Relative Bioavailability and Food Effect Study of Losmapimod 15 mg Tablets

NCT05002231 | Completed Phase 1 FDA Drug

• 1 other identifier: 1821-CLP-101
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy Adult Subjects

Keywords

Healthy Adult Subjects

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Treatment Regimen Part C: Days 1 and 2

Secondary Outcomes (4)

• Treatment-Emergent Adverse Events

  Up to approximately 4 weeks of monitoring

• Target Engagement in Blood

  Treatment Regimen A: Day 1

• Target Engagement in Blood

  Treatment Regimen B: Day 1

• Target Engagement in Blood

  Treatment Regimen C: Day 1

Study Arms (3)

Losmapimod 15 mg oral tablet in healthy subjects (Treatment Regimen A)

EXPERIMENTAL

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.

Drug: Losmapimod 15 mg oral tablet

Losmapimod two 7.5 mg oral tablets in healthy subjects (Treatment Regimen B)

EXPERIMENTAL

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.

Drug: Losmapimod two 7.5 mg oral tablets

Losmapimod one 15 mg oral tablet in healthy subjects (Treatment Regimen C)

EXPERIMENTAL

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.

Drug: Losmapimod one 15 mg oral tablet

Interventions

Losmapimod 15 mg oral tablet DRUG

Subjects will receive one losmapimod 15 mg tablet by mouth under fasted conditions.

Losmapimod 15 mg oral tablet in healthy subjects (Treatment Regimen A)

Losmapimod two 7.5 mg oral tablets DRUG

Subjects will receive two losmapimod 7.5 mg tablets by mouth under fasted conditions.

Losmapimod two 7.5 mg oral tablets in healthy subjects (Treatment Regimen B)

Losmapimod one 15 mg oral tablet DRUG

Subjects will receive one losmapimod 15 mg tablet by mouth under fed conditions.

Losmapimod one 15 mg oral tablet in healthy subjects (Treatment Regimen C)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• History of regular alcohol consumption within 6 months prior to screening defined as an average weekly intake of greater than 21 units. One unit is equivalent to approximately half pint \[200 mL\] of beer, 1 small glass \[100 mL\] of wine, or 1 measure \[25 mL\] of spirits.
• History of demonstrating an excess in xanthine consumption (more than 8 cups of coffee or equivalent per day).
• Received study drug in another investigational study within 30 days of dosing.
• Received the coronavirus disease 2019 (COVID-19) vaccine within 14 days before Day 1, or subjects who plan to receive a COVID-19 vaccine at any time during the study, including during the follow up period or has tested positive for COVID 19 within 3 months prior to screening.
• Use of any medication (prescription or over-the-counter) within 14 days of study drug administration, or use of herbal supplements, dietary supplements, or multivitamins within 7 days of study drug administration or less than five half-lives (whichever is longer), with the exception of contraceptives, hormonal replacement therapies, and acetaminophen (up to 3 grams per day). Other exceptions will only be made if the rationale is clearly documented by the investigator.

Sponsors & Collaborators

• Fulcrum Therapeutics: lead

Study Sites (1)

PPD Phase I Clinic

Austin, Texas, 78744, United States

Location

Related Publications (2)

• Barbour AM, Sarov-Blat L, Cai G, Fossler MJ, Sprecher DL, Graggaber J, McGeoch AT, Maison J, Cheriyan J. Safety, tolerability, pharmacokinetics and pharmacodynamics of losmapimod following a single intravenous or oral dose in healthy volunteers. Br J Clin Pharmacol. 2013 Jul;76(1):99-106. doi: 10.1111/bcp.12063.

  PMID: 23215699 BACKGROUND

• Mellion ML, Ronco L, Berends CL, Pagan L, Brooks S, van Esdonk MJ, van Brummelen EMJ, Odueyungbo A, Thompson LA, Hage M, Badrising UA, Raines S, Tracewell WG, van Engelen B, Cadavid D, Groeneveld GJ. Phase 1 clinical trial of losmapimod in facioscapulohumeral dystrophy: Safety, tolerability, pharmacokinetics, and target engagement. Br J Clin Pharmacol. 2021 Dec;87(12):4658-4669. doi: 10.1111/bcp.14884. Epub 2021 May 14.

  PMID: 33931884 BACKGROUND

MeSH Terms

Interventions

6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamide; Tablets

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Michelle Mellion, MD

  Fulcrum Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomized, single-dose, cross-over study
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: August 4, 2021
• First Posted: August 12, 2021
• Study Start: August 19, 2021
• Primary Completion: October 5, 2021
• Study Completion: October 22, 2021
• Last Updated: November 12, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)