Trial Outcomes & Findings for Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex (TSC) (NCT NCT01070316)
NCT ID: NCT01070316
Last Updated: 2017-03-13
Results Overview
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)
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Baseline (Weeks 1-4), Week 16
Results posted on
2017-03-13
Participant Flow
23 participants were screened; 3 participants were not eligible to begin treatment and were not enrolled
Participant milestones
| Measure |
Everolimus
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
|
|---|---|
|
Main Phase
STARTED
|
20
|
|
Main Phase
COMPLETED
|
20
|
|
Main Phase
NOT COMPLETED
|
0
|
|
Extension Phase
STARTED
|
18
|
|
Extension Phase
COMPLETED
|
14
|
|
Extension Phase
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Everolimus
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
|
|---|---|
|
Extension Phase
Lack of Efficacy
|
3
|
|
Extension Phase
Withdrawal by Subject
|
1
|
Baseline Characteristics
Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex (TSC)
Baseline characteristics by cohort
| Measure |
Everolimus
n=20 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
18 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
8.8 years
STANDARD_DEVIATION 5.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Weeks 1-4), Week 16The 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)
Outcome measures
| Measure |
Everolimus
n=20 Participants
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.
|
|---|---|
|
Reduction in Seizure Frequency
|
60 percentage
|
PRIMARY outcome
Timeframe: Individual subjects will be assessed every 6 months for up to 48 months; aggregate analysis will take place at end of studyOutcome measures
| Measure |
Everolimus
n=20 Participants
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.
|
|---|---|
|
Number of Participants Continuing Study Medication Over Time
16 weeks
|
20 participants
|
|
Number of Participants Continuing Study Medication Over Time
Entered Extension Phase (4 months)
|
18 participants
|
|
Number of Participants Continuing Study Medication Over Time
6 months
|
18 participants
|
|
Number of Participants Continuing Study Medication Over Time
12 months
|
17 participants
|
|
Number of Participants Continuing Study Medication Over Time
18 months
|
16 participants
|
|
Number of Participants Continuing Study Medication Over Time
24 months
|
16 participants
|
|
Number of Participants Continuing Study Medication Over Time
30 months
|
16 participants
|
|
Number of Participants Continuing Study Medication Over Time
36 months
|
15 participants
|
|
Number of Participants Continuing Study Medication Over Time
42 months
|
14 participants
|
|
Number of Participants Continuing Study Medication Over Time
48 months
|
14 participants
|
Adverse Events
Everolimus
Serious events: 8 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Everolimus
n=20 participants at risk
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
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Infection - URI/Sinus/Pneumonia
|
30.0%
6/20 • Number of events 7 • 5 years and 4 months
|
|
Renal and urinary disorders
Infection - GU
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Gastrointestinal disorders
Infection - GI
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Infections and infestations
Infection - unspecified
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Ear and labyrinth disorders
Infection - Otitis
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Nervous system disorders
Status epilepticus
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
Other adverse events
| Measure |
Everolimus
n=20 participants at risk
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
|
|---|---|
|
Skin and subcutaneous tissue disorders
Abrasion
|
20.0%
4/20 • Number of events 5 • 5 years and 4 months
|
|
Skin and subcutaneous tissue disorders
Acne
|
10.0%
2/20 • Number of events 2 • 5 years and 4 months
|
|
Psychiatric disorders
ADHD
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Psychiatric disorders
Agitation/Irritability
|
40.0%
8/20 • Number of events 12 • 5 years and 4 months
|
|
General disorders
Allergic Rhinitis
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Eye disorders
Allergic conjunctivitis
|
10.0%
2/20 • Number of events 2 • 5 years and 4 months
|
|
Gastrointestinal disorders
Anorexia
|
15.0%
3/20 • Number of events 6 • 5 years and 4 months
|
|
Nervous system disorders
Ataxia
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
General disorders
Back pain
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
General disorders
Bruising
|
10.0%
2/20 • Number of events 2 • 5 years and 4 months
|
|
Skin and subcutaneous tissue disorders
Cheilitis
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Investigations
Cholesterol
|
15.0%
3/20 • Number of events 4 • 5 years and 4 months
|
|
Respiratory, thoracic and mediastinal disorders
Congestion
|
25.0%
5/20 • Number of events 6 • 5 years and 4 months
|
|
Gastrointestinal disorders
Constipation
|
20.0%
4/20 • Number of events 8 • 5 years and 4 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
30.0%
6/20 • Number of events 6 • 5 years and 4 months
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
20.0%
4/20 • Number of events 7 • 5 years and 4 months
|
|
Gastrointestinal disorders
Diarrhea
|
40.0%
8/20 • Number of events 23 • 5 years and 4 months
|
|
Ear and labyrinth disorders
Ear Pain
|
10.0%
2/20 • Number of events 2 • 5 years and 4 months
|
|
Blood and lymphatic system disorders
Edema
|
10.0%
2/20 • Number of events 5 • 5 years and 4 months
|
|
General disorders
Fatigue
|
20.0%
4/20 • Number of events 7 • 5 years and 4 months
|
|
General disorders
Fever
|
45.0%
9/20 • Number of events 18 • 5 years and 4 months
|
|
General disorders
Flu-like symptoms
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
25.0%
5/20 • Number of events 9 • 5 years and 4 months
|
|
Gastrointestinal disorders
Gastrointestinal Other
|
10.0%
2/20 • Number of events 2 • 5 years and 4 months
|
|
General disorders
Headache
|
25.0%
5/20 • Number of events 5 • 5 years and 4 months
|
|
Blood and lymphatic system disorders
Hemorrhage
|
15.0%
3/20 • Number of events 3 • 5 years and 4 months
|
|
Respiratory, thoracic and mediastinal disorders
Hiccoughs
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Investigations
Hyperkalemia
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Investigations
Hypoalbuminemia
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Investigations
Hypokalemia
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Investigations
Hyponatremia
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Investigations
Hypophosphatemia
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Eye disorders
Infection - Conjunctivitis
|
10.0%
2/20 • Number of events 2 • 5 years and 4 months
|
|
Gastrointestinal disorders
Infection - GI
|
50.0%
10/20 • Number of events 22 • 5 years and 4 months
|
|
Renal and urinary disorders
Infection - GU
|
20.0%
4/20 • Number of events 6 • 5 years and 4 months
|
|
Blood and lymphatic system disorders
Infection - Lymphatics
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Ear and labyrinth disorders
Infection - Otitis
|
55.0%
11/20 • Number of events 26 • 5 years and 4 months
|
|
Skin and subcutaneous tissue disorders
Infection - Skin
|
45.0%
9/20 • Number of events 21 • 5 years and 4 months
|
|
Infections and infestations
Infection - Unspecified
|
15.0%
3/20 • Number of events 3 • 5 years and 4 months
|
|
Respiratory, thoracic and mediastinal disorders
Infection - URI/Sinus/Pneumonia
|
100.0%
20/20 • Number of events 131 • 5 years and 4 months
|
|
General disorders
Insomnia
|
30.0%
6/20 • Number of events 9 • 5 years and 4 months
|
|
Investigations
Laboratory - Other
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Injury, poisoning and procedural complications
Laceration
|
20.0%
4/20 • Number of events 6 • 5 years and 4 months
|
|
General disorders
Leg pain
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
General disorders
Malaise
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Investigations
Metabolic - Other
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Gastrointestinal disorders
Mucositis/Atomatitis
|
85.0%
17/20 • Number of events 78 • 5 years and 4 months
|
|
Musculoskeletal and connective tissue disorders
Muscle pain
|
10.0%
2/20 • Number of events 2 • 5 years and 4 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal - other
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Gastrointestinal disorders
Nausea
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Blood and lymphatic system disorders
Neutrophils - other
|
20.0%
4/20 • Number of events 16 • 5 years and 4 months
|
|
Musculoskeletal and connective tissue disorders
Osteopenia/Osteoporosis
|
5.0%
1/20 • Number of events 2 • 5 years and 4 months
|
|
Immune system disorders
Other
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Skin and subcutaneous tissue disorders
Other
|
25.0%
5/20 • Number of events 5 • 5 years and 4 months
|
|
Ear and labyrinth disorders
Otitis media
|
10.0%
2/20 • Number of events 2 • 5 years and 4 months
|
|
Cardiac disorders
Pericardial effusion
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Investigations
Proteinuria
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Psychiatric disorders
Psychosis
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
45.0%
9/20 • Number of events 12 • 5 years and 4 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
15.0%
3/20 • Number of events 4 • 5 years and 4 months
|
|
Gastrointestinal disorders
Sialorrhea
|
5.0%
1/20 • Number of events 2 • 5 years and 4 months
|
|
General disorders
Somnolence
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
General disorders
Speech impairment
|
10.0%
2/20 • Number of events 2 • 5 years and 4 months
|
|
Musculoskeletal and connective tissue disorders
Sprain/Strain/Soft tissue
|
25.0%
5/20 • Number of events 6 • 5 years and 4 months
|
|
Eye disorders
Stye
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Gastrointestinal disorders
Teeth
|
10.0%
2/20 • Number of events 2 • 5 years and 4 months
|
|
Gastrointestinal disorders
Thirst
|
10.0%
2/20 • Number of events 2 • 5 years and 4 months
|
|
Gastrointestinal disorders
Throat pain
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Investigations
Transaminase
|
10.0%
2/20 • Number of events 9 • 5 years and 4 months
|
|
General disorders
Unspecified pain
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Renal and urinary disorders
Urinary frequency
|
10.0%
2/20 • Number of events 2 • 5 years and 4 months
|
|
Renal and urinary disorders
Urinary retention
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Reproductive system and breast disorders
Vaginal discharge
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Reproductive system and breast disorders
Vaginal itching
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
|
Gastrointestinal disorders
Vomiting
|
55.0%
11/20 • Number of events 22 • 5 years and 4 months
|
|
General disorders
Weight loss
|
5.0%
1/20 • Number of events 1 • 5 years and 4 months
|
Additional Information
Elizabeth Hoskins
Cincinnati Children's Hospital Medical Center
Phone: (513) 803-7263
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place