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

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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Basic Science
Condition Solid Tumours
Interventions Drug: Selumetinib
Drug: Moxifloxacin
Drug: selumetinib placebo
Enrollment 54
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Selumetinib/Moxifloxacin/Selumetinib Placebo Moxifloxacin/Selumetinib/Selumetinib Placebo Moxifloxacin/Selumetinib Placebo/Selumetinib Selumetinib Placebo/Moxifloxacin/Selumetinib Selumetinib Placebo/Selumetinib/Moxifloxacin Selumetinib/Selumetinib Placebo/Moxifloxacin
Hide Arm/Group Description [Not Specified] [Not Specified] [Not Specified] [Not Specified] [Not Specified] [Not Specified]
Period Title: Overall Study
Started 10 9 9 9 8 9
Completed 8 8 6 9 7 9
Not Completed 2 1 3 0 1 0
Reason Not Completed
Lost to Follow-up             0             1             2             0             0             0
Protocol Violation             1             0             1             0             0             0
Withdrawal by Subject             1             0             0             0             1             0
Arm/Group Title 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
Hide Arm/Group Description [Not Specified] [Not Specified] [Not Specified] [Not Specified] [Not Specified] [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 10 9 9 9 8 9 54
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 9 participants 9 participants 9 participants 8 participants 9 participants 54 participants
26  (7) 25  (5) 25  (4) 31  (8) 28  (8) 30  (9) 27  (7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 9 participants 9 participants 8 participants 9 participants 54 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
10
 100.0%
9
 100.0%
9
 100.0%
9
 100.0%
8
 100.0%
9
 100.0%
54
 100.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 9 participants 9 participants 8 participants 9 participants 54 participants
White 7 5 4 4 5 4 29
Black or African American 3 4 5 5 3 5 25
1.Primary Outcome
Title Change From Baseline in QTcF
Hide Description Change from baseline in QTcF at 30 minutes (msec)
Time Frame 30 min
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who had evaluable pharmacodynamic data available for at least one treatment group were included in the PD analysis set
Arm/Group Title Moxifloxacin Placebo Selumetinib
Hide Arm/Group Description:
Moxiflxacin 400 mg (open label)
Selumetinib placebo (3 capsules)
Selumetinib 75mg bs (3x25mg capsules)
Overall Number of Participants Analyzed 50 49 50
Overall Number of Units Analyzed
Type of Units Analyzed: Change from baseline
50 49 50
Least Squares Mean (95% Confidence Interval)
Unit of Measure: msec
2.0
(0.5 to 3.5)
-4.1
(-5.6 to -2.5)
-4.2
(-5.7 to -2.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selumetinib
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 90%
-1.8 to 1.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moxifloxacin, Placebo
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.1
Confidence Interval (2-Sided) 90%
4.4 to 7.7
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in QTcF
Hide Description Change from baseline in QTcF at 1 hour (msec)
Time Frame 1 hour
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who had evaluable pharmacodynamic data available for at least one treatment group were included in the PD analysis set
Arm/Group Title Moxifloxacin Placebo Selumetinib
Hide Arm/Group Description:
Moxiflxacin 400 mg (open label)
Selumetinib placebo (3 capsules)
Selumetinib 75mg bs (3x25mg capsules)
Overall Number of Participants Analyzed 50 49 50
Overall Number of Units Analyzed
Type of Units Analyzed: Change from baseline
50 49 50
Least Squares Mean (95% Confidence Interval)
Unit of Measure: msec
7.9
(6.4 to 9.4)
-1.4
(-2.9 to 0.2)
-1.7
(-3.2 to -0.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selumetinib
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 90%
-2.0 to 1.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moxifloxacin, Placebo
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 9.2
Confidence Interval (2-Sided) 90%
7.6 to 10.8
Estimation Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in QTcF
Hide Description Change from baseline in QTcF at 1 hour 30 min (msec)
Time Frame 1 hour 30 min
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who had evaluable pharmacodynamic data available for at least one treatment group were included in the PD analysis set
Arm/Group Title Moxifloxacin Placebo Selumetinib
Hide Arm/Group Description:
Moxiflxacin 400 mg (open label)
Selumetinib placebo (3 capsules)
Selumetinib 75mg bs (3x25mg capsules)
Overall Number of Participants Analyzed 50 49 50
Overall Number of Units Analyzed
Type of Units Analyzed: Change from baseline
50 49 50
Least Squares Mean (95% Confidence Interval)
Unit of Measure: msec
8.1
(6.6 to 9.6)
-1.8
(-3.3 to -0.2)
-0.9
(-2.4 to 0.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selumetinib
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.9
Confidence Interval (2-Sided) 90%
-0.7 to 2.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moxifloxacin, Placebo
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 9.9
Confidence Interval (2-Sided) 90%
8.3 to 11.5
Estimation Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in QTcF
Hide Description Change from baseline in QTcF at 2 hours (msec)
Time Frame 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who had evaluable pharmacodynamic data available for at least one treatment group were included in the PD analysis set
Arm/Group Title Moxifloxacin Placebo Selumetinib
Hide Arm/Group Description:
Moxiflxacin 400 mg (open label)
Selumetinib placebo (3 capsules)
Selumetinib 75mg bs (3x25mg capsules)
Overall Number of Participants Analyzed 50 49 50
Overall Number of Units Analyzed
Type of Units Analyzed: Change from baseline
50 49 50
Least Squares Mean (95% Confidence Interval)
Unit of Measure: msec
7.9
(6.4 to 9.4)
-2.3
(-3.8 to -0.7)
-1.9
(-3.4 to -0.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selumetinib
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 90%
-1.2 to 2.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moxifloxacin
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10.1
Confidence Interval (2-Sided) 90%
8.5 to 11.8
Estimation Comments [Not Specified]
5.Primary Outcome
Title Change From Baseline in QTcF
Hide Description Change from baseline in QTcF at 3 hours (msec)
Time Frame 3 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who had evaluable pharmacodynamic data available for at least one treatment group were included in the PD analysis set
Arm/Group Title Moxifloxacin Placebo Selumetinib
Hide Arm/Group Description:
Moxiflxacin 400 mg (open label)
Selumetinib placebo (3 capsules)
Selumetinib 75mg bs (3x25mg capsules)
Overall Number of Participants Analyzed 50 49 50
Overall Number of Units Analyzed
Type of Units Analyzed: Change from baseline
50 49 50
Least Squares Mean (95% Confidence Interval)
Unit of Measure: msec
8.8
(7.3 to 10.3)
-3.2
(-4.7 to -1.6)
-3.3
(-4.8 to -1.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selumetinib
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 90%
-1.8 to 1.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moxifloxacin, Placebo
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 11.9
Confidence Interval 90%
10.3 to 13.6
Estimation Comments [Not Specified]
6.Primary Outcome
Title Change From Baseline in QTcF
Hide Description Change from baseline in QTcF at 4 hours (msec)
Time Frame 4 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who had evaluable pharmacodynamic data available for at least one treatment group were included in the PD analysis set
Arm/Group Title Moxifloxacin Placebo Selumetinib
Hide Arm/Group Description:
Moxiflxacin 400 mg (open label)
Selumetinib placebo (3 capsules)
Selumetinib 75mg bs (3x25mg capsules)
Overall Number of Participants Analyzed 50 49 50
Overall Number of Units Analyzed
Type of Units Analyzed: Change from baseline
50 49 50
Least Squares Mean (95% Confidence Interval)
Unit of Measure: msec
8.6
(7.1 to 10.1)
-2.2
(-3.7 to -0.7)
-3.7
(-5.2 to -2.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selumetinib
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.5
Confidence Interval (2-Sided) 90%
-3.1 to 0.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moxifloxacin, Placebo
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10.8
Confidence Interval (2-Sided) 90%
9.2 to 12.5
Estimation Comments [Not Specified]
7.Primary Outcome
Title Change From Baseline in QTcF
Hide Description Change from baseline in QTcF at 6 hours (msec)
Time Frame 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who had evaluable pharmacodynamic data available for at least one treatment group were included in the PD analysis set
Arm/Group Title Moxifloxacin Placebo Selumetinib
Hide Arm/Group Description:
Moxiflxacin 400 mg (open label)
Selumetinib placebo (3 capsules)
Selumetinib 75mg bs (3x25mg capsules)
Overall Number of Participants Analyzed 50 49 50
Overall Number of Units Analyzed
Type of Units Analyzed: Change from baseline
50 49 50
Least Squares Mean (95% Confidence Interval)
Unit of Measure: msec
4.7
(3.2 to 6.2)
-4.1
(-5.6 to -2.6)
-5.9
(-7.4 to -4.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selumetinib
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.8
Confidence Interval (2-Sided) 90%
-3.4 to -0.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moxifloxacin, Placebo
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 8.8
Confidence Interval (2-Sided) 90%
7.1 to 10.4
Estimation Comments [Not Specified]
8.Primary Outcome
Title Change From Baseline in QTcF
Hide Description Change from baseline in QTcF at 8 hours (msec)
Time Frame 8 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who had evaluable pharmacodynamic data available for at least one treatment group were included in the PD analysis set
Arm/Group Title Moxifloxacin Placebo Selumetinib
Hide Arm/Group Description:
Moxiflxacin 400 mg (open label)
Selumetinib placebo (3 capsules)
Selumetinib 75mg bs (3x25mg capsules)
Overall Number of Participants Analyzed 50 49 50
Overall Number of Units Analyzed
Type of Units Analyzed: Change from baseline
50 49 50
Least Squares Mean (95% Confidence Interval)
Unit of Measure: msec
3.6
(2.1 to 5.1)
-5.3
(-6.8 to -3.7)
-6.5
(-8.0 to -5.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selumetinib
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.3
Confidence Interval (2-Sided) 90%
-2.9 to 0.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moxifloxacin, Placebo
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 8.9
Confidence Interval (2-Sided) 90%
7.2 to 10.5
Estimation Comments [Not Specified]
9.Primary Outcome
Title Change From Baseline in QTcF
Hide Description Change from baseline in QTcF at 12 hours (msec)
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who had evaluable pharmacodynamic data available for at least one treatment group were included in the PD analysis set
Arm/Group Title Moxifloxacin Placebo Selumetinib
Hide Arm/Group Description:
Moxiflxacin 400 mg (open label)
Selumetinib placebo (3 capsules)
Selumetinib 75mg bs (3x25mg capsules)
Overall Number of Participants Analyzed 50 49 50
Overall Number of Units Analyzed
Type of Units Analyzed: Change from baseline
50 49 50
Least Squares Mean (95% Confidence Interval)
Unit of Measure: msec
4.2
(2.7 to 5.7)
-3.4
(-5.0 to -1.9)
-8.2
(-9.7 to -6.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selumetinib
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.7
Confidence Interval (2-Sided) 90%
-6.4 to -3.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moxifloxacin, Placebo
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.6
Confidence Interval (2-Sided) 90%
6.0 to 9.3
Estimation Comments [Not Specified]
10.Primary Outcome
Title Change From Baseline in QTcF
Hide Description Change from baseline in QTcF at 24 hours (msec)
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who had evaluable pharmacodynamic data available for at least one treatment group were included in the PD analysis set
Arm/Group Title Moxifloxacin Placebo Selumetinib
Hide Arm/Group Description:
Moxiflxacin 400 mg (open label)
Selumetinib placebo (3 capsules)
Selumetinib 75mg bs (3x25mg capsules)
Overall Number of Participants Analyzed 50 49 50
Overall Number of Units Analyzed
Type of Units Analyzed: Change from baseline
50 49 50
Least Squares Mean (95% Confidence Interval)
Unit of Measure: msec
2.4
(0.9 to 3.9)
-1.6
(-3.1 to -0.1)
-4.1
(-5.6 to -2.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Selumetinib
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.5
Confidence Interval (2-Sided) 90%
-4.1 to -0.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moxifloxacin, Placebo
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments All one-sided 95% confidence intervals at each time point for the selumetinib difference versus placebo (2-sided 90% CIs) should be less than 10ms.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.0
Confidence Interval (2-Sided) 90%
2.4 to 5.7
Estimation Comments [Not Specified]
Time Frame AEs were collected for up to 5 weeks, this was from the day before the first randomised treatment period (Day -1, Visit 2) until the follow-up visit.
Adverse Event Reporting Description 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).
 
Arm/Group Title Selumetinib Moxifloxacin Placebo
Hide Arm/Group Description Selumetinib 75mg bs (3x25mg capsules) Moxiflxacin 400 mg (open label) Selumetinib placebo (3 capsules)
All-Cause Mortality
Selumetinib Moxifloxacin Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Selumetinib Moxifloxacin Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/51 (0.00%)   0/51 (0.00%)   1/50 (2.00%) 
Gastrointestinal disorders       
Hemorrhoids   0/51 (0.00%)  0/51 (0.00%)  1/50 (2.00%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Selumetinib Moxifloxacin Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/51 (9.80%)   5/51 (9.80%)   4/50 (8.00%) 
Gastrointestinal disorders       
Abdominal pain   0/51 (0.00%)  1/51 (1.96%)  0/50 (0.00%) 
Dyspepsia   0/51 (0.00%)  1/51 (1.96%)  0/50 (0.00%) 
Rectal hemorrhage   0/51 (0.00%)  1/51 (1.96%)  0/50 (0.00%) 
Immune system disorders       
Hypersensitivity   0/51 (0.00%)  0/51 (0.00%)  1/50 (2.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia   0/51 (0.00%)  0/51 (0.00%)  1/50 (2.00%) 
Musculoskeletal pain   0/51 (0.00%)  0/51 (0.00%)  1/50 (2.00%) 
Pain in extremity   0/51 (0.00%)  1/51 (1.96%)  0/50 (0.00%) 
Nervous system disorders       
Headache   3/51 (5.88%)  1/51 (1.96%)  0/50 (0.00%) 
Disturbance in attention   0/51 (0.00%)  1/51 (1.96%)  0/50 (0.00%) 
Psychiatric disorders       
Insomnia   1/51 (1.96%)  0/51 (0.00%)  0/50 (0.00%) 
Skin and subcutaneous tissue disorders       
Blister   1/51 (1.96%)  0/51 (0.00%)  0/50 (0.00%) 
Skin irritation   0/51 (0.00%)  0/51 (0.00%)  1/50 (2.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gabriella Mariani
Organization: AstraZeneca
Phone: +44 7818 523 899
EMail: ClinicalTrialTransparency@astrazeneca.com
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02056392    
Other Study ID Numbers: D1532C00071
First Submitted: February 5, 2014
First Posted: February 6, 2014
Results First Submitted: July 31, 2015
Results First Posted: November 9, 2015
Last Update Posted: November 9, 2015