This is a study to assess the relative bioavailability and the effect of food on the pharmacokinetics of a new 15 mg tablet formulation of losmapimod
This study is a Phase 1, open-label, 3-period, 6-sequence, randomized, single-dose, crossover study designed to assess the relative bioavailability of a 15 mg tablet of losmapimod versus two 7.5 mg tablets of losmapimod under fasted conditions and to assess the effect of food on the pharmacokinetics of a 15 mg tablet of losmapimod under fasted and fed conditions in 18 healthy subjects. The study will consist of a screening period, 3 treatment periods with a single dose of study drug per treatment period, a 48-hour washout period between dosing, and an end of study visit. Subjects will be randomly assigned to receive 1 of 6 treatment sequences (3 subjects per treatment sequence) prior to dosing on Day 1 of Period 1. The primary endpoint of the study is to assess the relative bioavailability and the effect of food on the pharmacokinetics of a new 15 mg tablet formulation of losmapimod. Secondary endpoints include assessing the safety and tolerability and evaluating target engagement in the blood of a new 15 mg tablet formulation of losmapimod in healthy subjects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
18
Subjects will receive one losmapimod 15 mg tablet by mouth under fasted conditions.
Subjects will receive two losmapimod 7.5 mg tablets by mouth under fasted conditions.
Subjects will receive one losmapimod 15 mg tablet by mouth under fed conditions.
PPD Phase I Clinic
Austin, Texas, United States
Plasma Concentrations of Losmapimod
To assess the bioavailability of losmapimod (1 x 15 mg tablet) (test) versus losmapimod tablets (2 x 7.5 mg tablets) (reference), blood samples will be collected under fasted conditions to measure the plasma concentration of losmapimod at specified timepoints by liquid chromatography with tandem mass spectrometry.
Time frame: Treatment Regimen A: Days 1 and 2
Plasma Concentrations of Losmapimod
To assess the bioavailability of losmapimod (1 x 15 mg tablet) (test) versus losmapimod tablets (2 x 7.5 mg tablets) (reference), blood samples will be collected under fasted conditions to measure the plasma concentration of losmapimod at specified timepoints by liquid chromatography with tandem mass spectrometry.
Time frame: Treatment Regimen B: Days 1 and 2
Food Effect of Losmapimod
To assess the effect of food on the pharmacokinetics of losmapimod test versus reference, blood samples will be collected under fasted conditions to measure the plasma concentration of losmapimod at specified timepoints by liquid chromatography with tandem mass spectrometry.
Time frame: Treatment Regimen A: Days 1 and 2
Food Effect of Losmapimod
To assess the effect of food on the pharmacokinetics of losmapimod, blood samples will be collected after a high fat meal to measure the plasma concentration of losmapimod at specified timepoints by liquid chromatography with tandem mass spectrometry.
Time frame: Treatment Regimen Part C: Days 1 and 2
Treatment-Emergent Adverse Events
To evaluate the safety and tolerability of losmapimod 15 mg in healthy adult subjects based on the frequency of adverse events (AEs), frequency of serious adverse events (SAEs), and clinically significant laboratory test results, electrocardiograms (ECGs), vital signs and physical examination findings.
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Time frame: Up to approximately 4 weeks of monitoring
Target Engagement in Blood
Change from baseline in the ratio of phosphor-HSP27/total-HSP27 in sorbitol-stimulated whole blood lysate will be evaluated by enzyme linked immunosorbent assay (ELISA).
Time frame: Treatment Regimen A: Day 1
Target Engagement in Blood
Change from baseline in the ratio of phosphor-HSP27/total-HSP27 in sorbitol-stimulated whole blood lysate will be evaluated by enzyme linked immunosorbent assay (ELISA).
Time frame: Treatment Regimen B: Day 1
Target Engagement in Blood
Change from baseline in the ratio of phosphor-HSP27/total-HSP27 in sorbitol-stimulated whole blood lysate will be evaluated by enzyme linked immunosorbent assay (ELISA).
Time frame: Treatment Regimen C: Day 1