Clinical trial of (+)-α-dihydrotetrabenazine in patients with moderate to severe tardive dyskinesia with open-label Part I and randomized, double-blind, placebo-controlled Part II.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Adeptio Pharmaceuticals Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

13 Nov 2023 → ongoing

Decision date (initial)

2024-09-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Adeptio Pharmaceuticals Limited

External identifiers

EU CT number

2024-516852-17-00

EudraCT number

2022-001685-35

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate efficacy of ADE513 in reducing abnormal involuntary movements of tardive dyskinesia.

Secondary objectives 1

1. To evaluate safety and tolerability of ADE513 in titration and maintenance therapy in subjects with tardive dyskinesia in both Parts, and to confirm pharmacokinetic parameters in target population in Part I.

Conditions and MedDRA coding

Tardive dyskinesia

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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.

Exclusion criteria 17

1. Subject who received any of the following medications within 30 days of Screening or Baseline: o Tetrabenazine, deutetrabenazine, valbenazine, reserpine, α-methyl-p-tyrosine (AMPT), o Trihexyphenidyl, orphenadrine, procyclidine, biperiden or other strong anticholinergics o Metoclopramide, promethazine, and prochlorperazine o Methylphenidate, amphetamine/dextroamphetamine, or other stimulants, o Monoamine oxidase inhibitors (MAOIs) o Levodopa or dopamine agonists o Botulinum 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: o aspartate transaminase (AST) or alanine aminotransferase (ALT) >2.5 times the upper limit of normal (ULN) o alkaline phosphatase (ALP) or total bilirubin >2 times the ULN, o serum creatinine >1.5 times the ULN o any other results outside of laboratory reference ranges judged as clinically significant by the Investigator o positive 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.
17. Applicable only to investigator sites in Slovakia: Subject with presence of parkinsonism, pheochromocytoma and prolactin dependent tumours, e.g. pituitary or breast cancer.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in AIMS score (items 1 through 7) from Baseline (Day 0) to Week 12, as assessed by central rating.

Secondary endpoints 2

1. 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.
2. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Adeptio Pharmaceuticals Limited

Sponsor organisation

Adeptio Pharmaceuticals Limited

Address

Suite1 7th Floor, 50 Broadway 50 Broadway

City

London

Postcode

SW1H 0BL

Country

United Kingdom

Scientific contact point

Organisation

Adeptio Pharmaceuticals Limited

Contact name

Andrew Duffield

Public contact point

Organisation

Adeptio Pharmaceuticals Limited

Contact name

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

Third parties 3

Locations

4 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications