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Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex (TSC)

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ClinicalTrials.gov Identifier: NCT01070316
Recruitment Status : Completed
First Posted : February 18, 2010
Results First Posted : September 23, 2016
Last Update Posted : March 13, 2017
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Epilepsy
Tuberous Sclerosis Complex
Intervention Drug: Everolimus
Enrollment 20
Recruitment Details 23 participants were screened; 3 participants were not eligible to begin treatment and were not enrolled
Pre-assignment Details  
Arm/Group Title Everolimus
Hide Arm/Group Description

Subjects will be administered study drug if they meet study criteria after 4 weeks of baseline phase. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily.

Everolimus: Everolimus is available in tablet form. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily. After two weeks, serum trough level will be measured and dose adjusted according to the following algorithm If Blood trough level is less than 2.5 ng/ml than increase dose by 5 mg/m2/day; If Blood trough level is 2.5-5.0 ng/ml than increase dose by 2.5 mg/m2/day; If Blood trough level is 5.1-10.0 ng/ml than increase dose by 0 mg/m2/day (no change); If Blood trough level is 10.1-15.0 ng/ml than decrease dose by 2.5 mg/m2/day

Period Title: Main Phase
Started 20
Completed 20
Not Completed 0
Period Title: Extension Phase
Started 18 [1]
Completed 14
Not Completed 4
Reason Not Completed
Lack of Efficacy             3
Withdrawal by Subject             1
[1]
Two participants did not qualify for Extension Phase as defined by protocol
Arm/Group Title Everolimus
Hide Arm/Group Description

Main Study Phase:

Subjects will be administered study drug if they meet study criteria after 4 weeks of baseline phase. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, taken daily.

Everolimus: Everolimus is available in tablet form. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily. After two weeks, serum trough level will be measured and dose adjusted according to the following algorithm If trough level is less than 2.5 ng/ml than increase dose by 5 mg/m2/day; If trough level is 2.5-5.0 ng/ml than increase dose by 2.5 mg/m2/day; If trough level is 5.1-10.0 ng/ml than increase dose by 0 mg/m2/day (no change); If trough level is 10.1-15.0 ng/ml than decrease dose by 2.5 mg/m2/day

Following the 4 week titration, subjects will continue in an 8 week maintenance period.

If subjects qualify for the Extension Phase of the study, they will continue on study drug and be followed through 48 months.

Overall Number of Baseline Participants 20
Hide Baseline Analysis Population Description
20 study subjects were consented, screened, enrolled, and received study drug
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
<=18 years
18
  90.0%
Between 18 and 65 years
2
  10.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants
8.8  (5.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
10
  50.0%
Male
10
  50.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants
20
1.Primary Outcome
Title Reduction in Seizure Frequency
Hide Description The primary efficacy endpoint was the percentage of participants demonstrating a 50% or greater reduction in seizure frequency at the end of the maintenance phase (weeks 13-16) compared to baseline (weeks 1-4)
Time Frame Baseline (Weeks 1-4), Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Everolimus
Hide Arm/Group Description:

Main Study Phase:

Subjects will be administered study drug if they meet study criteria after 4 weeks of baseline phase. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, taken daily.

Everolimus: Everolimus is available in tablet form. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily. After two weeks, serum trough level will be measured and dose adjusted according to the following algorithm If trough level is less than 2.5 ng/ml than increase dose by 5 mg/m2/day; If trough level is 2.5-5.0 ng/ml than increase dose by 2.5 mg/m2/day; If trough level is 5.1-10.0 ng/ml than increase dose by 0 mg/m2/day (no change); If trough level is 10.1-15.0 ng/ml than decrease dose by 2.5 mg/m2/day

Following the 4 week titration, subjects will continue in an 8 week maintenance period.

If subjects qualify for the Extension Phase of the study, they will continue on study drug and be followed through 48 months.

Overall Number of Participants Analyzed 20
Measure Type: Number
Unit of Measure: percentage
60
2.Primary Outcome
Title Number of Participants Continuing Study Medication Over Time
Hide Description [Not Specified]
Time Frame Individual subjects will be assessed every 6 months for up to 48 months; aggregate analysis will take place at end of study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Everolimus
Hide Arm/Group Description:

Main Study Phase:

Subjects will be administered study drug if they meet study criteria after 4 weeks of baseline phase. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, taken daily.

Everolimus: Everolimus is available in tablet form. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily. After two weeks, serum trough level will be measured and dose adjusted according to the following algorithm If trough level is less than 2.5 ng/ml than increase dose by 5 mg/m2/day; If trough level is 2.5-5.0 ng/ml than increase dose by 2.5 mg/m2/day; If trough level is 5.1-10.0 ng/ml than increase dose by 0 mg/m2/day (no change); If trough level is 10.1-15.0 ng/ml than decrease dose by 2.5 mg/m2/day

Following the 4 week titration, subjects will continue in an 8 week maintenance period.

If subjects qualify for the Extension Phase of the study, they will continue on study drug and be followed through 48 months.

Overall Number of Participants Analyzed 20
Measure Type: Number
Unit of Measure: participants
16 weeks 20
Entered Extension Phase (4 months) 18
6 months 18
12 months 17
18 months 16
24 months 16
30 months 16
36 months 15
42 months 14
48 months 14
Time Frame 5 years and 4 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Everolimus
Hide Arm/Group Description

Subjects will be administered study drug if they meet study criteria after 4 weeks of baseline phase. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily.

Everolimus: Everolimus is available in tablet form. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily. After two weeks, serum trough level will be measured and dose adjusted according to the following algorithm If Blood trough level is less than 2.5 ng/ml than increase dose by 5 mg/m2/day; If Blood trough level is 2.5-5.0 ng/ml than increase dose by 2.5 mg/m2/day; If Blood trough level is 5.1-10.0 ng/ml than increase dose by 0 mg/m2/day (no change); If Blood trough level is 10.1-15.0 ng/ml than decrease dose by 2.5 mg/m2/day

All-Cause Mortality
Everolimus
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Everolimus
Affected / at Risk (%) # Events
Total   8/20 (40.00%)    
Ear and labyrinth disorders   
Infection - Otitis  1  1/20 (5.00%)  1
Gastrointestinal disorders   
Infection - GI  1  1/20 (5.00%)  1
Infections and infestations   
Infection - unspecified  1  1/20 (5.00%)  1
Nervous system disorders   
Status epilepticus  1  1/20 (5.00%)  1
Renal and urinary disorders   
Infection - GU  1  1/20 (5.00%)  1
Respiratory, thoracic and mediastinal disorders   
Infection - URI/Sinus/Pneumonia  1  6/20 (30.00%)  7
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Everolimus
Affected / at Risk (%) # Events
Total   20/20 (100.00%)    
Blood and lymphatic system disorders   
Edema  2  2/20 (10.00%)  5
Hemorrhage  2  3/20 (15.00%)  3
Infection - Lymphatics  2  1/20 (5.00%)  1
Neutrophils - other  2  4/20 (20.00%)  16
Cardiac disorders   
Pericardial effusion  2  1/20 (5.00%)  1
Ear and labyrinth disorders   
Ear Pain  2  2/20 (10.00%)  2
Infection - Otitis  2  11/20 (55.00%)  26
Otitis media  2  2/20 (10.00%)  2
Eye disorders   
Allergic conjunctivitis  2  2/20 (10.00%)  2
Infection - Conjunctivitis  2  2/20 (10.00%)  2
Stye  2  1/20 (5.00%)  1
Gastrointestinal disorders   
Anorexia  2  3/20 (15.00%)  6
Constipation  2  4/20 (20.00%)  8
Diarrhea  2  8/20 (40.00%)  23
Gastrointestinal Other  2  2/20 (10.00%)  2
Infection - GI  2  10/20 (50.00%)  22
Mucositis/Atomatitis  2  17/20 (85.00%)  78
Nausea  2  1/20 (5.00%)  1
Sialorrhea  2  1/20 (5.00%)  2
Teeth  2  2/20 (10.00%)  2
Thirst  2  2/20 (10.00%)  2
Throat pain  2  1/20 (5.00%)  1
Vomiting  2  11/20 (55.00%)  22
General disorders   
Allergic Rhinitis  2  1/20 (5.00%)  1
Back pain  2  1/20 (5.00%)  1
Bruising  2  2/20 (10.00%)  2
Fatigue  2  4/20 (20.00%)  7
Fever  2  9/20 (45.00%)  18
Flu-like symptoms  2  1/20 (5.00%)  1
Headache  2  5/20 (25.00%)  5
Insomnia  2  6/20 (30.00%)  9
Leg pain  2  1/20 (5.00%)  1
Malaise  2  1/20 (5.00%)  1
Somnolence  2  1/20 (5.00%)  1
Speech impairment  2  2/20 (10.00%)  2
Unspecified pain  2  1/20 (5.00%)  1
Weight loss  2  1/20 (5.00%)  1
Immune system disorders   
Other  2  1/20 (5.00%)  1
Infections and infestations   
Infection - Unspecified  2  3/20 (15.00%)  3
Injury, poisoning and procedural complications   
Laceration  2  4/20 (20.00%)  6
Investigations   
Cholesterol  2  3/20 (15.00%)  4
Hyperkalemia  2  1/20 (5.00%)  1
Hypoalbuminemia  2  1/20 (5.00%)  1
Hypokalemia  2  1/20 (5.00%)  1
Hyponatremia  2  1/20 (5.00%)  1
Hypophosphatemia  2  1/20 (5.00%)  1
Laboratory - Other  2  1/20 (5.00%)  1
Metabolic - Other  2  1/20 (5.00%)  1
Proteinuria  2  1/20 (5.00%)  1
Transaminase  2  2/20 (10.00%)  9
Musculoskeletal and connective tissue disorders   
Fracture  2  5/20 (25.00%)  9
Muscle pain  2  2/20 (10.00%)  2
Musculoskeletal - other  2  1/20 (5.00%)  1
Osteopenia/Osteoporosis  2  1/20 (5.00%)  2
Sprain/Strain/Soft tissue  2  5/20 (25.00%)  6
Nervous system disorders   
Ataxia  2  1/20 (5.00%)  1
Psychiatric disorders   
ADHD  2  1/20 (5.00%)  1
Agitation/Irritability  2  8/20 (40.00%)  12
Psychosis  2  1/20 (5.00%)  1
Renal and urinary disorders   
Infection - GU  2  4/20 (20.00%)  6
Urinary frequency  2  2/20 (10.00%)  2
Urinary retention  2  1/20 (5.00%)  1
Reproductive system and breast disorders   
Vaginal discharge  2  1/20 (5.00%)  1
Vaginal itching  2  1/20 (5.00%)  1
Respiratory, thoracic and mediastinal disorders   
Congestion  2  5/20 (25.00%)  6
Cough  2  6/20 (30.00%)  6
Hiccoughs  2  1/20 (5.00%)  1
Infection - URI/Sinus/Pneumonia  2  20/20 (100.00%)  131
Pleural effusion  2  1/20 (5.00%)  1
Rhinorrhea  2  3/20 (15.00%)  4
Skin and subcutaneous tissue disorders   
Abrasion  1  4/20 (20.00%)  5
Acne  2  2/20 (10.00%)  2
Cheilitis  2  1/20 (5.00%)  1
Dermatitis  2  4/20 (20.00%)  7
Infection - Skin  2  9/20 (45.00%)  21
Other  2  5/20 (25.00%)  5
Pruritus  2  1/20 (5.00%)  1
Rash  2  9/20 (45.00%)  12
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE 3.0
2
Term from vocabulary, CTCAE (3.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Elizabeth Hoskins
Organization: Cincinnati Children's Hospital Medical Center
Phone: (513) 803-7263
Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01070316     History of Changes
Other Study ID Numbers: 2009-0998
First Submitted: February 15, 2010
First Posted: February 18, 2010
Results First Submitted: August 1, 2016
Results First Posted: September 23, 2016
Last Update Posted: March 13, 2017