Trial Outcomes & Findings for Long-term Monitoring of Growth and Development of Pediatric Patients Previously Treated With Everolimus (NCT NCT02338609)
NCT ID: NCT02338609
Last Updated: 2024-08-09
Results Overview
Estrogen is a steroid hormone associated with the female reproductive organs and is responsible for developing female sexual characteristics.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
15 participants
Primary outcome timeframe
Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)
Results posted on
2024-08-09
Participant Flow
Participants took part in 6 investigative sites in 3 countries.
All the pediatric patients enrolled into the current study had been treated with everolimus in the parent study CRAD001M2301.
Participant milestones
| Measure |
Everolimus
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
Safety Analysis Set
|
14
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Everolimus
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Death
|
1
|
Baseline Characteristics
Long-term Monitoring of Growth and Development of Pediatric Patients Previously Treated With Everolimus
Baseline characteristics by cohort
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Age, Continuous
|
6.390 years
STANDARD_DEVIATION 3.5647 • n=99 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
14 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Annually, up to 14 years from the first visit in parent study CRAD001M2301 (including up to 9 years of follow-up in study CRAD001M2305)Population: The Full Analysis Set for sexual development (FAS Puberty) consisted of all participants enrolled in this study.
Tanner Staging, also known as Sexual Maturity Rating (SMR), is an objective classification system that providers use to document and track the development and sequence of secondary sex characteristics of children during puberty. Tanner Stage included two components for boys (testis and pubic hair) and two components for girls (breast development and pubic hair). Tanner Stage V: Males and females: Terminal hair that extends beyond the inguinal crease onto the thigh. Female Breast Development Scale: Areolar mound recedes into single breast contour with areolar hyperpigmentation, papillae development, and nipple protrusion. Male External Genitalia Scale: \> 20 ml (or \> 4.5 cm long)
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Number of Participants Who Achieved Tanner Stage V at or Before Age 16 (Females) or 17 (Males)
Female
|
4 Participants
|
|
Number of Participants Who Achieved Tanner Stage V at or Before Age 16 (Females) or 17 (Males)
Male
|
6 Participants
|
PRIMARY outcome
Timeframe: Baseline, annually up to Year 10 of treatment since the start of everolimus in parent study CRAD001M2301 (including a median of 5 years of exposure to everolimus in study CRAD001M2305)Population: The Full Analysis Set (FAS) consisted of all participants enrolled in this study.
Height and body weight (with minimal clothing, without shoes) were measured annually. The height standard deviation score (SDS) and BMI SDS were calculated based on height/BMI data collected during the study and published reference height/BMI information (De Onis M, et al. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ. 2007 Sep;85(9):660-7). The number of participants with height and BMI SDS values lower than the 5th percentile (notably low) or higher than the 95th percentile (notably high) are reported. The baseline corresponds to the last available assessment on or before the start of everolimus in the parent study CRAD001M2301. The assessment is performed up to age of 12 years.
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably low-Baseline
|
2 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably low-Year 1
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably low-Year 2
|
2 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably low-Year 3
|
2 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably low-Year 4
|
2 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably low-Year 5
|
2 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably low-Year 6
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably low-Year 7
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably low-Year 8
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably low-Year 9
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably low-Year 10
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably high-Baseline
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably high-Year 1
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably high-Year 2
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably high-Year 3
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably high-Year 4
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably high-Year 5
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably high-Year 6
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably high-Year 7
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably high-Year 8
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably high-Year 9
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
Height SDS-notably high-Year 10
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably low-Baseline
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably low-Year 1
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably low-Year 2
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably low-Year 3
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably low-Year 4
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably low-Year 5
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably low-Year 6
|
2 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably low-Year 7
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably low-Year 8
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably low-Year 9
|
2 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably low-Year 10
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably high-Baseline
|
4 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably high-Year 1
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably high-Year 2
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably high-Year 3
|
0 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably high-Year 4
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably high-Year 5
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably high-Year 6
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably high-Year 7
|
2 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably high-Year 8
|
2 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably high-Year 9
|
1 Participants
|
|
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
BMI SDS-notably high-Year 10
|
1 Participants
|
PRIMARY outcome
Timeframe: Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)Population: Male participants in the FAS with at least one available value of the outcome measure. In each row, the number of participants with an available value at the specified timepoint is reported.
Luteinizing hormone (LH) is a glycoprotein hormone that is co-secreted along with follicle-stimulating hormone by the gonadotrophin cells in the adenohypophysis (anterior pituitary). Untreated LH deficiency results in infertility, and if it occurs before puberty, the patient fails to develop puberty and secondary sexual characteristics. Follicle-stimulating hormone (FSH) is a hormone produced by the anterior pituitary in response to gonadotropin-releasing hormone (GnRH) from the hypothalamus. FSH plays a role in sexual development and reproduction in both males and females.
Outcome measures
| Measure |
Everolimus
n=7 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Endocrine Laboratory Values LH and FSH in Male Participants
10 years age-LH
|
1.0 IU/L
Standard Deviation 1.47
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
10 years age-FSH
|
1.5 IU/L
Standard Deviation 1.34
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
11 years age-LH
|
1.0 IU/L
Standard Deviation 0.77
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
11 years age-FSH
|
1.7 IU/L
Standard Deviation 1.11
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
12 years age-LH
|
1.8 IU/L
Standard Deviation 1.22
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
12 years age-FSH
|
2.1 IU/L
Standard Deviation 0.67
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
13 years age-LH
|
2.4 IU/L
Standard Deviation 2.26
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
13 years age-FSH
|
2.9 IU/L
Standard Deviation 1.81
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
14 years age-LH
|
2.9 IU/L
Standard Deviation 2.18
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
14 years age-FSH
|
4.6 IU/L
Standard Deviation 4.29
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
15 years age-LH
|
2.5 IU/L
Standard Deviation 1.07
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
15 years age-FSH
|
3.3 IU/L
Standard Deviation 0.61
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
16 years age-LH
|
3.5 IU/L
Standard Deviation 0.32
|
|
Endocrine Laboratory Values LH and FSH in Male Participants
16 years age-FSH
|
6.0 IU/L
Standard Deviation 3.01
|
PRIMARY outcome
Timeframe: Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)Population: Female participants in the FAS with at least one available value of the outcome measure. In each row, the number of participants with an available value at the specified timepoint is reported.
Luteinizing hormone (LH) is a glycoprotein hormone that is co-secreted along with follicle-stimulating hormone by the gonadotrophin cells in the adenohypophysis (anterior pituitary). Untreated LH deficiency results in infertility, and if it occurs before puberty, the patient fails to develop puberty and secondary sexual characteristics. Follicle-stimulating hormone (FSH) is a hormone produced by the anterior pituitary in response to gonadotropin-releasing hormone (GnRH) from the hypothalamus. FSH plays a role in sexual development and reproduction in both males and females.
Outcome measures
| Measure |
Everolimus
n=8 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Endocrine Laboratory Values LH and FSH in Female Participants
10 years age-LH
|
5.1 IU/L
Standard Deviation 3.89
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
10 years age-FSH
|
3.4 IU/L
Standard Deviation 2.68
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
11 years age-LH
|
3.2 IU/L
Standard Deviation 2.47
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
11 years age-FSH
|
3.5 IU/L
Standard Deviation 1.61
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
12 years age-LH
|
7.8 IU/L
Standard Deviation 6.73
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
12 years age-FSH
|
5.6 IU/L
Standard Deviation 2.43
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
13 years age-LH
|
4.4 IU/L
Standard Deviation 3.08
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
13 years age-FSH
|
5.0 IU/L
Standard Deviation 0.80
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
14 years age-LH
|
5.3 IU/L
Standard Deviation 6.97
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
14 years age-FSH
|
2.6 IU/L
Standard Deviation 2.05
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
15 years age-LH
|
7.5 IU/L
Standard Deviation 10.96
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
15 years age-FSH
|
2.5 IU/L
Standard Deviation 2.28
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
16 years age-LH
|
3.7 IU/L
Standard Deviation 2.69
|
|
Endocrine Laboratory Values LH and FSH in Female Participants
16 years age-FSH
|
2.8 IU/L
Standard Deviation 2.05
|
PRIMARY outcome
Timeframe: Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)Population: Male participants in the FAS with at least one available value of the outcome measure. In each row, the number of participants with an available value at the specified timepoint is reported.
Testosterone is the primary male hormone responsible for regulating sex differentiation, producing male sex characteristics, spermatogenesis, and fertility.
Outcome measures
| Measure |
Everolimus
n=7 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Endocrine Laboratory Values of Testosterone in Male Participants
10 years age
|
0.7 nmol/L
Standard Deviation 1.17
|
|
Endocrine Laboratory Values of Testosterone in Male Participants
11 years age
|
2.5 nmol/L
Standard Deviation 4.60
|
|
Endocrine Laboratory Values of Testosterone in Male Participants
12 years age
|
3.8 nmol/L
Standard Deviation 4.29
|
|
Endocrine Laboratory Values of Testosterone in Male Participants
13 years age
|
4.3 nmol/L
Standard Deviation 4.04
|
|
Endocrine Laboratory Values of Testosterone in Male Participants
14 years age
|
7.2 nmol/L
Standard Deviation 4.34
|
|
Endocrine Laboratory Values of Testosterone in Male Participants
15 years age
|
12.9 nmol/L
Standard Deviation 6.28
|
|
Endocrine Laboratory Values of Testosterone in Male Participants
16 years age
|
15.5 nmol/L
Standard Deviation 3.93
|
PRIMARY outcome
Timeframe: Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)Population: Female participants in the FAS with at least one available value of the outcome measure. In each row, the number of participants with an available value at the specified timepoint is reported.
Estrogen is a steroid hormone associated with the female reproductive organs and is responsible for developing female sexual characteristics.
Outcome measures
| Measure |
Everolimus
n=8 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Endocrine Laboratory Values of Estrogen in Female Participants
10 years age
|
139.8 ng/L
|
|
Endocrine Laboratory Values of Estrogen in Female Participants
11 years age
|
80.5 ng/L
Standard Deviation 119.22
|
|
Endocrine Laboratory Values of Estrogen in Female Participants
12 years age
|
43.7 ng/L
Standard Deviation 41.26
|
|
Endocrine Laboratory Values of Estrogen in Female Participants
13 years age
|
50.0 ng/L
Standard Deviation 7.07
|
|
Endocrine Laboratory Values of Estrogen in Female Participants
14 years age
|
139.0 ng/L
Standard Deviation 141.42
|
|
Endocrine Laboratory Values of Estrogen in Female Participants
15 years age
|
47.7 ng/L
Standard Deviation 48.89
|
|
Endocrine Laboratory Values of Estrogen in Female Participants
16 years age
|
149.7 ng/L
Standard Deviation 128.21
|
SECONDARY outcome
Timeframe: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.Population: The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
Number of participants with treatment emergent AEs (any AE regardless of seriousness), AEs led to study treatment discontinuation, SAEs and SAEs led to study treatment discontinuation.
Outcome measures
| Measure |
Everolimus
n=14 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE leading to discontinuation
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
At least one AE
|
12 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
At least one SAE
|
6 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAE leading to discontinuation
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to approximately 14.4 years from the first dose of everolimus in parent study CRAD001M2301 (including up to 9 years of follow-up in study CRAD001M2305)Population: The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment. At each row, only participants without menarche (females), thelarche (females) and adrenarche (males) prior to start of everolimus in the parent study CRAD001M2301 are included in the analysis.
Menarche is defined as the first menstrual period in a female adolescent. Menarche typically occurs between the ages of 10 and 16, with the average age of onset being 12.4 years. Thelarche is the beginning of adult breast development, marks the onset of puberty in the majority of women and occurs at a mean age of 10 years. Adrenarche refers to the time during puberty when the adrenal glands increase their production and secretion of adrenal androgens. Potential delayed puberty in girls is defined as failure to attain Tanner Stage II (for both breast development and pubic hair) by age 13, or absence of menarche by age 15 or within 5 years of attainment of Tanner Stage II. Potential delayed puberty in boys is defined as failure to attain Tanner Stage II (for both testis and pubic hair) by age 14.
Outcome measures
| Measure |
Everolimus
n=14 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Participants Age at Menarche/Thelarche (Females) or Adrenarche (Males)
Menarche
|
12.5 years
Interval 11.0 to 13.6
|
|
Participants Age at Menarche/Thelarche (Females) or Adrenarche (Males)
Thelarche
|
10.2 years
Interval 9.1 to
Not estimable due to insufficient number of participants with events
|
|
Participants Age at Menarche/Thelarche (Females) or Adrenarche (Males)
Adrenarche
|
11.0 years
Interval 10.0 to 11.6
|
SECONDARY outcome
Timeframe: Up to approximately 14.4 years from the first dose of everolimus in parent study CRAD001M2301 (including up to 9 years of follow-up in study CRAD001M2305)Population: The Full Analysis Set for sexual development (FAS Puberty) consisted of all participants enrolled in this study.
Tanner Staging, also known as Sexual Maturity Rating (SMR), is an objective classification system that providers use to document and track the development and sequence of secondary sex characteristics of children during puberty. Pubic Hair Scale Stages: II-Downy hair III-Scant terminal hair IV-Terminal hair that fills the entire triangle overlying the pubic region V-Terminal hair that extends beyond the inguinal crease onto the thigh Female Breast Development Scale Stages: II-Breast bud palpable under the areola (1st pubertal sign in females) III-Breast tissue palpable outside areola; no areolar development IV-Areola elevated above the contour of the breast, forming a "double scoop" appearance V-Areolar mound recedes into single breast contour with areolar hyperpigmentation, papillae development, and nipple protrusion Male External Genitalia Scale Stages: II- 2.5 to 3.3 cm long, 1st pubertal sign in males III- 3.4 to 4.0 cm long IV- 4.1 to 4.5 cm long V- or \> 4.5 cm long
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage II-pubic hair-male
|
11.8 years
Interval 10.2 to
Not estimable due to insufficient number of participants with events
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage II-genitalia
|
11.9 years
Interval 10.4 to
Not estimable due to insufficient number of participants with events
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage III-pubic hair-male
|
13.3 years
Interval 11.3 to
Not estimable due to insufficient number of participants with events
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage III-genitalia
|
12.6 years
Interval 11.3 to 14.2
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage IV-pubic hair-male
|
14.2 years
Interval 11.3 to
Not estimable due to insufficient number of participants with events
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage IV-genitalia
|
14.2 years
Interval 11.3 to
Not estimable due to insufficient number of participants with events
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage V-pubic hair-male
|
16.4 years
Interval 15.3 to
Not estimable due to insufficient number of participants with events
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage V-genitalia
|
16.4 years
Interval 12.7 to
Not estimable due to insufficient number of participants with events
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage II-pubic hair-female
|
10.4 years
Interval 7.3 to 11.8
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage II-Breast
|
11.5 years
Interval 9.9 to 11.8
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage III-pubic hair-female
|
12.2 years
Interval 10.4 to 12.8
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage III-Breast
|
12.5 years
Interval 10.4 to 14.6
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage IV-pubic hair-female
|
13.4 years
Interval 11.6 to 14.5
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage IV-Breast
|
13.8 years
Interval 12.7 to 14.6
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage V-pubic hair-female
|
16.0 years
Interval 13.8 to
Not estimable due to insufficient number of participants with events
|
|
Participants Age at Tanner Stage II, III, IV, V
Tanner stage V-Breast
|
NA years
Interval 13.8 to
Not estimable due to insufficient number of participants with events
|
SECONDARY outcome
Timeframe: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.Population: The Full Analysis Set (FAS) consisted of all participants enrolled in this study.
Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric disorders which refers to as TAND (TSC-Associated-Neuropsychiatric-Disorders). A specific TAND Checklist has been developed to assess Behavioral, Psychiatric, Intellectual, Academic, Neuropsychological and Psychosocial areas. This outcome measure assesses the TAND checklist part about basic development skills. Baseline is defined as the first available assessment on or after the enrollment date of the CRAD001M2305 study. Overall consists of all responses including baseline.
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
First smile-baseline
|
2.9 age (months)
Standard Error 1.85
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
First smile-overall
|
2.9 age (months)
Standard Error 1.85
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
Sat without support-baseline
|
7.5 age (months)
Standard Error 3.68
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
Sat without support-overall
|
7.5 age (months)
Standard Error 3.68
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
Walked without holding on-baseline
|
16.5 age (months)
Standard Error 8.23
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
Walked without holding on-overall
|
16.5 age (months)
Standard Error 8.23
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
First used single words other than "mama" or "dada"-baseline
|
29.5 age (months)
Standard Error 24.81
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
First used single words other than "mama" or "dada"-overall
|
29.5 age (months)
Standard Error 24.81
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
First used two words/short phrases-baseline
|
33.2 age (months)
Standard Error 16.66
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
First used two words/short phrases-overall
|
34.3 age (months)
Standard Error 19.77
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
Toilet trained during the day-baseline
|
46.2 age (months)
Standard Error 31.22
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
Toilet trained during the day-overall
|
51.5 age (months)
Standard Error 35.89
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
Toilet trained at night-baseline
|
52.5 age (months)
Standard Error 35.60
|
|
TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
Toilet trained at night-overall
|
60.1 age (months)
Standard Error 43.23
|
SECONDARY outcome
Timeframe: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.Population: The Full Analysis Set (FAS) consisted of all participants enrolled in this study.
Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric disorders which refers to as TAND (TSC-Associated-Neuropsychiatric-Disorders). A specific TAND Checklist has been developed to assess Behavioral, Psychiatric, Intellectual, Academic, Neuropsychological and Psychosocial areas. Behavioral level- This level refers to any observed behaviors that may cause concern to the individual. Behavioral presentations include anxiety, depressed mood, aggressive behaviors, temper tantrums, attention-related behaviors (such as difficulty concentrating, hyperactivity, impulsivity), social, and communication-related behaviors (such as speech and language delays, poor eye contact, difficulties in relationships with peers, repetitive behaviors), self-injurious behaviors, and eating or sleep difficulties. Baseline is defined as the first available assessment on or after the enrollment date of the CRAD001M2305 study. Overall consists of all responses including baseline.
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Anxiety-baseline
|
12 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Anxiety-overall
|
13 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Depressed mood-baseline
|
6 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Depressed mood-overall
|
8 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Extreme shyness-baseline
|
5 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Extreme shyness-overall
|
7 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Mood swings-baseline
|
10 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Mood swings-overall
|
12 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Aggressive outbursts-baseline
|
7 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Aggressive outbursts-overall
|
11 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Temper Tantrums-baseline
|
9 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Temper Tantrums-overall
|
12 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Self-injury, such as hitting self, biting self, scratching self-baseline
|
3 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Self-injury, such as hitting self, biting self, scratching self-overall
|
5 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Absent or delayed onset of language to communicate-baseline
|
11 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Absent or delayed onset of language to communicate-overall
|
12 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Repeating words or phrases over and over again-baseline
|
9 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Repeating words or phrases over and over again-overall
|
12 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Poor eye contact-baseline
|
6 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Poor eye contact-overall
|
8 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Difficulties getting on with other people of similar age-baseline
|
9 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Difficulties getting on with other people of similar age-overall
|
10 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Repetitive behaviours, such as doing the same thing over and over again-baseline
|
9 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Repetitive behaviours, such as doing the same thing over and over again-overall
|
11 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Very rigid or inflexible about how to do things or not liking change in routines-baseline
|
8 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Very rigid or inflexible about how to do things or not liking change in routines-overall
|
11 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Overactivity/hyperactivity, such as being constantly on the go-baseline
|
8 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Overactivity/hyperactivity, such as being constantly on the go-overall
|
9 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Difficulty paying attention or concentrating-baseline
|
13 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Difficulty paying attention or concentrating-overall
|
15 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Restlessness or fidgetiness, such as wriggling or squirming-baseline
|
13 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Restlessness or fidgetiness, such as wriggling or squirming-overall
|
14 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Impulsivity, such as butting in, not waiting turn-baseline
|
10 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Impulsivity, such as butting in, not waiting turn-overall
|
12 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Difficulties with eating, such as eating too much, too little, unusual things-baseline
|
5 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Difficulties with eating, such as eating too much, too little, unusual things-overall
|
8 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Sleep difficulties, such as with falling asleep or waking-baseline
|
6 Participants
|
|
TAND Checklist: Number of Participants With Behavioral Disorders
Sleep difficulties, such as with falling asleep or waking-overall
|
8 Participants
|
SECONDARY outcome
Timeframe: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.Population: The Full Analysis Set (FAS) consisted of all participants enrolled in this study.
Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric disorders which refers to as TAND (TSC-Associated-Neuropsychiatric-Disorders). A specific TAND Checklist has been developed to assess Behavioral, Psychiatric, Intellectual, Academic, Neuropsychological and Psychosocial areas. For psychiatric disorders some behaviors of concern are examined and evaluated in the context of the individual's overall developmental level and in terms of their biological, psychological, and social profile. Baseline is defined as the first available assessment on or after the enrollment date of the CRAD001M2305 study. Overall consists of all responses including baseline.
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
TAND Checklist - Number of Participants With Psychiatric Disorders
Autism Spectrum Disorder (ASD), including autism, Asperger's-baseline
|
4 Participants
|
|
TAND Checklist - Number of Participants With Psychiatric Disorders
Autism Spectrum Disorder (ASD), including autism, Asperger's-overall
|
7 Participants
|
|
TAND Checklist - Number of Participants With Psychiatric Disorders
Attention Deficit Hyperactivity Disorder (ADHD)-baseline
|
5 Participants
|
|
TAND Checklist - Number of Participants With Psychiatric Disorders
Attention Deficit Hyperactivity Disorder (ADHD)-overall
|
9 Participants
|
|
TAND Checklist - Number of Participants With Psychiatric Disorders
Anxiety Disorder, including as panic, phobia, separation anxiety disorder-baseline
|
4 Participants
|
|
TAND Checklist - Number of Participants With Psychiatric Disorders
Anxiety Disorder, including as panic, phobia, separation anxiety disorder-overall
|
7 Participants
|
|
TAND Checklist - Number of Participants With Psychiatric Disorders
Depressive Disorder-baseline
|
0 Participants
|
|
TAND Checklist - Number of Participants With Psychiatric Disorders
Depressive Disorder-overall
|
0 Participants
|
|
TAND Checklist - Number of Participants With Psychiatric Disorders
Obsessive Compulsive Disorder-baseline
|
2 Participants
|
|
TAND Checklist - Number of Participants With Psychiatric Disorders
Obsessive Compulsive Disorder-overall
|
2 Participants
|
|
TAND Checklist - Number of Participants With Psychiatric Disorders
Psychotic Disorder, including schizophrenia-baseline
|
0 Participants
|
|
TAND Checklist - Number of Participants With Psychiatric Disorders
Psychotic Disorder, including schizophrenia-overall
|
0 Participants
|
SECONDARY outcome
Timeframe: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.Population: The Full Analysis Set (FAS) consisted of all participants enrolled in this study.
Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric disorders which refers to as TAND (TSC-Associated-Neuropsychiatric-Disorders). A specific TAND Checklist has been developed to assess Behavioral, Psychiatric, Intellectual, Academic, Neuropsychological and Psychosocial areas. At academic level, it is described the specific learning disorders associated with school performance, such as reading, writing, mathematics, and spelling. Baseline is defined as the first available assessment on or after the enrollment date of the CRAD001M2305 study. Overall consists of all responses including baseline.
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
TAND Checklist - Number of Participants With Scholastic Issues
Reading-baseline
|
12 Participants
|
|
TAND Checklist - Number of Participants With Scholastic Issues
Reading-overall
|
14 Participants
|
|
TAND Checklist - Number of Participants With Scholastic Issues
Writing-baseline
|
12 Participants
|
|
TAND Checklist - Number of Participants With Scholastic Issues
Writing-overall
|
14 Participants
|
|
TAND Checklist - Number of Participants With Scholastic Issues
Spelling-baseline
|
12 Participants
|
|
TAND Checklist - Number of Participants With Scholastic Issues
Spelling-overall
|
14 Participants
|
|
TAND Checklist - Number of Participants With Scholastic Issues
Mathematics-baseline
|
12 Participants
|
|
TAND Checklist - Number of Participants With Scholastic Issues
Mathematics-overall
|
14 Participants
|
SECONDARY outcome
Timeframe: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.Population: The Full Analysis Set (FAS) consisted of all participants enrolled in this study.
Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric disorders which refers to as TAND (TSC-Associated-Neuropsychiatric-Disorders). A specific TAND Checklist has been developed to assess Behavioral, Psychiatric, Intellectual, Academic, Neuropsychological and Psychosocial areas. Neuropsychological evaluations are used to describe the strengths and weaknesses of brain referenced systems used for learning, thinking, and behavior regulation. Baseline is defined as the first available assessment on or after the enrollment date of the CRAD001M2305 study. Overall consists of all responses including baseline.
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
Memory-baseline
|
7 Participants
|
|
TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
Memory-overall
|
12 Participants
|
|
TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
Attention-baseline
|
12 Participants
|
|
TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
Attention-overall
|
14 Participants
|
|
TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
Dual-tasking/ Multi-tasking-baseline
|
12 Participants
|
|
TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
Dual-tasking/ Multi-tasking-overall
|
14 Participants
|
|
TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
Visuo-spatial tasks-baseline
|
8 Participants
|
|
TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
Visuo-spatial tasks-overall
|
13 Participants
|
|
TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
Executive skills-baseline
|
10 Participants
|
|
TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
Executive skills-overall
|
15 Participants
|
|
TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
Getting disoriented-baseline
|
7 Participants
|
|
TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
Getting disoriented-overall
|
12 Participants
|
SECONDARY outcome
Timeframe: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.Population: The Full Analysis Set (FAS) consisted of all participants enrolled in this study.
Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric disorders which refers to as TAND (TSC-Associated-Neuropsychiatric-Disorders). A specific TAND Checklist has been developed to assess Behavioral, Psychiatric, Intellectual, Academic, Neuropsychological and Psychosocial areas. At psychosocial level it is considered important determinants of quality of life, such as self-esteem, family functioning, parental stress, and relationship difficulties. All these are markers of resilience and burden of care, and all the psychosocial factors may be amenable to intervention and support. Baseline is defined as the first available assessment on or after the enrollment date of the CRAD001M2305 study. Overall consists of all responses including baseline.
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
TAND Checklist - Number of Participants With Psychological Issues
Low self-esteem-baseline
|
2 Participants
|
|
TAND Checklist - Number of Participants With Psychological Issues
Low self-esteem-overall
|
6 Participants
|
|
TAND Checklist - Number of Participants With Psychological Issues
Very high levels of stress in families, for instance between siblings-baseline
|
6 Participants
|
|
TAND Checklist - Number of Participants With Psychological Issues
Very high levels of stress in families, for instance between siblings-overall
|
8 Participants
|
|
TAND Checklist - Number of Participants With Psychological Issues
Very high levels of stress between parents leading to significant relationship difficulties-baseline
|
5 Participants
|
|
TAND Checklist - Number of Participants With Psychological Issues
Very high levels of stress between parents leading to significant relationship difficulties-overall
|
7 Participants
|
SECONDARY outcome
Timeframe: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.Population: The Full Analysis Set (FAS) consisted of all participants enrolled in this study.
Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric disorders which refers to as TAND (TSC-Associated-Neuropsychiatric-Disorders). A specific TAND Checklist has been developed to assess Behavioral, Psychiatric, Intellectual, Academic, Neuropsychological and Psychosocial areas. Neuropsychological evaluations are used to describe the strengths and weaknesses of brain referenced systems used for learning, thinking, and behavior regulation. These include language skills (including non-verbal, simple language, fluence of language). All the responses are categorical in nature from the TAND Checklist. The frequency of (baseline and) worst-post baseline is summarized.
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
TAND Checklist - Number of Participants With Varied Levels of Language Skills
Non-verbal
|
2 Participants
|
|
TAND Checklist - Number of Participants With Varied Levels of Language Skills
Simple language
|
6 Participants
|
|
TAND Checklist - Number of Participants With Varied Levels of Language Skills
Fluent
|
4 Participants
|
|
TAND Checklist - Number of Participants With Varied Levels of Language Skills
Missing
|
3 Participants
|
SECONDARY outcome
Timeframe: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.Population: The Full Analysis Set (FAS) consisted of all participants enrolled in this study.
Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric disorders which refers to as TAND (TSC-Associated-Neuropsychiatric-Disorders). A specific TAND Checklist has been developed to assess Behavioral, Psychiatric, Intellectual, Academic, Neuropsychological and Psychosocial areas. This outcome measure assesses the TAND checklist part about physical dependency. All the responses are categorical in nature from the TAND Checklist. The frequency of (baseline and) worst-post baseline is summarized.
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
TAND Checklist - Number of Participants With Different Levels of Physical Dependency
Dependent on others
|
4 Participants
|
|
TAND Checklist - Number of Participants With Different Levels of Physical Dependency
Some self-care skills
|
7 Participants
|
|
TAND Checklist - Number of Participants With Different Levels of Physical Dependency
Independent
|
1 Participants
|
|
TAND Checklist - Number of Participants With Different Levels of Physical Dependency
Missing
|
3 Participants
|
SECONDARY outcome
Timeframe: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.Population: The Full Analysis Set (FAS) consisted of all participants enrolled in this study.
Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric disorders which refers to as TAND (TSC-Associated-Neuropsychiatric-Disorders). A specific TAND Checklist has been developed to assess Behavioral, Psychiatric, Intellectual, Academic, Neuropsychological and Psychosocial areas. This outcome measure assesses the TAND checklist part about mobility. All the responses are categorical in nature from the TAND Checklist. The frequency of (baseline and) worst-post baseline is summarized.
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
TAND Checklist: Number of Participants With Different Levels of Mobility
Wheelchair
|
1 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Mobility
Needs significant support
|
1 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Mobility
Some difficulty
|
0 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Mobility
Completely mobile
|
10 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Mobility
Missing
|
3 Participants
|
SECONDARY outcome
Timeframe: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.Population: The Full Analysis Set (FAS) consisted of all participants enrolled in this study.
Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric disorders which refers to as TAND (TSC-Associated-Neuropsychiatric-Disorders). A specific TAND Checklist has been developed to assess Behavioral, Psychiatric, Intellectual, Academic, Neuropsychological and Psychosocial areas. At intellectual level, it is described the intellectual developmental abilities of an individual in comparison with others of the same chronological age. All the responses are categorical in nature from the TAND Checklist. The frequency of (baseline and) worst-post baseline is summarized.
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
TAND Checklist: Number of Participants With Different Levels of Intelligence Quotient
Moderate Intellectual Disability (IQ 35-49)
|
5 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Intelligence Quotient
Normal Intellectual Ability (IQ > 80)
|
2 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Intelligence Quotient
Borderline Intellectual Ability (IQ 70-80)
|
2 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Intelligence Quotient
Mild Intellectual Disability (IQ 50-69)
|
1 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Intelligence Quotient
Severe Intellectual Disability (IQ 21-34)
|
0 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Intelligence Quotient
Profound Intellectual Disability (IQ <20)
|
1 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Intelligence Quotient
Missing
|
4 Participants
|
SECONDARY outcome
Timeframe: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.Population: The Full Analysis Set (FAS) consisted of all participants enrolled in this study.
Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric disorders which refers to as TAND (TSC-Associated-Neuropsychiatric-Disorders). A specific TAND Checklist has been developed to assess Behavioral, Psychiatric, Intellectual, Academic, Neuropsychological and Psychosocial areas. At intellectual level, it is described the intellectual developmental abilities of an individual to identify their overall functional and adaptive behaviors in comparison with others of the same chronological age. This level is the combination of formal measures of intellectual ability (such as IQ-type tests) and evaluation of adaptive behaviors (such as self-care, daily living skills, communication, and social abilities in daily life). All the responses are categorical in nature from the TAND Checklist. The frequency of (baseline and) worst-post baseline is summarized.
Outcome measures
| Measure |
Everolimus
n=15 Participants
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
TAND Checklist: Number of Participants With Different Levels of Intellectual Ability
Normal Intellectual Ability
|
1 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Intellectual Ability
Mild-Moderate Intellectual Disability
|
8 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Intellectual Ability
Severe - Profound Intellectual Disability
|
3 Participants
|
|
TAND Checklist: Number of Participants With Different Levels of Intellectual Ability
Missing
|
3 Participants
|
Adverse Events
Everolimus
Serious events: 6 serious events
Other events: 12 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Everolimus
n=14 participants at risk
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
General disorders
Drowning
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
General disorders
Pyrexia
|
14.3%
2/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Arthritis infective
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Influenza
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Pneumonia
|
14.3%
2/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Staphylococcal infection
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Injury, poisoning and procedural complications
Near drowning
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma, low grade
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Nervous system disorders
Seizure
|
14.3%
2/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Nervous system disorders
Status epilepticus
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
Other adverse events
| Measure |
Everolimus
n=14 participants at risk
Participants were treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Blood and lymphatic system disorders
Anaemia
|
21.4%
3/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Blood and lymphatic system disorders
Hypofibrinogenaemia
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Cardiac disorders
Bradycardia
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Cardiac disorders
Right ventricular dilatation
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Ear and labyrinth disorders
Hypoacusis
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Eye disorders
Periorbital swelling
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
14.3%
2/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Gastrointestinal disorders
Constipation
|
14.3%
2/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Gastrointestinal disorders
Diarrhoea
|
21.4%
3/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Gastrointestinal disorders
Flatulence
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Gastrointestinal disorders
Gingival hypertrophy
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Gastrointestinal disorders
Mouth ulceration
|
14.3%
2/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Gastrointestinal disorders
Nausea
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Gastrointestinal disorders
Oral pain
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Gastrointestinal disorders
Stomatitis
|
21.4%
3/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
General disorders
Gait disturbance
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
General disorders
Microsomia
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
General disorders
Pyrexia
|
42.9%
6/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Immune system disorders
Seasonal allergy
|
21.4%
3/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Bronchitis
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Cellulitis
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Clostridium difficile infection
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Conjunctivitis
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Croup infectious
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Ear infection
|
28.6%
4/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Fungal skin infection
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Gastroenteritis
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Infectious mononucleosis
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Influenza
|
14.3%
2/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Nasopharyngitis
|
28.6%
4/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Otitis media
|
14.3%
2/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Pharyngitis streptococcal
|
14.3%
2/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Pneumonia
|
21.4%
3/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Sinusitis
|
21.4%
3/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Infections and infestations
Upper respiratory tract infection
|
21.4%
3/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Injury, poisoning and procedural complications
Contusion
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Injury, poisoning and procedural complications
Limb injury
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Investigations
Cardiac murmur
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Investigations
Cutibacterium test positive
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Investigations
SARS-CoV-2 test negative
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Metabolism and nutrition disorders
Abnormal weight gain
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma, low grade
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Nervous system disorders
Dizziness
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Nervous system disorders
Head discomfort
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Nervous system disorders
Headache
|
21.4%
3/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Nervous system disorders
Seizure
|
28.6%
4/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Nervous system disorders
Vasogenic cerebral oedema
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Psychiatric disorders
Aggression
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Psychiatric disorders
Anxiety
|
21.4%
3/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Psychiatric disorders
Attention deficit hyperactivity disorder
|
14.3%
2/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Psychiatric disorders
Euphoric mood
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Psychiatric disorders
Insomnia
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Reproductive system and breast disorders
Heavy menstrual bleeding
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Reproductive system and breast disorders
Ovarian cyst
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
Central sleep apnoea syndrome
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.3%
2/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
Acne
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
Blister
|
7.1%
1/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
21.4%
3/14 • From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Adverse events are assessed in the Safety Set. The Safety Set included all pediatric patients enrolled who had at least one-post baseline safety assessment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER