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

Tracking Information

• First Submitted Date: February 5, 2014
• First Posted Date: February 6, 2014
• Results First Submitted Date: July 31, 2015
• Results First Posted Date: November 9, 2015
• Last Update Posted Date: November 9, 2015
• Study Start Date: March 2014
• Actual Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 7, 2015)

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

Original Primary Outcome Measures (submitted: February 5, 2014)

Effect of a single dose of selumetinib (75 mg) on the change in time-matched QTcF interval compared to placebo. [ Time Frame: Digital ECGs recorded pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose ]

Performed during each of the 3 treatments

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: February 5, 2014)

• Pharmacokinetics of selumetinib, N-desmethyl selumetinib, and moxifloxacin by assessment of area under the plasma concentration-time from time zero to infinity (AUC) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48 hours post dose ]
  Curve taken during each of the 3 treatments
• Pharmacokinetics of selumetinib, N-desmethyl selumetinib, and moxifloxacin by assessment of area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration AUC(0-t) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48 hours post dose ]
  Curve taken during each of the 3 treatments
• Pharmacokinetics of selumetinib and moxifloxacin only, by assessment of apparent volume of distribution at equilibrium, mean residence time (MRT)*CL/F (Vss/F) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48 hours post dose ]
  Curve taken during each of the 3 treatments
• Pharmacokinetics of selumetinib and moxifloxacin only, by assessment of apparent systemic plasma clearance (CL/F) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48 hours post dose ]
  Curve taken during each of the 3 treatments
• Pharmacokinetics of selumetinib, N-desmethyl selumetinib, and moxifloxacin by assessment of apparent terminal phase of volume at distribution (selumetinib and moxifloxacin only) (Vz/F) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48 hours post dose ]
  Curve taken during each of the 3 treatments
• Pharmacokinetics of selumetinib, N-desmethyl selumetinib, and moxifloxacin by assessment of terminal half-life (t1/2). [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48 hours post dose ]
  Curve taken during each of the 3 treatments
• Pharmacokinetics of selumetinib, N-desmethyl selumetinib, and moxifloxacin by assessment of terminal rate constant (λz) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48 hours post dose ]
  Curve taken during each of the 3 treatments
• Pharmacokinetics of selumetinib, N-desmethyl selumetinib, and moxifloxacin by assessment of mean residence time (MRT) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48 hours post dose ]
  Curve taken during each of the 3 treatments
• Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of AUC metabolite to parent ratio, N-desmethyl selumetinib (MRAUC) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48 hours post dose ]
  Curve taken during each of the 3 treatments
• Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of Cmax metabolite to parent ratio, N-desmethyl selumetinib (MRCmax) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48 hours post dose ]
  Curve taken during each of the 3 treatments
• Pharmacokinetics of selumetinib, N-desmethyl selumetinib, and moxifloxacin by assessment of time to Cmax (tmax). [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48 hours post dose ]
  Curve taken during each of the 3 treatments
• Pharmacokinetics of selumetinib, N-desmethyl selumetinib, and moxifloxacin by assessment of maximum plasma concentration (Cmax) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48 hours post dose ]
  Curve taken during each of the 3 treatments
• The effect of selumetinib on additional ECG variables (QT, HR, RR, QRS, PR) and QTcB [ Time Frame: Digital ECGs recorded pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
  Performed during each of the 3 treatments
• The maximum of the mean changes in time-matched QTcF interval after moxifloxacin administration compared to placebo [ Time Frame: Digital ECGs recorded pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose ]
  Performed during each of the 3 treatments

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: February 5, 2014)

Safety variables (adverse events, physical examinations, ophthalmic assessments, vital signs, clinical laboratory assessments and 12 lead electrocardiograms) [ Time Frame: Baseline (Day -1) up to Day 28 ]

Assessments performed during each of the 3 treatments

Descriptive Information

• Brief Title: To Assess the Effects of Single Oral Dose of Selumetinib [AZD6244; ARRY-142886] [Hyd-Sulfate]), on QTc Interval in Healthy Male Volunteers
• 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
• Brief Summary: Study to assess the effect of Selumetinib [AZD6244; ARRY-142886] [Hyd-Sulfate]), on QTc interval in healthy male volunteers.
• 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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: Solid Tumours

Intervention

• Drug: Selumetinib
  Volunteers will receive 75 mg selumetinib oral dose (Treatment A)
  Other Name: AZD6244
• Drug: Moxifloxacin
  Volunteers will receive 400 mg Moxifloxacin oral dose (Treatment B)
  Other Name: Avelox®
• Drug: selumetinib placebo
  Volunteers will receive selumetinib placebo oral dose (Treatment C)
  Other Name: AZD6244 placebo

Study Arms

• Experimental: Selumetinib 75mg
  Volunteers will receive selumetinib 75mg administered by mouth, as a capsule
  Intervention: Drug: Selumetinib
• Active Comparator: Moxifloxacin 400 mg
  Volunteers will receive moxifloxacin 400mg administered by mouth, as a capsule
  Intervention: Drug: Moxifloxacin
• Placebo Comparator: Selumetinib 75mg placebo
  Volunteers will receive selumetinib 75mg placebo, administered by mouth, as a capsule.
  Intervention: Drug: selumetinib placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 5, 2014): 54
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 2014
• Actual Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02056392
• Other Study ID Numbers: D1532C00071
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: AstraZeneca
• Study Sponsor: AstraZeneca
• Collaborators: Not Provided

Investigators

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

• PRS Account: AstraZeneca
• Verification Date: September 2015