Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Reproductive Control Agents

Moxifloxacin

Norgestimate, ethinyl estradiol drug combination

Anti-Bacterial Agents

Enzyme Inhibitors

Volunteers will receive selumetinib 75mg administered by mouth, as a capsule

Volunteers will receive moxifloxacin 400mg administered by mouth, as a capsule

Volunteers will receive selumetinib 75mg placebo, administered by mouth, as a capsule.

Volunteers will receive 75 mg selumetinib oral dose (Treatment A)

Selumetinib

Volunteers will receive 400 mg Moxifloxacin oral dose (Treatment B)

Volunteers will receive selumetinib placebo oral dose (Treatment C)

selumetinib placebo

Scott Rasmussen, MD

Study to assess the effect of Selumetinib \[AZD6244; ARRY-142886\] \[Hyd-Sulfate\]), on QTc interval in healthy male volunteers.

A double-blind (Selumetinib \[AZD6244; ARRY-142886\] \[Hyd-Sulfate\]), Placebo-controlled, Open-Label (Moxifloxacin) Positive-controlled, Randomized, Three-period Crossover Study to Assess the Effects of Single Oral Dose of Selumetinib (75 mg) on QTc Interval Compared to Placebo, using AVELOX (Moxifloxacin) as a Positive Control, in Healthy Male Volunteers

To Assess the Effects of Single Oral Dose of Selumetinib [AZD6244; ARRY-142886] [Hyd-Sulfate]), on QTc Interval in Healthy Male Volunteers

A Phase I, Double-blind (Selumetinib [AZD6244; ARRY-142886] [Hyd-Sulfate]), Placebo-controlled, Open-Label (Moxifloxacin) Positive-controlled, Randomized, Three-period Crossover Study to Assess the Effects of Single Oral Dose of Selumetinib (75 mg) on QTc Interval Compared to Placebo, Using AVELOX (Moxifloxacin) as a Positive Control, in Healthy Male Volunteers Aged 18 to 45 Years

Change from baseline in QTcF at 30 minutes (msec)

Change from baseline in QTcF at 1 hour (msec)

Change from baseline in QTcF at 1 hour 30 min (msec)

Change from baseline in QTcF at 2 hours (msec)

Change from baseline in QTcF at 3 hours (msec)

Change from baseline in QTcF at 4 hours (msec)

Change from baseline in QTcF at 6 hours (msec)

Change from baseline in QTcF at 8 hours (msec)

Change from baseline in QTcF at 12 hours (msec)

Change from baseline in QTcF at 24 hours (msec)

AstraZeneca

Of the 54 participants in the study, 3 did not receive Selumetinib, 3 did not receive Moxifloxacin and 4 did not receive Selumetinib Placebo (due to discontinuing the study).

Placebo

Selumetinib/Moxifloxacin/Selumetinib Placebo

Moxifloxacin/Selumetinib/Selumetinib Placebo

Moxifloxacin/Selumetinib Placebo/Selumetinib

Selumetinib Placebo/Moxifloxacin/Selumetinib

Selumetinib Placebo/Selumetinib/Moxifloxacin

Selumetinib/Selumetinib Placebo/Moxifloxacin

Total

Age, Continuous

Sex: Female, Male

White

Black or African American

Race/Ethnicity, Customized

Gabriella Mariani

47 evaluable volunteers gives 90% power to show non-inferiority of selumetinib versus placebo across all 10 post-dose time points, using paired T-test, 1-sided alpha=0.05 and assuming a true difference of 3 msec.

All patients who had evaluable pharmacodynamic data available for at least one treatment group were included in the PD analysis set

Change From Baseline in QTcF

Overall Study

Micronutrients

Vitamins

Vitamin A

Retinol palmitate

Itraconazole

Fluconazole

Hydroxyitraconazole

Clotrimazole

Miconazole

Antifungal Agents

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Retinol

Volunteers will receive selumetinib 25mg alone; itraconazole 200mg pre-dosing; selumetinib 25mg and itraconazole 200mg; all adminstered by mouth as a capsule

Volunteers will receive selumetinib 25mg alone administered by mouth as a capsule; fluconazole 400mg and fluconazole 200mg pre-dosing, administered by mouth as a tablet; selumetinib 25mg and fluconazole 200mg.

Volunteers will recieve single oral dose of 25mg selumetinib in sequence 1, treatment A

selumetinib

Volunteers will receive oral doses of itraconazole 200 mg twice daily on Day 1 to Day 7 in sequence 1 treatment B:

itraconazole

Volunteers will recieve a single morning dose of 200mg itraconazole on Day 8 and twice daily doses of 200mg itraconazole on Day 8 to Day 11; sequence 1 treatment C.

Volunteers willl recieve a single oral dose of 25 mg selumetinib (4 hours fasted state) on Day 8; sequence 1 treatment C.

Volunteers will recieve single oral dose of 25mg selumetinib in sequence 2, treatment A.

Volunteers will recieve a single dose of 400 mg fluconazole on Day 1 and daily doses of 200 mg fluconazole on Day 2 to Day 7; sequence 2 treatment D.

fluconazole

Volunteers will receive a morning dose of 200mg fluconazole on Day 8 and daily doses of 200mg fluconazole on Day 8 to Day 11; sequence 2 treatment E

Volunteers will receive a single dose of 25mg selumetinib (4 hours fasted state) on Day 8; sequence 2 treatment E

David R Mathews, MD

Study to assess the effect of Itraconazole and Fluconazole on the pharmacokinetics of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Male Volunteers

A Open-label, Single-center Study to Assess the Effect of the CYP3A4 Inhibitor Itraconazole and the CYP2C19 Inhibitor Fluconazole on the Pharmacokinetics of a 25 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Volunteers

To Assess the Effect of Itraconazole and Fluconazole on the Pharmacokinetics of Selumetinib in Healthy Male Volunteers

A Phase I, Open-label, Single-center Study to Assess the Effect of the CYP3A4 Inhibitor Itraconazole and the CYP2C19 Inhibitor Fluconazole on the Pharmacokinetics of a 25 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Volunteers Aged 18 to 45 Years

Assessments performed during each of the 6 treatments

Samples taken during each of the 6 treatments

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
To Assess the Effects of Single Oral Dose of Selumetinib [AZD6244; ARRY-142886] [Hyd-Sulfate]), on QTc Interval in Healthy Male Volunteers	NCT02056392	Solid Tumours	Selumetinib Moxifloxacin selumetinib pla...	18 Years - 45 Years	AstraZeneca
To Assess the Effect of Itraconazole and Fluconazole on the Pharmacokinetics of Selumetinib in Healthy Male Volunteers	NCT02093728	Solid Tumours	selumetinib itraconazole itraconazole selumetinib selumetinib fluconazole fluconazole selumetinib	18 Years - 45 Years	AstraZeneca
To Assess the Effects of Single Oral Dose of Selumetinib [AZD6244; ARRY-142886] [Hyd-Sulfate]), on QTc Interval in Healthy Male Volunteers	NCT02056392	Solid Tumours	Selumetinib Moxifloxacin selumetinib pla...	18 Years - 45 Years	AstraZeneca

Spots Global Cancer Trial Database for phase i, healthy, pharmacokinetics