Trial Outcomes & Findings for A Study to Investigate the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) as an Adjunctive Therapy in Children and Adults With Lennox-Gastaut Syndrome (NCT NCT03355209)
NCT ID: NCT03355209
Last Updated: 2025-07-03
Results Overview
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline\* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
296 participants
Primary outcome timeframe
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Results posted on
2025-07-03
Participant Flow
The study started to enroll participants in November 2017 and concluded in May 2024. Cohort A included participants enrolled at sites in North America, Europe, and Australia. Cohort B included participants enrolled at sites in Japan only.
The Participant Flow refers to the All Enrolled Participants Set for Part 1 and OLE Safety Population for Part 2 of the study. As planned, Part 2 summaries were presented by the participant's Part 1 treatment groups (placebo, ZX008 0.2 mg/kg/day, ZX008 0.8 mg/kg/day).
Participant milestones
| Measure |
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol \[STP\]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Double-Blind Period
STARTED
|
87
|
89
|
87
|
11
|
11
|
11
|
|
Part 1: Double-Blind Period
COMPLETED
|
86
|
83
|
81
|
11
|
10
|
11
|
|
Part 1: Double-Blind Period
NOT COMPLETED
|
1
|
6
|
6
|
0
|
1
|
0
|
|
Part 2:Open-Label Extension (OLE) Period
STARTED
|
86
|
83
|
78
|
11
|
10
|
11
|
|
Part 2:Open-Label Extension (OLE) Period
COMPLETED
|
61
|
51
|
46
|
5
|
1
|
5
|
|
Part 2:Open-Label Extension (OLE) Period
NOT COMPLETED
|
25
|
32
|
32
|
6
|
9
|
6
|
Reasons for withdrawal
| Measure |
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol \[STP\]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Double-Blind Period
Adverse Event
|
0
|
4
|
4
|
0
|
1
|
0
|
|
Part 1: Double-Blind Period
Death
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Part 1: Double-Blind Period
Physician Decision
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Part 1: Double-Blind Period
Withdrawal by Subject
|
1
|
1
|
1
|
0
|
0
|
0
|
|
Part 2:Open-Label Extension (OLE) Period
Adverse Event
|
5
|
5
|
3
|
0
|
1
|
1
|
|
Part 2:Open-Label Extension (OLE) Period
Death
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Part 2:Open-Label Extension (OLE) Period
Lack of Efficacy
|
13
|
21
|
23
|
0
|
0
|
1
|
|
Part 2:Open-Label Extension (OLE) Period
Switching to commercial ZX008
|
0
|
0
|
0
|
5
|
6
|
3
|
|
Part 2:Open-Label Extension (OLE) Period
Withdrawal by Subject
|
6
|
5
|
4
|
0
|
2
|
0
|
|
Part 2:Open-Label Extension (OLE) Period
Physician Decision
|
0
|
0
|
0
|
1
|
0
|
1
|
|
Part 2:Open-Label Extension (OLE) Period
Rollover into ZX008-1900
|
1
|
0
|
2
|
0
|
0
|
0
|
Baseline Characteristics
A Study to Investigate the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) as an Adjunctive Therapy in Children and Adults With Lennox-Gastaut Syndrome
Baseline characteristics by cohort
| Measure |
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort A: ZX008 0.2 mg/kg/Day
n=89 Participants
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort A: ZX008 0.8 mg/kg/Day
n=87 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol \[STP\]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=11 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Total
n=296 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
14.4 years
STANDARD_DEVIATION 7.71 • n=5 Participants
|
13.4 years
STANDARD_DEVIATION 7.79 • n=7 Participants
|
13.4 years
STANDARD_DEVIATION 7.28 • n=5 Participants
|
18.5 years
STANDARD_DEVIATION 7.78 • n=4 Participants
|
20.1 years
STANDARD_DEVIATION 7.79 • n=21 Participants
|
18.5 years
STANDARD_DEVIATION 7.94 • n=8 Participants
|
14.3 years
STANDARD_DEVIATION 7.76 • n=8 Participants
|
|
Age, Customized
2 - < 12 years
|
32 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
117 Participants
n=8 Participants
|
|
Age, Customized
12 - < 18 years
|
29 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
87 Participants
n=8 Participants
|
|
Age, Customized
18 - 35 years
|
26 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
92 Participants
n=8 Participants
|
|
Sex: Female, Male
Female
|
41 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
126 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
9 Participants
n=8 Participants
|
170 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
White
|
71 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
70 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
208 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
12 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
11 Participants
n=8 Participants
|
42 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Not Reported
|
6 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
23 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
6 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
16 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
51 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
65 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
11 Participants
n=8 Participants
|
222 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]Population: The Modified Intent-to-Treat (mITT) Population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline\* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=87 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=11 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in the Combined Titration and Maintenance Period (T+M) in the ZX008 0.8 mg/kg/Day Group Compared to the Placebo Group
|
-26.49 percent change
Interval -95.2 to 402.1
|
-7.59 percent change
Interval -100.0 to 557.1
|
-17.89 percent change
Interval -97.3 to 61.8
|
-34.52 percent change
Interval -69.4 to 45.5
|
—
|
—
|
PRIMARY outcome
Timeframe: From Part 2 Baseline until end of the OLE Period (up to 72 months)Population: The OLE Safety Population included all participants who received at least 1 dose of ZX008 during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
An Adverse event (AE) was defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of investigational product, or whether considered related to the investigational product. A TEAE in Part 2 was defined as any AE with an onset on or after the first dose in Part 2. AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=247 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
|
96.9 percentage of participants
|
83.0 percentage of participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From Part 2 Baseline until end of the OLE Period (up to 72 months)Population: The OLE Safety Population included all participants who received at least 1 dose of ZX008 during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=247 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Percentage of Participants With Serious TEAEs
|
18.8 percentage of participants
|
16.6 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]Population: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline\* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=11 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in T+M in the ZX008 0.2 mg/kg/Day Group Compared to the Placebo Group
|
-14.16 percent change
Interval -100.0 to 3307.3
|
-7.59 percent change
Interval -100.0 to 557.1
|
-17.89 percent change
Interval -97.3 to 61.8
|
-14.12 percent change
Interval -95.6 to 66.4
|
—
|
—
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]Population: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. Participants who achieved a \>=50% reduction from Baseline in the DSF, ie, a decrease in DSF of at least 50 percentage points per 28 days during Titration and Maintenance Period.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percentage of Participants Who Achieve a >=50% Reduction From Baseline in the Frequency of Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
|
28.1 percentage of participants
|
10.3 percentage of participants
|
25.3 percentage of participants
|
9.1 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
SECONDARY outcome
Timeframe: At Day 99 (Visit 12)Population: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Clinical Global Impression - Improvement (CGI-I) scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=85 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=80 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=80 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percentage of Participants Who Achieve Improvement (Minimally, Much or Very Much Improved) in the CGI-I Scale as Assessed by Principal Investigator Comparing ZX008 0.8 and 0.2 mg/kg/Day Groups Independently Versus Placebo
|
44.7 percentage of participants
|
33.8 percentage of participants
|
48.8 percentage of participants
|
9.1 percentage of participants
|
45.5 percentage of participants
|
72.7 percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]Population: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Seizures that typically result in drops included all: generalized tonic-clonic seizures \[GTC\], secondarily generalized tonic-clonic \[SGTC\], tonic seizures \[TS\], atonic seizures \[AS\], and tonic/atonic seizures \[TA\], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient's position at the time of the seizure.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percent Change From Baseline in Frequency of All Seizures That Typically Result in Drops in T+M, Whether ESC-confirmed as Drop or Not in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
|
-11.75 percent change
Interval -100.0 to 3307.3
|
-8.43 percent change
Interval -100.0 to 557.1
|
-26.28 percent change
Interval -95.2 to 402.1
|
-17.89 percent change
Interval -97.3 to 61.8
|
-14.12 percent change
Interval -95.6 to 66.4
|
-34.04 percent change
Interval -69.4 to 45.5
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]Population: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures \[CS\], hemiclonic seizures \[HS\], and focal seizures \[FS\] with clearly observable signs.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
|
-11.75 percent change
Interval -100.0 to 3307.3
|
-8.43 percent change
Interval -80.8 to 497.8
|
-26.28 percent change
Interval -91.9 to 402.1
|
-17.89 percent change
Interval -97.3 to 61.8
|
-14.12 percent change
Interval -95.6 to 174.1
|
-34.04 percent change
Interval -69.4 to 45.5
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]Population: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Countable non-motor seizures included: focal seizures \[FS\] without clear observable signs, myoclonic seizures \[MS\], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
|
0.00 seizure frequency per 28 days
Interval -418.7 to 675.8
|
0.00 seizure frequency per 28 days
Interval -338.3 to 364.3
|
0.00 seizure frequency per 28 days
Interval -364.0 to 2952.7
|
-7.16 seizure frequency per 28 days
Interval -30.3 to 13.1
|
0.00 seizure frequency per 28 days
Interval -32.3 to 104.8
|
0.00 seizure frequency per 28 days
Interval -61.6 to 209.5
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]Population: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
|
-23.55 percent change
Interval -100.0 to 882.1
|
-9.40 percent change
Interval -85.4 to 497.8
|
-21.70 percent change
Interval -91.9 to 224.9
|
-17.69 percent change
Interval -97.2 to 61.8
|
-20.41 percent change
Interval -87.1 to 826.2
|
-13.85 percent change
Interval -64.9 to 63.8
|
SECONDARY outcome
Timeframe: During Maintenance Period (12 weeks), compared to BaselinePopulation: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=88 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=86 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) Between Baseline and the Maintenance Period
|
-18.63 percent change
Interval -100.0 to 964.0
|
-7.28 percent change
Interval -100.0 to 516.7
|
-27.16 percent change
Interval -100.0 to 643.3
|
-18.18 percent change
Interval -99.4 to 66.7
|
-12.88 percent change
Interval -100.0 to 239.4
|
-45.07 percent change
Interval -77.8 to 52.2
|
SECONDARY outcome
Timeframe: During Maintenance Period (12 weeks), compared to BaselinePopulation: The mITT Population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=88 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=86 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percent Change From Baseline in the Frequency of Seizures That Typically Result in Drops in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
|
-17.30 percent change
Interval -100.0 to 964.0
|
-9.37 percent change
Interval -100.0 to 516.7
|
-26.30 percent change
Interval -100.0 to 643.3
|
-18.18 percent change
Interval -99.4 to 66.7
|
-12.88 percent change
Interval -100.0 to 239.4
|
-46.88 percent change
Interval -77.8 to 52.2
|
SECONDARY outcome
Timeframe: During Maintenance Period (12 weeks), compared to BaselinePopulation: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Countable motor seizures included: GTC, SGTC,TS, AS, TA, CS, HS, and FS with clearly observable signs.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=88 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=86 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
|
-17.30 percent change
Interval -100.0 to 964.0
|
-10.21 percent change
Interval -81.1 to 439.8
|
-28.33 percent change
Interval -100.0 to 643.3
|
-18.18 percent change
Interval -99.4 to 66.7
|
-12.88 percent change
Interval -100.0 to 472.7
|
-46.88 percent change
Interval -77.8 to 52.2
|
SECONDARY outcome
Timeframe: During Maintenance Period (12 weeks), compared to BaselinePopulation: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Countable non-motor seizures included: focal seizures \[FS\] without clear observable signs, myoclonic seizures \[MS\], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=88 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=86 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
|
-0.13 seizure frequency per 28 days
Interval -442.3 to 588.1
|
-0.04 seizure frequency per 28 days
Interval -340.6 to 362.3
|
0.00 seizure frequency per 28 days
Interval -368.3 to 3219.3
|
-4.00 seizure frequency per 28 days
Interval -30.7 to 15.3
|
0.00 seizure frequency per 28 days
Interval -37.2 to 192.0
|
0.00 seizure frequency per 28 days
Interval -86.8 to 250.7
|
SECONDARY outcome
Timeframe: During Maintenance Period (12 weeks), compared to BaselinePopulation: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=88 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=86 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in the Maintenance Period in ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
|
-27.63 percent change
Interval -100.0 to 211.1
|
-9.49 percent change
Interval -85.7 to 439.8
|
-23.34 percent change
Interval -100.0 to 254.5
|
-18.18 percent change
Interval -99.5 to 66.7
|
-20.33 percent change
Interval -95.7 to 1626.7
|
-17.68 percent change
Interval -72.3 to 80.5
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]Population: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Non-drop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each participant as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=73 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=70 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=64 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=8 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=7 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=9 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percent Change From Baseline in Frequency of Countable Seizures That do Not Result in Drops (ESC Confirmed)
|
-31.32 percent change
Interval -100.0 to 571.8
|
-26.92 percent change
Interval -100.0 to 5070.3
|
-22.68 percent change
Interval -100.0 to 481.3
|
-23.38 percent change
Interval -96.9 to 657.1
|
0.27 percent change
Interval -32.3 to 2915.4
|
-22.99 percent change
Interval -85.7 to 138.8
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to BaselinePopulation: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, Number Analyzed included those participants who were evaluable at specified time point.
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
Worsening or No Change (T+M)
|
34.8 percentage of participants
|
37.9 percentage of participants
|
21.8 percentage of participants
|
36.4 percentage of participants
|
27.3 percentage of participants
|
9.1 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
> 0% reduction (T+M)
|
65.2 percentage of participants
|
62.1 percentage of participants
|
78.2 percentage of participants
|
63.6 percentage of participants
|
72.7 percentage of participants
|
90.9 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
>= 25% reduction (T+M)
|
47.2 percentage of participants
|
31.0 percentage of participants
|
51.7 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
63.6 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
>= 50% reduction (T+M)
|
28.1 percentage of participants
|
10.3 percentage of participants
|
25.3 percentage of participants
|
9.1 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
>= 75% reduction (T+M)
|
10.1 percentage of participants
|
4.6 percentage of participants
|
8.0 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
100% reduction (T+M)
|
1.1 percentage of participants
|
1.1 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
Near Seizure free (T+M)
|
2.2 percentage of participants
|
1.1 percentage of participants
|
1.1 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
Worsening or No Change (M)
|
35.2 percentage of participants
|
40.2 percentage of participants
|
20.9 percentage of participants
|
36.4 percentage of participants
|
27.3 percentage of participants
|
9.1 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
> 0% reduction (M)
|
64.8 percentage of participants
|
59.8 percentage of participants
|
79.1 percentage of participants
|
63.6 percentage of participants
|
72.7 percentage of participants
|
90.9 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
>= 25% reduction (M)
|
46.6 percentage of participants
|
33.3 percentage of participants
|
53.5 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
72.7 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
>= 50% reduction (M)
|
31.8 percentage of participants
|
12.6 percentage of participants
|
31.4 percentage of participants
|
9.1 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
>= 75% reduction (M)
|
11.4 percentage of participants
|
3.4 percentage of participants
|
14.0 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
100% reduction (M)
|
3.4 percentage of participants
|
1.1 percentage of participants
|
2.3 percentage of participants
|
0 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
Near Seizure free (M)
|
4.5 percentage of participants
|
1.1 percentage of participants
|
2.3 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to BaselinePopulation: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number analyzed included those participants who were evaluable at specified time point.
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
Worsening or No Change (T+M)
|
36.0 percentage of participants
|
35.6 percentage of participants
|
20.7 percentage of participants
|
36.4 percentage of participants
|
27.3 percentage of participants
|
9.1 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
> 0% reduction (T+M)
|
64.0 percentage of participants
|
64.4 percentage of participants
|
79.3 percentage of participants
|
63.6 percentage of participants
|
72.7 percentage of participants
|
90.9 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
>= 25% reduction (T+M)
|
46.1 percentage of participants
|
31.0 percentage of participants
|
50.6 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
63.6 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
>= 50% reduction (T+M)
|
27.0 percentage of participants
|
9.2 percentage of participants
|
26.4 percentage of participants
|
9.1 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
>= 75% reduction (T+M)
|
9.0 percentage of participants
|
3.4 percentage of participants
|
8.0 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
100% reduction (T+M)
|
1.1 percentage of participants
|
1.1 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
Near Seizure free (T+M)
|
1.1 percentage of participants
|
1.1 percentage of participants
|
1.1 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
Worsening or No Change (M)
|
37.5 percentage of participants
|
37.9 percentage of participants
|
19.8 percentage of participants
|
36.4 percentage of participants
|
27.3 percentage of participants
|
9.1 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
> 0% reduction (M)
|
62.5 percentage of participants
|
62.1 percentage of participants
|
80.2 percentage of participants
|
63.6 percentage of participants
|
72.7 percentage of participants
|
90.9 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
>= 25% reduction (M)
|
45.5 percentage of participants
|
33.3 percentage of participants
|
52.3 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
72.7 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
>= 50% reduction (M)
|
30.7 percentage of participants
|
10.3 percentage of participants
|
31.4 percentage of participants
|
9.1 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
>= 75% reduction (M)
|
10.2 percentage of participants
|
2.3 percentage of participants
|
12.8 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
100% reduction (M)
|
2.3 percentage of participants
|
1.1 percentage of participants
|
2.3 percentage of participants
|
0 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
Near Seizure free (M)
|
2.3 percentage of participants
|
1.1 percentage of participants
|
2.3 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to BaselinePopulation: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number analyzed included those participants who were evaluable at specified time point.
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
Worsening or No Change (T+M)
|
38.2 percentage of participants
|
34.5 percentage of participants
|
20.7 percentage of participants
|
36.4 percentage of participants
|
27.3 percentage of participants
|
9.1 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
> 0% reduction (T+M)
|
61.8 percentage of participants
|
65.5 percentage of participants
|
79.3 percentage of participants
|
63.6 percentage of participants
|
72.7 percentage of participants
|
90.9 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
>= 25% reduction (T+M)
|
44.9 percentage of participants
|
33.3 percentage of participants
|
50.6 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
63.6 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
>= 50% reduction (T+M)
|
24.7 percentage of participants
|
9.2 percentage of participants
|
25.3 percentage of participants
|
9.1 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
>= 75% reduction (T+M)
|
9.0 percentage of participants
|
2.3 percentage of participants
|
6.9 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
100% reduction (T+M)
|
1.1 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
Near Seizure free (T+M)
|
1.1 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
Worsening or No Change (M)
|
38.6 percentage of participants
|
36.8 percentage of participants
|
18.6 percentage of participants
|
36.4 percentage of participants
|
27.3 percentage of participants
|
9.1 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
> 0% reduction (M)
|
61.4 percentage of participants
|
63.2 percentage of participants
|
81.4 percentage of participants
|
63.6 percentage of participants
|
72.7 percentage of participants
|
90.9 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
>= 25% reduction (M)
|
45.5 percentage of participants
|
34.5 percentage of participants
|
53.5 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
72.7 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
>= 50% reduction (M)
|
28.4 percentage of participants
|
10.3 percentage of participants
|
26.7 percentage of participants
|
9.1 percentage of participants
|
36.4 percentage of participants
|
36.4 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
>= 75% reduction (M)
|
11.4 percentage of participants
|
1.1 percentage of participants
|
10.5 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
100% reduction (M)
|
2.3 percentage of participants
|
0 percentage of participants
|
1.2 percentage of participants
|
0 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
Near Seizure free (M)
|
2.3 percentage of participants
|
0 percentage of participants
|
1.2 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to BaselinePopulation: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment. Number analyzed included those participants who were evaluable at specified time point.
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=73 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=70 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=64 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=8 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=7 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=9 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
Worsening or No Change (T+M)
|
34.2 percentage of participants
|
35.7 percentage of participants
|
34.4 percentage of participants
|
25.0 percentage of participants
|
57.1 percentage of participants
|
44.4 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
> 0% reduction (T+M)
|
65.8 percentage of participants
|
64.3 percentage of participants
|
65.6 percentage of participants
|
75.0 percentage of participants
|
42.9 percentage of participants
|
55.6 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
>= 25% reduction (T+M)
|
53.4 percentage of participants
|
51.4 percentage of participants
|
46.9 percentage of participants
|
50.0 percentage of participants
|
14.3 percentage of participants
|
44.4 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
>= 50% reduction (T+M)
|
43.8 percentage of participants
|
30.0 percentage of participants
|
32.8 percentage of participants
|
25.0 percentage of participants
|
0 percentage of participants
|
22.2 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
>= 75% reduction (T+M)
|
26.0 percentage of participants
|
12.9 percentage of participants
|
12.5 percentage of participants
|
12.5 percentage of participants
|
0 percentage of participants
|
11.1 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
100% reduction (T+M)
|
5.5 percentage of participants
|
2.9 percentage of participants
|
4.7 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
Near Seizure free (T+M)
|
9.6 percentage of participants
|
2.9 percentage of participants
|
7.8 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
Worsening or No Change (M)
|
33.3 percentage of participants
|
31.4 percentage of participants
|
34.9 percentage of participants
|
25.0 percentage of participants
|
57.1 percentage of participants
|
44.4 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
> 0% reduction (M)
|
66.7 percentage of participants
|
68.6 percentage of participants
|
65.1 percentage of participants
|
75.0 percentage of participants
|
42.9 percentage of participants
|
55.6 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
>= 25% reduction (M)
|
56.9 percentage of participants
|
54.3 percentage of participants
|
49.2 percentage of participants
|
50.0 percentage of participants
|
14.3 percentage of participants
|
44.4 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
>= 50% reduction (M)
|
44.4 percentage of participants
|
31.4 percentage of participants
|
33.3 percentage of participants
|
25.0 percentage of participants
|
0 percentage of participants
|
22.2 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
>= 75% reduction (M)
|
29.2 percentage of participants
|
17.1 percentage of participants
|
17.5 percentage of participants
|
12.5 percentage of participants
|
0 percentage of participants
|
11.1 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
100% reduction (M)
|
9.7 percentage of participants
|
5.7 percentage of participants
|
6.3 percentage of participants
|
12.5 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
Near Seizure free (M)
|
13.9 percentage of participants
|
7.1 percentage of participants
|
9.5 percentage of participants
|
12.5 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to BaselinePopulation: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number analyzed included those participants who were evaluable at specified time point.
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
Worsening or No Change (T+M)
|
32.6 percentage of participants
|
36.8 percentage of participants
|
28.7 percentage of participants
|
27.3 percentage of participants
|
27.3 percentage of participants
|
36.4 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
> 0% reduction (T+M)
|
67.4 percentage of participants
|
63.2 percentage of participants
|
71.3 percentage of participants
|
72.7 percentage of participants
|
72.7 percentage of participants
|
63.6 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
>= 25% reduction (T+M)
|
48.3 percentage of participants
|
35.6 percentage of participants
|
46.0 percentage of participants
|
27.3 percentage of participants
|
27.3 percentage of participants
|
45.5 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
>= 50% reduction (T+M)
|
22.5 percentage of participants
|
11.5 percentage of participants
|
20.7 percentage of participants
|
9.1 percentage of participants
|
27.3 percentage of participants
|
27.3 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
>= 75% reduction (T+M)
|
6.7 percentage of participants
|
3.4 percentage of participants
|
4.6 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
100% reduction (T+M)
|
1.1 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
Near Seizure free (T+M)
|
1.1 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
Worsening or No Change (M)
|
33.0 percentage of participants
|
34.5 percentage of participants
|
27.9 percentage of participants
|
27.3 percentage of participants
|
27.3 percentage of participants
|
27.3 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
> 0% reduction (M)
|
67.0 percentage of participants
|
65.5 percentage of participants
|
72.1 percentage of participants
|
72.7 percentage of participants
|
72.7 percentage of participants
|
72.7 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
>= 25% reduction (M)
|
51.1 percentage of participants
|
34.5 percentage of participants
|
47.7 percentage of participants
|
27.3 percentage of participants
|
27.3 percentage of participants
|
45.5 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
>= 50% reduction (M)
|
28.4 percentage of participants
|
13.8 percentage of participants
|
24.4 percentage of participants
|
9.1 percentage of participants
|
27.3 percentage of participants
|
27.3 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
>= 75% reduction (M)
|
9.1 percentage of participants
|
3.4 percentage of participants
|
7.0 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
100% reduction (M)
|
1.1 percentage of participants
|
0 percentage of participants
|
1.2 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
Near Seizure free (M)
|
1.1 percentage of participants
|
0 percentage of participants
|
1.2 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to BaselinePopulation: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment. Number analyzed included those participants who were evaluable at specified time point.
Countable non-motor seizures include: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=64 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=63 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=57 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=8 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=7 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=8 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
100% reduction (M)
|
9.5 percentage of participants
|
6.3 percentage of participants
|
8.9 percentage of participants
|
12.5 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
Near Seizure free (M)
|
15.9 percentage of participants
|
7.9 percentage of participants
|
10.7 percentage of participants
|
12.5 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
Worsening or No Change (T+M)
|
34.4 percentage of participants
|
33.3 percentage of participants
|
36.8 percentage of participants
|
25.0 percentage of participants
|
57.1 percentage of participants
|
37.5 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
> 0% reduction (T+M)
|
65.6 percentage of participants
|
66.7 percentage of participants
|
63.2 percentage of participants
|
75.0 percentage of participants
|
42.9 percentage of participants
|
62.5 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
>= 25% reduction (T+M)
|
56.3 percentage of participants
|
52.4 percentage of participants
|
43.9 percentage of participants
|
50.0 percentage of participants
|
14.3 percentage of participants
|
37.5 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
>= 50% reduction (T+M)
|
48.4 percentage of participants
|
30.2 percentage of participants
|
35.1 percentage of participants
|
25.0 percentage of participants
|
0 percentage of participants
|
25.0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
>= 75% reduction (T+M)
|
32.8 percentage of participants
|
14.3 percentage of participants
|
12.3 percentage of participants
|
12.5 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
100% reduction (T+M)
|
6.3 percentage of participants
|
3.2 percentage of participants
|
3.5 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
Near Seizure free (T+M)
|
14.1 percentage of participants
|
3.2 percentage of participants
|
5.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
Worsening or No Change (M)
|
30.2 percentage of participants
|
30.2 percentage of participants
|
33.9 percentage of participants
|
12.5 percentage of participants
|
57.1 percentage of participants
|
37.5 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
> 0% reduction (M)
|
69.8 percentage of participants
|
69.8 percentage of participants
|
66.1 percentage of participants
|
87.5 percentage of participants
|
42.9 percentage of participants
|
62.5 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
>= 25% reduction (M)
|
60.3 percentage of participants
|
54.0 percentage of participants
|
48.2 percentage of participants
|
50.0 percentage of participants
|
14.3 percentage of participants
|
37.5 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
>= 50% reduction (M)
|
49.2 percentage of participants
|
34.9 percentage of participants
|
33.9 percentage of participants
|
25.0 percentage of participants
|
0 percentage of participants
|
37.5 percentage of participants
|
|
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
>= 75% reduction (M)
|
31.7 percentage of participants
|
17.5 percentage of participants
|
17.9 percentage of participants
|
12.5 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to BaselinePopulation: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number analyzed included those participants who were evaluable for specified category.
A day with no seizures leading to a drop was defined as a day for which electronic (e) diary data were available and no drop seizures were reported. The total number of drop seizure-free days was calculated per 28 days for Baseline and for T+M.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Change From Baseline in Number of Seizure-free Days During T+M and M Period
T+M Period
|
0.00 seizure free days per 28 days
Interval -9.0 to 16.8
|
0.27 seizure free days per 28 days
Interval -5.0 to 16.0
|
0.29 seizure free days per 28 days
Interval -6.1 to 20.0
|
0.00 seizure free days per 28 days
Interval -2.2 to 23.6
|
0.38 seizure free days per 28 days
Interval -2.3 to 22.0
|
6.65 seizure free days per 28 days
Interval -2.4 to 8.5
|
|
Part 1: Change From Baseline in Number of Seizure-free Days During T+M and M Period
M Period
|
0.00 seizure free days per 28 days
Interval -4.1 to 18.2
|
0.31 seizure free days per 28 days
Interval -5.4 to 15.7
|
0.16 seizure free days per 28 days
Interval -7.4 to 21.7
|
-0.65 seizure free days per 28 days
Interval -2.7 to 24.7
|
0.33 seizure free days per 28 days
Interval -7.3 to 26.0
|
7.72 seizure free days per 28 days
Interval -2.3 to 10.3
|
SECONDARY outcome
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]Population: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
The longest interval between seizures leading to drops were obtained from the eDiary entries in Titration and Maintenance Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Duration of Longest Interval (Days) Between Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
|
4.00 days
Interval 1.0 to 97.0
|
5.00 days
Interval 1.0 to 39.0
|
5.00 days
Interval 1.0 to 89.0
|
4.00 days
Interval 1.0 to 91.0
|
4.00 days
Interval 1.0 to 32.0
|
6.00 days
Interval 2.0 to 16.0
|
SECONDARY outcome
Timeframe: At Days 15, 43, 71 and 99Population: The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment. Number analyzed included those participants who were evaluable at specified time point.
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved, 2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=85 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=85 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=81 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
1=Very much improved (D15)
|
5.9 percentage of participants
|
2.4 percentage of participants
|
9.9 percentage of participants
|
9.1 percentage of participants
|
10.0 percentage of participants
|
9.1 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
2=Much improved (D15)
|
15.3 percentage of participants
|
4.7 percentage of participants
|
21.0 percentage of participants
|
18.2 percentage of participants
|
10.0 percentage of participants
|
18.2 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
3=Minimally improved (D15)
|
27.1 percentage of participants
|
31.8 percentage of participants
|
39.5 percentage of participants
|
9.1 percentage of participants
|
30.0 percentage of participants
|
27.3 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
4=No Change (D15)
|
42.4 percentage of participants
|
51.8 percentage of participants
|
18.5 percentage of participants
|
63.6 percentage of participants
|
30.0 percentage of participants
|
27.3 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
5=Minimally worse (D15)
|
5.9 percentage of participants
|
4.7 percentage of participants
|
7.4 percentage of participants
|
0 percentage of participants
|
20.0 percentage of participants
|
18.2 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
6=Much worse (D15)
|
3.5 percentage of participants
|
4.7 percentage of participants
|
2.5 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
7=Very much worse (D15)
|
0 percentage of participants
|
0 percentage of participants
|
1.2 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
1=Very much improved (D43)
|
7.3 percentage of participants
|
1.2 percentage of participants
|
13.8 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
10.0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
2=Much improved (D43)
|
19.5 percentage of participants
|
9.4 percentage of participants
|
25.0 percentage of participants
|
0 percentage of participants
|
22.2 percentage of participants
|
40.0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
3=Minimally improved (D43)
|
18.3 percentage of participants
|
20.0 percentage of participants
|
33.8 percentage of participants
|
18.2 percentage of participants
|
44.4 percentage of participants
|
30.0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
4=No Change (D43)
|
39.0 percentage of participants
|
60.0 percentage of participants
|
17.5 percentage of participants
|
63.6 percentage of participants
|
33.3 percentage of participants
|
0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
5=Minimally worse (D43)
|
11.0 percentage of participants
|
5.9 percentage of participants
|
5.0 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
20.0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
6=Much worse (D43)
|
4.9 percentage of participants
|
2.4 percentage of participants
|
5.0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
7=Very much worse (D43)
|
0 percentage of participants
|
1.2 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
1=Very much improved (D71)
|
4.0 percentage of participants
|
2.4 percentage of participants
|
10.7 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
2=Much improved (D71)
|
20.0 percentage of participants
|
6.1 percentage of participants
|
28.0 percentage of participants
|
0 percentage of participants
|
22.2 percentage of participants
|
11.1 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
3=Minimally improved (D71)
|
16.0 percentage of participants
|
24.4 percentage of participants
|
33.3 percentage of participants
|
18.2 percentage of participants
|
22.2 percentage of participants
|
55.6 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
4=No Change (D71)
|
48.0 percentage of participants
|
53.7 percentage of participants
|
24.0 percentage of participants
|
63.6 percentage of participants
|
55.6 percentage of participants
|
22.2 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
5=Minimally worse (D71)
|
8.0 percentage of participants
|
7.3 percentage of participants
|
1.3 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
11.1 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
6=Much worse (D71)
|
4.0 percentage of participants
|
6.1 percentage of participants
|
2.7 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
7=Very much worse (D71)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
1=Very much improved (D99)
|
8.2 percentage of participants
|
1.2 percentage of participants
|
10.0 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
18.2 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
2=Much improved (D99)
|
18.8 percentage of participants
|
3.7 percentage of participants
|
23.8 percentage of participants
|
0 percentage of participants
|
18.2 percentage of participants
|
18.2 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
3=Minimally improved (D99)
|
16.5 percentage of participants
|
32.1 percentage of participants
|
27.5 percentage of participants
|
18.2 percentage of participants
|
27.3 percentage of participants
|
36.4 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
4=No Change (D99)
|
37.6 percentage of participants
|
53.1 percentage of participants
|
27.5 percentage of participants
|
63.6 percentage of participants
|
45.5 percentage of participants
|
27.3 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
5=Minimally worse (D99)
|
8.2 percentage of participants
|
7.4 percentage of participants
|
5.0 percentage of participants
|
0 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
6=Much worse (D99)
|
7.1 percentage of participants
|
2.5 percentage of participants
|
5.0 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
7=Very much worse (D99)
|
3.5 percentage of participants
|
0 percentage of participants
|
1.3 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to 14 weeks + Taper/Transition (2 weeks)Population: The Safety Population included all randomized participants who received at least 1 dose of study drug.
Adverse events were defined as any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A TEAE in Part 1 was defined as any AE that, based on start date information, occurred after the first dose of study drug in Part 1, but not on or after the first dose of study drug in Part 2.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percentage of Participants With TEAEs
|
78.7 percentage of participants
|
80.5 percentage of participants
|
89.7 percentage of participants
|
72.7 percentage of participants
|
90.9 percentage of participants
|
63.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to 14 weeks + Taper/Transition (2 weeks)Population: The Safety Population included all randomized participants who received at least 1 dose of study drug.
A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=89 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
n=87 Participants
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
n=11 Participants
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
n=11 Participants
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Percentage of Participants With Serious TEAEs
|
4.5 percentage of participants
|
4.6 percentage of participants
|
11.5 percentage of participants
|
9.1 percentage of participants
|
9.1 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dosePopulation: The Pharmacokinetic (PK) analysis set included those participants who received at least one dose of ZX008 and at least one plasma concentration measurement in Study ZX008-1601.
Cmax is the maximum plasma concentration determined directly from the concentration time profile.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=80 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=84 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Maximum Observed Plasma Concentration of Fenfluramine and Norfenfluramine Determined Directly From the Concentration Time Profile [Cmax] at Steady State
Fenfluramine
|
44.8 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 47.0
|
11.9 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 56.1
|
—
|
—
|
—
|
—
|
|
Part 1: Maximum Observed Plasma Concentration of Fenfluramine and Norfenfluramine Determined Directly From the Concentration Time Profile [Cmax] at Steady State
Norfenfluramine
|
28.9 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 52.9
|
9.04 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 53.4
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dosePopulation: The PK analysis set included those participants who received at least one dose of ZX008 and at least one plasma concentration measurement in Study ZX008-1601.
Cmin is the minimum plasma concentration determined directly from the concentration-time profile.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=80 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=84 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Minimum Observed Plasma Concentration of Fenfluramine and Norfenfluramine at Steady State Determined Directly From the Concentration-time Profile [Cmin] at Steady State
Fenfluramine
|
31.8 ng/mL
Geometric Coefficient of Variation 60.8
|
8.19 ng/mL
Geometric Coefficient of Variation 75.6
|
—
|
—
|
—
|
—
|
|
Part 1: Minimum Observed Plasma Concentration of Fenfluramine and Norfenfluramine at Steady State Determined Directly From the Concentration-time Profile [Cmin] at Steady State
Norfenfluramine
|
26.2 ng/mL
Geometric Coefficient of Variation 58.9
|
8.23 ng/mL
Geometric Coefficient of Variation 61.3
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dosePopulation: The PK analysis set included those participants who received at least one dose of ZX008 and at least one plasma concentration measurement in Study ZX008-1601.
AUC0-24 is the area under the concentration-time curve from time 0 to 24 hours.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=80 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=84 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 1: Area Under the Concentration-time Curve of Fenfluramine and Norfenfluramine From Time Zero to Time 24 Hours [AUC0-24hours] at Steady State
Fenfluramine
|
933 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 52.1
|
246 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 63.0
|
—
|
—
|
—
|
—
|
|
Part 1: Area Under the Concentration-time Curve of Fenfluramine and Norfenfluramine From Time Zero to Time 24 Hours [AUC0-24hours] at Steady State
Norfenfluramine
|
667 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 55.1
|
209 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 56.3
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From OLE Month 1 to Month12, compared to Baseline (Part 1)Population: The Open-Label Extension Modified Intent-To-Treat (mITT) Population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) in OLE Period
|
-43.42 percent change
Interval -99.0 to 64.2
|
-29.53 percent change
Interval -100.0 to 2625.3
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From OLE Month 1 to Month12, compared to Baseline (Part 1)Population: The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Seizures that typically result in drops included all: generalized tonic-clonic seizures \[GTC\], secondarily generalized tonic-clonic \[SGTC\], tonic seizures \[TS\], atonic seizures \[AS\], and tonic/atonic seizures \[TA\], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient's position at the time of the seizure.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Percent Change From Baseline in the Frequency of All Seizures That Typically Result in Drops Between Baseline and the OLE Period Whether ESC Confirmed as Drop or Not
|
-43.78 percent change
Interval -99.0 to 64.2
|
-27.94 percent change
Interval -100.0 to 2625.3
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From OLE Month 1 to Month12, compared to Baseline (Part 1)Population: The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures \[CS\], hemiclonic seizures \[HS\], and focal seizures \[FS\] with clearly observable signs.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in OLE Period
|
-41.94 percent change
Interval -99.0 to 64.2
|
-28.18 percent change
Interval -100.0 to 2625.3
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From OLE Month 1 to Month12, compared to Baseline (Part 1)Population: The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Countable non-motor seizures included: focal seizures \[FS\] without clear observable signs, myoclonic seizures \[MS\], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Change From Baseline in the Frequency of All Countable Non-motor Seizures in OLE Period
|
0.00 seizure frequency per 28 days
Interval -89.4 to 258.9
|
0.00 seizure frequency per 28 days
Interval -4257.2 to 1774.3
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From OLE Month 1 to Month12, compared to Baseline (Part 1)Population: The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Percent Change From Baseline in the Frequency of All Countable Seizures (ESC Confirmed or Not) in OLE Period
|
-28.00 percent change
Interval -99.1 to 83.3
|
-28.83 percent change
Interval -100.0 to 606.1
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From OLE Month 1 to Month12, compared to Baseline (Part 1)Population: The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Nondrop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each subject as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Change From Baseline in the Frequency of All Countable Seizures That Did Not Result in Drops (ESC Confirmed) in OLE Period
|
0.00 seizure frequency per 28 days
Interval -89.4 to 258.9
|
-0.99 seizure frequency per 28 days
Interval -4482.2 to 1774.3
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From OLE Month 1 to Month12, compared to Baseline (Part 1)Population: The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)
Worsening or No Change
|
18.8 percentage of participants
|
31.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)
> 0%
|
81.3 percentage of participants
|
68.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)
>= 25%
|
62.5 percentage of participants
|
55.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)
>= 50%
|
43.8 percentage of participants
|
32.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)
>= 75%
|
21.9 percentage of participants
|
12.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)
100%
|
0 percentage of participants
|
1.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)
Near Seizure free
|
0 percentage of participants
|
1.7 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From OLE Month 1 to Month12, compared to Baseline (Part 1)Population: The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops
Worsening or No Change
|
21.9 percentage of participants
|
32.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops
> 0%
|
78.1 percentage of participants
|
68.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops
>= 25%
|
65.6 percentage of participants
|
53.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops
>= 50%
|
43.8 percentage of participants
|
29.9 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops
>= 75%
|
21.9 percentage of participants
|
11.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops
100%
|
0 percentage of participants
|
0.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops
Near Seizure free
|
0 percentage of participants
|
1.2 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From OLE Month 1 to Month12, compared to Baseline (Part 1)Population: The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures
Worsening or No Change
|
21.9 percentage of participants
|
29.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures
> 0%
|
78.1 percentage of participants
|
70.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures
>= 25%
|
62.5 percentage of participants
|
54.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures
>= 50%
|
40.6 percentage of participants
|
29.9 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures
>= 75%
|
21.9 percentage of participants
|
9.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures
100%
|
0 percentage of participants
|
0.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures
Near Seizure free
|
0 percentage of participants
|
0.8 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From OLE Month 1 to Month12, compared to Baseline (Part 1)Population: The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures
Worsening or No Change
|
37.5 percentage of participants
|
24.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures
> 0%
|
31.3 percentage of participants
|
46.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures
>= 25%
|
25.0 percentage of participants
|
41.9 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures
>= 50%
|
18.8 percentage of participants
|
34.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures
>= 75%
|
6.3 percentage of participants
|
22.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures
100%
|
3.1 percentage of participants
|
4.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures
Near Seizure free
|
6.3 percentage of participants
|
7.5 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From OLE Month 1 to Month12, compared to Baseline (Part 1)Population: The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie \<= 0% reduction); \>0%, \>=25%, \>=50%, \>=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures
Worsening or No Change
|
37.5 percentage of participants
|
30.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures
> 0%
|
62.5 percentage of participants
|
69.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures
>= 25%
|
56.3 percentage of participants
|
53.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures
>= 50%
|
28.1 percentage of participants
|
30.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures
>= 75%
|
12.5 percentage of participants
|
9.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures
100%
|
0 percentage of participants
|
0.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures
Near Seizure free
|
0 percentage of participants
|
0.4 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Part 2 Baseline until end of OLE Period (up to 72 months)Population: The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
A day with no seizures leading to a drop was defined as a day for which ediary data were available and no drop seizures were reported.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Change From Baseline in Number of Seizure-free Days Per 28 Days (ESC Confirmed) in OLE Period
|
4.24 seizure free days per 28 days
Interval -3.6 to 24.5
|
2.16 seizure free days per 28 days
Interval -23.0 to 27.8
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Part 2 Baseline until end of the OLE Period (up to 72 months)Population: OLE mITT:all participants who received at least 1 dose of ZX008 and had valid estimate of frequency of seizures that resulted in drops from Part 1 and at least 1 month(30 days) of valid seizure data during OLE. Number of participants analyzed=participants who were evaluable for assessment. As pre-specified in study design, participants in Part 2 received individualized optimized treatment(0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
The longest interval between seizures leading to drops were obtained from the eDiary entries in OLE Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=27 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=241 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Change From Baseline in Duration of Longest Interval Between Seizures That Result in Drops (ESC Confirmed) in OLE Period
|
6.0 days
Interval 0.0 to 200.0
|
4.0 days
Interval -10.0 to 360.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months)Population: OLE mITT:participants who received \>=1 dose of ZX008, had valid estimate of frequency of seizures that resulted in drops from Part 1 and at least 1 month(30 days) of valid seizure data during OLE. N: participants evaluable for assessment. n: participants evaluable at specified time point. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=237 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
4=No Change (OLE M2)
|
32.3 percentage of participants
|
27.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
1=Very much improved (OLE M2)
|
6.5 percentage of participants
|
5.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
2=Much improved (OLE M2)
|
19.4 percentage of participants
|
24.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
3=Minimally improved (OLE M2)
|
35.5 percentage of participants
|
34.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
1=Very much improved (OLE D1)
|
3.1 percentage of participants
|
2.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
2=Much improved (OLE D1)
|
18.8 percentage of participants
|
15.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
3=Minimally improved (OLE D1)
|
18.8 percentage of participants
|
25.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
4=No Change (OLE D1)
|
56.3 percentage of participants
|
48.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
5=Minimally worse (OLE D1)
|
3.1 percentage of participants
|
7.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
6=Much worse (OLE D1)
|
0 percentage of participants
|
0.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
7=Very much worse (OLE D1)
|
0 percentage of participants
|
0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
1=Very much improved (OLE M1)
|
9.4 percentage of participants
|
4.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
2=Much improved (OLE M1)
|
21.9 percentage of participants
|
20.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
3=Minimally improved (OLE M1)
|
37.5 percentage of participants
|
32.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
4=No Change (OLE M1)
|
31.3 percentage of participants
|
34.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
5=Minimally worse (OLE M1)
|
0 percentage of participants
|
7.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
6=Much worse (OLE M1)
|
0 percentage of participants
|
1.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
7=Very much worse (OLE M1)
|
0 percentage of participants
|
0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
5=Minimally worse (OLE M2)
|
6.5 percentage of participants
|
5.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
6=Much worse (OLE M2)
|
0 percentage of participants
|
3.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
7=Very much worse (OLE M2)
|
0 percentage of participants
|
0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
1=Very much improved (OLE M3)
|
6.9 percentage of participants
|
7.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
2=Much improved (OLE M3)
|
17.2 percentage of participants
|
25.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
3=Minimally improved (OLE M3)
|
55.2 percentage of participants
|
36.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
4=No Change (OLE M3)
|
20.7 percentage of participants
|
21.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
5=Minimally worse (OLE M3)
|
0 percentage of participants
|
7.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
6=Much worse (OLE M3)
|
0 percentage of participants
|
2.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
7=Very much worse (OLE M3)
|
0 percentage of participants
|
0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
1=Very much improved (OLE M6)
|
3.4 percentage of participants
|
8.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
2=Much improved (OLE M6)
|
27.6 percentage of participants
|
33.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
3=Minimally improved (OLE M6)
|
34.5 percentage of participants
|
31.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
4=No Change (OLE M6)
|
27.6 percentage of participants
|
20.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
5=Minimally worse (OLE M6)
|
6.9 percentage of participants
|
3.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
6=Much worse (OLE M6)
|
0 percentage of participants
|
3.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
7=Very much worse (OLE M6)
|
0 percentage of participants
|
0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
1=Very much improved (OLE M9)
|
3.6 percentage of participants
|
9.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
2=Much improved (OLE M9)
|
28.6 percentage of participants
|
37.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
3=Minimally improved (OLE M9)
|
28.6 percentage of participants
|
27.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
4=No Change (OLE M9)
|
35.7 percentage of participants
|
18.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
5=Minimally worse (OLE M9)
|
3.6 percentage of participants
|
6.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
6=Much worse (OLE M9)
|
0 percentage of participants
|
1.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
7=Very much worse (OLE M9)
|
0 percentage of participants
|
0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
1=Very much improved (OLE M12)
|
0 percentage of participants
|
9.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
2=Much improved (OLE M12)
|
53.8 percentage of participants
|
39.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
3=Minimally improved (OLE M12)
|
23.1 percentage of participants
|
26.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
4=No Change (OLE M12)
|
19.2 percentage of participants
|
18.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
5=Minimally worse (OLE M12)
|
3.8 percentage of participants
|
3.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
6=Much worse (OLE M12)
|
0 percentage of participants
|
2.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
7=Very much worse (OLE M12)
|
0 percentage of participants
|
0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
1=Very much improved (Last Assessment)
|
6.3 percentage of participants
|
7.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
2=Much improved (Last Assessment)
|
25.0 percentage of participants
|
27.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
3=Minimally improved (Last Assessment)
|
25.0 percentage of participants
|
21.9 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
4=No Change (Last Assessment)
|
40.6 percentage of participants
|
28.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
5=Minimally worse (Last Assessment)
|
3.1 percentage of participants
|
7.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
6=Much worse (Last Assessment)
|
0 percentage of participants
|
7.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
7=Very much worse (Last Assessment)
|
0 percentage of participants
|
0 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months)Population: OLE mITT:all participants who received \>= 1 dose of ZX008, had valid estimate of frequency of seizures that resulted in drops from Part 1 and \>= 1 month(30 days) of valid seizure data during OLE. N: participants evaluable for assessment. n: participants evaluable at specified time point. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
Outcome measures
| Measure |
Part 2: Cohort B- Overall
n=32 Participants
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort A: Placebo
n=237 Participants
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
|
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
1=Very much improved (OLE D1)
|
9.4 percentage of participants
|
6.9 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
2=Much improved (OLE D1)
|
12.5 percentage of participants
|
16.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
3=Minimally improved (OLE D1)
|
28.1 percentage of participants
|
24.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
4=No Change (OLE D1)
|
43.8 percentage of participants
|
40.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
5=Minimally worse (OLE D1)
|
3.1 percentage of participants
|
6.9 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
6=Much worse (OLE D1)
|
3.1 percentage of participants
|
3.9 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
7=Very much worse (OLE D1)
|
0 percentage of participants
|
0.9 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
1=Very much improved (OLE M1)
|
12.5 percentage of participants
|
7.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
2=Much improved (OLE M1)
|
15.6 percentage of participants
|
21.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
3=Minimally improved (OLE M1)
|
31.3 percentage of participants
|
32.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
4=No Change (OLE M1)
|
40.6 percentage of participants
|
29.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
5=Minimally worse (OLE M1)
|
0 percentage of participants
|
5.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
6=Much worse (OLE M1)
|
0 percentage of participants
|
4.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
7=Very much worse (OLE M1)
|
0 percentage of participants
|
0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
1=Very much improved (OLE M2)
|
12.9 percentage of participants
|
7.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
2=Much improved (OLE M2)
|
16.1 percentage of participants
|
25.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
3=Minimally improved (OLE M2)
|
41.9 percentage of participants
|
32.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
4=No Change (OLE M2)
|
22.6 percentage of participants
|
25.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
5=Minimally worse (OLE M2)
|
6.5 percentage of participants
|
6.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
6=Much worse (OLE M2)
|
0 percentage of participants
|
2.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
7=Very much worse (OLE M2)
|
0 percentage of participants
|
0.9 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
1=Very much improved (OLE M3)
|
13.8 percentage of participants
|
9.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
2=Much improved (OLE M3)
|
10.3 percentage of participants
|
30.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
3=Minimally improved (OLE M3)
|
37.9 percentage of participants
|
29.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
4=No Change (OLE M3)
|
37.9 percentage of participants
|
19.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
5=Minimally worse (OLE M3)
|
0 percentage of participants
|
9.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
6=Much worse (OLE M3)
|
0 percentage of participants
|
0.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
7=Very much worse (OLE M3)
|
0 percentage of participants
|
1.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
1=Very much improved (OLE M6)
|
10.3 percentage of participants
|
13.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
2=Much improved (OLE M6)
|
31.0 percentage of participants
|
30.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
3=Minimally improved (OLE M6)
|
34.5 percentage of participants
|
27.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
4=No Change (OLE M6)
|
20.7 percentage of participants
|
23.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
5=Minimally worse (OLE M6)
|
0 percentage of participants
|
3.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
6=Much worse (OLE M6)
|
3.4 percentage of participants
|
2.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
7=Very much worse (OLE M6)
|
0 percentage of participants
|
0.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
1=Very much improved (OLE M9)
|
14.3 percentage of participants
|
13.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
2=Much improved (OLE M9)
|
25.0 percentage of participants
|
37.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
3=Minimally improved (OLE M9)
|
21.4 percentage of participants
|
26.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
4=No Change (OLE M9)
|
32.1 percentage of participants
|
14.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
5=Minimally worse (OLE M9)
|
3.6 percentage of participants
|
8.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
6=Much worse (OLE M9)
|
3.6 percentage of participants
|
0.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
7=Very much worse (OLE M9)
|
0 percentage of participants
|
0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
1=Very much improved (OLE M12)
|
19.2 percentage of participants
|
16.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
2=Much improved (OLE M12)
|
26.9 percentage of participants
|
34.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
3=Minimally improved (OLE M12)
|
46.2 percentage of participants
|
26.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
4=No Change (OLE M12)
|
3.8 percentage of participants
|
14.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
5=Minimally worse (OLE M12)
|
3.8 percentage of participants
|
4.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
6=Much worse (OLE M12)
|
0 percentage of participants
|
2.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
7=Very much worse (OLE M12)
|
0 percentage of participants
|
0.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
1=Very much improved (Last Assessment)
|
12.5 percentage of participants
|
11.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
2=Much improved (Last Assessment)
|
28.1 percentage of participants
|
24.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
3=Minimally improved (Last Assessment)
|
18.8 percentage of participants
|
24.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
4=No Change (Last Assessment)
|
28.1 percentage of participants
|
25.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
5=Minimally worse (Last Assessment)
|
9.4 percentage of participants
|
9.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
6=Much worse (Last Assessment)
|
3.1 percentage of participants
|
3.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
7=Very much worse (Last Assessment)
|
0 percentage of participants
|
2.1 percentage of participants
|
—
|
—
|
—
|
—
|
Adverse Events
Part 1: Cohort A- Placebo
Serious events: 4 serious events
Other events: 60 other events
Deaths: 0 deaths
Part 1: Cohort A- ZX008 0.2 mg/kg/Day
Serious events: 4 serious events
Other events: 64 other events
Deaths: 0 deaths
Part 1: Cohort A- ZX008 0.8 mg/kg/Day
Serious events: 10 serious events
Other events: 68 other events
Deaths: 1 deaths
Part 2: Cohort A- Overall
Serious events: 41 serious events
Other events: 166 other events
Deaths: 1 deaths
Part 1: Cohort B- Placebo
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Part 1: Cohort B- ZX008 0.2 mg/kg/Day
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Part 1: Cohort B- ZX008 0.8 mg/kg/Day
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Part 2: Cohort B- Overall
Serious events: 6 serious events
Other events: 30 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part 1: Cohort A- Placebo
n=87 participants at risk
Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
|
Part 1: Cohort A- ZX008 0.2 mg/kg/Day
n=89 participants at risk
Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
|
Part 1: Cohort A- ZX008 0.8 mg/kg/Day
n=87 participants at risk
Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol \[STP\]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
|
Part 2: Cohort A- Overall
n=247 participants at risk
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
|
Part 1: Cohort B- Placebo
n=11 participants at risk
Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
|
Part 1: Cohort B- ZX008 0.2 mg/kg/Day
n=11 participants at risk
Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
|
Part 1: Cohort B- ZX008 0.8 mg/kg/Day
n=11 participants at risk
Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
|
Part 2: Cohort B- Overall
n=32 participants at risk
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|---|---|
|
Endocrine disorders
Thyroid mass
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Eye disorders
Eye movement disorder
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/89 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/89 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.81%
2/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
General disorders
Sudden unexplained death in epilepsy
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Infection
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/89 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.3%
2/87 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.0%
5/247 • Number of events 6 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.1%
1/32 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Subcutaneous abscess
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.81%
2/247 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Nervous system disorders
Change in seizure presentation
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.2%
2/89 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
4.0%
10/247 • Number of events 12 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Nervous system disorders
Seizure
|
2.3%
2/87 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.2%
3/247 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.2%
3/247 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.1%
1/32 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Nervous system disorders
Status epilepticus
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.4%
3/87 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.2%
8/247 • Number of events 25 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Psychiatric disorders
Irritability
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/89 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Psychiatric disorders
Stereotypy
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Blood and lymphatic system disorders
Haemolytic uraemic syndrome
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Eye disorders
Keratoconus
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Gastrointestinal disorders
Tooth loss
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
General disorders
Asthenia
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
General disorders
Complication of device insertion
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
General disorders
Pyrexia
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Dengue fever
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Influenza
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.81%
2/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Respiratory syncytial virus bronchiolitis
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Injury, poisoning and procedural complications
Foreign body in respiratory tract
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Investigations
Blood prolactin increased
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Investigations
Weight decreased
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.81%
2/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Nervous system disorders
Generalised tonic-clonic seizure
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Psychiatric disorders
Agitation
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Psychiatric disorders
Hallucination
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.2%
3/247 • Number of events 6 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Vascular disorders
Distributive shock
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.1%
1/32 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Enterobacter bacteraemia
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.1%
1/32 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.1%
1/32 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Injury, poisoning and procedural complications
Foreign body in gastrointestinal tract
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.1%
1/32 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Nervous system disorders
Seizure cluster
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
Other adverse events
| Measure |
Part 1: Cohort A- Placebo
n=87 participants at risk
Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
|
Part 1: Cohort A- ZX008 0.2 mg/kg/Day
n=89 participants at risk
Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
|
Part 1: Cohort A- ZX008 0.8 mg/kg/Day
n=87 participants at risk
Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol \[STP\]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
|
Part 2: Cohort A- Overall
n=247 participants at risk
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
|
Part 1: Cohort B- Placebo
n=11 participants at risk
Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
|
Part 1: Cohort B- ZX008 0.2 mg/kg/Day
n=11 participants at risk
Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
|
Part 1: Cohort B- ZX008 0.8 mg/kg/Day
n=11 participants at risk
Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
|
Part 2: Cohort B- Overall
n=32 participants at risk
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
|
|---|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Mitral valve incompetence
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Endocrine disorders
Hyperprolactinaemia
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.4%
3/87 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.2%
3/247 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Eye disorders
Diplopia
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Gastrointestinal disorders
Breath odour
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Gastrointestinal disorders
Constipation
|
5.7%
5/87 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
5.6%
5/89 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.2%
8/87 • Number of events 10 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
7.3%
18/247 • Number of events 22 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
15.6%
5/32 • Number of events 7 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.2%
2/89 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.81%
2/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.1%
1/32 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Gastrointestinal disorders
Diarrhoea
|
4.6%
4/87 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
11.2%
10/89 • Number of events 10 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
11.5%
10/87 • Number of events 11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
5.3%
13/247 • Number of events 15 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
27.3%
3/11 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
18.2%
2/11 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
15.6%
5/32 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Gastrointestinal disorders
Haemorrhoids
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Gastrointestinal disorders
Vomiting
|
5.7%
5/87 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
12.4%
11/89 • Number of events 16 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
10.3%
9/87 • Number of events 44 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
5.3%
13/247 • Number of events 17 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
General disorders
Asthenia
|
3.4%
3/87 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
4.5%
4/89 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
5.7%
5/87 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.8%
7/247 • Number of events 8 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
General disorders
Fatigue
|
12.6%
11/87 • Number of events 11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.0%
8/89 • Number of events 10 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
18.4%
16/87 • Number of events 18 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
13.4%
33/247 • Number of events 35 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
General disorders
Oedema peripheral
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
General disorders
Pyrexia
|
12.6%
11/87 • Number of events 13 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
12.4%
11/89 • Number of events 12 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
10.3%
9/87 • Number of events 10 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
10.1%
25/247 • Number of events 33 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
21.9%
7/32 • Number of events 12 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Beta haemolytic streptococcal infection
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.2%
2/89 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.3%
2/87 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.81%
2/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.4%
3/32 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/89 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.3%
2/87 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Corona virus infection
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.81%
2/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
37.5%
12/32 • Number of events 14 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Gastroenteritis
|
2.3%
2/87 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.81%
2/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Influenza
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
4.5%
4/89 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.2%
3/247 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.4%
3/32 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Nasopharyngitis
|
9.2%
8/87 • Number of events 10 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
4.5%
4/89 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
8.0%
7/87 • Number of events 8 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
12.6%
31/247 • Number of events 43 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
18.2%
2/11 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
18.2%
2/11 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
28.1%
9/32 • Number of events 18 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Oral herpes
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Rhinitis
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/89 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.0%
5/247 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Sinusitis
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/89 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.0%
5/247 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Upper respiratory tract infection
|
4.6%
4/87 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
7.9%
7/89 • Number of events 10 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.9%
6/87 • Number of events 7 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.5%
16/247 • Number of events 20 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.1%
1/32 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Infections and infestations
Urinary tract infection bacterial
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Injury, poisoning and procedural complications
Contusion
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.2%
2/89 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
5.7%
5/87 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.8%
7/247 • Number of events 10 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.4%
3/32 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Injury, poisoning and procedural complications
Face injury
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.2%
3/247 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/89 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.81%
2/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Injury, poisoning and procedural complications
Laceration
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.2%
2/89 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.4%
3/87 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
5.3%
13/247 • Number of events 13 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
2.3%
2/87 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/89 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.6%
4/247 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Injury, poisoning and procedural complications
Lip injury
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.4%
6/247 • Number of events 7 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.4%
3/32 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Injury, poisoning and procedural complications
Wound
|
2.3%
2/87 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/89 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.81%
2/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
12.5%
4/32 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Investigations
Blood prolactin increased
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.4%
3/87 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.6%
9/247 • Number of events 10 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
25.0%
8/32 • Number of events 14 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Investigations
Echocardiogram abnormal
|
6.9%
6/87 • Number of events 6 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.2%
2/89 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.3%
2/87 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.4%
6/247 • Number of events 7 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Investigations
Weight decreased
|
2.3%
2/87 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.4%
3/89 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
8.0%
7/87 • Number of events 7 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
4.9%
12/247 • Number of events 12 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
18.2%
2/11 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
36.4%
4/11 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
12.5%
4/32 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
14.9%
13/87 • Number of events 15 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
20.2%
18/89 • Number of events 18 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
36.8%
32/87 • Number of events 35 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
15.8%
39/247 • Number of events 42 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
18.2%
2/11 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
27.3%
3/11 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
27.3%
3/11 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
12.5%
4/32 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Nervous system disorders
Change in seizure presentation
|
2.3%
2/87 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.9%
17/247 • Number of events 19 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Nervous system disorders
Lethargy
|
3.4%
3/87 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
4.5%
4/89 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
5.7%
5/87 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
5.3%
13/247 • Number of events 13 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Nervous system disorders
Seizure
|
4.6%
4/87 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
12.4%
11/89 • Number of events 13 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
5.7%
5/87 • Number of events 6 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.7%
24/247 • Number of events 28 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Nervous system disorders
Seizure cluster
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Nervous system disorders
Somnolence
|
11.5%
10/87 • Number of events 10 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
11.2%
10/89 • Number of events 11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
17.2%
15/87 • Number of events 16 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.7%
24/247 • Number of events 26 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
36.4%
4/11 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
27.3%
3/11 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
34.4%
11/32 • Number of events 16 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Nervous system disorders
Tremor
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.2%
2/89 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.3%
2/87 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.8%
7/247 • Number of events 7 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Psychiatric disorders
Affective disorder
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Psychiatric disorders
Agitation
|
3.4%
3/87 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/89 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/87 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.6%
4/247 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Psychiatric disorders
Insomnia
|
3.4%
3/87 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.3%
2/87 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
4.5%
11/247 • Number of events 11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Psychiatric disorders
Irritability
|
5.7%
5/87 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
10.1%
9/89 • Number of events 9 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
4.6%
4/87 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.4%
6/247 • Number of events 6 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.4%
3/32 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.1%
1/89 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.0%
5/247 • Number of events 5 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.1%
1/32 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.4%
3/87 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.2%
2/89 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
4.6%
4/87 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
4.0%
10/247 • Number of events 11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.4%
3/32 • Number of events 4 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
1.2%
3/247 • Number of events 3 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
3.1%
1/32 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Skin and subcutaneous tissue disorders
Alopecia areata
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Skin and subcutaneous tissue disorders
Dermatitis diaper
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.40%
1/247 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/32 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
2.2%
2/89 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.81%
2/247 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
9.1%
1/11 • Number of events 1 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
15.6%
5/32 • Number of events 7 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
|
Skin and subcutaneous tissue disorders
Miliaria
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/89 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/87 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/247 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
0.00%
0/11 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
6.2%
2/32 • Number of events 2 • From Day 1 up to 72 months
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60