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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03272503
• Date of registration: 31/08/2017
• Prospective Registration: Yes
• Primary sponsor: University of Calgary
• Public title: A Clinical Trial of Pimozide in Patients With Amyotrophic Lateral Sclerosis (ALS) Pimozide2
• Scientific title: A Phase II Randomized, Placebo-Controlled, Double Blinded, Multi-Centre Clinical Trial of Pimozide in Patients With Amyotrophic Lateral Sclerosis
• Date of first enrolment: October 27, 2017
• Target sample size: 100
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT03272503
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Canada

Contacts

• Name: Pim2 Study

• Name: Lawrence Korngut, M.D.
• Affiliation: University of Calgary and Alberta Health Services

Key inclusion & exclusion 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 (see Appendix 2).

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 1
cycle 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, and/or concomitant use of drugs known to
prolong the QT interval (TCAs, opioids such as methodone, quinolone antibiotics
(ciprofloxacin), antimalarials (quinine), Detrol, azole antifungals, Class 1A, III and
1C antiarrhythmics, and macrolide antibiotics.

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
(including Withania) 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. Do not consider scores greater than 3 for Tremor in any region if due to Benign
Essential, Exaggerated, or Physiological Tremor.

28. The concomitant use of SSRIs and tricyclic antidepressants (e.g. amitriptyline,
amoxaprine, desipramine, doxepin, imipramine, nortriptyline, protripyline,
trimipramine) - and Tolterodine (Detrol) CYP2D6 inhibitor.

- Prohibited medications such as tricyclic antidepressants, antimalarials, and
serotonin reuptake inhibitors,(ie sertraline, paroxetine, citalopram, fluoxetine,
vilazodone 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).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Amyotrophic Lateral Sclerosis

ALS

Intervention(s)

Drug: Placebo Oral Tablet

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

Primary Outcome(s)

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.]

Secondary Outcome(s)

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.]

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.]

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]

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.]

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.]

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.]

Secondary ID(s)

Pimozide2_ALS-002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Brain Canada

ALS Canada