A Study to Evaluate Bioavailability and Food Effect of Selumetinib (AZD6244) in Healthy Male Participants
Condition: Neurofibromatosis Type 1 (NF1)-Related Plexiform Neurofibromas (PNs); Healthy Participants
MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurofibroma, Plexiform
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will evaluate bioavailability and food effect of selumetinib (AZD6244) in healthy
      male participants. A total of 24 healthy male participants will be included to ensure at
      least 20 evaluable participants. The study is divided in 2 study parts; the same participants
      will participate in both parts of the study. Part 1 of the study is to investigate the
      pharmacokinetics (PK) of the selumetinib granule compared to the PK of selumetinib capsule,
      when administered with water under the fasted conditions. Part 2 of the study is to
      investigate the PK of selumetinib granule and capsule under fed conditions. Participants will
      also receive a single 500 mg dose of acetaminophen at the same time as selumetinib
      administration.
    

Detailed description: 
      This study will be a 2-part, open-label, single-center relative bioavailability and food
      effect randomized crossover study of new granule and capsule formulations of selumetinib. A
      total of 24 healthy male participants aged between 18 to 45 years (inclusive), will be
      included to ensure at least 20 evaluable participants. The study is divided in 2 study parts;
      the same participants will participate in both parts of the study.

      Part 1 of the study is designed to investigate the PK of the selumetinib granule compared to
      the PK of selumetinib capsule, when administered with water under the fasted conditions. Part
      2 of the study is designed to investigate the PK of selumetinib granule and capsule under fed
      conditions. Participants will consume a low-fat, low-calorie meal. Thirty minutes after the
      start of the meal, selumetinib will be administered to the participants. In all treatment
      periods, participants will also receive a single 500 mg dose of acetaminophen at the same
      time as selumetinib administration where it will act as a marker for gastric emptying. The
      study will also assess the palatability of the selumetinib granule in both parts of the
      study.

      Each participant will receive the following treatments:

        -  Treatment A: 25 mg granule, fasted state

        -  Treatment B: 50 mg capsule, fasted state

        -  Treatment C: 25 mg granule, fed state

        -  Treatment D: 50 mg capsule, fed state Participant will be randomly assigned to 1 of 4
           treatment sequences. In all cases the treatments in Part 1 will be administered before
           the treatments in Part 2. The study will comprise of a screening period of maximum 28
           days. Four treatment periods during which participants will be resident from the day
           before dosing (Day -1) until at least 48 hours after dosing; discharged on the morning
           of Day 3. A follow-up visit, will be within 7 to 10 days after the last dose of
           investigational medicinal product (IMP). There will be a minimum washout period of at
           least 5 days between each IMP administration. Each participant will be involved in the
           study for approximately 8 to 9 weeks.
    

Intervention name(s): Treatment A; Treatment B; Treatment C; Treatment D; Acetaminophen
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): During Part 1 of the study, participants will receive single doses of selumetinib 25 mg granule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.; During Part 1 of the study, participants will receive single doses of selumetinib 50 mg capsule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.; During Part 2 of the study, participants will receive single doses of selumetinib 25 mg granule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.; During Part 2 of the study, participants will receive single doses of selumetinib 50 mg capsule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.; Participants will receive a single 500mg dose of acetaminophen at the same time.
Intervention MeSH terms: Acetaminophen
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: MEK Inhibitor; Selumetinib capsule; Selumetinib granule; PK; Bioavailibilty; Crossover study; Open-label; Food effect