E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
developmental and epileptic encephalopathies |
|
E.1.1.1 | Medical condition in easily understood language |
developmental and epileptic encephalopathies |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the long-term safety and tolerability of TAK-935 when administered for 2 years as adjunctive therapy in patients with rare epilepsies |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effect of TAK-935 on seizure frequency over 2 years |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patients must have participated in a previous TAK-935 study and meet one of the following conditions:
Successfully completed a TAK-935 clinical study.
Received at least 10 weeks of treatment (combined dose optimization and maintenance period) with the study
drug in a TAK-935 clinical study and the patient did not have a serious or severe AE that, in the
investigator’s or Sponsor's opinion, was related to the study drug and would make it unsafe for the patient to
continue receiving the study drug.
2) In the opinion of the investigator, the patient has the potential to benefit from the administration of TAK-
935.
3) The patient provides written informed consent, or the patient’s legal representative (parent or legal guardian) provides written
informed consent and the patient provides assent, before any study procedures are performed.
4) The patient and legal representative (parent or guardian) are willing to comply with all study requirements.
5) Sexually active female patients of childbearing potential (defined as first menarche) must agree to use a
highly effective method of birth control during the study and for 30 days following the last dose of study. Highly effective contraceptive methods are as follows:
a) Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of
ovulation:
Oral
Intravaginal
Transdermal
b) Progestogen-only hormonal contraception associated with inhibition of ovulation:
Oral
Injectable
Implantable
c) Intrauterine device
d) Intrauterine hormone-releasing system
e) Bilateral tubal occlusion
f) Vasectomized partner
g) Sexual abstinence
Sexually active male patients (post-pubertal unless permanently sterilized by bilateral orchidectomy) must
agree to use male contraception (condom) during the study and for a minimum of 90 days following the
last dose of study drug. Male patients must also not donate sperm during the Screening and Treatment
Periods and for at least 90 days after the last dose of study drug. |
|
E.4 | Principal exclusion criteria |
1. Clinically significant disease, that, in the investigator’s opinion, precludes study participation
2. Enrollment in any other clinical trial involving an investigational drug, device, or treatment in the past 90 days (with the exception of an antecedent study involving TAK-935)
3. Patient is currently pregnant or breastfeeding or is planning to become pregnant during the study or
within 90 days of the last study drug administration
4. Suicide attempt within the last year, at significant risk of suicide (either in the opinion of the investigator or defined as ‘yes’ to suicidal ideation question 4 or 5 on the Columbia- Suicide Severity Rating Scale [C-SSRS] at Screening) or appearing suicidal per investigator judgment |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoints - Safety
•Incidence of AEs
•Change from Baseline in behavioral and adaptive functional measures using the Vineland Adaptive
Behavior Scale
•Change from Baseline in behavior measures using total scores and subscale scores of the Aberrant
Behavior Checklist-Community Edition for patients ≥6 years of age
•Change from Baseline in the Columbia-Suicide Severity Rating Scale categorization based onColumbia Classification Algorithm of Suicide Assessment categories 1,2,3,4, and 7 for patients
≥6 years of age.
•Absolute values and change from Baseline in clinical laboratory assessments, vital sign measurements,
body weight, and ECG parameters
•Incidence of potentially clinically significant clinical safety laboratory test values, vital signs, weight,
height/length, and ECG evaluations
Exploratory Endpoints - Quality of Life
•Change from Baseline in overall Quality of Life Childhood Epilepsy score (pediatric patients)
•Change from Baseline in the Sleep Disruption Numerical Rating Scale
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary end points will be assessed throughout the study. |
|
E.5.2 | Secondary end point(s) |
Secondary Endpoints - Efficacy
•Change from Baseline in all seizure frequency over 28-days at Weeks 12, 24, 36, 48, 64, 80, 104, and 108
•Change from Baseline in mean drop seizure frequency over 28-days at Weeks 12, 24, 36, 48, 64, 80, 104, and 108
•Change from Baseline in mean convulsive seizure frequency over 28-days at Weeks 12, 24, 36, 48, 64, 80, 104, and 108
•Change from Baseline in mean motor seizure frequency over 28-days at Weeks 12, 24, 36, 48, 64, 80, 104, and 108
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At Weeks 12, 24, 36, 48, 64, 80, 104, and 108
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
China |
Israel |
Poland |
Portugal |
Spain |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
It has been defined as the last subject last visit |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 1 |