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Completed

NCT Number: NCT04840823

Enoxacin for Amyotrophic Lateral Sclerosis (ALS)

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

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Key information

Conditions

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

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Montreal Neurological Institute-Hospital

Montreal, Quebec, H3A 2B4, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Enoxacin

Drug

Oral 200mg tablet

Placebo

Drug

Oral tablet

Primary outcomes

  1. Incidence of adverse events (AEs) and serious adverse events (SAEs)

    Time frame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit

    The incidence of adverse events (new or worsened from baseline (where baseline refers to those AEs recorded prior to dosing on day 1 of dosing)) will be summarized by primary system organ class and preferred term as frequency count and percentage of participants with AEs.

  2. Incidence of abnormalities in clinical laboratory assessments

    Time frame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit

    Clinical laboratory data will be characterized by abnormalities in values and in changes from baseline values, where baseline refers to measurements taken prior to dosing on day 1 of dosing.

  3. Incidence of abnormalities in vital signs

    Time frame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit

    Vital sign data will be characterized by abnormalities in values and in changes from baseline values, where baseline refers to measurements taken prior to dosing on day 1 of dosing.

  4. Incidence of abnormalities in physical and neurological examinations

    Time frame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit

    Physical and neurological examinations will be characterized by abnormalities and in changes from baseline, where baseline refers to measurements taken prior to dosing on day 1 of dosing.

  5. Incidence of abnormalities in electrocardiograms (ECGs)

    Time frame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit

    ECG data will be characterized by abnormalities in values and in changes from baseline values, where baseline refers to measurements taken prior to dosing on day 1 of dosing.

  6. Ability of participants to remain on their assigned dose for the full 30 day treatment period

    Time frame: From the beginning (day 1) to the end (day 30) of the 30 day treatment period

    The ability of participants to remain on each dose level will be measured by the mean number of missed doses.

Secondary outcomes

  1. Maximum plasma concentration (Cmax) of enoxacin after administration on day 1 and 30

    Time frame: Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.

    Enoxacin plasma concentrations measured in each individual participant prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing will be used to derive the Cmax.

  2. Time of maximum plasma concentration (Tmax) of enoxacin after administration on day 1 and 30

    Time frame: Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.

    Enoxacin plasma concentrations measured in each individual participant prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing will be used to derive the Tmax.

  3. 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

    Time frame: Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.

    Enoxacin plasma concentrations measured in each individual participant prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing will be used to derive the (AUC) 0-last.

  4. Area under the plasma concentration-time curve extrapolated to infinity (AUC 0-inf) of enoxacin after administration on day 1 and 30

    Time frame: Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.

    Enoxacin plasma concentrations measured in each individual participant prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing will be used to derive the AUC 0-inf.

  5. Terminal half-life (t1/2) of enoxacin after administration on day 1 and 30

    Time frame: Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.

    Enoxacin plasma concentrations measured in each individual participant prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing will be used to derive the t1/2.

  6. Accumulation ratio (R) of enoxacin after administration on day 1 and 30

    Time frame: Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.

    Enoxacin plasma concentrations measured in each individual participant prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing will be used to derive the R.

  7. Trough plasma concentration at pre-dose of enoxacin on day 7, 14, 21, and 30

    Time frame: Prior to morning dosing on days 7, 14, 21, and 30.

    Enoxacin plasma concentrations measured in each individual participant prior to morning dosing on days 7, 14, 21, and 30 will be used to derive the trough plasma concentration at pre-dose.

  8. Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score at baseline and at the end of the follow-up period

    Time frame: At baseline (prior to dosing on day 1 of dosing) and at the 14 day +/- 2 day follow-up visit

    The ALSFRS-R will be used to measure activities of daily living (ADL) and global function across four domains (respiratory, bulbar function, gross motor skills, and fine motor skills) and consists of 12 questions, each scored from 0 to 4, for a total possible score of 48, with higher scores representing better function.

  9. King's College (KINGS) stage at baseline and at the end of the follow-up period

    Time frame: At baseline (prior to dosing on day 1 of dosing) and at the 14 day +/- 2 day follow-up visit

    The KINGS staging system for ALS will be used to assess the course of the disease and is based on the number of involved regions (where the three possible regions are bulbar, upper limb or lower limb) for the first three stages and the need for gastrostomy and non-invasive ventilation for the subsequent stages. The possible stages in the KINGS staging system are as follows: Stage 1: First Region Involved; Stage 2: Second Region Involved; Stage 3: Third Region Involved; Stage 4a: Nutritional Failure (need for gastrostomy); Stage 4b: Respiratory Failure (need for non-invasive ventilation); and Stage 5: Death.

  10. Forced Vital Capacity (FVC) measurements at baseline and at the end of the follow-up period

    Time frame: At baseline (prior to dosing on day 1 of dosing) and at the 14 day +/- 2 day follow-up visit

Other outcomes

  1. Ability of enoxacin to modulate the expression of one or more miRNA species in cerebrospinal fluid (CSF) and/or plasma

    Time frame: 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.

    Expression levels of miRNA species will be measured in CSF and/or plasma

Sponsors and collaborators

Lead sponsor

McGill University

Other

Collaborators

  • Apotex Inc.
  • Weizmann Institute of Science

Registry information

Official study 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

Acronym: REALS-1

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Apr 12, 2021
Registry last updated
Jan 26, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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