Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE February 5, 2014
First Posted Date  ICMJE February 6, 2014
Results First Submitted Date  ICMJE July 31, 2015
Results First Posted Date  ICMJE November 9, 2015
Last Update Posted Date November 9, 2015
Study Start Date  ICMJE March 2014
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (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  ICMJE To Assess the Effects of Single Oral Dose of Selumetinib [AZD6244; ARRY-142886] [Hyd-Sulfate]), on QTc Interval in Healthy Male Volunteers
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Solid Tumours
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 5, 2014)
54
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2014
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02056392
Other Study ID Numbers  ICMJE D1532C00071
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Scott Rasmussen, MD Quintiles 6700 W 115th Street, Kansas, US
PRS Account AstraZeneca
Verification Date September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP