Clinical trial NCT04840823: Enoxacin for Amyotrophic Lateral Sclerosis (ALS)
Official title: A Randomized, Double-blind, Parallel Group, Single Centre, Phase 1b/2 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Three Orally Administered Doses of Enoxacin (200mg Twice Daily, 400mg Twice Daily and 600mg Twice Daily) in Adults With Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Enoxacin
Lead sponsor: McGill University
Sponsor class: OTHER
Collaborators: name: Weizmann Institute of Science
name: Apotex Inc.
First posted: 2021-04-12
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will assess the safety of the drug enoxacin at specific dose levels in adults with ALS.

Detailed description: Participants will be randomized to one of three doses of enoxacin (200, 400, or 600mg twice daily) for 30 days. On day 1, 7, 14, 21, and 30 of treatment and at a follow-up visit 14 days after the last dose, participants will be assessed for safety measures and blood will be collected to assist with the determination of enoxacin pharmacokinetics (PK) and pharmacodynamics (PD). On day 1 and day 30 of dosing, participants will only take one dose of study medication (the morning dose) to assist with determination of enoxacin single dose PK over a 24-hour period. A lumbar puncture (LP) to collect cerebrospinal fluid (CSF) for PD assessments will occur on day 1 and day 30.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of familial or sporadic ALS
* FVC of ≥ 50 percent predicted
* If female, is not breastfeeding and is not pregnant
* Has been on a stable dose of riluzole, or has not taken riluzole, for at least 30 days prior to screening
* If taking concomitant edaravone at study entry, must have completed at least one cycle of edaravone therapy prior to screening
* Not currently taking and has not taken for at least 30 days prior to screening any Theophylline containing medications, clozapine, or duloxetine
* No active infection in the 30 days prior to randomization
* Has not taken any fluoroquinolone antibiotics for at least 30 days prior to screening

Exclusion Criteria:

* Hypersensitivity/allergy to fluoroquinolones
* Diagnosed with another neurodegenerative disease
* Significant pulmonary disorder not attributed to ALS, central nervous system disorder associated with seizures, myasthenia gravis, active rheumatologic disease, tendinopathy, or any severe uncontrolled medical condition (other than ALS)
* Severe renal impairment or impaired liver function
* Baseline prolongation of QT interval/corrected QT interval (QTc) at screening, treatment with any agent that may prolong Qt/QTc interval, or history of any other at-risk other cardiac condition
* Currently enrolled in another clinical trial involving an experimental drug or device

Primary outcomes:
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit
measure: Incidence of abnormalities in clinical laboratory assessments
timeFrame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit
measure: Incidence of abnormalities in vital signs
timeFrame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit
measure: Incidence of abnormalities in physical and neurological examinations
timeFrame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit
measure: Incidence of abnormalities in electrocardiograms (ECGs)
timeFrame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit
measure: Ability of participants to remain on their assigned dose for the full 30 day treatment period
timeFrame: From the beginning (day 1) to the end (day 30) of the 30 day treatment period
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of enoxacin after administration on day 1 and 30
timeFrame: Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.
measure: Time of maximum plasma concentration (Tmax) of enoxacin after administration on day 1 and 30
timeFrame: Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.
measure: Area under the plasma concentration-time curve from time zero until the time corresponding with the last observed quantifiable concentration (AUC 0-last) of enoxacin after administration on day 1 and 30
timeFrame: Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.
measure: Area under the plasma concentration-time curve extrapolated to infinity (AUC 0-inf) of enoxacin after administration on day 1 and 30
timeFrame: Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.
measure: Terminal half-life (t1/2) of enoxacin after administration on day 1 and 30
timeFrame: Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.
measure: Accumulation ratio (R) of enoxacin after administration on day 1 and 30
timeFrame: Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.
measure: Trough plasma concentration at pre-dose of enoxacin on day 7, 14, 21, and 30
timeFrame: Prior to morning dosing on days 7, 14, 21, and 30.
measure: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score at baseline and at the end of the follow-up period
timeFrame: At baseline (prior to dosing on day 1 of dosing) and at the 14 day +/- 2 day follow-up visit
measure: King's College (KINGS) stage at baseline and at the end of the follow-up period
timeFrame: At baseline (prior to dosing on day 1 of dosing) and at the 14 day +/- 2 day follow-up visit
measure: Forced Vital Capacity (FVC) measurements at baseline and at the end of the follow-up period
timeFrame: At baseline (prior to dosing on day 1 of dosing) and at the 14 day +/- 2 day follow-up visit
Other outcomes:
measure: Ability of enoxacin to modulate the expression of one or more miRNA species in cerebrospinal fluid (CSF) and/or plasma
timeFrame: Blood: prior to morning dosing on days 1, 7 (+/- 2 days), 14 (+/- 2 days), 21 (+/- 2 days) and 30, and at the 14 day +/- 2 day follow-up visit. CSF: prior to dosing on day 1, and 2 hours (+/-1 hour) post dosing on day 30.
Locations:
city: Montreal
country: Canada
facility: Montreal Neurological Institute-Hospital
state: Quebec
Study officials:
affiliation: McGill University
name: Angela Genge, MD, FRCP
role: PRINCIPAL_INVESTIGATOR
References:
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