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

• ClinicalTrials.gov Identifier: NCT02056392
• Recruitment Status: Completed
• First Posted: February 6, 2014
• Results First Posted: November 9, 2015
• Last Update Posted: November 9, 2015
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Solid Tumours	Drug: Selumetinib; Drug: Moxifloxacin; Drug: selumetinib placebo	Phase 1

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: 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
• Study Start Date: March 2014
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Selumetinib 75mg; Volunteers will receive selumetinib 75mg administered by mouth, as a capsule	Drug: Selumetinib; Volunteers will receive 75 mg selumetinib oral dose (Treatment A); Other Name: AZD6244
Active Comparator: Moxifloxacin 400 mg; Volunteers will receive moxifloxacin 400mg administered by mouth, as a capsule	Drug: Moxifloxacin; Volunteers will receive 400 mg Moxifloxacin oral dose (Treatment B); Other Name: Avelox®
Placebo Comparator: Selumetinib 75mg placebo; Volunteers will receive selumetinib 75mg placebo, administered by mouth, as a capsule.	Drug: selumetinib placebo; Volunteers will receive selumetinib placebo oral dose (Treatment C); Other Name: AZD6244 placebo

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in QTcF [ Time Frame: 30 min ]
   Change from baseline in QTcF at 30 minutes (msec)
2. Change From Baseline in QTcF [ Time Frame: 1 hour ]
   Change from baseline in QTcF at 1 hour (msec)
3. Change From Baseline in QTcF [ Time Frame: 1 hour 30 min ]
   Change from baseline in QTcF at 1 hour 30 min (msec)
4. Change From Baseline in QTcF [ Time Frame: 2 hours ]
   Change from baseline in QTcF at 2 hours (msec)
5. Change From Baseline in QTcF [ Time Frame: 3 hours ]
   Change from baseline in QTcF at 3 hours (msec)
6. Change From Baseline in QTcF [ Time Frame: 4 hours ]
   Change from baseline in QTcF at 4 hours (msec)
7. Change From Baseline in QTcF [ Time Frame: 6 hours ]
   Change from baseline in QTcF at 6 hours (msec)
8. Change From Baseline in QTcF [ Time Frame: 8 hours ]
   Change from baseline in QTcF at 8 hours (msec)
9. Change From Baseline in QTcF [ Time Frame: 12 hours ]
   Change from baseline in QTcF at 12 hours (msec)
10. Change From Baseline in QTcF [ Time Frame: 24 hours ]
    Change from baseline in QTcF at 24 hours (msec)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria: 1. Have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg (inclusive). 2. Must have not smoked in the last 30 days prior to screening for this study. 3. Have a calculated creatinine clearance (CrCL) greater than 50 mL/min using the Cockcroft-Gault formula.

Exclusion Criteria: 1. Subjects of Japanese or non-Japanese Asian ethnicity. 2. Subjects where any one parent or grandparent (maternal or paternal) is Japanese or non-Japanese Asian (e.g. China, Taiwan, Korea, Philippines, Thailand, Vietnam, and Malaysia). Asian Indians are acceptable. 3. Past history of central serous retinopathy or retinal vein thrombosis,intraocular pressure greater than 21 mmHg or uncontrolled glaucoma. 4. Any clinically relevant abnormal findings in physical examination, hematology, clinical chemistry, urinalysis, vital signs or ECG at baseline in the opinion of the investigator. 5. History or presence of any clinically significant disease or disorder in the opinion of the investigator.

Contacts and Locations

Locations

United States, Kansas

Research Site

Overland Park, Kansas, United States

Sponsors and Collaborators

AstraZeneca

Investigators

• Principal Investigator: Scott Rasmussen, MD; Quintiles 6700 W 115th Street, Kansas, US

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02056392
• Other Study ID Numbers: D1532C00071
• First Posted: February 6, 2014
• Results First Posted: November 9, 2015
• Last Update Posted: November 9, 2015
• Last Verified: September 2015

Keywords provided by AstraZeneca:

Phase I, healthy, pharmacokinetics

Additional relevant MeSH terms:

Moxifloxacin; Norgestimate, ethinyl estradiol drug combination; Anti-Bacterial Agents; Anti-Infective Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs