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

Phase 1
Completed
Conditions
Tourette Syndrome
Chronic Motor Tic Disorder
Interventions
Drug: Placebo Comparator
Registration Number
NCT03058562
Lead Sponsor
Abide Therapeutics
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
23
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Crossover Sequence DPlacebo ComparatorEach with a standard high fat meal: Period 3: Single-dose ABX-1431 Period 4: Single-dose matching placebo
Crossover Sequence CPlacebo ComparatorEach with a standard high fat meal: Period 3: Single-dose matching placebo Period 4: Single-dose ABX-1431
Crossover Sequence APlacebo ComparatorEach in the fasting state: Period 1: Single-dose matching placebo Period 2: Single-dose ABX-1431
Crossover Sequence BPlacebo ComparatorEach in the fasting state: Period 1: Single-dose ABX-1431 Period 2: Single-dose matching placebo
Crossover Sequence AABX-1431Each in the fasting state: Period 1: Single-dose matching placebo Period 2: Single-dose ABX-1431
Crossover Sequence BABX-1431Each in the fasting state: Period 1: Single-dose ABX-1431 Period 2: Single-dose matching placebo
Crossover Sequence CABX-1431Each with a standard high fat meal: Period 3: Single-dose matching placebo Period 4: Single-dose ABX-1431
Crossover Sequence DABX-1431Each with a standard high fat meal: Period 3: Single-dose ABX-1431 Period 4: Single-dose matching placebo
Primary Outcome Measures
NameTimeMethod
Change of rating in Premonitory Urge for Tics Scale (PUTS) over timepre-dose, post-dose (4 hours, 8 hours, 12 hours)
Change of rating in Modified Rush Video Scale (MRVS) over timepre-dose, post-dose (4 hours, 8 hours)
Change in rating of Yale Global Tic Severity Scale (YGTSS) over timepre-dose, post-dose (4 hours, 8 hours)
Change of rating in Adult Tic Questionnaire (ATQ) over timepre-dose, post-dose (4 hours, 8 hours, 12 hours)
Secondary Outcome Measures
NameTimeMethod
ABX-1431 and metabolite (M55) plasma pharmacokineticspre-dose, post-dose (2 hours, 4 hours, 8 hours, 24 hours)
2-AG hydrolysis in PBMCpre-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
12-lead ECG assessmentsscreening, pre-dose, post-dose (4 hours)
Number of patients with clinically significant change in vital signsscreening, pre-dose, post-dose (2 hours, 4 hours, 8 hours, 24 hours)

The following vital signs will be assessed:

heart rate, blood pressure, respiratory rate, temperature

Number of patients with clinically significant change in Laboratory safety testsscreening, pre-dose, post-dose (24 hours)

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

Trial Locations

Locations (1)

Medizinische Hochschule Hannover

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Hannover, Niedersachsen, Germany

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