A Phase 1, Open-Label, 3-Period, Randomized, Single-Dose, Crossover Study to Assess the Relative Bioavailability and the Effect of Food on the Pharmacokinetics of a New 15 mg Tablet of Losmapimod Versus the Current 7.5 mg Tablet
Overview
- Phase
- Phase 1
- Intervention
- Losmapimod 15 mg oral tablet
- Conditions
- Healthy Adult Subjects
- Sponsor
- Fulcrum Therapeutics
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Plasma Concentrations of Losmapimod
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
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
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male or female subjects, 18 to 65 years of age, inclusive, at screening.
- •Body mass index 18 to 30 kg/m2, inclusive, at screening with a minimum weight of 50 kg.
- •Good general health, based upon the opinion of the investigator as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead electrocardiogram (ECG) results, and physical examination findings at screening.
- •Willingness of men and women of reproductive potential must agree to use 2 effective and acceptable methods of contraception throughout study participation until 90 days after last dose of study drug. Female subjects must have a negative pregnancy test at screening and before the first dose of study drug.
- •Willing and able to comply with all protocol requirements.
- •The subject is able to provide written informed consent.
Exclusion Criteria
- •History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to, history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; history or presence of clinically significant pathology; clinically significant history of mental disease; and history of cancer, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical carcinoma in situ (all 3 with no recurrence for the last 5 years).
- •History of febrile illness within 5 days before the first dose of study drug.
- •Current clinically significant liver or kidney dysfunction.
- •Acute or chronic history of liver disease or current alanine aminotransferase elevation \>1.5 × upper limit of normal (ULN) and/or total bilirubin \>1.5 × ULN at screening.
- •Positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 or 2 antibodies at screening.
- •Any condition possibly affecting drug absorption (e.g., gastrectomy, cholecystectomy, or other gastrointestinal tract surgery, except appendectomy).
- •Standard 12 lead ECG demonstrating QT interval corrected for heart rate using Fridericia's formula (QTcF) \>450 msec for male subjects and QTcF \>470 msec for female subjects at screening. If QTcF exceeds 450 msec for males or 470 msec for females, the ECG will be repeated 2 more times, and the average of the 3 QTcF values will be used to determine the subject's eligibility.
- •History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s) or history or evidence of abnormal ECGs that, in the opinion of the investigator or medical monitor, would preclude the subject's participation in the study.
- •Blood or blood product (e.g., plasma/serum) donation (of approximately 1 pint \[500 mL\] or more) or has any significant loss of blood within 3 months (males) or 4 months (females) prior to screening or intention to donate blood or blood products during the study as determined by the investigator.
- •History of abuse of addictive substances such as drug abuse, or regular user of sedatives, hypnotics, tranquilizers, or any other addictive agent within 6 months prior to screening.
Arms & Interventions
Losmapimod 15 mg oral tablet in healthy subjects (Treatment Regimen A)
Subjects will be randomized to 1 of 6 treatment sequences to receive one 15 mg tablet of losmapimod administered orally under fasted conditions. Subjects will fast overnight (nothing to eat or drink except water) for at least 10 hours before each study drug administration. Subjects will remain fasted for 4 hours after dosing with study drug. Washout period of 48 hours between dosing.
Intervention: Losmapimod 15 mg oral tablet
Losmapimod two 7.5 mg oral tablets in healthy subjects (Treatment Regimen B)
Subjects will be randomized to 1 of 6 treatment sequences to receive two 7.5 mg tablets of losmapimod administered orally under fasted conditions. Subjects will fast overnight (nothing to eat or drink except water) for at least 10 hours before each study drug administration. Subjects will remain fasted for 4 hours after dosing with study drug. Washout period of 48 hours between dosing.
Intervention: Losmapimod two 7.5 mg oral tablets
Losmapimod one 15 mg oral tablet in healthy subjects (Treatment Regimen C)
Subjects will be randomized to 1 of 6 treatment sequences to receive one 15 mg tablet of losmapimod administered orally under fed conditions. Subjects will fast overnight (nothing to eat or drink except water) for at least 10 hours before breakfast and will receive a high-fat breakfast approximately 30 minutes before dose administration. Subjects must consume the meal within 25 minutes or less. Washout period of 48 hours between dosing.
Intervention: Losmapimod one 15 mg oral tablet
Outcomes
Primary Outcomes
Plasma Concentrations of Losmapimod
Time Frame: Treatment Regimen B: Days 1 and 2
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.
Food Effect of Losmapimod
Time Frame: Treatment Regimen Part C: Days 1 and 2
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.
Secondary Outcomes
- Treatment-Emergent Adverse Events(Up to approximately 4 weeks of monitoring)
- Target Engagement in Blood(Treatment Regimen C: Day 1)