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A Clinical Trial of Pimozide in Patients With Amyotrophic Lateral Sclerosis (ALS) (Pimozide2)

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ClinicalTrials.gov Identifier: NCT03272503
Recruitment Status : Recruiting
First Posted : September 5, 2017
Last Update Posted : July 6, 2018
Sponsor:
Collaborators:
ALS Canada
Brain Canada
Information provided by (Responsible Party):
DR. LAWRENCE KORNGUT, University of Calgary

Brief Summary:

This study will look at whether Pimozide may help to slow the progression of Amyotrophic Lateral Sclerosis.

100 people from several Canadian centres with ALS who have provided their consent will be randomly assigned into one of 2 groups. The first group will receive a dose of up to 4mg of Pimozide per day and the second group will receive placebo (lactose tablets). Subjects will be assigned randomly (like by a flip of a coin) to receive either Pimozide 4 mg per day or placebo tablets. There will be a fifty-fifty chance of receiving Pimozide or placebo.

Participants will be on study medication up to 22 weeks, and on study up to 26 weeks. There are 8 clinic visits and 1 phone visit over the course of the Treatment Phase of the study. The second phase which is Observational, is optional with follow-up for up to 5 years from the end of the Treatment Phase.


Condition or disease Intervention/treatment Phase
ALS Amyotrophic Lateral Sclerosis Drug: Pimozide 4 mg/day Drug: Placebo Oral Tablet Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Placebo-Controlled, Double Blinded, Multi-Centre Clinical Trial of Pimozide in Patients With Amyotrophic Lateral Sclerosis
Actual Study Start Date : October 27, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019


Arm Intervention/treatment
Experimental: Group 1 (Pimozide 4 mg/day)
Pimozide will be initiated at 2 mg once daily for 7 days. On Day 8, subjects will begin taking 2 mg twice daily. The maximum dose will then be administered for a target period of 154 days.
Drug: Pimozide 4 mg/day
Pimozide 2mg tablets will be taken once daily for the first 7 days of the study, and then increased to 2 mg twice daily for the duration of the study.

Placebo Comparator: Group 2 Placebo
Placebo tablets will be utilized and administered in an identical manner for subjects in Group 1
Drug: Placebo Oral Tablet
Identical matching placebo lactose tablets




Primary Outcome Measures :
  1. Change in ALS Functional Rating Scale-Revised (ALSFRS-R) [ Time Frame: Change from Baseline (week 2), at visit each of visit weeks 4, 8,12,16,20, week 24 Final Study visit, and week 26 follow-up phone call. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit. ]
    The Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) consists of a 12 item questionnaire which asks about function in certain daily activities. Takes around 5-10 mins with a study staff member.


Secondary Outcome Measures :
  1. Change in Slow Vital Capacity (SVC) [ Time Frame: Change from screen, at each of visit weeks 8, week 16, and week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit. ]
    The SVC is the maximum volume of air which can be exhaled after a deep breath in, during a slow/steady maneuver. A nose clip will be placed on the nose during the testing.

  2. Change in Decremental responses on repetitive nerve stimulation (DRRNS) [ Time Frame: Change from Baseline (week 2) at week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit. ]
    Repetitive Nerve Stimulation is where electrical stimulation is applied to a motor nerve repeatedly several times per second. This will involve testing each thumb.

  3. Change in Motor Power - the MRC (Medical Research Council) Sum Score [ Time Frame: Change from screen, at each of week 8, week 16, and week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit. ]
    Assessment of Muscle Strength

  4. Change in Common Terminology Criteria for Adverse Events (CTCAE) will be entered for each visit for adverse effect profile analysis [ Time Frame: Change from Baseline (week 2), at each of weeks 4,8,12,16,20, week 24 Final Study visit, and week 26 follow-up phone call. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit. ]
    Adverse events will be assessed.

  5. Change in ALS-Specific QOL -Revised [ Time Frame: Change from Baseline (week 2), at week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit. ]
    The Amyotrophic Lateral Sclerosis Specific Quality of Life - Revised (ALSSQOL-R) questionnaire consists of 50 items regarding quality of life. Takes approximately 15 minutes to complete

  6. Change in Cramp Frequency and Severity [ Time Frame: Change from Baseline (week 2), at each of weeks 4,8,12,16,20, and week 24 Final Study visit. Will also be done for a study drug withdrawal visit or if applicable, an edaravone initiation visit ]
    Consists of 2 questions asking if subject has had cramps in the last 24 hours, how bad and how severe they were. Takes 1 or 2 minutes to complete.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients classified as having clinically definite, clinically probable, clinically probable (laboratory-supported) or clinically possible ALS according to the El-Escorial diagnostic criteria for ALS.
  2. Able to comprehend and willing to sign Informed Consent Form (ICF).
  3. Age 18 years of age or greater.
  4. ALS Symptom onset of muscle weakness or speech impairment no more than 48 months prior to screen visit. Fasiculations should not be considered.
  5. Slow Vital Capacity (SVC) greater than or equal to 50% predicted for sex, age and height at screen.
  6. Has the ability to swallow tablets/capsules whole at study entry.
  7. Subject with clinical laboratory findings within the normal range or, if outside the normal range, determined by the Investigator at the Screening visit to be not clinically significant.
  8. If the subject is taking Riluzole the dose must be stable for 30 days prior to the randomization visit. Riluzole cannot be initiated during the study.
  9. If the subject is receiving Edaravone therapy, the dose must be stable for at least 2 cycles of infusion treatments before the randomization visit.

Exclusion Criteria:

  1. History of laryngeal spasm, dystonia, or akathisia.
  2. Diagnosis of ongoing symptomatic Restless Leg Syndrome or undergoing current treatment for Restless Leg Syndrome. If subject has symptoms that resemble or have the potential to be Restless Leg Syndrome, then further investigation should be undertaken to confirm or rule out diagnosis of Restless Leg Syndrome.
  3. Any history of moderate or severe traumatic brain injury as defined by a Glasgow Coma Scale Score of less than 13/15 at any time point following a head injury without sedation or other reason for a decreased level of consciousness.
  4. History of neuroleptic malignant syndrome.
  5. History of hypersensitivity or serious adverse reaction(s) to a neuroleptic medication.
  6. History of hyponatremia < 130 mmol/L
  7. Subject with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value >3.0 times the upper limit of normal at the Screening visit.
  8. Current heparin or warfarin use.
  9. History of hepatic and/or renal impairment that may affect pimozide metabolism
  10. History of current pregnancy, or breastfeeding women, or women planning to become pregnant. Female subjects of childbearing potential (sexually mature female who has not undergone a hysterectomy or who has not been post-menopausal for 12 consecutive months), must practise effective contraception during the study and be willing and able to continue contraception until the Follow-up phone visit after discontinuing study medication. Abstinence can be considered an acceptable method of contraception at the discretion of the investigator.
  11. Current antipsychotic use
  12. Presence of central nervous system depression, comatose states, liver disorders, renal insufficiency, and blood dyscrasias
  13. Presence of Parkinson's syndrome
  14. Presence of major depressive disorders as determined by site Investigator.
  15. History of clinically significant ECG abnormalities at screen visit, including QTc>500ms.
  16. History of congenital long QT syndrome or with a family history of this syndrome and in patients with a history of cardiac arrhythmias or Torsade de Pointes
  17. Presence of acquired long QT interval, such as associated with concomitant use of drugs known to prolong the QT interval
  18. Presence of clinically significant bradycardia (heart rate < 50 beats per minute)
  19. Presence of hypokalemia or hypomagnesemia
  20. The concomitant use of CYP 3A4-inhibiting drugs such as azole antimycotics, antiviral protease inhibitors, macrolide antibiotics and nefazodone
  21. The concomitant use of CYP 2D6-inhibiting drugs such as quinidine is also contraindicated
  22. Concomitant use of serotonin reuptake inhibitors, such as, sertraline, paroxetine, citalopram and escitalopram.*
  23. Has taken any compound under current or known future study as a potential therapy for ALS less than 30 days prior to dosing OR history of exposure to stem cell therapy for treatment of ALS at any time.
  24. Current Neurological impairment due to a condition other than ALS:

    1. Subject in whom causes of neuromuscular weakness other than ALS have not been excluded.
    2. Subject with a diagnosis of other neurodegenerative diseases (e.g., Parkinson's disease, Frontotemporal dementia, Alzheimer's disease, etc.)
  25. Use of non-invasive ventilation (BiPAP or CPAP) prior to Baseline visit at any time.
  26. Cognitive impairment as determined by the Site Investigator, subject must not have an impaired ability to provide informed consent and must be able to understand study processes and comply with study procedures.
  27. Extrapyramidal Symptom Rating Scale (ESRS) Parkinsonism score of 2 on 2 items or a score > 3 on 1 item; OR Dystonia score of >3 on at least 1 item or a score of 2 on 2 items; OR Tardive Dyskinesia score of >3 on at least 1 item or a score of 2 on 2 items.

    • Serotonin reuptake inhibitors, such as, sertraline, paroxetine, citalopram and escitalopram may be weaned to full discontinuation at the screening visit after consent has been signed (no study procedures including adjustments to medication may occur until informed consent has been provided).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03272503


Contacts
Contact: Pim2 Study 403-210-7006 Pimozide2@ucalgary.ca
Contact: Janet Petrillo, M.Sc. 403-210-7006 japetril@ucalgary.ca

Locations
Canada, Alberta
Dr. Lawrence Korngut -South Health Campus Recruiting
Calgary, Alberta, Canada, T3M 1M4
Contact: Brianna Salverda, M.Sc.    403-956-3428    brianna.salverda@ucalgary.ca   
Canada, New Brunswick
Dr. Colleen O'Connell - Stan Cassidy Centre for Rehabilitation Recruiting
Fredericton, New Brunswick, Canada, E3B 0C7
Contact: Susan McCully, MN    506-447-4095    susan.mccully@horizonnb.ca   
Canada, Ontario
Dr. John Turnbull McMaster University/Hamilton Health Services Recruiting
Hamilton, Ontario, Canada, L8N 3Z5
Contact: Daniela Trapsa    905-521-2100 ext 76365    trapsd@mcmaster.ca   
Dr. Lorne Zinman Sunnybrook Research Institute Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Liane Phung, BSc    416-480-6100 ext 87561    liane.phung@sri.utoronto.ca   
Contact: Shirley Pham, BA    416-480-6860    shirley.pham@sunnybrook.ca   
Canada, Quebec
Dr. Sandrine Larue - Reserche Sepmus Inc. Recruiting
Greenfield Park, Quebec, Canada, J4V 2J2
Contact: Kim Desilets, B.Sc.    450-672-1931 ext 247    k.desilets@sepmus.com   
Sponsors and Collaborators
University of Calgary
ALS Canada
Brain Canada
Investigators
Principal Investigator: Lawrence Korngut, M.D. University of Calgary and Alberta Health Services

Responsible Party: DR. LAWRENCE KORNGUT, M.D. Director Calgary ALS and Motor Neuron Disease Clinic, University of Calgary
ClinicalTrials.gov Identifier: NCT03272503     History of Changes
Other Study ID Numbers: Pimozide2_ALS-002
First Posted: September 5, 2017    Key Record Dates
Last Update Posted: July 6, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by DR. LAWRENCE KORNGUT, University of Calgary:
Pimozide

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Pimozide
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents