Trial · NCT01713946
A Placebo-controlled Study of Efficacy & Safety of 2 Trough-ranges of Everolimus as Adjunctive Therapy in Patients With Tuberous Sclerosis Complex (TSC) & Refractory Partial-onset Seizures
NCT01713946, Phase 3, Completed, Novartis Pharmaceuticals; results first posted 2018-11-07
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Placebo-controlled Study of Efficacy & Safety of 2 Trough-ranges of Everolimus as Adjunctive Therapy in Patients With Tuberous Sclerosis Complex (TSC) & Refractory Partial-onset Seizures. Trials, record NCT01713946. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01713946
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Placebo-controlled Study of Efficacy & Safety of 2 Trough-ranges of Everolimus as Adjunctive Therapy in Patients With Tuberous Sclerosis Complex (TSC) & Refractory Partial-onset Seizures
- NCT number
- NCT01713946
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 366 participants, actual
- Lead sponsor
- Novartis Pharmaceuticals
- Conditions
- Tuberous Sclerosis Complex-associated Refractory Seizures
- Interventions
- RAD001, Placebo, Antiepileptic drug (1 to 3 only), open label RAD001 (only used for post-extension phase)
- First posted
- 2012-10-25
- Last updated
- 2018-11-07
- Other registries' IDs
- eudract:2011-000860-90
- Results first posted
- 2018-11-07
Source ClinicalTrials.gov
Registered outcomes22
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Core Phase: European Medicine Agency (EMA): Seizure Frequency Response Rate | Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase) | Comparison of response rates in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm. Response means at least a 50% reduction from baseline in partial-onset seizure frequency during the maintenance period of the core phase. |
| Primary | Core Phase: Food & Drug Administration (FDA): Percentage Change From Baseline in Partial Onset-seizure Frequency | Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase) | Comparison of median percent change from baseline in weekly seizure frequency in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. Percentage change from baseline in average weekly seizure frequency during the maintenance period of the Core phase (SFcfb) = 100 × (SFB - SFM) ÷ SFB where: SFB is the average weekly seizure frequency in the Baseline phase SFM is the average weekly seizure frequency in the maintenance period of the Core phase A positive percentage change from baseline (SFcfb) means a reduction in seizure frequency whereas a negative percentage change from baseline (SFcfb) means an increase in seizure frequency. |
| Secondary | Percentage of Seizure-free Patients During the Maintenance Period of the Core Phase | Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase) | Comparison of seizure freedom (100% reduction in seizure frequency) in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. Seizure free means a 100% reduction from baseline in partial-onset seizure frequency during maintenance period of the core phase. |
| Secondary | Core Phase: Percentage of Patients With at Least a 25% Reduction in Seizure Frequency | Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase) | Comparison of percentage of patients with at least ≥ 25% reduction in seizure frequency in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase. At least 25% reduction from baseline in partial-onset seizure frequency during maintenance period of the core phase. |
| Secondary | Core Phase: Distribution of Reduction From Baseline in Seizure Frequency | Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase) | Comparison of percentage of patients in six categories of seizure reduction from baseline (≤ -25% (exacerbation); \> -25% to \< 25% (no change); ≥ 25% to \< 50%; ≥ 50% to \< 75%; ≥ 75% to \< 100%; 100% (seizure-freedom)) in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase |
| Secondary | Core Phase: Changes From Baseline in Number of Seizure-free Days | Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase) | Comparison of seizure-free days relative to baseline in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during maintenance period of the core phase |
| Secondary | Core Phase: Probability That a Patient Remains On-treatment up to a Specified Time Point | Week 6, Week 12, Week 18 | Comparison of time to treatment discontinuation in the everolimus low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm during the core phase. Treatment duration is defined as the time from randomization until the date of permanent study treatment discontinuation (for any reason) at any time during the Core phase. The percentage event-free probability estimate is the estimated probability that a patient will remain on-treatment up to a specified time point (Week 6, 12, 18) |
| Secondary | Core Phase: Change From Baseline in the QOLCE Overall Quality-of-life Score for Patients <11 Years | Baseline, Week 18 | Comparison of quality of life in the everolimus (from 3 age specific questionnaires) low-trough treatment arm (3-7 ng/mL), high-trough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life Childhood Epilepsy (QOLCE) questionnaire, used for patients \< 11 years at baseline, was completed by the patient's parent or caregiver. It consists of 16 subscales (13 multi-item scales and 3 single item scales) and one overall quality-of-life score. Scores range from 0-100, with higher scores corresponding to improved QoL. The Overall Quality of Life Score is computed by adding each subscale score for each individual and then dividing by 16. |
| Secondary | Core Phase: Change From Baseline in the QOLIE-AD-48 Overall Quality-of-life Score for Patients >=11 to 18 Years | Baseline, Week 18 | Comparison of quality of life (from 3 age specific questionnaires) in the everolimus low-trough treatment arm (3-7 ng/mL), hightrough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life in Epilepsy Inventory for Adolescents-48 (QOLIE-AD-48) is a survey of health-related quality of life for adolescents 11 to 18 years of age with epilepsy. The QOLIE-AD-48 is completed by the patient. It contains 48 items which assess 8 subscales. Scores range from 0-100, with higher scores corresponding to improved QoL. The overall quality of life score is obtained by summing a linear combination of the 8 subscale scores, where each subscale is multiplied by a relative weight that is provided in the original publication. |
| Secondary | Core Phase: Change From Baseline in the QOLIE-31-P Overall Quality-of-life Score for Patients Aged >=18 Years | Baseline, Week 18 | Comparison of quality of life (from 3 age specific questionnaires) in the everolimus low-trough treatment arm (3-7 ng/mL), hightrough treatment arm (9-15 ng/mL) and placebo arm at the end of the core phase. The Quality of Life in Epilepsy Inventory-31-Problems (QOLIE-31-P) is a survey of health-related quality of life for adults with epilepsy. The QOLIE-31-P is completed by the patient. It contains 39 items, of which a total of 30 are used to make up 7 different subscales. Scores range from 0-100, with higher scores indicating a greater level of functioning and QoL. The overall quality of life score is obtained by summing a linear combination of the 7 subscale scores, where each subscale is multiplied by a relative weight that is obtained from the patient's answer to 7 items of this questionnaire. |
1 to 10 of 22Source ClinicalTrials.gov
See all 22 registered outcomesOutcomes22
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Core Phase: European Medicine Agency (EMA): Seizure Frequency Response Rate | Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase) | The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization | Percentage of responders | NUMBER |
| PRIMARY | Core Phase: Food & Drug Administration (FDA): Percentage Change From Baseline in Partial Onset-seizure Frequency | Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase) | The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization | Percentage change from baseline | MEDIAN |
| SECONDARY | Percentage of Seizure-free Patients During the Maintenance Period of the Core Phase | Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase) | The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization | Percentage of seizure-free participants | NUMBER |
| SECONDARY | Core Phase: Percentage of Patients With at Least a 25% Reduction in Seizure Frequency | Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase) | The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization | Percentage of participants | NUMBER |
| SECONDARY | Core Phase: Distribution of Reduction From Baseline in Seizure Frequency | Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase) | The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization | Percentage of participants | NUMBER |
| SECONDARY | Core Phase: Changes From Baseline in Number of Seizure-free Days | Baseline (8-week period before randomization), Week 7 to 18 (12-week maintenance period of the core phase) | The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization | Number of seizure-free days -per 28 days | MEDIAN |
| SECONDARY | Core Phase: Probability That a Patient Remains On-treatment up to a Specified Time Point | Week 6, Week 12, Week 18 | The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization | Percentage event-free prob. estimates | NUMBER |
| SECONDARY | Core Phase: Change From Baseline in the QOLCE Overall Quality-of-life Score for Patients <11 Years | Baseline, Week 18 | The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization | scores on a scale | MEDIAN |
| SECONDARY | Core Phase: Change From Baseline in the QOLIE-AD-48 Overall Quality-of-life Score for Patients >=11 to 18 Years | Baseline, Week 18 | The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization | scores on a scale | MEDIAN |
| SECONDARY | Core Phase: Change From Baseline in the QOLIE-31-P Overall Quality-of-life Score for Patients Aged >=18 Years | Baseline, Week 18 | The Full Analysis Set (FAS) comprised all patients to whom study treatment was assigned by randomization | scores on a scale | MEDIAN |
1 to 10 of 22Source ClinicalTrials.gov
See all 22 outcomesResults by group160
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Core Phase: European Medicine Agency (EMA): Seizure Frequency Response Rate | Everolimus LT Target of 3 to 7 ng/mL | 28.2 | 95% Confidence Interval 20.3 to 37.3 | Percentage of responders | |
| Core Phase: European Medicine Agency (EMA): Seizure Frequency Response Rate | Everolimus HT Target of 9 to 15 ng/mL | 40.0 | 95% Confidence Interval 31.5 to 49.0 | Percentage of responders | |
| Core Phase: European Medicine Agency (EMA): Seizure Frequency Response Rate | Placebo | 15.1 | 95% Confidence Interval 9.2 to 22.8 | Percentage of responders | |
| Core Phase: Food & Drug Administration (FDA): Percentage Change From Baseline in Partial Onset-seizure Frequency | Everolimus LT Target of 3 to 7 ng/mL | 29.29 | 95% Confidence Interval 18.82 to 41.88 | Percentage change from baseline | |
| Core Phase: Food & Drug Administration (FDA): Percentage Change From Baseline in Partial Onset-seizure Frequency | Everolimus HT Target of 9 to 15 ng/mL | 39.55 | 95% Confidence Interval 35.03 to 48.74 | Percentage change from baseline | |
| Core Phase: Food & Drug Administration (FDA): Percentage Change From Baseline in Partial Onset-seizure Frequency | Placebo | 14.86 | 95% Confidence Interval 0.11 to 21.71 | Percentage change from baseline | |
| Percentage of Seizure-free Patients During the Maintenance Period of the Core Phase | Everolimus LT Target of 3 to 7 ng/mL | 5.1 | 95% Confidence Interval 1.9 to 10.8 | Percentage of seizure-free participants | |
| Percentage of Seizure-free Patients During the Maintenance Period of the Core Phase | Everolimus HT Target of 9 to 15 ng/mL | 3.8 | 95% Confidence Interval 1.3 to 8.7 | Percentage of seizure-free participants | |
| Percentage of Seizure-free Patients During the Maintenance Period of the Core Phase | Placebo | 0.8 | 95% Confidence Interval 0.0 to 4.6 | Percentage of seizure-free participants | |
| Core Phase: Percentage of Patients With at Least a 25% Reduction in Seizure Frequency | Everolimus LT Target of 3 to 7 ng/mL | 52.1 | 95% Confidence Interval 42.7 to 61.5 | Percentage of participants |
1 to 10 of 160Source ClinicalTrials.gov
See all 160 results by groupParticipant flow30
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Everolimus LT Target of 3 to 7 ng/mL | 117 | |
| Overall Study | STARTED | Everolimus HT Target of 9 to 15 ng/mL | 130 | |
| Overall Study | STARTED | Placebo | 119 | |
| Overall Study | Completed Core Phase | Everolimus LT Target of 3 to 7 ng/mL | 110 | |
| Overall Study | Completed Core Phase | Everolimus HT Target of 9 to 15 ng/mL | 122 | |
| Overall Study | Completed Core Phase | Placebo | 114 | |
| Overall Study | Continued in Ext. Phase | Everolimus LT Target of 3 to 7 ng/mL | 110 | |
| Overall Study | Continued in Ext. Phase | Everolimus HT Target of 9 to 15 ng/mL | 119 | |
| Overall Study | Continued in Ext. Phase | Placebo | 114 | |
| Overall Study | Completed Ext. Phase | Everolimus LT Target of 3 to 7 ng/mL | 79 |
1 to 10 of 30Source ClinicalTrials.gov
See all 30 participant flowAdverse events820
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Everolimus LT Target of 3 to 7 ng/mL | 10 | 117 | |
| other | Anaemia | Blood and lymphatic system disorders | Everolimus HT Target of 9 to 15 ng/mL | 7 | 130 | |
| other | Anaemia | Blood and lymphatic system disorders | Everolimus Start Ext | 4 | 114 | |
| other | Anaemia | Blood and lymphatic system disorders | Everolimus All | 21 | 361 | |
| other | Neutropenia | Blood and lymphatic system disorders | Everolimus LT Target of 3 to 7 ng/mL | 4 | 117 | |
| other | Neutropenia | Blood and lymphatic system disorders | Everolimus HT Target of 9 to 15 ng/mL | 9 | 130 | |
| other | Neutropenia | Blood and lymphatic system disorders | Everolimus Start Ext | 1 | 114 | |
| other | Neutropenia | Blood and lymphatic system disorders | Everolimus All | 14 | 361 | |
| other | Abdominal pain | Gastrointestinal disorders | Everolimus LT Target of 3 to 7 ng/mL | 10 | 117 | |
| other | Abdominal pain | Gastrointestinal disorders | Everolimus HT Target of 9 to 15 ng/mL | 4 | 130 |
1 to 10 of 820Source ClinicalTrials.gov
See all 820 adverse eventsAdverse event totals12
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Everolimus LT Target of 3 to 7 ng/mL | 1 | 117 |
| Total, all-cause mortality | Everolimus HT Target of 9 to 15 ng/mL | 2 | 130 |
| Total, all-cause mortality | Everolimus Start Ext | 1 | 114 |
| Total, all-cause mortality | Everolimus All | 4 | 361 |
| Total, other adverse events | Everolimus LT Target of 3 to 7 ng/mL | 110 | 117 |
| Total, other adverse events | Everolimus HT Target of 9 to 15 ng/mL | 126 | 130 |
| Total, other adverse events | Everolimus Start Ext | 109 | 114 |
| Total, other adverse events | Everolimus All | 345 | 361 |
| Total, serious adverse events | Everolimus LT Target of 3 to 7 ng/mL | 50 | 117 |
| Total, serious adverse events | Everolimus HT Target of 9 to 15 ng/mL | 49 | 130 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 adverse event totalsPapers3
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT01713946
GET https://conductscience.org/api/trials/v1/NCT01713946/registered?page=2