A Study to Evaluate the Effects of ABX-1431 on Patients With Tourette Syndrome

A Randomized, Placebo-Controlled, Single-Dose Crossover Study of ABX-1431 HCl in Adult Patients With Tourette Syndrome (TS) and Chronic Motor Tic Disorder

The study will investigate the effects and the safety of a single-dose of ABX-1431 HCl on tics and other symptoms of Tourette Syndrome.

During part 1 (periods 1 and 2) each patient will receive study drug once and placebo once.

Patients who complete part 1 with adequate clinical safety will be offered the option to participate in part 2 (periods 3 and 4) and again willl receive study drug once and placebo once where, in contrast to part 1, administration will take place with a standard high fat meal.

Study Overview

• Status: Completed
• Conditions: Tourette Syndrome; Chronic Motor Tic Disorder
• Intervention / Treatment: Drug: ABX-1431; Drug: Placebo Comparator; Drug: ABX-1431

Detailed Description

This is a single dose, double-blind, randomized, placebo-controlled, cross-over study. This study will assess the single dose effects of ABX-1431 HCl on tics and other symptoms of Tourette Syndrome.

All patients will undergo a screening visit for enrollment criteria. Eligible patients will be treated with a single dose of ABX-1431 HCl or placebo followed by efficacy, safety and pharmacokinetics assessments. After a washout period of 1-3 weeks, patients will undergo identical procedures with the other treatment.

Only patients who complete the first part of the study with adequate clinical safety will be offered the option to participate in an additional two period crossover, where ABX-1431 HCl or placebo is taken with a standard high fat meal. Again, efficacy, safety and pharmacokinetics assessments will be done. After a washout period of 1-3 weeks, patients will undergo identical procedures with the other treatment.

This study will enroll 20 patients with a diagnosis of Tourette Syndrome OR chronic motor tic disorder.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Principal Inclusion Criteria:

• Patient is a male or female between the age of 18 and 65 years of age at the Screening Visit.
• Patient has a diagnosis of Tourette Syndrome OR chronic motor tic disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.
• Patient's Yale Global Tic Severity Scale (YGTSS) total tic sub-scale (TTS) results must be ≥ 18 (Range 0-50) at the Screening Visit.
• Patients taking daily medications for symptoms of Tourette Syndrome [e.g. neuroleptics (e.g. aripiprazole, risperidone) or selective serotonin reuptake inhibitors (e.g. fluoxetine)] must be on a stable dose of medication for at least 30 days before the Screening Visit and must be expected to remain on a stable dose during this study.

Principal Exclusion Criteria:

• Patient is taking potent cytochrome P450 3A4/5 inducers [e.g. carbamazepine, oxcarbazine, rifampin, St. John's Wort (Hypericum perforatum), or phenytoin]. Patient is taking strong P450 3A4/5 inhibitors including atazanavir, bocepravir, clarithromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, or voriconazole.
• Patients with a diagnosis of any psychiatric comorbidity (obsessive compulsive disorder, attention deficit hyperactivity disorder) OR generalized anxiety disorder, depression or post-traumatic stress disorder that is unstable or requires alteration in therapy are excluded. Patients with a past history of psychosis or schizophrenia at any time are excluded. Patients with stable OCD or ADHD requiring no alteration in therapy may be enrolled.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crossover Sequence A; Each in the fasting state: Period 1: Single-dose matching placebo Period 2: Single-dose ABX-1431	Drug: ABX-1431; ABX-1431, capsules, 40 mg in the fasting state; Drug: Placebo Comparator; Matching Placebo; Drug: ABX-1431; ABX-1431, capsules, 20 mg with a high fat meal
Experimental: Crossover Sequence B; Each in the fasting state: Period 1: Single-dose ABX-1431 Period 2: Single-dose matching placebo	Drug: ABX-1431; ABX-1431, capsules, 40 mg in the fasting state; Drug: Placebo Comparator; Matching Placebo; Drug: ABX-1431; ABX-1431, capsules, 20 mg with a high fat meal
Experimental: Crossover Sequence C; Each with a standard high fat meal: Period 3: Single-dose matching placebo Period 4: Single-dose ABX-1431	Drug: ABX-1431; ABX-1431, capsules, 40 mg in the fasting state; Drug: Placebo Comparator; Matching Placebo; Drug: ABX-1431; ABX-1431, capsules, 20 mg with a high fat meal
Experimental: Crossover Sequence D; Each with a standard high fat meal: Period 3: Single-dose ABX-1431 Period 4: Single-dose matching placebo	Drug: ABX-1431; ABX-1431, capsules, 40 mg in the fasting state; Drug: Placebo Comparator; Matching Placebo; Drug: ABX-1431; ABX-1431, capsules, 20 mg with a high fat meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change of rating in Modified Rush Video Scale (MRVS) over time	pre-dose, post-dose (4 hours, 8 hours)
Change in rating of Yale Global Tic Severity Scale (YGTSS) over time	pre-dose, post-dose (4 hours, 8 hours)
Change of rating in Adult Tic Questionnaire (ATQ) over time	pre-dose, post-dose (4 hours, 8 hours, 12 hours)
Change of rating in Premonitory Urge for Tics Scale (PUTS) over time	pre-dose, post-dose (4 hours, 8 hours, 12 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ABX-1431 and metabolite (M55) plasma pharmacokinetics		pre-dose, post-dose (2 hours, 4 hours, 8 hours, 24 hours)
2-AG hydrolysis in PBMC		pre-dose, post-dose (2 hours, 4 hours, 8 hours, 24 hours)
Number and severity of adverse events (AEs), serious adverse events (SAEs), and suspected unexpected serious adverse reactions (SUSARs)		screening, pre-dose, post-dose (0 hours, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours), follow-up
Number of patients with clinically significant change in vital signs	The following vital signs will be assessed: heart rate, blood pressure, respiratory rate, temperature	screening, pre-dose, post-dose (2 hours, 4 hours, 8 hours, 24 hours)
Number of patients with clinically significant change in Laboratory safety tests	The following laboratory safety tests will be assessed: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Albumin, Alkaline phosphatase, Bicarbonate, Calcium, Chloride, Cholesterol, Creatinine, Glucose, Potassium, Sodium, Bilirubin, total (bilirubin to be fractionated if total bilirubin is elevated), Blood urea nitrogen (BUN)/Urea, hemoglobin, hematocrit, red blood cell (RBC) count, platelet count, white blood cell (WBC) count (total and differential count), polymorphonuclear leukocytes (neutrophils), lymphocytes, eosinophils, monocytes, basophils; Urinalysis: pH, specific gravity, glucose, ketones, leukocyte, esterase, nitrites, occult blood, protein	screening, pre-dose, post-dose (24 hours)
12-lead ECG assessments		screening, pre-dose, post-dose (4 hours)

Collaborators and Investigators

• Sponsor: Abide Therapeutics
• Investigators: Study Director: Chan Beals, Abide Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): October 4, 2017
• Study Completion (Actual): October 4, 2017

Study Registration Dates

• First Submitted: February 13, 2017
• First Submitted That Met QC Criteria: February 16, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: November 2, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Disease; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Syndrome; Tourette Syndrome; Tic Disorders; Tics
• Other Study ID Numbers: ABX-1431_PN015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No