An open label, cross over pilot study to evaluate the effect of a single dose of TW001 on the oxidative stress and pharmacokinetics with and without food in patients with amyotrophic lateral sclerosis

Completed

• Conditions: ALS; muscle disease; 10029317

• Registration Number: NL-OMON42324
• Lead Sponsor: Treeway B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 8

Inclusion Criteria

1. Provision of written informed consent and compliance with study procedures
2. Diagnoses of definite, probable or possible ALS according to the El Escorial criteria, supported by laboratory values and confirmed by a trained and qualified expert physician
3. Aged between 18 and 70 years of age (both inclusive)
4. Women must not be able to become pregnant (post-menopausal for at least a year, surgically sterile or practicing adequate birth control methods) for the duration of the study
5. Women of childbearing potential must have a negative serum pregnancy test at screening and be non-lactating
6. Vital capacity equal to or more than 70% predicted normal value for gender, height and age at screening
7. No clinically significant abnormality on 12-lead ECG performed at screening

Exclusion Criteria

1. Other causes of neuromuscular weakness have not been excluded
2. Significant cognitive impairment, clinical dementia or psychiatric illness
3. Diagnosis of other neurodegenerative disease
4. Significant pulmonary disorder not attributed to ALS, requirement of treatment complicating evaluation of ALS on respiratory function
5. History of known sensitivity or intolerability of edaravone or to any related compound
6. Severe disturbance of consciousness
7. Hepatic impairment as indicated by Child-Pugh Class B or C (moderate to severe hepatic insufficiency)
8. Renal impairment as indicated by a creatinine clearance of less than 50 mL/min as calculated by the Cockcroft Gault equation using serum creatinine.
9. Serious difficulty swallowing and/or inability to eat high-fat high-calorie meal
10. Tracheostomy or non-invasive ventilation
11. Administration of antibiotics, CYP3A4 and or PgP inhibitors
12. Smoking
13. Advanced cancer
14. Exposure to any investigational drug within 30 days of the screening visit
15. Malnourishment based on laboratory data, dehydration or on a sodium free diet
16. Presence of any of the following clinical conditions:
a. Substance abuse within the past year
b. Uncontrolled cardiac, pulmonary, renal, hepatic, endocrine, hematologic or active infectious disease
c. AIDS or AIDS related disease, hepatitis B virus (HBV) or hepatitis C virus (HCV)
d. Unstable psychiatric illness defined as psychosis, untreated major depression within 90 days of the screening visit

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1. To establish the pharmacokinetic profile of a single dose TW001<br /><br>2. To evaluate the effect of single dose TW001 on oxidative stress parameters<br /><br>in CSF (3NT) and blood (3NT, calcium, albumin, creatinine)<br /><br>3. To evaluate the effect of food on the PK of TW001 and oxidative stress</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. To evaluate the safety and tolerability of TW001<br /><br>2. To investigate the PK/PD relationship</p><br>