) | 69.37 score on a scale | Standard Deviation 21.92 |
| RAD001 | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (left hand) | 66.46 score on a scale | Standard Deviation 23.02 |
| RAD001 | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | DCDQ Total Score | 37.51 score on a scale | Standard Deviation 12.38 |
| RAD001 | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (dominant hand) | 67.92 score on a scale | Standard Deviation 21.92 |
| RAD001 | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (right hand) | 66.92 score on a scale | Standard Deviation 22.83 |
| Placebo | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (dominant hand) | 58.63 score on a scale | Standard Deviation 27.91 |
| Placebo | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (non-dominant hand) | 61.89 score on a scale | Standard Deviation 27.91 |
| Placebo | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | DCDQ Total Score | 36.29 score on a scale | Standard Deviation 14.2 |
| Placebo | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (left hand) | 61.82 score on a scale | Standard Deviation 20.91 |
| Placebo | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (right hand) | 58.64 score on a scale | Standard Deviation 27.83 |
| Total | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (dominant hand) | 75.60 score on a scale | Standard Deviation 24.78 |
| Total | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (right hand) | 71.68 score on a scale | Standard Deviation 30.18 |
| Total | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (left hand) | 75.92 score on a scale | Standard Deviation 24.76 |
| Total | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (non-dominant hand) | 75.58 score on a scale | Standard Deviation 24.78 |
| Total | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | DCDQ Total Score | 40.01 score on a scale | Standard Deviation 10.62 |
| Placebo - 6 Months | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (non-dominant hand) | 62.36 score on a scale | Standard Deviation 32.48 |
| Placebo - 6 Months | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (left hand) | 60.26 score on a scale | Standard Deviation 29.3 |
| Placebo - 6 Months | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (right hand) | 61.47 score on a scale | Standard Deviation 35.48 |
| Placebo - 6 Months | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | Purdue Pegboard (dominant hand) | 59.25 score on a scale | Standard Deviation 32.48 |
| Placebo - 6 Months | Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ) | DCDQ Total Score | 37.64 score on a scale | Standard Deviation 16.37 |
Secondary
Change in Processing Speed at 6 Months, Conner's Continuous Performance Test (CPT)-3
Processing speed will be evaluated using mean reaction time on the Conner's Continuous Performance Test (CPT)-3. This outcome evaluates the change from baseline to 6 months.
Time frame: 6 months
Population: Change in processing speed scores were obtained from Conner's Continuous Performance Test (CPT)-3. Change in processing speed subscale scores were converted to standard scores, where a higher score indicates a better result (range 0-100).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAD001 | Change in Processing Speed at 6 Months, Conner's Continuous Performance Test (CPT)-3 | 87.78 score on a scale | Standard Deviation 20 |
| Placebo | Change in Processing Speed at 6 Months, Conner's Continuous Performance Test (CPT)-3 | 86.30 score on a scale | Standard Deviation 16.16 |
| Total | Change in Processing Speed at 6 Months, Conner's Continuous Performance Test (CPT)-3 | 89.26 score on a scale | Standard Deviation 22.35 |
| Placebo - 6 Months | Change in Processing Speed at 6 Months, Conner's Continuous Performance Test (CPT)-3 | 90.15 score on a scale | Standard Deviation 15.46 |