The study will assess the safety of the drug enoxacin at specific dose levels in adults with ALS.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
8
Montreal Neurological Institute-Hospital
Montreal, Quebec, Canada
Incidence of adverse events (AEs) and serious adverse events (SAEs)
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.
Time frame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit
Incidence of abnormalities in clinical laboratory assessments
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.
Time frame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit
Incidence of abnormalities in vital signs
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.
Time frame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit
Incidence of abnormalities in physical and neurological examinations
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.
Time frame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit
Incidence of abnormalities in electrocardiograms (ECGs)
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.
Time frame: From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit
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Ability of participants to remain on their assigned dose for the full 30 day treatment period
The ability of participants to remain on each dose level will be measured by the mean number of missed doses.
Time frame: From the beginning (day 1) to the end (day 30) of the 30 day treatment period
Maximum plasma concentration (Cmax) of enoxacin after administration on day 1 and 30
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.
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.
Time of maximum plasma concentration (Tmax) of enoxacin after administration on day 1 and 30
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.
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.
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
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.
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.
Area under the plasma concentration-time curve extrapolated to infinity (AUC 0-inf) of enoxacin after administration on day 1 and 30
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.
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.
Terminal half-life (t1/2) of enoxacin after administration on day 1 and 30
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.
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.
Accumulation ratio (R) of enoxacin after administration on day 1 and 30
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.
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.
Trough plasma concentration at pre-dose of enoxacin on day 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.
Time frame: Prior to morning dosing on days 7, 14, 21, and 30.
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score at baseline and at the end of the follow-up period
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.
Time frame: At baseline (prior to dosing on day 1 of dosing) and at the 14 day +/- 2 day follow-up visit
King's College (KINGS) stage at baseline and at the end of the follow-up period
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.
Time frame: At baseline (prior to dosing on day 1 of dosing) and at the 14 day +/- 2 day follow-up visit
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