A Study to Evaluate Bioavailability and Food Effect of Selumetinib (AZD6244) in Healthy Male Participants

Phase 1

Completed

• Conditions: Neurofibromatosis Type 1 (NF1)-Related Plexiform Neurofibromas (PNs); Healthy Participants
• Interventions: Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D; Drug: Acetaminophen

• Registration Number: NCT03649165
• Lead Sponsor: AstraZeneca

Brief 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.

Study Timeline

• Study First Submitted: 2018-08-24
• Study First Submitted QC: 2018-08-24
• Study First Posted: 2018-08-28
• Study Start: 2018-09-05
• Primary Completion: 2018-10-21
• Study Completion: 2018-10-21
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-07
• Last Update Posted: 2018-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Sequence 1	Treatment A	Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3, and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 1	Treatment B	Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3, and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 1	Treatment C	Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3, and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 2	Treatment A	Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3 and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 2	Treatment B	Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3 and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 2	Treatment C	Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3 and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 3	Treatment A	Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 3	Treatment B	Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 3	Treatment C	Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 3	Treatment D	Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 4	Treatment A	Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 4	Treatment B	Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 4	Treatment C	Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 1	Treatment D	Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3, and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 2	Treatment D	Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3 and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 4	Treatment D	Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 1	Acetaminophen	Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3, and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 2	Acetaminophen	Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3 and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 3	Acetaminophen	Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. 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.
Treatment Sequence 4	Acetaminophen	Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. 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.

Primary Outcome Measures

Name	Time	Method
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Dose normalized area under plasma concentration-time curve from time zero to infinity (AUC/D)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3)	To compare the AUC/D of the new selumetinib granule formulation with selumetinib capsule formulation in fasted state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Dose normalized area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast/D)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3)	To compare the AUClast/D of the new selumetinib granule formulation with selumetinib capsule formulation in fasted state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Dose normalized maximum observed plasma concentration (Cmax/D)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3)	To compare the Cmax/D of the new selumetinib granule formulation with selumetinib capsule formulation in fasted state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Fraction of administered selumetinib granule dose systemically available relative to the capsule reference (Frel)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3)	To compare the Frel. of the new selumetinib granule formulation with selumetinib capsule formulation in fasted state.

Secondary Outcome Measures

Name	Time	Method
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Area under plasma concentration time curve from time zero to infinity (AUC)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3)	To compare AUC of selumetinib capsule fasted versus capsule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare AUClast of selumetinib capsule fasted versus capsule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Area under the plasma concentration-time curve from zero to 12 hours post-dose [AUC(0-12)]	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare AUC (0-12) of selumetinib capsule fasted versus capsule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Maximum observed plasma concentration (Cmax)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare Cmax of selumetinib capsule fasted versus capsule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Ratio of AUC in fed state to AUC in the fasted state (FRAUC)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare FRAUC of selumetinib capsule fasted versus capsule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Ratio of Cmax in fed state to Cmax in the fasted state (FRCmax)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare FRCmax of selumetinib capsule fasted versus capsule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare t½λz of selumetinib capsule fasted versus capsule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Time to reach maximum observed plasma concentration (tmax)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare tmax of selumetinib capsule fasted versus capsule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Terminal elimination rate constant (λz)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare λz of selumetinib capsule fasted versus capsule low-fat fed state.
Selumetinib plasma PK parameters: Apparent total body clearance of drug from plasma after extravascular administration (parent drug only) (CL/F)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare CL/F of selumetinib capsule fasted versus capsule low-fat fed state.
Selumetinib plasma PK parameters: Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare Vz/F of selumetinib capsule fasted versus capsule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: AUC	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare AUC of selumetinib granule fasted versus granule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: AUClast	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare AUClast of selumetinib granule fasted versus granule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: AUC(0-12)	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare AUC (0-12) of selumetinib granule fasted versus granule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: Cmax	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare Cmax of selumetinib granule fasted versus granule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: FRAUC	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare FRAUC of selumetinib granule fasted versus granule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: FRCmax	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare FRCmax of selumetinib granule fasted versus granule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: t½λz	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare t½λz of selumetinib granule fasted versus granule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: tmax	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare tmax of selumetinib granule fasted versus granule low-fat fed state.
Selumetinib and N-desmethyl selumetinib plasma PK parameter: λz	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare λz of selumetinib granule fasted versus granule low-fat fed state.
Selumetinib plasma PK parameters: CL/F	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare CL/F of selumetinib granule fasted versus granule low-fat fed state.
Selumetinib plasma PK parameters: Vz/F	At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3)	To compare Vz/F of selumetinib granule fasted versus granule low-fat fed state.
Taste questionnaire	At Days -1 to 3 (within 10 minutes following intake of selumetinib granule)	To assess palatability of selumetinib granule formulation. The standardized questionnaire will be administered to participants within 10 minutes following intake of selumetinib granule. Questionnaire about taste include sweet, salty, sour, bitter, metallic, and hot/spicy. Where 0 indicates not at all and 10 indicates extremely.
Number of participants with adverse events (AEs)	From the time of informed consent, throughout the treatment periods up to and including the Follow-up Visit (7 to 10 days after last dose)	To assess the safety and tolerability of single doses of selumetinib in healthy participants.
Vital signs (systolic blood pressure [BP])	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess systolic BP as a variable of safety and tolerability of single doses of selumetinib in healthy participants. Participants should be supine and at rest for at least 5 minutes before the measurements.
Vital signs (diastolic BP)	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess diastolic BP as a variable of safety and tolerability of single doses of selumetinib in healthy participants. Participants should be supine and at rest for at least 5 minutes before the measurements.
Pulse rate	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess pulse rate as a variable of safety and tolerability of single doses of selumetinib in healthy participants.; Participants should be supine and at rest for at least 5 minutes before the measurements.
12-lead electrocardiogram (ECG)	From baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess 12-lead ECG as variable of safety and tolerability of single doses of selumetinib in healthy participants. Participants should be supine and at rest 10 minutes before recording the ECG.
Number of participants with abnormal findings in physical examination	From baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess physical examination as a variable safety and tolerability of single doses of selumetinib in healthy participants.
Ophthalmic examinations	At screening Visit or on Day -1 of Treatment Period 1	To assess ophthalmic examination as a variable of safety and tolerability of single doses of selumetinib in healthy participants. Ophthalmic examination included best corrected visual acuity, intra-ocular pressure and slit-lamp fundoscopy.
Laboratory assessments: hematology - Hemoglobin (Hb)	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess Hb as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: hematology - erythrocyte count	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess erythrocyte count as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: hematology: Platelet count	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess platelet count as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: hematology: leucocyte differential count (absolute count)	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess leucocyte differential count as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: hematology: leucocyte cell count	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess leucocyte cell count as variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments:hematology - differential count	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess differential count of neutrophils, lymphocytes, monocyets, eosinophils and basophils) as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Serum clinical chemistry - electrolytes	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess serum level of sodium, potassium, magnesium and phosphate as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Serum clinical chemistry - urea nitrogen	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess urea nitrogen as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Serum clinical chemistry - creatinine	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess creatinine as variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Serum clinical chemistry: albumin	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess albumin as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Serum clinical chemistry: Total Calcium	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess total calcium as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Serum clinical chemistry: Total protein	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess total protein as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Serum clinical chemistry: Total bilirubin	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess total bilirubin as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Serum clinical chemistry: Creatine phosphokinase (CPK)	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess CPK as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Serum clinical chemistry: Troponin (isoform as per institutional norm)	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess troponin as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Serum clinical chemistry - Liver enzymes	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess serum of Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Gamma glutamyl transpeptidase (GGT) as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Clinical urinalysis - glucose	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess urine glucose as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Clinical Urinalysis - protein	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess urine protein as a variable of safety and tolerability of single doses of selumetinib in healthy participants.
Laboratory assessments: Clinical Urinalysis - blood	Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose)	To assess urine blood as a variable of safety and tolerability of single doses of selumetinib in healthy participants.; If urinalysis is positive for blood, a microscopy test will be performed to assess RBC, white blood cell \[WBC\], casts \[cellular, granular, hyaline\]).

Trial Locations

Locations (1)

Research Site; 🇺🇸 Baltimore, Maryland, United States