Evaluate the Efficacy, Safety and Tolerability of (+)-α-dihydrotetrabenazine for Treatment of 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

23 Aug 2023 → ongoing

Decision date (initial)

2025-01-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Adeptio Pharmaceuticals Limited

External identifiers

EU CT number

2024-519105-35-00

EudraCT number

2022-000271-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Safety, Therapy

The objectives of this study are to evaluate the efficacy, safety, and tolerability of different ascending doses (10 to 20 mg) of (+)-αDHTBZ administered once daily (od) and 25 mg administered twice daily (bid) for the treatment of tardive dyskinesia in subjects with schizophrenia, schizoaffective disorder, mood disorder, gastrointestinal disorder or neuroleptic-induced TD.

Conditions and MedDRA coding

tardive dyskinesia

Regulatory references

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Male or female aged 18 to 85 years (inclusive).
2. Dated and signed informed consent.
3. Meet clinical diagnoses of schizophrenia, schizoaffective disorder, mood disorder, gastrointestinal disorder (e.g., gastroparesis, gastroesophageal reflux disease), and have a clinical diagnosis of neuroleptic-induced TD as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) for at least 3 months prior to screening with TD assessed as moderate or severe by AIMS Item 8 (≥3)
4. Maintenance medication(s) for schizophrenia or schizoaffective disorder, mood disorders, or gastrointestinal disorders (except metoclopramide) must be at a stable dose for ≥30 days before screening.
5. Subjects who are not using an antipsychotic medication must have a stable psychiatric status as clinically determined by the investigator. Subjects with a diagnosis of bipolar disorder must be on stable dose of mood stabilizer(s) (e.g., lithium, valproate, olanzapine) for a minimum of 30 days before screening.
6. Have the doses of concurrent medications and the conditions being treated be stable for a minimum of 30 days before study start and be expected to remain stable during the study.
7. Subjects of childbearing potential must agree to use a highly effective contraception method during the study.
8. Be in good general health and expected to complete the clinical study as designed.
9. Have a body mass index (BMI) of 18 to 38 kg/m2.
10. Have adequate hearing, vision, and language skills to perform the procedures specified in the protocol.
11. Have a negative urine drug screen at screening and study start (negative for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids), except for any subject receiving a stable dose of benzodiazepine or opiates. Subjects with positive cannabinoid results may be allowed to participate in the study provided that the subject is given thorough counselling and agrees to refrain from using cannabinoids for the duration of his/her study participation. Subjects must also have a negative alcohol breath test at screening and study start.

Exclusion criteria 14

1. Have an active, clinically significant unstable medical condition within 1 month (30 days) prior to screening.
2. Have a history of substance dependence or substance (drug) or alcohol abuse within the 3 months before study start (nicotine and caffeine dependence are not exclusionary).
3. Have a significant risk of suicidal or violent behavior. Subjects with any suicidal behavior or suicidal ideation of type 4 (active suicidal ideation with some intent to act, without specific plan) or type 5 (active suicidal ideation with specific plan and intent), based on the C-SSRS in the 3 months prior to screening, will be excluded.
4. Have a known history of neuroleptic malignant syndrome.
5. Have a known history of long QT syndrome or cardiac tachyarrhythmia
6. Have a screening or Day -1 average triplicate ECG QT interval corrected for heart rate using QTcF of >450 ms (males) or >470 ms (females) or the presence of any clinically significant cardiac abnormality.
7. Subjects with clinical diagnoses of schizophrenia or schizoaffective disorder must not have a CDSS total score ≥10 at screening or Day -1 or PANSS total score ≥70 at Day -1.
8. Female pregnant women.
9. Receiving any excluded concomitant medication such as reserpine, metoclopramide, carbamazepine, stimulants, or tetrabenazine, or any other specified in the protocol.
10. Receiving medication for the treatment of tardive dyskinesia.
11. Have a positive human immunodeficiency virus antibody, (HIV-Ab), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody result at screening or have a history of positive result.
12. Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than (+)-α-DHTBZ) during the study
13. Have an allergy, hypersensitivity, or intolerance to tetrabenazine.
14. Have had previous exposure with (+)-α-DHTBZ

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. AIMS Dyskinesia Total Score at week 8 compared to baseline. Severity of TD symptoms assessed by AIMS dyskinesia total score, as assessed by investigators. The AIMS Total Dyskinesia Score rates a total of 7 items, rating involuntary movement from 0 to 4. Items 1 through 7 include facial and oral movements, extremity movements, and trunk movements. The total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity.
2. An exploratory central blinded AIMS video rating will also be performed in 50% of patients per site at baseline and week 8, on basis of voluntary agreement, to assess the degree of concordance of measurements and feasibility for future clinical development
3. Safety: Number of Participants with Adverse Events following dosing with (+)-α-DHTBZ. Outcome assessment includes monitoring of: o Nature and frequency of clinical adverse events o Clinical laboratory tests o Vital signs o Physical examinations o 12-lead ECG o Changes from baseline in tests of psychiatric symptoms and cognitive function

Secondary endpoints 7

1. AIMS Dyskinesia Total Score at weeks specified in the SoA compared to baseline
2. Clinical Global Impression of Tardive Dyskinesia (CGI-TD) at weeks specified in the SoA compared to baseline. Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse).
3. Calgary Depression Scale for Schizophrenia (CDSS) at weeks specified in the SoA compared to baseline. The Calgary Depression Scale for Schizophrenia (CDSS) is a nine-item structured interview scale that was designed in 1990 specifically to assess depression independently of symptoms of psychosis in schizophrenia.
4. C-SSRS at weeks specified in the SoA compared to baseline. It rates an individual's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent and behaviors." The scale identifies specific behaviors which may be indicative of an individual's intent to complete suicide. An individual exhibiting even a single behavior identified by the scale was 8 to 10 times more likely to complete suicide
5. Positive and Negative Syndrome Scale (PANSS) at weeks specified in the SoA compared to baseline. It is a scale used for measuring symptom severity of patients with schizophrenia
6. The University of California, San Diego Brief Assessment of Capacity to Consent (UBACC) at weeks specified in the SoA compared to baseline. A test for assessing decisional capacity for clinical research
7. Pharmacokinetics. Plasma samples will be collected at the end of weeks 2, 4, 6, 8 and 2 weeks after the last dose of the study drug (or early termination) for determination of plasma concentrations of (+)- α-DHTBZ, to assess treatment compliance

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

Andrew Duffield

Third parties 3

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Documents 6 files

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

Application history

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