| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| E.1.1.1 | Medical condition in easily understood language | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10043118 | | E.1.2 | Term | Tardive dyskinesia | | E.1.2 | System Organ Class | 10029205 - Nervous system disorders | |
| 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 evaluate efficacy of ADE513 in reducing abnormal involuntary movements of tardive dyskinesia. | |
| E.2.2 | Secondary objectives of the trial | | To evaluate safety and tolerability of ADE513 in titration and maintenance therapy in subjects with tardive dyskinesia. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1.Subject aged between 18 and 75 years, inclusive.
2.Subject with a clinical diagnosis of tardive dyskinesia.
3.Subject with symptoms of TD which are bothersome and/or cause functional impairment.
4.Subject with total motor AIMS score of ≥6, and with abnormal movements judged as moderate or severe by the Investigator (based on Item 8 of the AIMS).
5.Subject with body weight of not less than 45kg for females and 55kg for males.
6.Subject in a psychiatrically stable condition with no change in psychoactive medications (eg. neuroleptics, benzodiazepines, anticonvulsants, mood stabilizers etc.) within the last 30 days before Screening, and with no anticipated changes to the subject’s treatment regimen in the next 3 months.
7.Subject living in a stable environment as judged by the Investigator, with adequate supervision when necessary.
8.Subject having a caregiver who is in regular personal contact with the subject (no less than 5 days a week); if locally required.
9.Subject compliant with prescribed treatment regimen as judged by the Investigator.
10.Subject in good general health with expectation to attend all study visits and complete all study assessments as judged by the Investigator.
11.Subject able to read, comprehend and provide the written informed consent.
12.Subject able to complete subject-facing rating scales.
13.Female subject of childbearing potential who agrees to use a highly effective form of contraception (as defined by the Protocol) throughout the Study.
| |
| E.4 | Principal exclusion criteria | 1.Subject who received any of the following medications within 30 days of Screening or Baseline:
oTetrabenazine, deutetrabenazine, valbenazine, reserpine, α-methyl-p-tyrosine (AMPT),
oTrihexyphenidyl, orphenadrine, procyclidine, biperiden or other strong anticholinergics
oMetoclopramide, promethazine, and prochlorperazine
oMethylphenidate, amphetamine/dextroamphetamine, or other stimulants,
oMonoamine oxidase inhibitors (MAOIs)
oLevodopa or dopamine agonists
oBotulinum toxin (within 3 months of Screening)
Note: Existing medication for the subject’s TD symptoms must not be discontinued solely for the purpose of inclusion in this clinical trial.
2.Subject with a neurological condition that may interfere with the assessment of dyskinesia severity.
3.Subject with a serious psychiatric condition that is untreated or undertreated at Screening and/or Baseline.
4.Subject with active suicidal ideation at Screening or Baseline.
5.Subject with history of either previous intent to act on a suicidal ideation with a specific plan, or previous preparatory acts to commit suicide or suicidal behaviour, or a previous actual, interrupted or aborted suicide attempt.
6.Subject with an abnormal score on the depression subscale of the Hospital Anxiety and Depression Scale (HADS) at Screening or Baseline. Abnormal score is defined as score ≥11.
7.Subject with an unstable or serious medical condition at Screening or Baseline.
8.Subject with developmental disability or evidence of dementia confirmed by Mini-Mental State Exam (MMSE score ≤24).
9.Subject showing violent behaviour, or subject with a history thereof within 3 months of start of study participation.
10.Subject with clinically significant cardiac abnormality or QTcF >450 ms (males) or >470 ms (females) on 12-lead ECG at Screening.
11.Subject with any of the following abnormal values in laboratory test results at Screening:
oaspartate transaminase (AST) or alanine aminotransferase (ALT) >2.5 times the upper limit of normal (ULN)
oalkaline phosphatase (ALP) or total bilirubin >2 times the ULN,
oserum creatinine >1.5 times the ULN
o any other results outside of laboratory reference ranges judged as clinically significant by the Investigator
opositive hepatitis B surface antigen (HbSAg, indicating ongoing hepatitis B infection), or
positive human immunodeficiency virus antibody (HIV-Ab), , or positive hepatitis C antibodies (HCV) test result.
12.Subject with a known allergy or hypersensitivity to any component of ADE513, or to a VMAT2 inhibitor e.g. tetrabenazine, deutetrabenazine, valbenazine.
13.Subject who has received any investigational drug product within 30 days (or 5 drug half-lives, if longer than 30 days) of Screening.
14.Subject acknowledging present alcohol or substance abuse at Screening, or subject with a history thereof within 12 months of Screening, or subject expected to be unable to refrain from substance abuse during the study.
15.Subject with a positive urine drug screen at Screening.
16.Pregnant or breastfeeding subject.
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| E.5 End points |
| E.5.1 | Primary end point(s) | | Change in AIMS score (items 1 through 7) from Baseline (Day 0) to Week 12, as assessed by central rating. | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | |
| E.5.2 | Secondary end point(s) | -Dose level associated with adequate control of dyskinesia (defined as dose level used in Maintenance period).
-Proportion of subjects with the value of Much or Very Much Improved on the Clinical Global Impression of Change (CGIC) at Week 12.
-Proportion of subjects with the value of Much or Very Much Improved on the Patient Global Impression of Change (PGIC) at Week 12.
| |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | |
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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 | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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 | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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 | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
