Trial Outcomes & Findings for Trial of RAD001 and Neurocognition in Tuberous Sclerosis Complex (TSC) (NCT NCT01289912)
NCT ID: NCT01289912
Last Updated: 2018-01-25
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
52 participants
Primary outcome timeframe
6 months
Results posted on
2018-01-25
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
32
|
15
|
|
Overall Study
COMPLETED
|
29
|
13
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Trial of RAD001 and Neurocognition in Tuberous Sclerosis Complex (TSC)
Baseline characteristics by cohort
| Measure |
RAD001
n=32 Participants
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.
|
Placebo
n=15 Participants
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.
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
13.25 years
STANDARD_DEVIATION 5.06 • n=5 Participants
|
11.47 years
STANDARD_DEVIATION 5.30 • n=7 Participants
|
12.68 years
STANDARD_DEVIATION 5.15 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsEvaluation 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.
Outcome measures
| Measure |
RAD001 - 6 Months
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 in the morning after a light, nonfat breakfast.
|
Placebo - Baseline
n=32 Participants
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.
|
RAD001 - Baseline
n=15 Participants
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.
|
Placebo - 6 Months
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.
|
|---|---|---|---|---|
|
Evaluation of the Safety of RAD001 on Neurocognition in Patients With TSC Compared With Placebo in Patients With TSC.
|
—
|
325 Adverse Events
|
147 Adverse Events
|
—
|
PRIMARY outcome
Timeframe: 6 monthsBaseline 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.
Outcome measures
| Measure |
RAD001 - 6 Months
n=29 Participants
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 in the morning after a light, nonfat breakfast.
|
Placebo - Baseline
n=15 Participants
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.
|
RAD001 - Baseline
n=32 Participants
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.
|
Placebo - 6 Months
n=13 Participants
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.
|
|---|---|---|---|---|
|
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
|
101.33 units on a scale
Standard Deviation 54.27
|
103.06 units on a scale
Standard Deviation 41.18
|
89.83 units on a scale
Standard Deviation 24.99
|
|
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
|
105.27 units on a scale
Standard Deviation 37.10
|
119.30 units on a scale
Standard Deviation 44.19
|
92.15 units on a scale
Standard Deviation 34.26
|
|
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
|
86.00 units on a scale
Standard Deviation 17.78
|
81.06 units on a scale
Standard Deviation 23.96
|
88.54 units on a scale
Standard Deviation 17.21
|
|
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
|
85.47 units on a scale
Standard Deviation 12.22
|
90.00 units on a scale
Standard Deviation 21.15
|
89.15 units on a scale
Standard Deviation 16.08
|
|
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
|
8.00 units on a scale
Standard Deviation 2.00
|
7.14 units on a scale
Standard Deviation 3.16
|
8.46 units on a scale
Standard Deviation 2.44
|
|
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
|
7.07 units on a scale
Standard Deviation 2.94
|
7.52 units on a scale
Standard Deviation 2.53
|
8.23 units on a scale
Standard Deviation 3.49
|
|
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
|
78.79 units on a scale
Standard Deviation 19.69
|
72.06 units on a scale
Standard Deviation 13.90
|
79.00 units on a scale
Standard Deviation 15.26
|
|
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
|
81.27 units on a scale
Standard Deviation 21.87
|
73.68 units on a scale
Standard Deviation 15.45
|
81.77 units on a scale
Standard Deviation 16.66
|
|
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 16.40
|
79.07 units on a scale
Standard Deviation 19.67
|
74.10 units on a scale
Standard Deviation 15.46
|
80.38 units on a scale
Standard Deviation 17.78
|
|
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
|
78.80 units on a scale
Standard Deviation 19.50
|
74.68 units on a scale
Standard Deviation 15.69
|
81.69 units on a scale
Standard Deviation 14.74
|
|
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
|
89.87 units on a scale
Standard Deviation 18.26
|
78.83 units on a scale
Standard Deviation 21.68
|
92.69 units on a scale
Standard Deviation 18.65
|
PRIMARY outcome
Timeframe: 6 monthsScores 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
Outcome measures
| Measure |
RAD001 - 6 Months
n=29 Participants
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 in the morning after a light, nonfat breakfast.
|
Placebo - Baseline
n=15 Participants
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.
|
RAD001 - Baseline
n=32 Participants
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.
|
Placebo - 6 Months
n=13 Participants
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.
|
|---|---|---|---|---|
|
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
|
-1.48 units on a scale
Standard Deviation 1.9
|
-1.23 units on a scale
Standard Deviation 2.11
|
-.91 units on a scale
Standard Deviation 1.6
|
|
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
|
-2.33 units on a scale
Standard Deviation 1.4
|
-2.24 units on a scale
Standard Deviation 1.33
|
-2.62 units on a scale
Standard Deviation 1.58
|
|
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
|
-1.32 units on a scale
Standard Deviation 1.18
|
-1.02 units on a scale
Standard Deviation 1.20
|
-1.29 units on a scale
Standard Deviation 1.41
|
|
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
|
-.66 units on a scale
Standard Deviation .79
|
-.67 units on a scale
Standard Deviation 1.57
|
-.73 units on a scale
Standard Deviation .97
|
|
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
|
-2.24 units on a scale
Standard Deviation 3.63
|
-1.15 units on a scale
Standard Deviation 2.22
|
-.88 units on a scale
Standard Deviation 1.38
|
|
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
|
-.96 units on a scale
Standard Deviation 2.59
|
-1.41 units on a scale
Standard Deviation 2.8
|
-.97 units on a scale
Standard Deviation 2.71
|
|
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
|
-1.38 units on a scale
Standard Deviation 1.32
|
-1.89 units on a scale
Standard Deviation 1.47
|
-.58 units on a scale
Standard Deviation 1.11
|
|
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
|
-1.02 units on a scale
Standard Deviation 1.65
|
-1.48 units on a scale
Standard Deviation 2.05
|
-1.05 units on a scale
Standard Deviation 1.64
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Data was not collected reliably and therefore was not analyzed.
Comparison of absolute change from baseline in frequency of epileptiform events as recorded on seizure diaries between patients taking RAD001 vs. placebo
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 monthsPopulation: Data was not collected reliably and therefore was not analyzed.
Comparison of sleep disturbances between patients taking RAD001 vs. placebo, measured by the Pediatric Sleep Questionnaire (PSQ) and sleep logs
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 monthsScores 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.
Outcome measures
| Measure |
RAD001 - 6 Months
n=29 Participants
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 in the morning after a light, nonfat breakfast.
|
Placebo - Baseline
n=15 Participants
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.
|
RAD001 - Baseline
n=32 Participants
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.
|
Placebo - 6 Months
n=13 Participants
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.
|
|---|---|---|---|---|
|
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
|
76.71 units on a scale (SRS)
Standard Deviation 17.32
|
80.03 units on a scale (SRS)
Standard Deviation 20.24
|
79.77 units on a scale (SRS)
Standard Deviation 24.50
|
|
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
|
77.14 units on a scale (SRS)
Standard Deviation 17.50
|
76.43 units on a scale (SRS)
Standard Deviation 18.62
|
80.62 units on a scale (SRS)
Standard Deviation 22.83
|
|
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
|
67.40 units on a scale (SRS)
Standard Deviation 14.69
|
62.90 units on a scale (SRS)
Standard Deviation 15.32
|
67.38 units on a scale (SRS)
Standard Deviation 15.51
|
|
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
|
76.43 units on a scale (SRS)
Standard Deviation 19.59
|
75.70 units on a scale (SRS)
Standard Deviation 18.77
|
81.15 units on a scale (SRS)
Standard Deviation 18.86
|
|
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
|
74.36 units on a scale (SRS)
Standard Deviation 16.75
|
72.23 units on a scale (SRS)
Standard Deviation 17.18
|
76.85 units on a scale (SRS)
Standard Deviation 21.55
|
|
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
|
69.80 units on a scale (SRS)
Standard Deviation 16.60
|
69.60 units on a scale (SRS)
Standard Deviation 14.76
|
72.77 units on a scale (SRS)
Standard Deviation 20.77
|
SECONDARY outcome
Timeframe: 6 monthsScores 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).
Outcome measures
| Measure |
RAD001 - 6 Months
n=29 Participants
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 in the morning after a light, nonfat breakfast.
|
Placebo - Baseline
n=15 Participants
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.
|
RAD001 - Baseline
n=32 Participants
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.
|
Placebo - 6 Months
n=13 Participants
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.
|
|---|---|---|---|---|
|
Comparison of Academic Skills Between Patients Taking RAD001 vs. Placebo
Word Reading (WRAT 4)
|
84.45 units on a scale
Standard Deviation 20.45
|
86.80 units on a scale
Standard Deviation 16.79
|
84.28 units on a scale
Standard Deviation 20.07
|
91.15 units on a scale
Standard Deviation 20.76
|
|
Comparison of Academic Skills Between Patients Taking RAD001 vs. Placebo
Math Computation (WRAT 4)
|
73.81 units on a scale
Standard Deviation 16.01
|
76.00 units on a scale
Standard Deviation 15.64
|
74.60 units on a scale
Standard Deviation 17.99
|
77.31 units on a scale
Standard Deviation 16.93
|
SECONDARY outcome
Timeframe: 6 monthsScores 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
Outcome measures
| Measure |
RAD001 - 6 Months
n=29 Participants
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 in the morning after a light, nonfat breakfast.
|
Placebo - Baseline
n=15 Participants
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.
|
RAD001 - Baseline
n=32 Participants
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.
|
Placebo - 6 Months
n=13 Participants
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.
|
|---|---|---|---|---|
|
Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo
BRIEF Global Executive Composite
|
64.68 units on a scale
Standard Deviation 10.88
|
70.50 units on a scale
Standard Deviation 15.13
|
69.48 units on a scale
Standard Deviation 12.98
|
62.25 units on a scale
Standard Deviation 12.53
|
|
Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo
BRIEF Behavioral Regulation Index
|
62.57 units on a scale
Standard Deviation 12.00
|
70.93 units on a scale
Standard Deviation 16.89
|
66.53 units on a scale
Standard Deviation 14.50
|
60.83 units on a scale
Standard Deviation 12.41
|
|
Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo
BRIEF Metacognition Index
|
64.57 units on a scale
Standard Deviation 10.65
|
68.07 units on a scale
Standard Deviation 14.52
|
68.93 units on a scale
Standard Deviation 12.12
|
61.83 units on a scale
Standard Deviation 12.97
|
|
Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo
BASC2 Behavioral Symptoms Index
|
55.41 units on a scale
Standard Deviation 11.26
|
62.29 units on a scale
Standard Deviation 12.61
|
58.97 units on a scale
Standard Deviation 10.87
|
57.54 units on a scale
Standard Deviation 10.02
|
|
Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo
BASC2 Externalizing Problems
|
52.34 units on a scale
Standard Deviation 8.59
|
57.36 units on a scale
Standard Deviation 15.58
|
53.24 units on a scale
Standard Deviation 9.85
|
52.62 units on a scale
Standard Deviation 9.26
|
|
Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo
BASC2 Internalizing Problems
|
51.45 units on a scale
Standard Deviation 14.42
|
58.43 units on a scale
Standard Deviation 18.34
|
51.55 units on a scale
Standard Deviation 12.09
|
56.00 units on a scale
Standard Deviation 19.37
|
|
Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo
BASC2 Adaptive Skills
|
40.00 units on a scale
Standard Deviation 12.02
|
38.79 units on a scale
Standard Deviation 13.16
|
36.72 units on a scale
Standard Deviation 10.22
|
42.08 units on a scale
Standard Deviation 13.27
|
|
Comparison of Behavioral Problems Between Patients Taking RAD001 vs Placebo
SDQ Total Difficulties Scale
|
13.20 units on a scale
Standard Deviation 5.90
|
16.00 units on a scale
Standard Deviation 6.93
|
15.46 units on a scale
Standard Deviation 5.61
|
14.42 units on a scale
Standard Deviation 5.09
|
Adverse Events
RAD001
Serious events: 3 serious events
Other events: 30 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
RAD001
n=32 participants at risk
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.
|
Placebo
n=15 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Septicemia
|
3.1%
1/32 • Number of events 1
|
0.00%
0/15
|
|
Renal and urinary disorders
Pyelonephritis
|
3.1%
1/32 • Number of events 1
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
high fever/pneumonia
|
3.1%
1/32 • Number of events 2
|
0.00%
0/15
|
|
Social circumstances
Personality/Behavior
|
3.1%
1/32 • Number of events 3
|
0.00%
0/15
|
Other adverse events
| Measure |
RAD001
n=32 participants at risk
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.
|
Placebo
n=15 participants at risk
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.
|
|---|---|---|
|
Eye disorders
Conjunctivitis
|
6.2%
2/32 • Number of events 2
|
0.00%
0/15
|
|
Gastrointestinal disorders
Constipation
|
6.2%
2/32 • Number of events 2
|
0.00%
0/15
|
|
Gastrointestinal disorders
Diarrhea
|
34.4%
11/32 • Number of events 18
|
33.3%
5/15 • Number of events 8
|
|
Gastrointestinal disorders
Nausea
|
12.5%
4/32 • Number of events 5
|
6.7%
1/15 • Number of events 2
|
|
Gastrointestinal disorders
Stomach ache/pain/upset/irritation
|
25.0%
8/32 • Number of events 11
|
40.0%
6/15 • Number of events 8
|
|
Gastrointestinal disorders
Stomach flu
|
3.1%
1/32 • Number of events 1
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
15.6%
5/32 • Number of events 5
|
26.7%
4/15 • Number of events 4
|
|
Gastrointestinal disorders
stomach bug/virus/flu
|
6.2%
2/32 • Number of events 2
|
13.3%
2/15 • Number of events 2
|
|
General disorders
Bloody nose/nosebleed
|
6.2%
2/32 • Number of events 6
|
6.7%
1/15 • Number of events 5
|
|
General disorders
Body pain/swelling/generalized pain NOS
|
25.0%
8/32 • Number of events 8
|
20.0%
3/15 • Number of events 6
|
|
General disorders
Cavity
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Cold
|
25.0%
8/32 • Number of events 14
|
13.3%
2/15 • Number of events 3
|
|
General disorders
Cold Sores
|
3.1%
1/32 • Number of events 1
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Congestion
|
3.1%
1/32 • Number of events 1
|
6.7%
1/15 • Number of events 5
|
|
General disorders
Cough
|
21.9%
7/32 • Number of events 8
|
40.0%
6/15 • Number of events 11
|
|
General disorders
Fall
|
3.1%
1/32 • Number of events 2
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Fatigue
|
21.9%
7/32 • Number of events 12
|
6.7%
1/15 • Number of events 2
|
|
General disorders
Feeling Cold
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Fever
|
31.2%
10/32 • Number of events 17
|
26.7%
4/15 • Number of events 5
|
|
General disorders
Increased Energy
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Ingrown toenail
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Irritability
|
9.4%
3/32 • Number of events 3
|
0.00%
0/15
|
|
General disorders
Muscle cramp/soreness
|
6.2%
2/32 • Number of events 2
|
6.7%
1/15 • Number of events 2
|
|
General disorders
Runny nose
|
12.5%
4/32 • Number of events 5
|
20.0%
3/15 • Number of events 4
|
|
Infections and infestations
Cellulitis
|
6.2%
2/32 • Number of events 2
|
0.00%
0/15
|
|
Infections and infestations
Ear Infection
|
9.4%
3/32 • Number of events 5
|
13.3%
2/15 • Number of events 2
|
|
Infections and infestations
Mouth Sore
|
40.6%
13/32 • Number of events 28
|
33.3%
5/15 • Number of events 7
|
|
Infections and infestations
Mouth Ulcer
|
25.0%
8/32 • Number of events 13
|
20.0%
3/15 • Number of events 5
|
|
Infections and infestations
Mouth irritation/pain
|
12.5%
4/32 • Number of events 4
|
6.7%
1/15 • Number of events 3
|
|
Infections and infestations
Painful Urination
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
Infections and infestations
Sore throat
|
25.0%
8/32 • Number of events 9
|
13.3%
2/15 • Number of events 2
|
|
Infections and infestations
Stomach Infection
|
6.2%
2/32 • Number of events 2
|
0.00%
0/15
|
|
Infections and infestations
Strep throat
|
9.4%
3/32 • Number of events 4
|
6.7%
1/15 • Number of events 1
|
|
Infections and infestations
Viral infection
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
Injury, poisoning and procedural complications
Bruising/contusion
|
9.4%
3/32 • Number of events 3
|
13.3%
2/15 • Number of events 2
|
|
Injury, poisoning and procedural complications
Cuts/Abrasion
|
6.2%
2/32 • Number of events 2
|
6.7%
1/15 • Number of events 1
|
|
Injury, poisoning and procedural complications
Soreness due to injury
|
3.1%
1/32 • Number of events 1
|
6.7%
1/15 • Number of events 1
|
|
Metabolism and nutrition disorders
Loss of appetite
|
6.2%
2/32 • Number of events 2
|
0.00%
0/15
|
|
Nervous system disorders
Dizziness
|
3.1%
1/32 • Number of events 1
|
20.0%
3/15 • Number of events 4
|
|
Nervous system disorders
Headache
|
40.6%
13/32 • Number of events 40
|
33.3%
5/15 • Number of events 18
|
|
Nervous system disorders
Seizures
|
15.6%
5/32 • Number of events 7
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Sleep Disturbance/Insomnia
|
3.1%
1/32 • Number of events 1
|
13.3%
2/15 • Number of events 2
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
Psychiatric disorders
Behavioral/personality changes
|
15.6%
5/32 • Number of events 5
|
6.7%
1/15 • Number of events 1
|
|
Renal and urinary disorders
UTI/urinary frequency/incontinence
|
21.9%
7/32 • Number of events 10
|
0.00%
0/15
|
|
Reproductive system and breast disorders
Genital irritation
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.1%
1/32 • Number of events 1
|
6.7%
1/15 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Phlegm
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Stuffy nose
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection/Upper Airways NOS
|
18.8%
6/32 • Number of events 9
|
20.0%
3/15 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Abscess
|
6.2%
2/32 • Number of events 3
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Acne/Pimples
|
9.4%
3/32 • Number of events 3
|
20.0%
3/15 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Athlete's foot
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
6.2%
2/32 • Number of events 3
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Dry/itchy skin
|
0.00%
0/32
|
13.3%
2/15 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash/hives
|
31.2%
10/32 • Number of events 11
|
13.3%
2/15 • Number of events 2
|
|
Nervous system disorders
Tremor
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
|
Metabolism and nutrition disorders
Triglyceride-serum high
|
0.00%
0/32
|
6.7%
1/15 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place