Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis

Arimoclomol is an investigational drug for amyotrophic lateral sclerosis (ALS) that amplifies heat shock protein gene expression during cell stress. The objectives of the present study were to assess the safety, tolerability, and pharmacokinetics of arimoclomol in ALS. Eighty‐four participants with...

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Bibliographic Details
Published in:Muscle & nerve 2008-07, Vol.38 (1), p.837-844
Main Authors: Cudkowicz, Merit E., Shefner, Jeremy M., Simpson, Elizabeth, Grasso, Daniela, Yu, Hong, Zhang, Hui, Shui, Amy, Schoenfeld, David, Brown, Robert H., Wieland, Scott, Barber, Jack R.
Format: Article
Language:English
Subjects:
Aged
amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - drug therapy
Amyotrophic Lateral Sclerosis - metabolism
arimoclomol
Biological and medical sciences
Blood-Brain Barrier
clinical trial
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Dose-Response Relationship, Drug
Double-Blind Method
Female
Humans
Hydroxylamines - administration & dosage
Hydroxylamines - adverse effects
Hydroxylamines - pharmacokinetics
Male
Medical sciences
Middle Aged
Neurology
protein aggregation
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Summary:Arimoclomol is an investigational drug for amyotrophic lateral sclerosis (ALS) that amplifies heat shock protein gene expression during cell stress. The objectives of the present study were to assess the safety, tolerability, and pharmacokinetics of arimoclomol in ALS. Eighty‐four participants with ALS received arimoclomol at one of three oral doses (25, 50, or 100 mg three times daily) or placebo. The primary outcome measure was safety and tolerability. A subset of 44 participants provided serum and cerebrospinal fluid (CSF) samples for pharmacokinetic analysis. Participants who completed 12 weeks of treatment could enroll in a 6‐month open‐label study. Arimoclomol at doses up to 300 mg/day was well tolerated and safe. Arimoclomol resulted in dose‐linear pharmacologic exposures and the half‐life did not change with continued treatment. Arimoclomol CSF levels increased with dose. Arimoclomol was shown to be safe, and it crosses the blood–brain barrier. Serum pharmacokinetic profiles support dosing of three times per day. An efficacy study in ALS is planned. Muscle Nerve, 2008
ISSN:0148-639X
1097-4598
DOI:10.1002/mus.21059