(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":"- Male and female subjects aged 18-75 years, inclusive at the time of enrollment to parent study"}
• {"criterion_text":"- Subject able to complete subject-facing rating scales."}
• {"criterion_text":"- Subject having a caregiver who is in regular personal contact with the subject (no less than 5 days a week) if locally required"}
• {"criterion_text":"- Female subject of childbearing potential who agrees to use highly effective form of contraception (as defined by the Protocol) throughout the study."}
• {"criterion_text":"- Subject who has completed treatment within an open-label parent study or part thereof, or treatment within a double-blind, placebo controlled parent study or part thereof followed by at least 1-week washout."}
• {"criterion_text":"- Subject with a clinical diagnosis of TD."}
• {"criterion_text":"- For subjects with underlying psychiatric disorders: o\tSubject in a stable psychiatric status with no change in psychoactive medications (e.g. neuroleptics, benzodiazepines, anticonvulsants, mood stabilizers, etc.) within the last 30 days before Baseline"}
• {"criterion_text":"- Subject with not anticipated changes to the subject’s treatment regimen."}
• {"criterion_text":"- Subject compliant with prescribed treatment regimen as judged by the Investigator."}
• {"criterion_text":"- Subject with a body weight of not less than 45 kg and 55 kg for females and males respectively."}
• {"criterion_text":"- Subject living in a stable environment as judged by the Investigator, with adequate supervision when necessary to comply with all study procedures, attend all study visits, and safely participate in the trial."}
• {"criterion_text":"- Subject able to read, comprehend and provide the written informed consent."}

Exclusion criteria

• {"criterion_text":"- Subject who has an allergy, hypersensitivity, or intolerance to any component of ADE513, or to a VMAT2 inhibitor e.g. tetrabenazine, deutetrabenazine, valbenazine."}
• {"criterion_text":"- Subject who received any of the following medications within 30 days of Baseline: •\tReserpine, α-methyl-p-tyrosine (AMPT) •\tBotulinum toxin within 3 months of Baseline •\tTrihexyphenidyl, orphenadrine, procyclidine, biperiden, or other strong anticholinergics •\tMetoclopramide, promethazine, and prochlorperazine •\tMethylphenidate, amphetamine/dextroamphetamine, or other stimulants •\tMonoamine oxidase inhibitors (MAOIs) •\tLevodopa or dopamine agonists •\tBotulinum toxin (within 3 months of Baseline)"}
• {"criterion_text":"- Subject with a neurological condition other than TD that may interfere with the assessment of dyskinesia severity."}
• {"criterion_text":"- Subject with presence of parkinsonism, pheochromocytoma and prolactin dependent tumours, e.g. pituitary or breast cancer."}
• {"criterion_text":"- Subject with an active clinically significant unstable psychiatry disorder that is untreated or undertreated at Baseline."}
• {"criterion_text":"- Subject with active suicidal ideation at Baseline."}
• {"criterion_text":"- Subject who has a history of any of the following within the last 6 months before Baseline: •\tHistory of previous intent to act on suicidal ideation with a specific plan (positive answer to question 5 on C-SSRS), regardless of level of ambivalence at the time of suicide. •\tPrevious preparatory acts to commit suicide or suicidal behavior. •\tPrevious actual, interrupted, or aborted suicide attempt."}
• {"criterion_text":"- Subject with an abnormal (≥11) score on the depression subscale of the Hospital Anxiety and Depression Scale (HADS) at Baseline."}
• {"criterion_text":"- Subject who is developmentally disabled or has evidence of dementia confirmed by Mini-Mental State Exam (MMSE) value ≤24."}
• {"criterion_text":"- Subject with any of the following abnormal values in laboratory test results at Baseline: •\tAspartate transaminase (AST) or alanine aminotransferase (ALT) > 2.5 times the upper limit of normal (ULN) •\tAlkaline phosphatase (ALP) or total bilirubin >2 times the ULN •\tSerum creatinine >1.5 times the ULN. •\tAny other results outside of laboratory reference ranges judged as clinically significant by the Investigator."}
• {"criterion_text":"- Subject who has participated in an investigational trial other than the parent study within 30 days of Baseline."}
• {"criterion_text":"- Subject who acknowledges present use of illicit drugs at Baseline."}
• {"criterion_text":"- Subject who has a history of alcohol or substance abuse within 12 months before Screening, or subject expected to be unable to refrain from substance abuse during the study."}
• {"criterion_text":"- Subject who is pregnant or breastfeeding at Baseline."}
• {"criterion_text":"- Subject with a history of violent behavior in the past 3 months before Baseline."}
• {"criterion_text":"- Subject with a clinically significant cardiac abnormality or QTcF >450 ms (males) or >470 ms (females), on 12-lead ECG at Baseline."}

Primary endpoints

• {"endpoint_text":"- Change in Abnormal Involuntary Movement Scale (AIMS) score (items 1 through 7) from Baseline of this study to the end of long-term therapy (Week 54), as assessed by the blinded central video rating.","definition_or_measurement_approach":"Change in AIMS score (items 1-7) from Baseline to Week 54; assessed by the blinded central video rating."}

Secondary endpoints

• {"endpoint_text":"- Incidence of AEs, SAEs, drug-related AEs, severe AEs, AEs leading to discontinuation during the following periods: \t1.\tOverall 2.\tTitration period 3.\tLong-term treatment","definition_or_measurement_approach":"Incidence counts of AEs/SAEs/drug-related AEs/severe AEs/AEs leading to discontinuation during overall, titration, and long-term treatment periods."}
• {"endpoint_text":"- Observed values and changes in clinical laboratory parameters (haematology, chemistry including prolactin, and urinalysis)","definition_or_measurement_approach":"Observed values and change from baseline in haematology, clinical chemistry (including prolactin), and urinalysis parameters."}
• {"endpoint_text":"- Observed values and changes in vital signs","definition_or_measurement_approach":"Observed values and change from baseline in vital signs."}
• {"endpoint_text":"- Observed values and changes in ECG parameters and abnormal findings","definition_or_measurement_approach":"Observed values and change from baseline in ECG parameters; record of abnormal ECG findings."}
• {"endpoint_text":"- Observed values and changes in HADS and, C-SSRS.","definition_or_measurement_approach":"Observed values and change from baseline in Hospital Anxiety and Depression Scale (HADS) and Columbia-Suicide Severity Rating Scale (C-SSRS)."}
• {"endpoint_text":"- The proportion of subjects who have a treatment success at the end of long-term therapy (Week 54) based on a Clinical Global Impression of Change (CGIC). A treatment success is defined as Much or Very Much Improved on the CGIC at the end of long-term therapy (Week 54).","definition_or_measurement_approach":"Proportion achieving 'Much' or 'Very Much Improved' on CGIC at Week 54 (treatment success defined as such)."}
• {"endpoint_text":"- The proportion of subjects who have ≥3-point reduction in AIMS score from Baseline of this study to the end of long-term therapy (Week 54).","definition_or_measurement_approach":"Proportion of subjects with ≥3-point reduction in AIMS score from Baseline to Week 54."}
• {"endpoint_text":"- The percent change in AIMS score from Baseline of this study to the end of long-term therapy (Week 54).","definition_or_measurement_approach":"Percent change in AIMS score from Baseline to Week 54."}
• {"endpoint_text":"- The proportion of subjects who have a treatment success at the end of long-term therapy (Week 54) based on a Patient Global Impression of Change (PGIC). A treatment success is defined as Much or Very Much Improved on the PGIC at the end of long-term therapy (Week 54).","definition_or_measurement_approach":"Proportion achieving 'Much' or 'Very Much Improved' on PGIC at Week 54 (treatment success defined as such)."}

Czechia

Earliest CTIS Part Ii Submission Date

08-12-2023

Latest Decision Or Authorization Date

17-04-2026

Processing Time Days

861

Number Of Sites

3

Number Of Participants

40

Poland

Earliest CTIS Part Ii Submission Date

28-03-2025

Latest Decision Or Authorization Date

27-04-2025

Processing Time Days

30

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

codes: 10,6,7

Name

Tepsivo Oy

Responsibilities

codes: 8

Name

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

Responsibilities

codes: 1,11,12,2,5,9

Third parties

• {"country":"Czechia","full_name":"Anova CRO s.r.o.","duties_or_roles":"codes: 10,6,7","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Tepsivo Oy","duties_or_roles":"codes: 8","organisation_type":"Pharmaceutical company"}
• {"country":"Czechia","full_name":"P H A R M N E T s.r.o.","duties_or_roles":"codes: 1,11,12,2,5,9","organisation_type":"Pharmaceutical company"}