A Phase 2, Dose-Finding, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Study, Evaluating the Safety and Efficacy of Pridopidine 45 mg, 67.5 mg, 90 mg, and 112.5 mg Twice-Daily versus Placebo for Symptomatic Treatment in Patients with Huntington’s Disease
- Conditions
- Huntington’s diseaseMedDRA version: 14.1Level: PTClassification code 10070668Term: Huntington's diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2013-001888-23-IT
- Lead Sponsor
- Teva Branded Pharmaceutical Products R&D, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 408
a. Diagnosis of Huntington’s Disease (HD) based on clinical features and the presence of =36 cytosine-adenosine-guanine (CAG) repeats in the huntingtin gene (from historical data).
b. Male or female age =21 years, with an onset of HD after 18 years’ old.
c. Females of child bearing potential have to be compliant in using adequate birth control throughout the duration of the study, including the follow-up period. Male study participants have to be compliant in using adequate birth control with their partners throughout the duration of the study.
d. Body weight =50 kg.
e. A sum of =25 points on the UHDRS-TMS at the screening visit
f. UHDRS Independence Score (IS) below 90% at the screening visit.
g. Able and willing to provide written informed consent prior to any study related procedure being performed at the screening visit.
h. Willing to provide a blood sample for genetic analyses (including CAG analysis, cytochrome P450[CYP] 2D6 status, genetic long QT syndrome in patients who had QT prolongation following study drug administration or any other genetic analyses related to pridopidine response or HD) at the screening visit.
i. Willing and able to take oral medication and able to comply with the study specific procedures.
j. Ambulatory, being able to travel to the study centre, and judged by the investigator as likely to be able to continue to travel for the duration of the study.
k. Availability and willingness of a caregiver, informant or family member to accompany the patient to the clinic at study visits assessing CIBIC-Plus, HD QoL, and CGI-S/ CGI-C.
l. For patients taking allowed antipsychotic, antidepressant or other psychotropic medication, the dosing of medication must have been kept constant for at least 6 weeks before screening and must be kept constant during the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 368
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32
a. A prolonged Fridericia-corrected QT (QTcF) interval (defined as a QTcF interval of >450 msec) at the screening or baseline visit.
b. Patients with clinically significant heart disease at the screening visit.
c. Patients with a known history of Long QT Syndrome or a first degree relative with this condition.
d. Patients with a history of epilepsy or seizures within the last 5 years.
e. Have other serious medical illnesses which in the opinion of the investigator may put the patient at risk when participating in the study or may influence the results of the study or affect the patient's ability to take part in the study.
f. Patients with serum potassium, magnesium and/or calcium levels outside of the central laboratory’s reference range at the screening visit.
g. Patients receiving medications (within the last 6 weeks prior to screening) that have been proven to prolong QT interval or who may require such medications during the course of the study such as but not limited to non allowed anti psychotic medications, tricyclic antidepressants and/or Class I antiarrhythmics.
h. Patients receiving medications (within the last 6 weeks prior to screening) that are metabolized by CYP2D6 and have the potential of reducing seizure threshold.
i. Creatinine clearance <60 mL/min at screening, calculated using the Cockcroft-Gault equation.
j. Any clinically significant, abnormal, screening laboratory result which in the opinion of the investigator, affects the patients’ suitability for the study or puts the patient at risk if he/she enters the study.
k. Alcohol and/or drug abuse within the 6 months prior to screening as defined by Diagnostic and Statistical Manual – Fourth Edition Text Revision criteria for substance abuse.
l. Patients with active suicidal ideation as measured by a most severe suicide ideation score of 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) or patients who answer Yes” on any of the 5 C-SSRS Suicidal Behavior Items, or patients who, in the opinion of the investigator, present a serious risk of suicide.
m. Patients with known intracranial neoplasms, vascular malformations, history of cerebrovascular accident, or intracranial hemorrhage.
n. Females who are pregnant or lactating.
o. Known allergy to any ingredients of the study medication or placebo.
p. Previous exposure with pridopidine.
q. Treatment with tetrabenazine within 6 weeks of study screening.
r. Treatment with any investigational product within 6 weeks of screening or patients planning to participate in another clinical study assessing any investigational product during the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy of pridopidine 67.5 to 112.5 mg twice daily(bid) on motor impairment in patients with Huntington’s Disease (HD) after 26 weeks of treatment using the Unified Huntington’s Disease Rating Scale Total Motor Score(TMS).;Secondary Objective: To assess the effect of 26 weeks treatment with pridopidine 67.5 to 112.5 mg twice daily (bid) on the Physical Performance Test (PPT).<br><br>The other secondary objectives are:<br>-To evaluate the safety and tolerability of a range of pridopidine doses in patients with HD during 26 weeks of treatment<br>-To explore the pharmacokinetics (PK) of pridopidine in the study population<br>-To investigate the relationship between exposure to pridopidine and outcome measures (eg, clinical efficacy and toxicity parameters);Primary end point(s): Change from baseline in the UHDRS-TMS (defined as the sum of all UHDRS motor domains ratings) at Week 26;Timepoint(s) of evaluation of this end point: week 26
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Change from baseline in the Physical Performance Test at Week 26;Timepoint(s) of evaluation of this end point: week 26