Study of the Effects of the Organism on Monomethyl Fumarate (MMF) After the Administration of LAS41008
Condition: Psoriasis
MeSH terms: Psoriasis
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      The present study will be conducted to further investigate the pharmacokinetics (PK) of
      LAS41008 (containing DMF) after single oral dose administrations of a 120 mg gastro-resistant
      tablet under fed and fasting conditions.

      Two previous Phase 1 studies allowed exploring the PK of LAS41008 30 mg and 120 mg separately
      after multiple dosing. In the current study, an improved bioanalytical method will allow the
      detection of lower MMF concentrations, and thus the same gastro-resistant tablet formulation
      (LAS41008) as used in the previous Phase 1 study will be investigated, but on a larger
      population and after single oral dose administration. Only the higher LAS41008 dose (120 mg)
      will be tested, as this is the formulation to be most frequently used during a standard
      treatment course for psoriasis with LAS41008. Similarly, single oral doses of Fumaderm® 120
      mg (defined mixture of DMF and calcium (Ca), magnesium (Mg), and zinc (Zn) salts of
      ethylhydrogenfumarate (EHF, mono-ethyl fumarate (MEF)) will be tested in order to provide
      better comparative PK data. The comparison of LAS41008 and Fumaderm® PK will be evaluated in
      an exploratory manner.

      The study will be conducted according to a randomised, open-label, four-way complete
      crossover, single dose design in 32 healthy male and female subjects. Up to 4 discontinued
      subjects may be replaced in case of early dropouts or a dropout rate greater than 15% (5 or
      more subjects). Gender balance will also be taken into consideration to ensure that roughly
      the same number of males and females are randomised. Upon inclusion into the treatment phase,
      each subject will be randomly allocated to one of four treatment sequences in a 4x4 Williams
      design. On Day 1 of each treatment period subjects will receive a single oral dose of either
      LAS41008 120 mg gastro-resistant tablet or Fumaderm® 120 mg gastro-resistant tablet under
      fasting or fed conditions. The drug administrations will be separated by a wash-out-phase of
      7 ± 3 days. Blood sampling for PK will be performed until 24 hours after each study drug
      administration.

      The Informed Consent Form (ICF) will be signed before any study activity, including the
      withdrawal of any concomitant medication (at least 2 weeks before this screening visit) if
      required for study participation. The Screening Visit will take place within 28 days before
      randomisation and after signing of the ICF to check subjects' eligibility. In each period,
      subjects will be admitted to the study centre from the morning of Day -1 until discharge in
      the morning of Day 2 (after collection of last blood sampling for PK).

      The duration of study participation for each subject from Visit 1 (Screening) to the
      Follow-up Visit 7 ± 3 days after the last study drug administration is estimated to be
      approximately 7 to 10 weeks considering study visits time-window allowance.
    

Intervention name(s): LAS41008 120 mg / Fumaderm® 120 mg
Intervention type(s): Drug
Intervention description(s): Single dose of LAS41008 120 mg or Fumaderm® 120 mg in each Period
Other intervention name(s): LAS41008: DMF / Fumaderm®: DMF + Ca, Mg and Zn salts of EHF
Intervention MeSH terms: Dimethyl Fumarate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pharmacokinetics; Healthy volunteers; Monomethylfumarate; Dimethyl fumarate; Fumaderm®; Ethyl fumarate