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

NCT03272503 | Unknown Phase 2 DMC

• 1 other identifier: Pimozide2_ALS-002
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 9

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 2mg 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 2 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.

Conditions

ALS; Amyotrophic Lateral Sclerosis

Keywords

Pimozide

Outcome Measures

Primary Outcomes (1)

• Change in ALS Functional Rating Scale-Revised (ALSFRS-R)

  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.

  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.

Secondary Outcomes (6)

• Change in Slow Vital Capacity (SVC)

  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.

• Change in Decremental responses on repetitive nerve stimulation (DRRNS)

  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.

• Change in Motor Power - the MRC (Medical Research Council) Sum Score

  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.

• Change in Common Terminology Criteria for Adverse Events (CTCAE) will be entered for each visit for adverse effect profile analysis

  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.

• Change in ALS-Specific QOL -Revised

  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.

Study Arms (2)

Group 1 Pimozide 2 mg (current) or 4 mg/day (study initiation)

EXPERIMENTAL

Pimozide will be initiated at 2 mg once daily. The maximum dose will then be administered for a target period of 22 weeks.

Drug: Pimozide 2mg/day (current) or 4 mg/day (study initiation)

Group 2 Placebo

PLACEBO COMPARATOR

Placebo tablets will be utilized and administered in an identical manner for subjects in Group 1

Drug: Placebo Oral Tablet

Interventions

Pimozide 2mg/day (current) or 4 mg/day (study initiation) DRUG

Pimozide 2mg tablets will be taken once daily.

Group 1 Pimozide 2 mg (current) or 4 mg/day (study initiation)

Placebo Oral Tablet DRUG

Identical matching placebo lactose tablets

Group 2 Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (see Appendix 2).
• Able to comprehend and willing to sign Informed Consent Form (ICF).
• Age 18 years of age or greater.
• ALS Symptom onset of muscle weakness or speech impairment no more than 48 months prior to screen visit. Fasiculations should not be considered.
• Slow Vital Capacity (SVC) greater than or equal to 50% predicted for sex, age and height at screen.
• Has the ability to swallow tablets/capsules whole at study entry.
• 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.
• 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.
• If the subject is receiving Edaravone therapy, the dose must be stable for at least 1 cycle of infusion treatments before the randomization visit.

You may not qualify if:

• History of laryngeal spasm, dystonia, or akathisia.
• 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.
• 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.
• History of neuroleptic malignant syndrome.
• History of hypersensitivity or serious adverse reaction(s) to a neuroleptic medication.
• History of hyponatremia \< 130 mmol/L
• Subject with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value \>3.0 times the upper limit of normal at the Screening visit.
• Current heparin or warfarin use.
• History of hepatic and/or renal impairment that may affect pimozide metabolism
• 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.
• Current antipsychotic use
• Presence of central nervous system depression, comatose states, liver disorders, renal insufficiency, and blood dyscrasias
• Presence of Parkinson's syndrome
• Presence of major depressive disorders as determined by site Investigator.
• History of clinically significant ECG abnormalities at screen visit, including QTc\>500ms.

Sponsors & Collaborators

• University of Calgary: lead
• ALS Canada: collaborator
• Brain Canada: collaborator

Study Sites (9)

Dr. Lawrence Korngut -South Health Campus

Calgary, Alberta, T3M 1M4, Canada

RECRUITING

Dr. Wendy Johnston - University of Alberta

Edmonton, Alberta, T6G2G3, Canada

RECRUITING

Dr. Colleen O'Connell - Stan Cassidy Centre for Rehabilitation

Fredericton, New Brunswick, E3B 0C7, Canada

RECRUITING

Dr. John Turnbull McMaster University/Hamilton Health Services

Hamilton, Ontario, L8N 3Z5, Canada

RECRUITING

Dr. Christen Shoesmith - London Health Sciences Centre

London, Ontario, N6A5A5, Canada

RECRUITING

Dr. Ariel Breiner -Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y4E9, Canada

RECRUITING

Dr. Lorne Zinman Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Dr. Sandrine Larue - Reserche Sepmus Inc.

Greenfield Park, Quebec, J4V 2J2, Canada

RECRUITING

Dr. Genevieve Matte

Montreal, Quebec, H2L4M1, Canada

RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Pimozide

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Lawrence Korngut, M.D.

  University of Calgary and Alberta Health Services

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pim2 Study

CONTACT

403-210-7006; Pimozide2@ucalgary.ca

Janet Petrillo, M.Sc.

CONTACT

403-210-7006; japetril@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D. Director Calgary ALS and Motor Neuron Disease Clinic

Study Record Dates

• First Submitted: August 31, 2017
• First Posted: September 5, 2017
• Study Start: October 27, 2017
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: May 28, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (9)