An Open label, Safety Clinical trial of (+)-α-dihydrotetrabenazine in patients with moderate to severe tardive dyskinesia

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

16 Apr 2024 → ongoing

Decision date (initial)

2024-04-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Adeptio Pharmaceuticals Limited

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

To evaluate the safety and tolerability of long-term maintenance therapy with ADE513 (+)-α-DHTBZ.

Secondary objectives 1

1. To evaluate the long-term effects of ADE513 (+)-α-DHTBZ in patients with moderate to severe TD.

Conditions and MedDRA coding

Tardive dyskinesia

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Male and female subjects aged 18-75 years, inclusive at the time of enrollment to parent study
2. 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.
3. Subject with a clinical diagnosis of TD.
4. For subjects with underlying psychiatric disorders: o Subject 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
5. Subject with not anticipated changes to the subject’s treatment regimen.
6. Subject compliant with prescribed treatment regimen as judged by the Investigator.
7. Subject with a body weight of not less than 45 kg and 55 kg for females and males respectively.
8. 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.
9. Subject able to read, comprehend and provide the written informed consent.
10. Subject able to complete subject-facing rating scales.
11. Subject having a caregiver who is in regular personal contact with the subject (no less than 5 days a week) if locally required
12. Female subject of childbearing potential who agrees to use highly effective form of contraception (as defined by the Protocol) throughout the study.

Exclusion criteria 17

1. Subject who has an allergy, hypersensitivity, or intolerance to any component of ADE513, or to a VMAT2 inhibitor e.g. tetrabenazine, deutetrabenazine, valbenazine.
2. Subject who received any of the following medications within 30 days of Baseline: • Reserpine, α-methyl-p-tyrosine (AMPT) • Botulinum toxin within 3 months of Baseline • Trihexyphenidyl, orphenadrine, procyclidine, biperiden, or other strong anticholinergics • Metoclopramide, promethazine, and prochlorperazine • Methylphenidate, amphetamine/dextroamphetamine, or other stimulants • Monoamine oxidase inhibitors (MAOIs) • Levodopa or dopamine agonists • Botulinum toxin (within 3 months of Baseline)
3. Subject with a neurological condition other than TD that may interfere with the assessment of dyskinesia severity.
4. Subject with presence of parkinsonism, pheochromocytoma and prolactin dependent tumours, e.g. pituitary or breast cancer.
5. Subject with an active clinically significant unstable psychiatry disorder that is untreated or undertreated at Baseline.
6. Subject with active suicidal ideation at Baseline.
7. Subject who has a history of any of the following within the last 6 months before Baseline: • History 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. • Previous preparatory acts to commit suicide or suicidal behavior. • Previous actual, interrupted, or aborted suicide attempt.
8. Subject with an abnormal (≥11) score on the depression subscale of the Hospital Anxiety and Depression Scale (HADS) at Baseline.
9. Subject who is developmentally disabled or has evidence of dementia confirmed by Mini-Mental State Exam (MMSE) value ≤24.
10. Subject with an unstable or serious medical condition at Baseline.
11. Subject with a history of violent behavior in the past 3 months before Baseline.
12. Subject with a clinically significant cardiac abnormality or QTcF >450 ms (males) or >470 ms (females), on 12-lead ECG at Baseline.
13. Subject with any of the following abnormal values in laboratory test results at Baseline: • Aspartate transaminase (AST) or alanine aminotransferase (ALT) > 2.5 times the upper limit of normal (ULN) • Alkaline phosphatase (ALP) or total bilirubin >2 times the ULN • Serum creatinine >1.5 times the ULN. • Any other results outside of laboratory reference ranges judged as clinically significant by the Investigator.
14. Subject who has participated in an investigational trial other than the parent study within 30 days of Baseline.
15. Subject who acknowledges present use of illicit drugs at Baseline.
16. 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.
17. Subject who is pregnant or breastfeeding at Baseline.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 9

1. Incidence of AEs, SAEs, drug-related AEs, severe AEs, AEs leading to discontinuation during the following periods: 1. Overall 2. Titration period 3. Long-term treatment
2. Observed values and changes in clinical laboratory parameters (haematology, chemistry including prolactin, and urinalysis)
3. Observed values and changes in vital signs
4. Observed values and changes in ECG parameters and abnormal findings
5. Observed values and changes in HADS and, C-SSRS.
6. 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).
7. 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).
8. The percent change in AIMS score from Baseline of this study to the end of long-term therapy (Week 54).
9. 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).

Investigational products

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

Test 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

2 EU/EEA countries · 4 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 19 files

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

Application history

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