Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1) (EXIST-1)

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 24 centers in 10 countries.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 117 participants were enrolled and randomized into the core period. Only 111 participants completing the core period, continued in the open-label extension period of the study.

Reporting Groups

	Description
Everolimus	Participants received oral dose of everolimus 4.5 milligram/square meter (mg/m^2) daily as an initial starting dose to attain the whole blood trough concentrations in range of 5-15 nanogram/millilitre (ng/mL). Dose adjustments were permitted based on safety and whole blood trough concentrations.
Placebo	Participants received oral dose of placebo matching to everolimus daily.

Participant Flow for 2 periods

Period 1:   Core Period (48 Weeks)

	Everolimus	Placebo
STARTED	78	39
COMPLETED	78	33
NOT COMPLETED	0	6
Administrative problems	0	1
Withdrawal by Subject	0	4
Lost to Follow-up	0	1

Period 2:   Open-label Extension Period (4 Years)

	Everolimus	Placebo
STARTED	111 [1]	0 [2]
COMPLETED	82	0
NOT COMPLETED	29	0
Adverse Event	10	0
Withdrawal by Subject	6	0
Lost to Follow-up	3	0
Administrative problems	7	0
Death	1	0
Disease progression	1	0
New treatment for indication under study	1	0

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups

	Description
Everolimus (Core Period)	Participants received oral dose of everolimus 4.5 mg/m^2 daily as an initial starting dose to attain the whole blood trough concentrations in range of 5-15 ng/mL. Dose adjustments were permitted based on safety and whole blood trough concentrations.
Placebo (Core Period)	Participants received oral dose of placebo matching to everolimus daily.
Total	Total of all reporting groups

Baseline Measures

	Everolimus (Core Period)	Placebo (Core Period)	Total
Overall Participants Analyzed  [Units: Participants]	78	39	117
Age  [Units: Years] Mean (Standard Deviation)	10.1  (5.9)	10.3  (7.3)	10.2  (6.4)
Age, Customized  [Units: Participants]
<3 years	13	7	20
3-18 years	55	26	81
≥18 years	10	6	16
Gender  [Units: Participants]
Female	29	21	50
Male	49	18	67

1.  Primary:

Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response   [ Time Frame: End of core period (Week 48), and end of extension period (up to 4 years) ]

2.  Secondary:

Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period   [ Time Frame: Baseline (Core period) to Week 24 (Core period), Baseline (Extension period, Week 24 post-core baseline) to Week 24 (Extension period, Week 48 post-core baseline) ]

3.  Secondary:

Time to SEGA Progression   [ Time Frame: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) ]

4.  Secondary:

Time to SEGA Response   [ Time Frame: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) ]

5.  Secondary:

Duration of SEGA Response   [ Time Frame: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) ]

6.  Secondary:

Time to SEGA Worsening   [ Time Frame: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) ]

7.  Secondary:

Percentage of Participants With Skin Lesions Assessed Using Physician's Global Assessement Overall Score   [ Time Frame: End of core period (Week 48), and end of extension period (up to 4 years) ]

8.  Secondary:

Duration of Skin Lesion Response in Everolimus Treated Participants   [ Time Frame: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) ]

9.  Secondary:

Everolimus Blood Concentration (C2h) at 2 Hours Post Dose   [ Time Frame: 2 hours post dose on Week 6, Week 24, Week 48, Week 96, Week 144, and Week 240 ]

10.  Secondary:

Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose   [ Time Frame: 24 hours post dose on Week 6, Week 24, Week 48, Week 72, Week 96, Week 144, and Week 240 ]

11.  Secondary:

Percentage of Participants With Renal Impairment During Core Period   [ Time Frame: Day 1 up to 28 days after end of treatment (Core period) ]

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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