(2R,3R,11BR)-1,3,4,6,7,11B-HEXAHYDRO-9,10-DIMETHOXY-3-(2-METHYLPROPYL)-2H-BENZO[A]QUINOLIZIN-2-OL for Tardive dyskinesia

Inclusion criteria

• {"criterion_text":"- Subject aged between 18 and 75 years, inclusive.\n- Subject in good general health with expectation to attend all study visits and complete all study assessments as judged by the Investigator.\n- Subject able to read, comprehend and provide the written informed consent.\n- Subject able to complete subject-facing rating scales.\n- Female subject of childbearing potential who agrees to use a highly effective form of contraception (as defined by the Protocol) throughout the Study.\n- Subject with a clinical diagnosis of tardive dyskinesia.\n- Subject with symptoms of TD which are bothersome and/or cause functional impairment.\n- 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).\n- Subject with body weight of not less than 45kg for females and 55kg for males.\n- 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.\n- Subject living in a stable environment as judged by the Investigator, with adequate supervision when necessary.\n- Subject having a caregiver who is in regular personal contact with the subject (no less than 5 days a week); if locally required.\n- Subject compliant with prescribed treatment regimen as judged by the Investigator."}

Exclusion criteria

• {"criterion_text":"- Subject who received any of the following medications within 30 days of Screening or Baseline: o\tTetrabenazine, deutetrabenazine, valbenazine, reserpine, α-methyl-p-tyrosine (AMPT), o\tTrihexyphenidyl, orphenadrine, procyclidine, biperiden or other strong anticholinergics o\tMetoclopramide, promethazine, and prochlorperazine o\tMethylphenidate, amphetamine/dextroamphetamine, or other stimulants, o\tMonoamine oxidase inhibitors (MAOIs) o\tLevodopa or dopamine agonists o\tBotulinum 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.\n- Subject with clinically significant cardiac abnormality or QTcF >450 ms (males) or >470 ms (females) on 12-lead ECG at Screening.\n- Subject with any of the following abnormal values in laboratory test results at Screening: o\taspartate transaminase (AST) or alanine aminotransferase (ALT) >2.5 times the upper limit of normal (ULN) o\talkaline phosphatase (ALP) or total bilirubin >2 times the ULN, o\tserum creatinine >1.5 times the ULN o\t any other results outside of laboratory reference ranges judged as clinically significant by the Investigator o\tpositive 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.\n- Subject with a known allergy or hypersensitivity to any component of ADE513, or to a VMAT2 inhibitor e.g. tetrabenazine, deutetrabenazine, valbenazine.\n- Subject who has received any investigational drug product within 30 days (or 5 drug half-lives, if longer than 30 days) of Screening.\n- 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.\n- Subject with a positive urine drug screen at Screening.\n- Pregnant or breastfeeding subject.\n- Applicable only to investigator sites in Slovakia: Subject with presence of parkinsonism, pheochromocytoma and prolactin dependent tumours, e.g. pituitary or breast cancer.\n- Subject with a neurological condition that may interfere with the assessment of dyskinesia severity.\n- Subject with a serious psychiatric condition that is untreated or undertreated at Screening and/or Baseline.\n- Subject with active suicidal ideation at Screening or Baseline.\n- 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.\n- 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.\n- Subject with an unstable or serious medical condition at Screening or Baseline.\n- Subject with developmental disability or evidence of dementia confirmed by Mini-Mental State Exam (MMSE score ≤24).\n- Subject showing violent behaviour, or subject with a history thereof within 3 months of start of study participation."}

Primary endpoints

• {"endpoint_text":"- Change in AIMS score (items 1 through 7) from Baseline (Day 0) to Week 12, as assessed by central rating.","definition_or_measurement_approach":"Change in AIMS score (items 1 through 7) from Baseline (Day 0) to Week 12 assessed by central rating."}

Secondary endpoints

• {"endpoint_text":"- Part I Secondary Endpoints: - Change in AIMS score (items 1 through 7) from Baseline (Day 0) to Week 12) in Part I, as assessed by the on-site Investigator. - Change in AIMS score (items 1 through 7 from Baseline (Day 0) to Week 9 in Part I, as assessed by the on-site Investigator. - Change in AIMS score (items 1 through 7) from Week 6 to Week 12 in Part I, as assessed by the on-site Investigator.","definition_or_measurement_approach":"Change in AIMS score (items 1 through 7) over specified timepoints in Part I assessed by the on-site Investigator (Baseline to Week 12, Baseline to Week 9, Week 6 to Week 12)."}
• {"endpoint_text":"- Part II Secondary Endpoints: - Dose level associated with adequate control of dyskinesia (defined as dose level used in Maintenance period) in Part II. - Proportion of subjects with the value of Much or Very Much Improved on the Clinical Global Impression of Change (CGIC) at Week 12 in Part II. - Proportion of subjects with the value of Much or Very Much Improved on the Patient Global Impression of Change (PGIC) at Week 12 in Part II.","definition_or_measurement_approach":"Part II assessments include maintenance dose level associated with control of dyskinesia and proportions of subjects rated Much or Very Much Improved on CGIC and PGIC at Week 12."}

Hungary

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

25-09-2024

Processing Time Days

20

Number Of Sites

2

Number Of Participants

15

Czechia

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

26-09-2024

Processing Time Days

21

Number Of Sites

4

Number Of Participants

42

Slovakia

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

30-09-2024

Processing Time Days

25

Number Of Sites

1

Number Of Participants

15

Poland

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

13-10-2024

Processing Time Days

38

Number Of Sites

1

Number Of Participants

30

Primary sponsor

Full Name

Adeptio Pharmaceuticals Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Anova CRO s.r.o.

Responsibilities

IVRS – treatment randomisation; other duties (codes: 10, 15, 6, 7)

Name

P H A R M N E T s.r.o.

Responsibilities

Sponsor-related duties (codes: 1, 11, 12, 2, 9); public contact for sponsor

Third parties

• {"country":"Finland","full_name":"Tepsivo Oy","duties_or_roles":"Pharmacovigilance","organisation_type":"Pharmaceutical company"}
• {"country":"Czechia","full_name":"P H A R M N E T s.r.o.","duties_or_roles":"sponsorDuties codes: 1, 11, 12, 2, 9","organisation_type":"Pharmaceutical company"}
• {"country":"Czechia","full_name":"Anova CRO s.r.o.","duties_or_roles":"IVRS – treatment randomisation; sponsorDuties codes: 10, 15, 6, 7","organisation_type":"Pharmaceutical company"}