A study testing different doses of pridopidine (45 mg, 67.5 mg, 90 mg, 112.5 mg twice-daily) against placebo to establish which one works best and is safe when treating certain symptoms of patients with Huntington´s Disease.

• Register: EUCTR
• Last refreshed on: 1 December 2014
• Main ID: EUCTR2013-001888-23-GB
• Date of registration: 27/11/2013
• Prospective Registration: Yes
• Primary sponsor: Teva Branded Pharmaceutical Products R&D, Inc
• Public title: A study testing different doses of pridopidine (45 mg, 67.5 mg, 90 mg, 112.5 mg twice-daily) against placebo to establish which one works best and is safe when treating certain symptoms of patients with Huntington´s Disease.
• Scientific title: 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
• Date of first enrolment: 22/01/2014
• Target sample size: 400
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001888-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 5

Countries of recruitment

Australia, Austria, Canada, Czech Republic, Denmark, France, Germany, Italy, Netherlands, Poland, Russian Federation, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Teva Pharma GmbH

• Name: Clinical Trial Information Desk
• Affiliation: Teva Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
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. Adequate birth control is defined as consistent practice of an effective and accepted method of contraception (hormonebased, intrauterine device, or double-barrier contraception, ie, condom and diaphragm). Abstinence is an acceptable method of contraception only when this is preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation
methods), withdrawal (coitus interruptus), and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. 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) equal to or less than 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. Patients with a legal guardian should be consented according to local requirements.
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 baseline 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

Exclusion criteria:
a. A prolonged Fridericia-corrected QT (QTcF) interval (defined as a QTcF interval of >450 msec) at the screening 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 baseline) 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 baseline) 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, if the attempt or acts were performed within 1
year of screening, 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 baseline.
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Huntington’s disease
MedDRA version: 17.1 Level: PT Classification code 10070668 Term: Huntington's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Pridopidine
Product Code: TV-7820
Pharmaceutical Form: Capsule
INN or Proposed INN: pridopidine
CAS Number: 882737-42-0
Current Sponsor code: TV-7820
Other descriptive name: ACR16 hydrochloride, ASP2314 hydrochloride, FR310826
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 22.5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Pridopidine
Product Code: TV-7820
Pharmaceutical Form: Capsule
INN or Proposed INN: pridopidine
CAS Number: 882737-42-0
Current Sponsor code: TV-7820
Other descriptive name: ACR16 hydrochloride, ASP2314 hydrochloride, FR310826
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 45-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To assess the effect of 26 weeks treatment with pridopidine 67.5 to 112.5 mg twice daily (bid) on the modified Physical Performance Test (mPPT).

The other secondary objectives are:
-To evaluate the safety and tolerability of a range of pridopidine doses in patients with HD during 26 weeks of treatment
-To explore the pharmacokinetics (PK) of pridopidine in the study population
-To investigate the relationship between exposure to pridopidine and outcome measures (eg, clinical efficacy and toxicity parameters)

Timepoint(s) of evaluation of this end point: week 26

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).

Primary end point(s): Change from baseline in the UHDRS-TMS (defined as the sum of all UHDRS motor domains ratings) at Week 26

Secondary Outcome(s)

Secondary end point(s): Change from baseline in the modified Physical Performance Test at Week 26

Timepoint(s) of evaluation of this end point: week 26

Secondary ID(s)

TV7820-CNS-20002

Source(s) of Monetary Support

Teva Pharmaceutical Industries Ltd