NCT01713946 · OUTCOME

Long Term Evaluation: Relationship Between Seizure Frequency and Time-normalized Everolimus Concentration at Trough (Cmin,TN) - Repeated Measures Analysis

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 · Source last updated 2018-11-07

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure: MEAN
Unit: % change over 2-wk in seizures freq.
Interval / dispersion: 95% Confidence Interval
Time frame: During everolimus treatment from start of everolimus up to the end of the extension phase, an average of 1.7 year

What was measured

A repeated measures analysis considering fixed 2-week intervals and including the level of exposure (time-normalized Cmin values), the time on-treatment and the seizure frequency at baseline quantified the estimated percentage change over 2 weeks in seizure frequency associated with a double exposure to everolimus, 15 days more on treatment and half the seizure frequency at baseline. A positive percentage change means a reduction in seizure frequency whereas a negative percentage change means an increase in seizure frequency.

Analysis population: Confirmed PK Sample Set from all everolimus-treated patients in the Longer-term Evaluation (LTE) Safety Set, was defined as follows: Cmin collected prior to dose administration on the same treatment day and 20-28 hours after the previous dose, at steady state, and with no evidence of vomiting within 4 hours of the previous dose

Groups in this outcome

Everolimus LT Target of 3 to 7 ng/mL

Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL

Everolimus HT Target of 9 to 15 ng/mL

Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL

Placebo

Participants were randomized to receive placebo dispersible tablets for oral suspension.

Everolimus Long Term Evaluation (LTE)

Participants who were treated with everolimus either in the Core or Extension phases of the study and were evaluated for longer term safety and efficacy.

Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.

Analysis denominator · Participants

Group	Source count
Everolimus LT Target of 3 to 7 ng/mL	0
Everolimus HT Target of 9 to 15 ng/mL	0
Placebo	0
Everolimus Long Term Evaluation (LTE)	358

Reported measurements

By doubling the time-normalized Cmin (log scale)

Values in % change over 2-wk in seizures freq. · Interval/dispersion: 95% Confidence Interval
Group	Value	Spread	Lower	Upper	Comment
Everolimus Long Term Evaluation (LTE)	8.93	Not reported	6.87	10.95	Not reported

By reporting half the seizure freq. at baseline

Values in % change over 2-wk in seizures freq. · Interval/dispersion: 95% Confidence Interval
Group	Value	Spread	Lower	Upper	Comment
Everolimus Long Term Evaluation (LTE)	48.82	Not reported	46.37	51.15	Not reported

By adding 12 weeks on treatmen

Values in % change over 2-wk in seizures freq. · Interval/dispersion: 95% Confidence Interval
Group	Value	Spread	Lower	Upper	Comment
Everolimus Long Term Evaluation (LTE)	6.42	Not reported	4.53	8.27	Not reported

Complete source fields

classes

categories
measurements
group Id
OG003
lower Limit
6.87
upper Limit
10.95
value
8.93
title
By doubling the time-normalized Cmin (log scale)
categories
measurements
group Id
OG003
lower Limit
46.37
upper Limit
51.15
value
48.82
title
By reporting half the seizure freq. at baseline
categories
measurements
group Id
OG003
lower Limit
4.53
upper Limit
8.27
value
6.42
title
By adding 12 weeks on treatmen

denoms

counts
group Id
OG000
value
0
group Id
OG001
value
0
group Id
OG002
value
0
group Id
OG003
value
358
units
Participants

description

dispersion Type

95% Confidence Interval

groups

description
Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a low trough (LT) range of 3 to 7 ng/mL
id
OG000
title
Everolimus LT Target of 3 to 7 ng/mL
description
Participants were randomized to receive everolimus dispersible tablets for oral suspension with titration to a high trough (HT) range of 9 to 15 ng/mL
id
OG001
title
Everolimus HT Target of 9 to 15 ng/mL
description
Participants were randomized to receive placebo dispersible tablets for oral suspension.
id
OG002
title
Placebo
description
Participants who were treated with everolimus either in the Core or Extension phases of the study and were evaluated for longer term safety and efficacy.
id
OG003
title
Everolimus Long Term Evaluation (LTE)

param Type

MEAN

population Description

Confirmed PK Sample Set from all everolimus-treated patients in the Longer-term Evaluation (LTE) Safety Set, was defined as follows: Cmin collected prior to dose administration on the same treatment day and 20-28 hours after the previous dose, at steady state, and with no evidence of vomiting within 4 hours of the previous dose

reporting Status

POSTED

time Frame

During everolimus treatment from start of everolimus up to the end of the extension phase, an average of 1.7 year

title

Long Term Evaluation: Relationship Between Seizure Frequency and Time-normalized Everolimus Concentration at Trough (Cmin,TN) - Repeated Measures Analysis

type

SECONDARY

unit Of Measure

% change over 2-wk in seizures freq.

Download exact source JSON → · Snapshot ctgov-results-191f4516d4760045304b24a0

Preserved source evidence · Not medical advice