A Multicenter, Open-label, Pilot Study of Soticlestat (TAK-935/OV935) in Participants With 15Q Duplication Syndrome (Dup 15q) or Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficiency Disorder (ARCADE STUDY)
Study Details
Study Description
Brief Summary
The purpose of this study is to investigate the effect of soticlestat on the frequency of motor seizures for participants with Dup15q or CDD during the Maintenance Period.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Detailed Description
The drug being tested in this study is called soticlestat. Soticlestat is being tested to treat people with Dup 15q or CDD. This study will assess the effects of TAK-935 on seizure frequency, safety.
The study will enroll approximately 30 participants. Participants will be enrolled into 2 groups based on their diagnosis as: Dup 15q or CDD.
All participants will be asked to take soticlestat tablets twice daily with or without food.
The study comprises of 2 periods: Screening/Baseline Period and Treatment Period (Dose Optimization and Maintenance). The overall time to participate in this study is approximately 30 weeks, including 4 to 6 weeks Screening/Baseline Period, 20 weeks Treatment Period, 2 weeks Taper, and 2 weeks safety follow up period. Participants completing this study will have an option to enroll in the open-label extension (OLE) study, under a separate protocol.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Soticlestat Dup 15q Soticlestat tablets twice daily (BID) orally or via gastrostomy tube (G-tube)/ percutaneous endoscopic gastrostomy (PEG) tube, BID. Participants with Dup 15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Drug: Soticlestat
TAK-935 tablets
Other Names:
|
Experimental: Soticlestat CDD Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Drug: Soticlestat
TAK-935 tablets
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Maintenance Period [Maintenance Period: Weeks 9 to 20]
Seizure frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period multiplied by 28. Percent Change from Baseline is defined as (frequency of seizures per 28 days during maintenance period - frequency of seizures per 28 days at Baseline) divided by frequency of seizures per 28 days at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease.
Secondary Outcome Measures
- Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Treatment Period [Treatment Period: Weeks 0 to 20]
Seizure frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period multiplied by 28. Percent Change from Baseline is defined as (frequency of seizures per 28 days during the treatment period - frequency of seizures per 28 days at Baseline) divided by frequency of seizures per 28 days at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease.
- Percentage of Participants Considered as Treatment Responders During the Maintenance Period [Maintenance Period: Weeks 9 to 20]
Responders are defined as having over 50% motor seizure reduction compared to Baseline. Percent reduction from Baseline (%) is defined as [(Maintenance Period motor Seizure Frequency - Baseline Period motor Seizure Frequency) divided by Baseline motor Seizure Frequency] multiplied by 100. Data is reported as reduction of 25%, 50%, 75% and 100% or more in motor seizures from Baseline.
- Percent Change From Baseline in Frequency of Motor Seizures Longer Than 5 Minutes in Participants With CDD [Treatment Period: Weeks 0 to 20]
Seizure frequency is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period. Percent Change from Baseline is defined as (frequency of seizures during Treatment period - frequency of seizures at Baseline) divided by frequency of seizures at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease. The data is reported only for CDD participants.
- Proportion of Motor Seizure-free Days in Participants During the Maintenance Period [Maintenance Period: Weeks 9 to 20]
Seizure-free days is defined as number of days with zero motor seizure during the period the Maintenance Period divided by number of days participant was in the Maintenance Period.
- Change From Baseline in Clinician's Global Impression of Severity (CGI-S) Responses of Investigator [Baseline to Week 20]
The CGI-S focuses on clinician's observations of the participant's cognitive, functional, and behavioral performance since the beginning of the study. The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses where, 1= normal, not at all ill, 2= borderline mentally ill, 3= mildly ill, 4= moderately ill, 5= markedly ill, 6= severely ill and 7=amongst the most extremely ill participants. Negative change from Baseline indicates improvement.
- Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression [Week 20]
CGI-Change (CGI-C) treatment response ratings should take account of both therapeutic efficacy and treatment-related AEs. Each component of the CGI is rated separately; the instrument does not yield a global score. The CGI-C is rated on a 5-point scale, where, 0 = marked improvement and no side-effects, 1 = marked improvement and minimal side-effects, 2 = no change, 3 = minimal improvement and marked side-effects and 4 = unchanged or worse and side-effects outweigh the therapeutic effect. Lower scores indicated improvement.
- Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family [Week 20]
CGI-Change (CGI-C) treatment response ratings should take account of both therapeutic efficacy and treatment-related AEs. Each component of the CGI is rated separately; the instrument does not yield a global score. The CGI-C is rated on a 7-point scale where, 1 = very much improved, 2 = much improved, 3 = slightly improved, 4= no change, 5= slightly worse, 6= much worse and 7= very much worse and marked side-effects. Lower scores indicated improvement.
- Change From Baseline of Plasma 24S-hydroxycholesterol (24HC) Levels [Baseline to Week 20]
- Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy [Baseline to Week 20]
Seizure Frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure during the period seizures were assessed multiplied by 28. Positive change from Baseline indicates seizure increase and negative change from Baseline indicates seizure decrease.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Clinical diagnosis of Dup 15q or CDKL5 deficiency disorder.
-
Currently taking 1 to 6 antiepileptic drugs (AEDs) at a stable dose.
Exclusion Criteria:
-
Two or more episodes of convulsive status epilepticus per 3 months requiring hospitalization and intubation.
-
Currently receiving a study drug or participated in a clinical study involving another investigational product in the previous month.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | UCLA | Los Angeles | California | United States | 90095 |
2 | Research Institute Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
3 | Center for Rare Neurological Diseases | Norcross | Georgia | United States | 30093 |
4 | Center for Rare Neurological Diseases (CRND)--Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
5 | Boston Children's Hospital Translational Neuroscience Center | Boston | Massachusetts | United States | 02115 |
6 | Minnesota Epilepsy Group, P.A. | Saint Paul | Minnesota | United States | 55102 |
7 | New York University (NYU) | New York | New York | United States | 10017 |
8 | Columbia University Medical Center | New York | New York | United States | 10032 |
Sponsors and Collaborators
- Takeda
- Ovid Therapeutics Inc.
Investigators
- Study Director: Medical Director Clinical Science, Takeda
Study Documents (Full-Text)
More Information
Publications
None provided.- TAK-935-18-002 (OV935)
- U1111-1219-5787
- 2022-001315-44
Study Results
Participant Flow
Recruitment Details | Participants took part in the study at 8 investigative sites in the United States from 10 September 2018 to 31 July 2020. |
---|---|
Pre-assignment Detail | Participants with a diagnosis of 15q duplication syndrome (Dup15q) or CDKL5 deficiency disorder (CDD) were enrolled in 2 cohorts to receive treatment with TAK-935 for up to 20 weeks Treatment Period (8-week Dose Optimization Period and 12-week Maintenance Period). |
Arm/Group Title | Soticlestat Dup15q | Soticlestat CDD |
---|---|---|
Arm/Group Description | Soticlestat tablets twice daily (BID) orally or via gastrostomy tube (G-tube)/ percutaneous endoscopic gastrostomy (PEG) tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Period Title: Overall Study | ||
STARTED | 8 | 12 |
COMPLETED | 8 | 10 |
NOT COMPLETED | 0 | 2 |
Baseline Characteristics
Arm/Group Title | Soticlestat Dup15q | Soticlestat CDD | Total |
---|---|---|---|
Arm/Group Description | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Total of all reporting groups |
Overall Participants | 8 | 12 | 20 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
15.4
(6.00)
|
7.6
(5.30)
|
10.7
(6.70)
|
Sex: Female, Male (Count of Participants) | |||
Female |
3
37.5%
|
9
75%
|
12
60%
|
Male |
5
62.5%
|
3
25%
|
8
40%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
Not Hispanic or Latino |
8
100%
|
12
100%
|
20
100%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
0
0%
|
0
0%
|
White |
8
100%
|
11
91.7%
|
19
95%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
1
8.3%
|
1
5%
|
Region of Enrollment (Count of Participants) | |||
United States |
8
100%
|
12
100%
|
20
100%
|
Height (cm) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [cm] |
148.54
(14.965)
|
124.59
(26.882)
|
134.17
(25.412)
|
Weight (kg) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [kg] |
43.40
(13.678)
|
26.28
(12.511)
|
33.13
(15.283)
|
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [kg/m^2] |
19.21
(4.149)
|
16.00
(1.874)
|
17.28
(3.314)
|
Outcome Measures
Title | Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Maintenance Period |
---|---|
Description | Seizure frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period multiplied by 28. Percent Change from Baseline is defined as (frequency of seizures per 28 days during maintenance period - frequency of seizures per 28 days at Baseline) divided by frequency of seizures per 28 days at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease. |
Time Frame | Maintenance Period: Weeks 9 to 20 |
Outcome Measure Data
Analysis Population Description |
---|
Modified Intent-to-Treat (mITT) Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed are the number of participants with data available for analyses. |
Arm/Group Title | Soticlestat Dup15q | Soticlestat CDD |
---|---|---|
Arm/Group Description | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Measure Participants | 8 | 11 |
Median (Full Range) [percent change] |
11.7
|
-23.6
|
Title | Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Treatment Period |
---|---|
Description | Seizure frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period multiplied by 28. Percent Change from Baseline is defined as (frequency of seizures per 28 days during the treatment period - frequency of seizures per 28 days at Baseline) divided by frequency of seizures per 28 days at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease. |
Time Frame | Treatment Period: Weeks 0 to 20 |
Outcome Measure Data
Analysis Population Description |
---|
mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. |
Arm/Group Title | Soticlestat Dup15q | Soticlestat CDD |
---|---|---|
Arm/Group Description | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Measure Participants | 8 | 12 |
Median (Full Range) [percent change] |
13.4
|
-13.6
|
Title | Percentage of Participants Considered as Treatment Responders During the Maintenance Period |
---|---|
Description | Responders are defined as having over 50% motor seizure reduction compared to Baseline. Percent reduction from Baseline (%) is defined as [(Maintenance Period motor Seizure Frequency - Baseline Period motor Seizure Frequency) divided by Baseline motor Seizure Frequency] multiplied by 100. Data is reported as reduction of 25%, 50%, 75% and 100% or more in motor seizures from Baseline. |
Time Frame | Maintenance Period: Weeks 9 to 20 |
Outcome Measure Data
Analysis Population Description |
---|
mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed is the number of participants with data available for analyses. |
Arm/Group Title | Soticlestat Dup15q | Soticlestat CDD |
---|---|---|
Arm/Group Description | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Measure Participants | 8 | 11 |
<=0% Reduction |
62.5
781.3%
|
27.3
227.5%
|
>0% to <25% Reduction |
12.5
156.3%
|
27.3
227.5%
|
>=25% to <50% Reduction |
12.5
156.3%
|
18.2
151.7%
|
>=50% to <75% Reduction |
0
0%
|
18.2
151.7%
|
>=75% to 100% Reduction |
12.5
156.3%
|
9.1
75.8%
|
Title | Percent Change From Baseline in Frequency of Motor Seizures Longer Than 5 Minutes in Participants With CDD |
---|---|
Description | Seizure frequency is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period. Percent Change from Baseline is defined as (frequency of seizures during Treatment period - frequency of seizures at Baseline) divided by frequency of seizures at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease. The data is reported only for CDD participants. |
Time Frame | Treatment Period: Weeks 0 to 20 |
Outcome Measure Data
Analysis Population Description |
---|
mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed are all participants whose analyses were conducted using observed values and no imputation was done for missing data. |
Arm/Group Title | Soticlestat CDD |
---|---|
Arm/Group Description | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Measure Participants | 6 |
Median (Full Range) [percent change] |
-54.0
|
Title | Proportion of Motor Seizure-free Days in Participants During the Maintenance Period |
---|---|
Description | Seizure-free days is defined as number of days with zero motor seizure during the period the Maintenance Period divided by number of days participant was in the Maintenance Period. |
Time Frame | Maintenance Period: Weeks 9 to 20 |
Outcome Measure Data
Analysis Population Description |
---|
mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed is the number of participants with data available for analyses. |
Arm/Group Title | Soticlestat Dup15q | Soticlestat CDD |
---|---|---|
Arm/Group Description | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Measure Participants | 8 | 11 |
Median (Full Range) [days/28 days] |
0.1
|
0.1
|
Title | Change From Baseline in Clinician's Global Impression of Severity (CGI-S) Responses of Investigator |
---|---|
Description | The CGI-S focuses on clinician's observations of the participant's cognitive, functional, and behavioral performance since the beginning of the study. The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses where, 1= normal, not at all ill, 2= borderline mentally ill, 3= mildly ill, 4= moderately ill, 5= markedly ill, 6= severely ill and 7=amongst the most extremely ill participants. Negative change from Baseline indicates improvement. |
Time Frame | Baseline to Week 20 |
Outcome Measure Data
Analysis Population Description |
---|
mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Number analyzed is the number of participants with data available for analyses at the given timepoint. |
Arm/Group Title | Soticlestat Dup15q | Soticlestat CDD |
---|---|---|
Arm/Group Description | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Measure Participants | 8 | 12 |
Baseline |
5.0
|
5.0
|
Change From Baseline at Week 20 |
0.0
|
0.0
|
Title | Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression |
---|---|
Description | CGI-Change (CGI-C) treatment response ratings should take account of both therapeutic efficacy and treatment-related AEs. Each component of the CGI is rated separately; the instrument does not yield a global score. The CGI-C is rated on a 5-point scale, where, 0 = marked improvement and no side-effects, 1 = marked improvement and minimal side-effects, 2 = no change, 3 = minimal improvement and marked side-effects and 4 = unchanged or worse and side-effects outweigh the therapeutic effect. Lower scores indicated improvement. |
Time Frame | Week 20 |
Outcome Measure Data
Analysis Population Description |
---|
mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed is the number of participants with data available for analyses at given timepoint. |
Arm/Group Title | Soticlestat Dup15q | Soticlestat CDD |
---|---|---|
Arm/Group Description | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Measure Participants | 6 | 12 |
Week 20, Score 0 |
33.3
416.3%
|
33.3
277.5%
|
Week 20, Score 1 |
0
0%
|
33.3
277.5%
|
Week 20, Score 2 |
50.0
625%
|
33.3
277.5%
|
Week 20, Score 3 |
16.7
208.8%
|
0
0%
|
Week 20, Score 4 |
0
0%
|
0
0%
|
Title | Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family |
---|---|
Description | CGI-Change (CGI-C) treatment response ratings should take account of both therapeutic efficacy and treatment-related AEs. Each component of the CGI is rated separately; the instrument does not yield a global score. The CGI-C is rated on a 7-point scale where, 1 = very much improved, 2 = much improved, 3 = slightly improved, 4= no change, 5= slightly worse, 6= much worse and 7= very much worse and marked side-effects. Lower scores indicated improvement. |
Time Frame | Week 20 |
Outcome Measure Data
Analysis Population Description |
---|
mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed is the number of participants with data available for analyses at the given timepoint. |
Arm/Group Title | Soticlestat Dup15q | Soticlestat CDD |
---|---|---|
Arm/Group Description | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Measure Participants | 6 | 12 |
Week 20, Score 1 |
0
0%
|
16.7
139.2%
|
Week 20, Score 2 |
16.7
208.8%
|
25.0
208.3%
|
Week 20, Score 3 |
33.3
416.3%
|
50.0
416.7%
|
Week 20, Score 4 |
50.0
625%
|
0
0%
|
Week 20, Score 5 |
0
0%
|
8.3
69.2%
|
Week 20, Score 6 |
0
0%
|
0
0%
|
Week 20, Score 7 |
0
0%
|
0
0%
|
Title | Change From Baseline of Plasma 24S-hydroxycholesterol (24HC) Levels |
---|---|
Description | |
Time Frame | Baseline to Week 20 |
Outcome Measure Data
Analysis Population Description |
---|
mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the given timepoint. |
Arm/Group Title | Soticlestat Dup15q | Soticlestat CDD |
---|---|---|
Arm/Group Description | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Measure Participants | 8 | 11 |
Baseline |
57.08
(24.195)
|
115.29
(73.587)
|
Change from Baseline at Week 20 |
-34.71
(16.578)
|
-75.64
(29.284)
|
Title | Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy |
---|---|
Description | Seizure Frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure during the period seizures were assessed multiplied by 28. Positive change from Baseline indicates seizure increase and negative change from Baseline indicates seizure decrease. |
Time Frame | Baseline to Week 20 |
Outcome Measure Data
Analysis Population Description |
---|
mITT Analysis Set included all participants who have received at least 1 dose of study drug and have been assessed for at least 1 day in the Treatment Period. |
Arm/Group Title | Soticlestat Dup15q | Soticlestat CDD |
---|---|---|
Arm/Group Description | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. |
Measure Participants | 8 | 12 |
Baseline |
128.4
|
77.8
|
Change From Baseline |
13.2
|
-3.4
|
Adverse Events
Time Frame | From the first dose to 30 days post-last dose of study treatment (Up to 24 weeks) | |||
---|---|---|---|---|
Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||
Arm/Group Title | Soticlestat Dup15q | Soticlestat CDD | ||
Arm/Group Description | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with Dup15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | ||
All Cause Mortality |
||||
Soticlestat Dup15q | Soticlestat CDD | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/8 (0%) | 0/12 (0%) | ||
Serious Adverse Events |
||||
Soticlestat Dup15q | Soticlestat CDD | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/8 (12.5%) | 2/12 (16.7%) | ||
Immune system disorders | ||||
Anaphylactic reaction | 1/8 (12.5%) | 0/12 (0%) | ||
Infections and infestations | ||||
Respiratory syncytial virus bronchiolitis | 0/8 (0%) | 1/12 (8.3%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Acute respiratory failure | 0/8 (0%) | 1/12 (8.3%) | ||
Other (Not Including Serious) Adverse Events |
||||
Soticlestat Dup15q | Soticlestat CDD | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 7/8 (87.5%) | 12/12 (100%) | ||
Blood and lymphatic system disorders | ||||
Eosinophilia | 1/8 (12.5%) | 0/12 (0%) | ||
Gastrointestinal disorders | ||||
Constipation | 0/8 (0%) | 4/12 (33.3%) | ||
Diarrhoea | 1/8 (12.5%) | 0/12 (0%) | ||
Frequent bowel movements | 0/8 (0%) | 1/12 (8.3%) | ||
General disorders | ||||
Fatigue | 2/8 (25%) | 0/12 (0%) | ||
Asthenia | 0/8 (0%) | 1/12 (8.3%) | ||
Peripheral swelling | 0/8 (0%) | 1/12 (8.3%) | ||
Pain | 1/8 (12.5%) | 0/12 (0%) | ||
Immune system disorders | ||||
Seasonal allergy | 0/8 (0%) | 1/12 (8.3%) | ||
Infections and infestations | ||||
Ear infection | 0/8 (0%) | 2/12 (16.7%) | ||
Nasopharyngitis | 1/8 (12.5%) | 1/12 (8.3%) | ||
Respiratory tract infection | 0/8 (0%) | 1/12 (8.3%) | ||
Sinusitis | 1/8 (12.5%) | 0/12 (0%) | ||
Upper respiratory tract infection | 1/8 (12.5%) | 0/12 (0%) | ||
Urinary tract infection | 0/8 (0%) | 1/12 (8.3%) | ||
Injury, poisoning and procedural complications | ||||
Face injury | 1/8 (12.5%) | 0/12 (0%) | ||
Fall | 1/8 (12.5%) | 0/12 (0%) | ||
Investigations | ||||
Blood bicarbonate decreased | 0/8 (0%) | 2/12 (16.7%) | ||
Activated partial thromboplastin time prolonged | 1/8 (12.5%) | 0/12 (0%) | ||
Anticonvulsant drug level increased | 1/8 (12.5%) | 0/12 (0%) | ||
Blood cholesterol increased | 0/8 (0%) | 1/12 (8.3%) | ||
Blood creatine phosphokinase increased | 0/8 (0%) | 1/12 (8.3%) | ||
Blood triglycerides increased | 0/8 (0%) | 1/12 (8.3%) | ||
C-reactive protein increased | 0/8 (0%) | 1/12 (8.3%) | ||
Electrocardiogram QT prolonged | 0/8 (0%) | 1/12 (8.3%) | ||
Electrocardiogram ST-T change | 0/8 (0%) | 1/12 (8.3%) | ||
Haematocrit increased | 0/8 (0%) | 1/12 (8.3%) | ||
International normalised ratio increased | 1/8 (12.5%) | 0/12 (0%) | ||
Low density lipoprotein increased | 0/8 (0%) | 1/12 (8.3%) | ||
Neutrophil count decreased | 0/8 (0%) | 1/12 (8.3%) | ||
Oxygen saturation decreased | 0/8 (0%) | 1/12 (8.3%) | ||
Platelet count increased | 0/8 (0%) | 1/12 (8.3%) | ||
White blood cell count increased | 0/8 (0%) | 1/12 (8.3%) | ||
Nervous system disorders | ||||
Seizure | 2/8 (25%) | 1/12 (8.3%) | ||
Lethargy | 2/8 (25%) | 0/12 (0%) | ||
Partial seizures | 0/8 (0%) | 2/12 (16.7%) | ||
Tonic convulsion | 0/8 (0%) | 2/12 (16.7%) | ||
Atonic seizures | 0/8 (0%) | 1/12 (8.3%) | ||
Balance disorder | 1/8 (12.5%) | 0/12 (0%) | ||
Drooling | 1/8 (12.5%) | 0/12 (0%) | ||
Hypersomnia | 1/8 (12.5%) | 0/12 (0%) | ||
Hypotonia | 1/8 (12.5%) | 0/12 (0%) | ||
Somnolence | 0/8 (0%) | 1/12 (8.3%) | ||
Tremor | 0/8 (0%) | 1/12 (8.3%) | ||
Psychiatric disorders | ||||
Agitation | 1/8 (12.5%) | 1/12 (8.3%) | ||
Initial insomnia | 0/8 (0%) | 1/12 (8.3%) | ||
Irritability | 0/8 (0%) | 1/12 (8.3%) | ||
Sleep disorder | 0/8 (0%) | 1/12 (8.3%) | ||
Renal and urinary disorders | ||||
Neurogenic bladder | 0/8 (0%) | 1/12 (8.3%) | ||
Urinary retentio | 0/8 (0%) | 1/12 (8.3%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Apnoea | 1/8 (12.5%) | 0/12 (0%) | ||
Hyperventilation | 0/8 (0%) | 1/12 (8.3%) | ||
Pneumonia aspiration | 0/8 (0%) | 1/12 (8.3%) | ||
Skin and subcutaneous tissue disorders | ||||
Rash | 1/8 (12.5%) | 2/12 (16.7%) | ||
Pruritus | 1/8 (12.5%) | 0/12 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Name/Title | Medical Director |
---|---|
Organization | Takeda |
Phone | +1-877-825-3327 |
trialdisclosures@takeda.com |
- TAK-935-18-002 (OV935)
- U1111-1219-5787
- 2022-001315-44