A Phase 2 Trial Evaluating SNC-102 in Drug-Induced Tardive Dyskinesia

Study Overview
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Brief Summary
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This Phase 2 study was designed to evaluate the efficacy and safety of SNC-102 in subjects with drug-induced Tardive Dyskinesia (TD). To ensure an adequate evaluation of SNC-102, a randomized, double-blind, parallel-group, placebo-controlled trial was designed. Two dosing levels of SNC-102 are employed to evaluate the proposed dosing range. A target enrollment of 90 subjects with drug-induced TD will provide sufficient data to assess the efficacy and safety profiles of SNC-102 in the target population.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Efficacy, Safety, and Pharmacokinetic Behavior of Orally Administered SNC-102 in Subjects With Drug-Induced Tardive Dyskinesia

Conditions
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Drug-induced Tardive Dyskinesia

Intervention / Treatment
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* Drug: SNC-102
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females 18-75 years of age. Diagnosis, at least 3 months prior to the Screening Visit, of drug-induced TD AIMS ≥3 (moderate or worse) for ≥1 body area, or AIMS = 2 (mild) for ≥2 body areas; and >3 months exposure to antipsychotic drug or metoclopramide; and Other causes of dyskinesia have been ruled out. AIMS score is confirmed at the Screening Visit by the Principal Investigator and the Trial Reading Center, and at the Baseline Visit at least 1 week later by the Principal Investigator. If using antipsychotic medication or metoclopramide, dose has been stable for at least 60 days prior to the Baseline Visit and is expected to remain stable through the course of the trial. If using opioid medication, dose has been stable for at least 14 days prior to the Baseline Visit and is expected to remain stable through the course of the trial. If using vitamin or dietary supplements, dose and type has been stable for at least 14 days prior to the Baseline Visit and is expected to remain stable through the course of the trial. If using alcohol, willingness to limit intake to no more than 2 drinks/day through the course of participation in the trial, and to abstain for at least 12 hours prior to any assessment visit. Exclusion Criteria: Unstable psychiatric status, as indicated by any change in psychotropic medication (unless approved by the Sponsor), or by hospitalization, within 60 days prior to the Screening Visit. Active drug or alcohol dependence or abuse. Current use of cocaine, amphetamine, phencyclidine (PCP), or ketamine, documented either by history or by urinary drug screening at Screening and Baseline Visits. Drugs used to treat attention deficit-hyperactivity disorder are allowed if stable for at least 14 days prior to the Baseline Visit and are expected to remain stable through the course of the trial. Risk of significant medication non-adherence, based on the judgment of the Principal Investigator. Neurologic or psychiatric disorder that could interfere with the attribution of observed involuntary movements to TD, such as a primary movement disorder unrelated to medication. History of neuroleptic malignant syndrome. Significant risk, in the judgment of the Principal Investigator, of suicidal or violent behavior. Receipt of new medication for the treatment of TD within 4 weeks prior to the Baseline Visit or anticipated while participating in the trial. Initiation of oral contraceptive medication, or change in dose, within 30 days prior to the Screening Visit, or anticipated while participating in the trial. Gastrointestinal disease such as short-bowel or other malabsorption syndrome which, in the judgment of the Principal Investigator, could interfere with absorption of orally-administered medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SNC-102, low dose<br>SNC-102 (Acamprosate calcium) tablet 4 week duration dosing | Drug: SNC-102<br>* Acamprosate calcium (SNC-102) tablet, administered orally for 4 weeks<br>* Other names: calcium N-acetylhomotaurinate;|
| Experimental: SNC-102, high dose<br>SNC-102 (Acamprosate calcium) tablet 4 week duration dosing | Drug: SNC-102<br>* Acamprosate calcium (SNC-102) tablet, administered orally for 4 weeks<br>* Other names: calcium N-acetylhomotaurinate;|
| Placebo Comparator: Placebo<br>Placebo tablet 4 week duration dosing | Drug: Placebo<br>* Placebo tablet, administered orally for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy as measured by changes from baseline in summary scores on the Abnormal Involuntary Movement Scale (AIMS) | Determine the efficacy relative to placebo of SNC-102 in subjects with drug-induced tardive dyskinesia (TD), as assessed by changes from baseline to four weeks in summary scores on the Abnormal Involuntary Movement Scale (AIMS) | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the effectiveness of low dose and high dose of SNC-102 | Compare the effectiveness of low dose and high dose, as assessed by changes from baseline to four weeks in summary scores on the Abnormal Involuntary Movement Scale (AIMS) | 4 weeks | 
| Assess safety and tolerability of SNC-102 in the tardive dyskinesia population | Nature and frequency of adverse events; changes from baseline in tests of psychiatric symptoms and cognitive function. | 4 weeks | 
| Assess the pharmacokinetic (PK) profile in TD subjects | Measure and analyze the serum concentration of acamprosate. | 4 weeks | 
| Determine the relationship between the PK profile and clinical effects of SNC-102 | Describe the correlation between change in AIMS score and serum levels of acamprosate. | 4 weeks |