Study of the Effects of the Organism on Monomethyl Fumarate (MMF) After the Administration of LAS41008

• Status: Completed
• Trial end date: 2016-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine how the organism affects MMF (metabolite of dimethyl fumarate [DMF]) after single oral dose administration of LAS41008 120 mg gastroresistant tablet and Fumaderm® 120 mg gastro-resistant tablet under fasting and fed conditions. The study also aims to assess the safety of the study treatments.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Almirall, S.A.
• Treatments: Dimethyl Fumarate

Criteria

Inclusion Criteria:

• Subjects who are able to understand and follow instructions during the study as determined by the Investigator.

• Signed and dated informed consent.

• Men and women of any ethnic origin between 18 and 55 years of age (inclusive, at the time of Screening) in general good physical health as determined by medical and surgical history, physical examination, ECG, vital signs, and clinical laboratory tests (including clinically significant changes in laboratory test).

• Weight within the normal range according to accepted values for the body mass index (BMI) within 18.0 to 29.0 kg/m2 (inclusive, at the time of Screening), and a body weight of at least 50 kg.

• Normal blood pressure (Systolic Blood Pressure ≥ 90, ≤ 139 mmHg; Diastolic Blood Pressure ≥ 55, ≤ 89 mmHg) measured after at least 5 minutes rest in supine position.

• A pulse rate of ≥ 45 and ≤ 99 beats per minute measured after at least 5 minutes rest in supine position.

• ECG recording, in triplicate, taken at least 1 minute apart; after at least 5 minutes of rest in a supine position without clinically significant abnormalities.

Exclusion Criteria:

• Subject who has received live-attenuated vaccine(s) within 4 weeks of Day 1 or plan to receive a vaccination during the study until 6 months after the last dose of study medication.

• More than moderate smoker (> 10 cigarettes/day).

• Demonstrating excess in xanthine consumption (more than five cups of coffee or equivalent per day).

• More than moderate alcohol consumption (subjects will be advised to consume no more than 2 units of alcohol per day and completely abstain from 72 hours prior to any visit (1 unit is equal to approximately 10 g of pure alcohol [250 mL] of beer [5%], 1 small glass [100 mL] of wine [12%] or 35 mL of spirits [35%]).

• Any history of alcohol or drug abuse or excessive intake of alcohol, as judged by the Investigator.

• Any history of drug hypersensitivity, asthma (with the exception of childhood asthma), urticaria or other severe allergic diathesis as well as active hay fever.

• Any history of hypersensitivity or lack of tolerability to the ingredients of the investigational medicinal product (IMP).

• Having febrile or infectious illness within at least 7 days prior to the Visit 1 (Screening) and Day -1 of Period 1.

• Any presence of acute or chronic liver or renal diseases.

• Any history or presence of gastrointestinal disease or problems including chronic gastritis, peptic ulcers, diarrhoea, or inflammatory bowel disease.

• Any history of clinically significant chronic or recurrent metabolic, pulmonary, neurological (especially history of epileptic seizures), endocrinological, immunological, psychiatric or cardiovascular disease, myopathies, and bleeding tendency.

• Subjects who have ever received immunosuppressant treatment (excluding topical or oral steroids taken 1 and 5 years before Visit 1 [Screening] respectively).

• Any history of frequent headache or migraine.

• Any history of malignancies (excluding basal skin cell cancer), as judged by the Investigator.

• Non-vasectomised man not using barrier contraception during the study.

• Nursing (breastfeeding) woman.

• Women with a positive serum pregnancy test at Visit 1 (Screening) or a positive urine pregnancy test on Day -1 of each Period or women of childbearing potential not using one highly effective method of birth control in combination with a barrier method during the study.

• Vegetarians.

• Unable or unwilling to comply with the dietary conditions in this study.

• Blood donation of more than 500 mL within 60 days prior to Visit 1 (Screening) or Day -1 of Period 1.

• Participation in the treatment phase of a clinical study within 90 days (or five half-life times, whichever is longer) prior to Visit 1 (Screening).

• Any abnormal safety laboratory values considered clinically significant by the Investigator, especially serum creatinine, alkaline phosphatase (AP), triglycerides or cholesterol, or medically relevant changes in haematology (especially differential cell count and thrombocytes), or relevant observations of protein in urine.

• Subjects with lymphocyte and white blood cell counts below the lower normal range (1.2 x 10^9L and 3.0 x 10^9L, respectively) or eosinophils above the upper normal range (0.4 x 10^9L) will not be included in the study.

• Liver enzyme results (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT)) above the upper limit of normal (ULN female/male: AST: 31/37 IU/L; ALT: 35/50 IU/L; GGT: 42/71 IU/L).

• Creatinine values above the upper limit of normal and an estimated glomerular filtration rate below 90 mL/min.

• Positive test for human immunodeficiency virus (HIV) antibodies and antigen. Positive Hepatitis B virus surface antigen (HBsAg) test.

• Positive Anti-hepatitis C virus antibodies (Anti-HCV) test.

• Any history or suspicion of barbiturate, amphetamine, benzodiazepine, cocaine, opiates and cannabis abuse within the last 12 months (verified on-site by a urine test).

• Subject is not willing to refrain from xanthine-containing food or beverages as well as grapefruit products within 48 hour prior to first administration until discharge.

• Any gastrointestinal complaints within seven days prior to Visit 1 (Screening) or first study drug administration.

• Use of any medication (over the counter or prescription medication) within two weeks prior to Visit 1 (Screening) and Day -1 of Period 1 (or at least 10 times the respective elimination halflife, whichever is longer). Paracetamol may be concomitantly used, at the discretion of the Investigator (up to 1000 mg per day).

• Demonstrating any other active physical or mental disease, acute or chronic.