Trial Outcomes & Findings for Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1) (NCT NCT00789828)

Last Updated: 2016-02-03

Results Overview

Participants were assessed for SEGA response, defined as 50% reduction from baseline in SEGA volume (where SEGA volume was the sum of the volumes of all target SEGA lesions identified at baseline, and confirmed with a second scan performed approximately 12 weeks later), no unequivocal worsening of non-target SEGA lesions, no new SEGA lesions (≥ 1 cm in longest diameter), and no new or worsening hydrocephalus. Multi-phase brain MRI was utilized to identify SEGA lesions. SEGA response rate was defined as the percentage of participants whose best overall status was SEGA response as determined by Independent Central Radiology Review. The Kaplan-Meier estimate was used for determining time to SEGA response.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

117 participants

Primary outcome timeframe

End of core period (Week 48), and end of extension period (up to 4 years)

Results posted on

2016-02-03

Participant Flow

The study was conducted at 24 centers in 10 countries.

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.

Participant milestones

Participant milestones
Measure	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.
Core Period (48 Weeks) STARTED	78	39
Core Period (48 Weeks) COMPLETED	78	33
Core Period (48 Weeks) NOT COMPLETED	0	6
Open-label Extension Period (4 Years) STARTED	111	0
Open-label Extension Period (4 Years) COMPLETED	82	0
Open-label Extension Period (4 Years) NOT COMPLETED	29	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Core Period (48 Weeks) Administrative problems	0	1
Core Period (48 Weeks) Withdrawal by Subject	0	4
Core Period (48 Weeks) Lost to Follow-up	0	1
Open-label Extension Period (4 Years) Adverse Event	10	0
Open-label Extension Period (4 Years) Withdrawal by Subject	6	0
Open-label Extension Period (4 Years) Lost to Follow-up	3	0
Open-label Extension Period (4 Years) Administrative problems	7	0
Open-label Extension Period (4 Years) Death	1	0
Open-label Extension Period (4 Years) Disease progression	1	0
Open-label Extension Period (4 Years) New treatment for indication under study	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus (Core Period) n=78 Participants 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) n=39 Participants Participants received oral dose of placebo matching to everolimus daily.	Total n=117 Participants Total of all reporting groups
Age, Continuous	10.1 years STANDARD_DEVIATION 5.9 • n=5 Participants	10.3 years STANDARD_DEVIATION 7.3 • n=7 Participants	10.2 years STANDARD_DEVIATION 6.4 • n=5 Participants
Age, Customized <3 years	13 Participants n=5 Participants	7 Participants n=7 Participants	20 Participants n=5 Participants
Age, Customized 3-18 years	55 Participants n=5 Participants	26 Participants n=7 Participants	81 Participants n=5 Participants
Age, Customized ≥18 years	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	21 Participants n=7 Participants	50 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	18 Participants n=7 Participants	67 Participants n=5 Participants

PRIMARY outcome

Timeframe: End of core period (Week 48), and end of extension period (up to 4 years)

Population: The primary analysis was performed in Full Analysis Set (FAS) population, defined as all randomized participants involved in the study.

Outcome measures

Outcome measures
Measure	Everolimus (Core Period) n=78 Participants 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) n=39 Participants Participants received oral dose of placebo matching to everolimus daily.	Everolimus (Extension Period) n=111 Participants Participants received oral dose of everolimus 4.5 mg/m\^2 daily as an initial starting dose to attain blood trough concentrations in range of 5-15 ng/mL.
Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response	34.6 Percentage of participants Interval 24.2 to 46.2	0.0 Percentage of participants Interval 0.0 to 9.0	57.7 Percentage of participants Interval 47.9 to 67.0

SECONDARY outcome

Timeframe: 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)

Population: The analysis was performed in the FAS population. Missing values were imputed using last observation carried forward approach for core period while raw count for extension period.

Seizure frequency per 24 hours was defined as the number of seizures in the electroencephalography (EEG) divided by the number of hours in the EEG, multiplied by 24. Seizure frequency was evaluated using a 24-hour video-EEG. Seizure frequency was listed as missing if the actual EEG recording duration was \< 18 hours.

Outcome measures

Outcome measures
Measure	Everolimus (Core Period) n=78 Participants 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) n=39 Participants Participants received oral dose of placebo matching to everolimus daily.	Everolimus (Extension Period) n=34 Participants Participants received oral dose of everolimus 4.5 mg/m\^2 daily as an initial starting dose to attain blood trough concentrations in range of 5-15 ng/mL.
Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period	-1.24 Seizure frequency Standard Deviation 6.12	-0.24 Seizure frequency Standard Deviation 5.7	-6.07 Seizure frequency Standard Deviation 9.719

SECONDARY outcome

Timeframe: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)

Population: The analysis was performed in the FAS population. Here "Number of participants analysed" signifies the participants assessed for time to SEGA progression during the study for each arm, respectively.

Time to SEGA progression was defined as time between randomisation to time to first SEGA progression. SEGA progression was defined as either one or more of the following criteria: 1. increase from nadir of ≥ 25% in SEGA volume to a value greater than baseline SEGA volume (where SEGA volume is the sum of the volumes of all target SEGA lesions identified at baseline, and nadir is the lowest SEGA volume obtained for the participant previously in the trial), 2. unequivocal worsening of non-target SEGA lesions, 3. appearance of new SEGA lesion ≥ 1.0 cm in longest diameter, 4. new or worsening hydrocephalus. The median TTSP based on central radiology review was not reached in any treatment arms; Only 6 events of SEGA progressions were observed in the placebo group of core period.

Outcome measures

Outcome measures
Measure	Everolimus (Core Period) n=78 Participants 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) n=39 Participants Participants received oral dose of placebo matching to everolimus daily.	Everolimus (Extension Period) n=111 Participants Participants received oral dose of everolimus 4.5 mg/m\^2 daily as an initial starting dose to attain blood trough concentrations in range of 5-15 ng/mL.
Time to SEGA Progression	NA months Median was not reached as no participant experienced disease progression during core period.	NA months Median was not reached as only 6 participants experienced disease progression during core period.	NA months Median was not reached as no participant experienced disease progression during extension period.

SECONDARY outcome

Timeframe: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)

Population: The analysis was performed in the FAS population.

Participants were assessed for time to SEGA response, defined as 50% reduction from baseline in SEGA volume (where SEGA volume was the sum of the volumes of all target SEGA lesions identified at baseline, and confirmed with a second scan performed approximately 12 weeks later), no unequivocal worsening of non-target SEGA lesions, no new SEGA lesions (≥ 1 cm in longest diameter), and no new or worsening hydrocephalus. Multi-phase brain MRI was utilised to identify SEGA lesions. SEGA response rate was defined as the percentage of participants whose best overall status was SEGA response as determined by Independent Central Radiology Review. The Kaplan-Meier estimate was used for determining time to SEGA response.

Outcome measures

Outcome measures
Measure	Everolimus (Core Period) n=27 Participants 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) n=64 Participants Participants received oral dose of placebo matching to everolimus daily.	Everolimus (Extension Period) Participants received oral dose of everolimus 4.5 mg/m\^2 daily as an initial starting dose to attain blood trough concentrations in range of 5-15 ng/mL.
Time to SEGA Response	2.99 months Interval 2.79 to 5.36	5.32 months Interval 3.02 to 5.59	—

SECONDARY outcome

Timeframe: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)

Population: The analysis was performed in the FAS population. Here, "Number of participants analysed" signifies the participants assessed for SEGA progression during the study for each arm, respectively.

Duration of SEGA response was defined as time from the date of the first documented SEGA response until the date of the first documented SEGA progression. Duration of SEGA response was evaluated only for participants who achieved a SEGA response. The time to SEGA progression was censored if SEGA progression was not observed before the first to occur out of (i) analysis cut-off date (ii) the date when systemic anti-SEGA medication is started, (iii) the date of a SEGA-related surgery or (iv) the date of death. Since, no case of SEGA progression was observed in core study which resulted in censored duration of SEGA response. Only 5 SEGA responders experienced a SEGA progression in extension period.

Outcome measures

Outcome measures
Measure	Everolimus (Core Period) n=27 Participants 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) n=64 Participants Participants received oral dose of placebo matching to everolimus daily.	Everolimus (Extension Period) Participants received oral dose of everolimus 4.5 mg/m\^2 daily as an initial starting dose to attain blood trough concentrations in range of 5-15 ng/mL.
Duration of SEGA Response	NA months Median was not achieved as no case of SEGA progression was observed.	NA months Median was not achieved as only 5 events of SEGA progression were observed.	—

SECONDARY outcome

Timeframe: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)

Population: The analysis was performed in the FAS population. Here, "Number of participants analysed" signifies the participants assessed for time to SEGA worsening during the study for each arm, respectively.

Time to SEGA worsening was defined as the time from the start of everolimus to date of the first SEGA worsening. SEGA worsening was defined as either; increase from nadir of ≥ 25% in SEGA volume or unequivocal worsening of non-target SEGA lesions, or appearance of new SEGA lesion ≥ 1.0 cm in longest diameter, or new or worsening hydrocephalus. The median value was not reached in either treatment arm of core period as SEGA worsening was observed in less participants (everolimus - 7 and placebo - 8).

Outcome measures

Outcome measures
Measure	Everolimus (Core Period) n=78 Participants 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) n=39 Participants Participants received oral dose of placebo matching to everolimus daily.	Everolimus (Extension Period) n=111 Participants Participants received oral dose of everolimus 4.5 mg/m\^2 daily as an initial starting dose to attain blood trough concentrations in range of 5-15 ng/mL.
Time to SEGA Worsening	NA months Median was not achieved as only 7 events of SEGA progression were observed.	NA months Median was not achieved as only 8 events of SEGA progression were observed.	55.72 months Interval 55.72 to Median upper value was not available as only single of SEGA progression were observed.

SECONDARY outcome

Timeframe: End of core period (Week 48), and end of extension period (up to 4 years)

Population: The analysis was performed in the FAS population. Here, "Number of participants analysed" signifies the participants assessed for skin lesion response during the study for each arm, respectively.

Skin lesions included hypomelanotic macules, the shagreen patch, periungual or subungual fibromas, facial angiofibromas and/or forehead plaques. Response was evaluated using the Physician's Global Assessment of Clinical Condition (PGA) on a 7-point scale: Grade 0 = complete clinical response, indicated absence of disease, Grade 1, 2, and 3 = partial response, indicated improvements of ≥ 50% but \< 100%, Grade 4, 5 = stable disease, indicated some or no improvements of 25% - \< 50% and 6 = progressive disease, indicated worse than at baseline evaluation by \> 25%. Response rate was determined for participants with ≥ 1 skin lesion at baseline, defined as the percentage of participants with overall status as complete clinical response or partial response.

Outcome measures

Outcome measures
Measure	Everolimus (Core Period) n=72 Participants 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) n=38 Participants Participants received oral dose of placebo matching to everolimus daily.	Everolimus (Extension Period) n=105 Participants Participants received oral dose of everolimus 4.5 mg/m\^2 daily as an initial starting dose to attain blood trough concentrations in range of 5-15 ng/mL.
Percentage of Participants With Skin Lesions Assessed Using Physician's Global Assessement Overall Score	41.7 Percentage of participants Interval 30.2 to 53.9	10.5 Percentage of participants Interval 2.9 to 24.8	58.1 Percentage of participants Interval 48.1 to 67.7

SECONDARY outcome

Timeframe: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)

Population: The analysis was performed in the FAS population. Here, "Number of participants analysed" signifies everolimus treated responders with best overall skin lesion response during the core and extension period, respectively.

Duration of skin lesion response was defined as the time from the first skin lesion response until the first skin lesion progression, defined as worsening of lesion by \> 25% or more from baseline.

Outcome measures

Outcome measures
Measure	Everolimus (Core Period) n=30 Participants 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) n=61 Participants Participants received oral dose of placebo matching to everolimus daily.	Everolimus (Extension Period) Participants received oral dose of everolimus 4.5 mg/m\^2 daily as an initial starting dose to attain blood trough concentrations in range of 5-15 ng/mL.
Duration of Skin Lesion Response in Everolimus Treated Participants	NA months Median was not achieved as no case of skin lesion was observed.	NA months Median was not achieved as no case of skin lesion was observed.	—

SECONDARY outcome

Timeframe: 2 hours post dose on Week 6, Week 24, Week 48, Week 96, Week 144, and Week 240

Population: The analysis was performed in the Safety Set population (Only evaluable PK Samples), defined as participants who received at least one dose of the double-blind study drug, with a valid post baseline assessment. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.

The participants were assessed for everolimus blood concentration at 2 hours time point after dose administration on the same day, if the participant did not vomit between previous dose and blood sample collection. Tandem liquid chromatography-mass spectrometry method was used for evaluation. C2h values were categorized as \< 20 ng/mL, 20-50 ng/mL, and \> 50 ng/mL, concentrations below the lower limit of quantification were entered as 0 ng/mL.

Outcome measures

Outcome measures
Measure	Everolimus (Core Period) n=78 Participants 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) n=111 Participants Participants received oral dose of placebo matching to everolimus daily.	Everolimus (Extension Period) Participants received oral dose of everolimus 4.5 mg/m\^2 daily as an initial starting dose to attain blood trough concentrations in range of 5-15 ng/mL.
Everolimus Blood Concentration (C2h) at 2 Hours Post Dose Week 6 (n= 37, 47)	27.52 ng/mL Standard Deviation 15.24	27.74 ng/mL Standard Deviation 16.202	—
Everolimus Blood Concentration (C2h) at 2 Hours Post Dose Week 24 (n= 11, 13)	38.7 ng/mL Standard Deviation 15.76	39.25 ng/mL Standard Deviation 14.662	—
Everolimus Blood Concentration (C2h) at 2 Hours Post Dose Week 48 (n= 1, 3)	23.2 ng/mL Standard Deviation NA Only one participant was evaluable, so value was not available.	49.73 ng/mL Standard Deviation 28.884	—
Everolimus Blood Concentration (C2h) at 2 Hours Post Dose Week 96 (n= 0, 6)	NA ng/mL Standard Deviation NA No participant was evaluable, so value was not available.	31.63 ng/mL Standard Deviation 21.902	—
Everolimus Blood Concentration (C2h) at 2 Hours Post Dose Week 144 (n= 0, 6)	NA ng/mL Standard Deviation NA No participant was evaluable, so value was not available.	26.33 ng/mL Standard Deviation 11.908	—
Everolimus Blood Concentration (C2h) at 2 Hours Post Dose Week 240 (n= 0, 0)	NA ng/mL Standard Deviation NA No participant was evaluable, so value was not available.	NA ng/mL Standard Deviation NA No participant was evaluable, so value was not available.	—

SECONDARY outcome

Timeframe: 24 hours post dose on Week 6, Week 24, Week 48, Week 72, Week 96, Week 144, and Week 240

Population: The analysis was performed in the Safety Set population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.

The participants were assessed for everolimus trough concentration (Cmin) at 24 hours time point after previous dose administration, at a steady state following 5 days of consistent dosing, if the participant did not vomit within 4 hours of previous dose. Tandem liquid chromatography-mass spectrometry method was used for evaluation. Cmin values were categorized as \<5 ng/mL, 5-10 ng/mL, and \>10 ng/mL, concentrations below the lower limit of quantification were entered as 0 ng/mL.

Outcome measures

Outcome measures
Measure	Everolimus (Core Period) n=78 Participants 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) n=111 Participants Participants received oral dose of placebo matching to everolimus daily.	Everolimus (Extension Period) Participants received oral dose of everolimus 4.5 mg/m\^2 daily as an initial starting dose to attain blood trough concentrations in range of 5-15 ng/mL.
Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose Week 72 (n= 4, 92)	6.08 ng/mL Standard Deviation 2.19	7.25 ng/mL Standard Deviation 3.66	—
Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose Week 6 (n= 64, 94)	5.8 ng/mL Standard Deviation 3.68	6.09 ng/mL Standard Deviation 3.708	—
Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose Week 24 (n= 64, 89)	6.59 ng/mL Standard Deviation 3.43	6.86 ng/mL Standard Deviation 3.504	—
Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose Week 48 (n= 23, 86)	7.28 ng/mL Standard Deviation 3.11	7.07 ng/mL Standard Deviation 3.214	—
Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose Week 96 (n= 0, 83)	NA ng/mL Standard Deviation NA No participant was evaluable, so value was not available.	7.09 ng/mL Standard Deviation 3.697	—
Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose Week 144 (n= 0, 69)	NA ng/mL Standard Deviation NA No participant was evaluable, so value was not available.	7.28 ng/mL Standard Deviation 3.35	—
Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose Week 240 (n= 0, 13)	NA ng/mL Standard Deviation NA No participant was evaluable, so value was not available.	5.85 ng/mL Standard Deviation 2.507	—

SECONDARY outcome

Timeframe: Day 1 up to 28 days after end of treatment (Core period)

Population: The analysis was performed in the SAF population. Here, "Number of participants analysed" signifies the participants assessed for renal function during the study for each arm, respectively.

Renal function was assessed using glomerular filtration rate (GFR) based on age measure; Modification of Diet in Renal Disease (MDRD) formula for participants aged 18 years or older, defined as GFR equal to 32788\*(serum creatinine (micromol/L)\^-1.154)\*(age\^-0.203 )\*(0.742, if female)\*(1.210, if black), and Schwartz formula for participants less than 18 years defined as GFR equal to 0.41\*height (cm)/ Serum creatinine (mg/dL). Participants with severe renal impairment defined as GFR \< 30 mL/min/1.73 m\^2 and participants with National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade 3/4 serum creatinine were reported.

Outcome measures

Outcome measures
Measure	Everolimus (Core Period) n=78 Participants 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) n=39 Participants Participants received oral dose of placebo matching to everolimus daily.	Everolimus (Extension Period) Participants received oral dose of everolimus 4.5 mg/m\^2 daily as an initial starting dose to attain blood trough concentrations in range of 5-15 ng/mL.
Percentage of Participants With Renal Impairment During Core Period Grade 1 or 2	3.8 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Renal Impairment During Core Period Grade 3 or 4	0 Percentage of participants	0 Percentage of participants	—
Percentage of Participants With Renal Impairment During Core Period Grade 0	96.2 Percentage of participants	100 Percentage of participants	—

Adverse Events

Everolimus Treated (Core and Extension Period)

Serious events: 33 serious events

Other events: 77 other events

Deaths: 0 deaths

Placebo (Core) Then Everolimus Treated (Extension Period)

Serious events: 17 serious events

Other events: 33 other events

Deaths: 0 deaths

Placebo Treated (Core Period)

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. The terms and conditions of Novartis' agreements with its investigators may vary. 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