PRIDE-HD

Overview

Status: Not yet recruiting
Keywords: Huntington's Disease , Chorea , Pridopidine , Pride-HD , Movement Disorder , Neurodegenerative Disorder
IRB Number: 00071697
Specialty: Neurology, Neurology, Neurology, Neurology
Sub Specialties: Movement Disorders, Chorea, Huntington Disease, Neurodegenerative Disorders

Brief Summary

PURPOSE OF THE STUDY

This is a randomized, double blind, placebo controlled parallel group study to see what effect pridopidine has on movement, thinking, and behavior, compared to placebo, in people with Huntington’s disease after 26 weeks of treatment. In addition, information will be collected about safety and tolerability of pridopidine in people with HD. Subjects who qualify for the study will be randomized to receive either pridopidine or placebo in a 4:5 ratio.

Dopamine is a substance that is naturally made by the human body. It is made in many areas of the brain, and affects how people behave, think and move. It has been suggested that changes in the way dopamine works in Huntington’s disease creates signs and symptoms of the condition.

Pridopidine, the drug being studied in this project, is a new drug that may have an effect on some of the symptoms of Huntington’s disease that depend on dopamine. This study is being conducted to determine if pridopidine helps with the signs and symptoms of Huntington’s disease.  Research of this type has to be carried out before the treatment can be made available to people with Huntington’s disease, as it needs to be shown that the drug is safe and that it works.  Pridopidine is therefore an investigational drug, which means it has not been approved for sale to the public by the Food and Drug Administration (FDA) because the appropriate research still needs to be done. 

 

STUDY OBJECTIVES

The primary objective of this study is to assess the efficacy of pridopidine 67.5 to 112.5 mg bid on motor impairment in patients with HD after 26 weeks of treatment using the UHDRS-TMS.

The secondary efficacy objective of the study is to assess the effect of 26 weeks of treatment with pridopidine 67.5 to 112.5 mg bid on the Physical Performance Test (PPT).

The other secondary objectives are as follows:

      · To evaluate the safety and tolerability of a range of pridopidine doses in patients with HD during 26 weeks of treatment

      · To explore the PK of pridopidine in the study population

      · To investigate the relationship between exposure to pridopidine and outcome measures (eg, clinical efficacy and toxicity parameters)

Screening Period

After all questions about the study are answered and subject has signed the informed consent form, the following screening procedures will be performed within a period of up to 12 weeks in order to determine eligibility, before receiving study treatment. The investigator should aim to perform the baseline visit as soon as possible after the screening visit. The purpose of these activities is to be sure it is appropriate for the subject to participate. These procedures include:

  • Review of inclusion/exclusion criteria
  • Complete medical and psychiatric history, including information on subject general health, any medications subject are taking, and demographics
  • Complete physical and neurological exam, including subject’s height, weight, vital signs (i.e. oral temperature, heart rate and blood pressure), cognitive and motor assessments
  • Blood samples for standard blood tests, including blood counts and tests of liver and kidney function, (approximately 13.5 ml)

·         If subject is female and able to get pregnant, a part of this sample will be used for a serum pregnancy test

·         A urine sample for standard urine tests

·         An electrocardiogram (ECG) that records the electrical activity of the subject’s heart, possibly repeated depending on results.

·         Subject will be asked questions by study doctor and complete questionnaires/tests to assess general state and any changes in illness over time. These will assess movement, current mental state, ability to learn, remember things, think at a certain speed, concentrate, reason, and solve problems. 

·         Subject will be informed of restrictions and given instructions to follow for the study.

·         A blood sample of approximately 12 ml will be drawn for genetic analyses. This blood will be drawn because we will be looking at the particular part of the subject’s DNA involved in Huntington’s disease, the HD gene.  Analyses will include counting CAG repeats, which are parts of the HD gene that exceed a normal range.  In addition, a liver enzyme participating in the metabolism of pridopidine called CYP2D6 will be assessed. This will help us learn how the body processes the drug. Genetic testing may also be done to assess risk for heart problems (long QT syndrome) should the subject electrocardiograms during the study show certain changes in heartbeat. Other genetic analyses related to pridopidine response or Huntington’s disease may also be done. Subject will not have access to the results of this testing. If subject refuse this procedure subject will not be able to take part in the study.

The procedures and assessments for the screening visit may be performed over several days, as long as they are completed within the defined time period as described by the study doctor.

Genetic Sample Storage

This blood test will check subject DNA, which contains hereditary genetic information (e.g. color of hair or eyes) that is different from person to person. These differences in DNA make certain people more likely to get certain diseases like Huntington’s disease. It may also make some people respond differently or have different side effects to a certain treatment. We are trying to understand whether there is a relationship between these genetic differences and the way the subject is responding to treatment. This may help to identify certain people that respond differently to the study drug.

Samples are stored for a period of up to 15 years from the time of the last subject last visit for the study and then destroyed. The blood samples will be stored at a secure facility selected by Teva, in a country where an adequate level of data protection is practiced. The subject’s genetic records will only be used for investigations related to Huntington’s disease, or the response to pridopidine and drugs like it, in the context of this clinical program. They will not be used for broad-based, exploratory studies on unspecified diseases or population genetic analysis.

Blood samples are labeled with a coded number that will be assigned to the subject and patient initials (or dummy initials) only. The sample can be traced or linked back to the patient only by the investigator or investigational center staff. After DNA extraction, the samples are labeled with a new code, so genetic data will not be recorded with patient number or initials.

If the subject is eligible to participate, the subject will be randomly assigned during the baseline visit to receive one of four doses of the study drug (45 mg, 67.5 mg, 90 mg, 112.5 mg) or placebo, a capsule that looks like pridopidine but has no active ingredient. The subject assignment has not been decided in advance and is random, like the flipping of a coin. Study drug will be taken twice per day for 26 weeks. The subject will need to take 3 capsules in the morning and 3 capsules 7-10 hours after subject's morning dose during the entire study period.  During weeks 1-4 (up to Day 27) subject will gradually increase up to full dose of study drug. During weeks 5-26 (Days 28-182) subject will take the full dose of study drug they are assigned to. Subject will always take 3 capsules of study drug in the morning and 3 in the afternoon except on day 182, when only the morning dose is taken. Neither subject nor study doctor will be able to choose what treatment the subject is assigned to, nor will the subject or study doctor know what treatment subject were assigned to.

It is best if subject stay on the same medications that subject always take, at stable doses, before entering the study unless the study doctor tells you otherwise. Subject should tell the study doctor or study nurse if they changed medication in any way. Subject will not be allowed to take certain medications while in the study. This is to protect the subject from undue risk based on how certain medications interact with the study drug. The study doctor will review with subject which medications subject can and cannot take. Subject should consult study doctor prior to taking any new medications.

Baseline Visit (Visit 1)

The following procedures will be performed at Baseline before dosing begins on site:

  • Review inclusion/ exclusion criteria
  • Complete physical and neurological exam, including your weight
  • Vital signs (i.e. oral temperature, heart rate and blood pressure)
  • Subject will be asked about any medications or changes in the medications that they are currently taking
  • Subject will be asked about any changes in health since subject signed the informed consent, including any serious health events
  • Blood samples for standard blood tests (approximately 13.5 ml)

·         A urine sample for standard urine tests

·         If subject is female and able to get pregnant, a urine sample will be taken for a pregnancy test

·         Three 12-lead electrocardiogram (ECG), taken three times for a total of 9 ECGs.

·         Blood sample (approximately 4 ml) to determine plasma concentration of study drug (the quantity of study drug in subject’s blood) prior to first dose

·         Subject will be asked questions by study doctor and complete questionnaires/tests to assess general state and any changes in illness over time. These will assess movement, current mental state, ability to learn, remember things, think at a certain speed, concentrate, reason, and solve problems. 

·         Study drug administration

·         Review study compliance

·         Dispense study drug

The following procedures will be performed at Baseline after the first dose is administered on

site:

  • A 12-lead ECG taken three times (“in triplicate”) (1 to 2 hours after dose administration).
  • A blood sample of approximately 4 ml to determine plasma concentration (1 to 2 hours after dose administration)
  • Blood samples (approximately 13.5 ml) for standard blood tests and to check electrolytes
  • A urine sample for standard urine tests

Estimated time of study visit = 6 hours

Patient Diary

Subject will be asked to record each dose of study medication in a patient diary book provided to subject. It is important that subject completes this diary every day. Subject should bring their diary back to the site at every visit.

Telephone Contact at Weeks 1, 3 and 5 (Days 6, 20 and 35)

Subject will be contacted by telephone on Days 6, 20, and 35 to evaluate tolerability of the study drug.  Subject will be asked about any new medications or changes in the medications that they are currently taking and any changes in health since their last visit, including any serious health events. 

Week 2 – Day 14 (Visit 2)

Subject will be asked to take afternoon dose of study drug at the site.

Before study drug is taken at the site the subject will have the following procedures:

  • Subject will be asked about any new medications or changes in the medications that subject are currently taking
  • Subject will be asked about any changes in health, including any serious health events
  • Vital signs (i.e. oral temperature, heart rate and blood pressure)
  • A 12-lead ECG in triplicate (1-2 hours after dose administration) (performed after at least 5 minutes of supine rest)
  • Review of study compliance
  • Study drug administration- afternoon dose
  • Collect any unused study drug and dispense study drug
  • Review of Patient Diary

After study drug is taken at the site subject will have the following procedures:

  • A 12-lead ECG in triplicate (1 to 2 hours after dose administration) (performed after at least 5 minutes of supine rest)
  • Blood sample  (approximately 4 ml) to determine plasma concentration (1 to 2 hours after dose administration)
  • Blood samples to check electrolytes (approximately 4 ml)

Estimated time of study visit = 4 hours

Weeks 4, 6, 8, 12, 16, 20 --Days 28, 42, 56, 84, 112 and 140 (Visits 3-8)

The following procedures/assessments will be performed:

Subject will be asked to take afternoon dose of study drug at the site.

Before study drug is taken at the site subject will have the following procedures:

  • Subject will be asked about any new medications or changes in the medications that they are currently taking
  • Subject will be asked about any changes in health, including any serious health events
  • Complete physical and neurological exam that includes weight (Days 28 and 84)
  • Vital signs (i.e. oral temperature, heart rate and blood pressure)
  • If subject is female and able to get pregnant, a urine sample will be taken for a pregnancy test (All visits except Day 42)
  • A 12-lead ECG in triplicate– Day 56 is optional, to be performed at investigator’s discretion
  • Blood sample  (approximately 4 ml) to determine plasma concentration of study drug prior to receiving dose (Days 28, 42, and 112 only)
  • Subject will be asked questions by study doctor and complete questionnaires/tests to assess general state and any changes in illness over time. These will assess movement, current mental state, ability to learn, remember things, think at a certain speed, concentrate, reason, and solve problems.(All visits except Day 42). 
  • Collect any unused study drug and dispense study drug (All visits except Day 42).
  • Review study compliance

Study drug administration- afternoon dose

·         Review of Patient Diary

After drug is taken at the site the subject will have the following procedures:

  • A 12-lead ECG in triplicate (1 to 2 hours after dose administration). Day 56 is optional, to be performed at investigator’s discretion.
  • Blood sample  (approximately 4 ml) to determine plasma concentration of study drug (1 to 2 hours after dose administration) (All visits except Day 56)
  • Blood samples (approximately 13.5 ml) for standard blood tests
  • A urine sample for standard urine tests

The procedures and assessments for visits 4-8 (weeks 6, 8, 12, 16, 20) may be performed over several days, as long as they are completed within the defined time period as described by the study doctor.

Estimated time of study visit = 6 hours

 

Week 26 – Day 182 (Visit 9) or Early Termination

The following procedures/assessments will be performed:

Subject will be asked to take morning dose of study drug at the site.

Before study drug is taken at the site they will have the following procedures:

  • Subject will be asked about any new medications or changes in the medications that subject is currently taking
  • Subject will be asked about any changes in health since subject signed the informed consent, including any serious health events
  • Complete physical and neurological exam that includes weight , vital signs (i.e. oral temperature, heart rate and blood pressure)
  • Blood samples (approximately 13.5 ml) for standard blood tests
  • A urine sample for standard urine tests
  • If subject is female and able to get pregnant, a urine sample will be taken for a pregnancy test
  • A 12-lead ECG in triplicate
  • Blood sample (approximately 4 ml) to determine plasma concentration of study drug prior to receiving dose.
  • Subject will be asked questions by study doctor and complete questionnaires/tests to assess general state and any changes in illness over time. These will assess movement, current mental state, ability to learn, remember things, think at a certain speed, concentrate, reason, and solve problems. 

·         Review study compliance.

Study drug administration- morning dose.  There will be no afternoon dose on this day (If this will be the subject’s early termination visit study drug will not be administered)

  • The investigator will collect any unused study drug
  • Review of Patient Diary

The procedures and assessments for this visit may be performed over several days, as long as they are completed within the defined time period as described by the study doctor.

Estimated time of study visit = 6 hours

Follow-up Visit

There will be a follow-up visit approximately 2 weeks after the last dose of study drug. The following procedures/assessments will be performed:

  • Subject will be asked about any new medications or changes in the medications that they are currently taking
  • Subject will be asked about any changes in health since subject signed the informed consent, including any serious health events
  • Complete physical and neurological exam that includes weight , vital signs (i.e. oral temperature, heart rate and blood pressure)
  • Blood samples (approximately 13.5 ml) for standard blood tests
  • A urine sample for standard urine tests
  • If subject are female and able to get pregnant, a urine sample will be taken for a pregnancy test
  • A 12-lead ECG in triplicate (optional)
  • Subject will be asked questions by study doctor and complete questionnaires/tests to assess general state and any changes in illness over time. These will assess movement and current mental state. 
  • Blood sample  (approximately 4 ml) to determine plasma concentration of study drug

Subject will give a total of about 1 cup (206 mL) of blood during the study.

The procedures and assessments for this visit may be performed over several days, as long as they are completed within the defined time period as described by the study doctor.

Estimated time of study visit = 6 hours

Detailed Description

Pridopidine, the drug being studied in this project, is a new drug that may have an effect on some of the symptoms of Huntington’s disease that depend on dopamine. This study is being conducted to determine if pridopidine helps with the signs and symptoms of Huntington’s disease. Research of this type has to be carried out before the treatment can be made available to people with Huntington’s disease, as it needs to be shown that the drug is safe and that it works. Pridopidine is therefore an investigational drug, which means it has not been approved for sale to the public by the Food and Drug Administration (FDA) because the appropriate research still needs to be done. The purpose of this randomized, double blind study is to see what effect pridopidine has on movement, thinking, and behavior, compared to placebo, in people with Huntington’s disease after 26 weeks of treatment. In addition, information will be collected about safety and tolerability of pridopidine in people with HD. Before you can start the study, the study doctor or study staff will talk to you in detail about the study. If you decide to participate, you will be asked to sign this informed consent form before any study procedures are done. You will be given a copy of this signed and dated form. Your study doctor will be required to perform the procedures listed below. The results of these procedures will be used to determine if you are eligible to participate, or, if you enroll in the study, to continue participation in this study. Your regular doctor may also be contacted for some information. To participate in this study, you will have a caregiver come to your study appointments with you. It is preferred that you bring the same caregiver to the required visits. Your study doctor will ask your caregiver questions about your general well-being, movement, current mental state, memory, concentration, and ability to solve problems. Please be aware that certain site staff will not have full access to all the information regarding your participation in this study. You will be made aware of which site staff this pertains to and what information they do and do not have access to. Please do not share information that they do not have access to with them during your visit. Screening Period After all of your questions about the study are answered and you have signed this informed consent form, the following screening procedures will be performed within 14 days of receiving study treatment. The purpose of these activities is to be sure it is appropriate for you to participate. These procedures include: • Review of inclusion/exclusion criteria • Complete medical and psychiatric history, including information on your general health, any medications you are taking, and demographics • Complete physical and neurological exam, including your height, weight, vital signs (i.e. oral temperature, heart rate and blood pressure), cognitive and motor assessments • Blood samples for standard blood tests, including blood counts and tests of liver and kidney function, (approximately 13.5 ml) • If you are female and able to get pregnant, a part of this sample will be used for a serum pregnancy test • A urine sample for standard urine tests • An electrocardiogram (ECG) that records the electrical activity of your heart, possibly repeated depending on results. • You will be asked questions by your study doctor and complete questionnaires/tests to assess your general state and any changes in your illness over time. These will assess your movement, current mental state, your ability to learn, remember things, think at a certain speed, concentrate, reason, and solve problems. • You will be informed of restrictions and given instructions to follow for the study. • A blood sample of approximately 10 ml will be drawn for genetic analyses. This blood will be drawn because we will be looking at the particular part of your DNA involved in Huntington’s disease, the HD gene. Analyses will include counting CAG repeats, which are parts of the HD gene that exceed a normal range. In addition, a liver enzyme participating in the metabolism of pridopidine called CYP2D6 will be assessed. This will help us learn how your body processes the drug. Genetic testing may also be done to assess your risk for heart problems (long QT syndrome) should your electrocardiograms during the study show certain changes in your heartbeat. Other genetic analyses related to pridopidine response or Huntington’s disease may also be done. You will not have access to the results of this testing. If you refuse this procedure you will not be able to take part in the study. Genetic Sample Storage This blood test will check your DNA, which contains hereditary genetic information (e.g. color of your hair or eyes) that is different from person to person. These differences in DNA make certain people more likely to get certain diseases like Huntington’s disease. It may also make some people respond differently or have different side effects to a certain treatment. We are trying to understand whether there is a relationship between these genetic differences and the way you are responding to treatment. This may help to identify certain people that respond differently to the study drug. Samples are stored for a period of up to 15 years from the time of the last subject last visit for the study and then destroyed. The blood samples will be stored at a secure facility selected by Teva, in a country where an adequate level of data protection is practiced. Your genetic records will only be used for investigations related to Huntington’s disease, or the response to pridopidine and drugs like it, in the context of this clinical program. They will not be used for broad-based, exploratory studies on unspecified diseases or population genetic analysis. Blood samples are labeled with a coded number that will be assigned to you and patient initials (or dummy initials) only. The sample can be traced or linked back to the patient only by the investigator or investigational center staff. After DNA extraction, the samples are labeled with a new code, so genetic data will not be recorded with patient number or initials. If you are eligible to participate, you will be randomly assigned during the baseline visit to receive one of four doses of the study drug (45 mg, 67.5 mg, 90 mg, 112.5 mg) or placebo, a capsule that looks like pridopidine but has no active ingredient. Your assignment has not been decided in advance and is random, like the flipping of a coin. Study drug will be taken twice per day for 26 weeks. You will need to take 3 capsules in the morning and 3 capsules 7-10 hours after your morning dose during the entire study period. During weeks 1-4 (up to Day 27) you will gradually increase up to your full dose of study drug. During weeks 5-26 (Days 28-182) you will take the full dose of study drug you are assigned to. You will always take 3 capsules of study drug in the morning and 3 in the afternoon except on day 182, when only the morning dose is taken. Neither you nor your study doctor will be able to choose what treatment you are assigned to, nor will you or your study doctor know what treatment you were assigned to. It is best if you stay on the same medications that you always take, at stable doses, before entering the study. You should tell the study doctor or study nurse if you change your medication in any way. You will not be allowed to take certain medications while in the study. This is to protect you from undue risk based on how certain medications interact with the study drug. Your study doctor will review with you which medications you can and cannot take. You should consult your study doctor prior to taking any new medications. Baseline Visit (Visit 1) The following procedures will be performed at Baseline before dosing begins on site: • Review inclusion/ exclusion criteria • Vital signs (i.e. oral temperature, heart rate and blood pressure) • You will be asked about any medications or changes in the medications that you are currently taking • You will be asked about any changes in your health since you signed the informed consent, including any serious health events • Blood samples for standard blood tests (approximately 13.5 ml) • A urine sample for standard urine tests • If you are female and able to get pregnant, a urine sample will be taken for a pregnancy test • Three 12-lead electrocardiogram (ECG), taken three times for a total of 9 ECGs. • Blood sample (approximately 4 ml) to determine plasma concentration of study drug (the quantity of study drug in your blood) prior to first dose • You will be asked questions by your study doctor and complete questionnaires/tests to assess your general state and any changes in your illness over time. These will assess your movement, current mental state, your ability to learn, remember things, think at a certain speed, concentrate, reason, and solve problems. • Study drug administration • Review study compliance • Dispense study drug The following procedures will be performed at Baseline after the first dose is administered on site: • A 12-lead ECG taken three times (“in triplicate”) (1 to 2 hours after dose administration). • A blood sample of approximately 4 ml to determine plasma concentration (1 to 2 hours after dose administration) Estimated time of study visit = 6 hours Patient Diary You will be asked to record each dose of study medication in a patient diary book provided to you. It is important that you complete this diary every day. You should bring your diary back to the site at every visit. Telephone Contact at Weeks 1, 3 and 5 (Days 6, 20 and 35) You will be contacted by telephone on Days 6, 20, and 35 to evaluate tolerability of the study drug. You will be asked about any new medications or changes in the medications that you are currently taking and any changes in your health since your last visit, including any serious health events. Week 2 – Day 14 (Visit 2) You will be asked to take your afternoon dose of study drug at the site. Before study drug is taken at the site you will have the following procedures: • You will be asked about any new medications or changes in the medications that you are currently taking • You will be asked about any changes in your health, including any serious health events • Vital signs (i.e. oral temperature, heart rate and blood pressure) • Blood samples to check electrolytes (approximately 4 ml) • A 12-lead ECG in triplicate • Review of study compliance • Study drug administration- afternoon dose • Collect any unused study drug and dispense study drug • Review of Patient Diary After study drug is taken at the site you will have the following procedures: • A 12-lead ECG in triplicate (1 to 2 hours after dose administration). • Blood sample (approximately 4 ml) to determine plasma concentration (1 to 2 hours after dose administration) Estimated time of study visit = 4 hours Weeks 4, 6, 8, 12, 16, 20 --Days 28, 42, 56, 84, 112 and 140 (Visits 3-8) The following procedures/assessments will be performed: You will be asked to take your afternoon dose of study drug at the site. Before study drug is taken at the site you will have the following procedures: • You will be asked about any new medications or changes in the medications that you are currently taking • You will be asked about any changes in your health, including any serious health events • Complete physical and neurological exam that includes your, weight (Days 28 and 84) • Vital signs (i.e. oral temperature, heart rate and blood pressure) • Blood samples (approximately 13.5 ml) for standard blood tests • A urine sample for standard urine tests • If you are female and able to get pregnant, a urine sample will be taken for a pregnancy test (All visits except Day 42) • A 12-lead ECG in triplicate– Day 56 is optional, to be performed at investigator’s discretion • Blood sample (approximately 4 ml) to determine plasma concentration of study drug prior to receiving dose (Days 28, 42, and 112 only) • You will be asked questions by your study doctor and complete questionnaires/tests to assess your general state and any changes in your illness over time. These will assess your movement, current mental state, your ability to learn, remember things, think at a certain speed, concentrate, reason, and solve problems.(All visits except Day 42). • Collect any unused study drug and dispense study drug (All visits except Day 42). • Review study compliance Study drug administration- afternoon dose • Review of Patient Diary After drug is taken at the site you will have the following procedures: • A 12-lead ECG in triplicate (1 to 2 hours after dose administration). Blood sample (approximately 4 ml) to determine plasma concentration of study drug (1 to 2 hours after dose administration) (All visits except Day 56) Estimated time of study visit = 6 hours Week 26 – Day 182 (Visit 9) or Early Termination The following procedures/assessments will be performed: You will be asked to take your morning dose of study drug at the site. Before study drug is taken at the site you will have the following procedures: • You will be asked about any new medications or changes in the medications that you are currently taking • You will be asked about any changes in your health since you signed the informed consent, including any serious health events • Complete physical and neurological exam that includes your, weight , vital signs (i.e. oral temperature, heart rate and blood pressure) • Blood samples (approximately 13.5 ml) for standard blood tests • A urine sample for standard urine tests • If you are female and able to get pregnant, a urine sample will be taken for a pregnancy test • A 12-lead ECG in triplicate • Blood sample (approximately 4 ml) to determine plasma concentration of study drug prior to receiving dose. • You will be asked questions by your study doctor and complete questionnaires/tests to assess your general state and any changes in your illness over time. These will assess your movement, current mental state, your ability to learn, remember things, think at a certain speed, concentrate, reason, and solve problems. • Review study compliance. Study drug administration- morning dose. There will be no afternoon dose on this day (If this will be your early termination visit study drug will not be administered) • The investigator will collect any unused study drug • Review of Patient Diary Estimated time of study visit = 6 hours Follow-up Visit There will be a follow-up visit approximately 2 weeks after the last dose of study drug. The following procedures/assessments will be performed: • You will be asked about any new medications or changes in the medications that you are currently taking • You will be asked about any changes in your health since you signed the informed consent, including any serious health events • Complete physical and neurological exam that includes your, weight , vital signs (i.e. oral temperature, heart rate and blood pressure) • Blood samples (approximately 13.5 ml) for standard blood tests • A urine sample for standard urine tests • If you are female and able to get pregnant, a urine sample will be taken for a pregnancy test • A 12-lead ECG in triplicate (optional) • You will be asked questions by your study doctor and complete questionnaires/tests to assess your general state and any changes in your illness over time. These will assess your movement and current mental state. • Blood sample (approximately 4 ml) to determine plasma concentration of study drug You will give a total of about 1 cup (204 mL) of blood during the study. Unscheduled Visits In case you feel any change in your condition you should contact the study staff. You may be invited to an unscheduled visit in which your study doctor will decide what tests to perform. Estimated time of study visit = 6 hours If you complete this study you may have an opportunity to enter an open-label extension study. Your doctor can provide you with more information. If you choose to take part in this research, your major responsibilities will include: • Take your study drug as prescribed and return all study drug bottles • Tell the study staff if you take any other medication • Tell the study staff if you have any change in your health status • Carrying a patient card If you want to stop your study participation early for any reason, please let the research doctor know, you will be asked to return for a final study visit. In the event that you do end your participation in this study, the information you have already provided will be kept confidential. In addition to attendance at study visits as noted above, we will ask caregivers to answer questions up to seven (7) times during the 26-week study. When the patient comes to the clinic for the second time (day 0 visit) and then at day 28, 56, 84, 112, 140, and 182, you will be asked questions at the same time as the patient is completing study procedures. Each set of questions will take 5-10 minutes to complete. We will ask you questions about the patient’s past and current physical and mental state. The caregiver will also be asked to sign the caregiver consent form to acknowledge their part in this study. Time Duration of the Procedures and Study You will be in this study for about 30 weeks, consisting of a 2-week screening period, a 26-week treatment period, and a 2-week follow-up period following the last dose of study drug.

Principal Investigator: David Shprecher
Department: Neurology
Co Investigator:

Contact Information

Name:Paola Wall
Phone: 801-581-4543
Email: paola.wall@hsc.utah.edu

Inclusion Criteria

Inclusion Criteria

1.      Diagnosis of HD based on clinical features and the presence of ≥36 CAG repeats in the huntington gene.

2.      Male or female age ≥21 years, with an onset of HD after 18 years’ old.

3.      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 (hormone-based, intrauterine device, or double barrier contraception, ie, condom and diaphragm). Abstinence is an acceptable method of contraception only when this is the 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 (as defined above) throughout the duration of the study.

4.      Body weight ≥50 kg.

5.      A sum of ≥25 points on the UHDRS-TMS at the screening visit.

6.      UHDRS-IS score equal to or less than 90% at the screening visit.

7.      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.

8.      Willing to provide a blood sample for genetic analyses (including CAG analysis, CYP2D6 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.

9.      Willing and able to take oral medication and able to comply with the study specific procedures.

10.  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.

11.  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. For the purposes of this study, a caregiver is recommended to be someone who attends to the patient at least 2 to 3 times per week for at least 3 hours per occasion, and the suitability of the caregiver should be judged by the investigator.

12.  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.

 

Exclusion Criteria

Exclusion Criteria

1.      A prolonged QTcF interval (defined as a QTcF interval of >450 msec) at the screening visit. If there is evidence of a prolonged QTcF interval at screening from the initial (single) measurement, then the ECG will be repeated twice, and the mean of the 3 screening measurements will be used to determine whether or not the patient is suitable for inclusion in the study.

2.      Patients with clinically significant heart disease at the screening visit, defined as follows: (i) significant cardiac event (eg, myocardial infarction), angina pectoris or episode of congestive heart failure with symptoms >Grade 2 New York Heart Association classification within 12 weeks before randomization, or presence of cardiac disease that in the opinion of the investigator increased the risk of ventricular arrhythmia, (ii) history of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia) that was symptomatic or required treatment (Common Terminology Criteria for Adverse Events Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia, (iii) presence of left bundle branch block.

3.      Patients with a known history of Long QT Syndrome or a first degree relative with this condition.

4.      Patients with a history of epilepsy or of seizures within the last 5 years.

5.      Have other serious medical illnesses (including but not limited to uncontrolled hypertension, respiratory disease including severe form of asthma, hepatic disease, renal disease, AIDS, unstable psychiatric or other neurologic disorder) 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.

6.      Patients with serum potassium, magnesium and/or calcium levels outside of the central laboratory’s reference range at the screening visit and considered clinically significantly abnormal by the investigator. Repeat testing is allowed (up to a maximum of 3 tests) if required to establish whether values are within normal range or clinically significantly abnormal.

7.      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.

8.      Patients receiving medications (within the last 6 weeks prior to baseline) that are metabolized by CYP2D6 and have the potential of reducing seizure threshold (see Section 5.3.2.4).

9.      Creatinine clearance <60 mL/min at screening, calculated using the Cockcroft-Gault equation: (140 - age) × mass (kg) × [0.85 if female] / 72 × serum creatinine (mg/dL)

10.  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.

11.  Alcohol and/or drug abuse within the 6 months prior to screening, as defined by Diagnostic and Statistical Manual – Fourth Edition Text Revision (DSM-IV TR) criteria for substance abuse.

12.  Patients with active suicidal ideation as measured by a most severe suicide ideation score of 4 (Active Suicidal Ideation with Some Intent to Act, without Specific Plan) or 5 (Active Suicidal Ideation with Specific Plan and Intent) on the C-SSRS, or patients who answer “Yes” on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) 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.

13.  Patients with known intracranial neoplasms, vascular malformations, history of cerebrovascular accident, or intracranial hemorrhage.

14.  Females who are pregnant or lactating.

15.  Known allergy to any ingredients of the study medication or placebo (pridopidine, silicified microcrystalline cellulose, magnesium stearate).

16.  Previous exposure with pridopidine.

17.  Treatment with tetrabenazine within 6 weeks of study baseline.

18.  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.