To Assess the Effects of Single Oral Dose of Selumetinib... | NCT02056392

To Assess the Effects of Single Oral Dose of Selumetinib... | NCT02056392 | Trialant

Arms/Interventions Module

Arm Groups

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

Name	Type	Description	Arm Group Labels	Other Names
Selumetinib	Drug	Volunteers will receive 75 mg selumetinib oral dose (Treatment A)	Selumetinib 75mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in QTcF	Change from baseline in QTcF at 30 minutes (msec)	30 min
Change From Baseline in QTcF	Change from baseline in QTcF at 1 hour (msec)	1 hour
Change From Baseline in QTcF	Change from baseline in QTcF at 1 hour 30 min (msec)	1 hour 30 min
Change From Baseline in QTcF	Change from baseline in QTcF at 2 hours (msec)	2 hours
Change From Baseline in QTcF	Change from baseline in QTcF at 3 hours (msec)	3 hours
Change From Baseline in QTcF	Change from baseline in QTcF at 4 hours (msec)	4 hours
Change From Baseline in QTcF	Change from baseline in QTcF at 6 hours (msec)	6 hours
Change From Baseline in QTcF	Change from baseline in QTcF at 8 hours (msec)	8 hours
Change From Baseline in QTcF

Contacts/Locations Module

Name	Affiliation	Role
Scott Rasmussen, MD	Quintiles 6700 W 115th Street, Kansas, US	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Overland Park	Kansas		United States

Results Section

Participant Flow Module

ID	Title	Description
FG000	Selumetinib/Moxifloxacin/Selumetinib Placebo
FG001	Moxifloxacin/Selumetinib/Selumetinib Placebo
FG002	Moxifloxacin/Selumetinib Placebo/Selumetinib

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Lost to Follow-up		FG0000 subjects FG0011 subjects FG0022 subjects FG0030 subjects FG0040 subjects FG0050 subjects
Protocol Violation		FG0001 subjects FG0010 subjects FG0021 subjects FG0030 subjects FG004
Withdrawal by Subject		FG0001 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Arm/Group Information

ID	Title	Description
BG000	Selumetinib/Moxifloxacin/Selumetinib Placebo
BG001	Moxifloxacin/Selumetinib/Selumetinib Placebo
BG002	Moxifloxacin/Selumetinib Placebo/Selumetinib
BG003	Selumetinib Placebo/Moxifloxacin/Selumetinib
BG004	Selumetinib Placebo/Selumetinib/Moxifloxacin
BG005	Selumetinib/Selumetinib Placebo/Moxifloxacin
BG006	Total	Total of all reporting groups

Units	Counts
Participants	BG00010 BG0019 BG0029 BG0039 BG0048 BG0059 BG00654

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00026± 7 BG00125± 5 BG00225± 4 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000 BG0010 BG002

Race/Ethnicity, Customized

Number

Participants

Title

Denominators

Categories

White

Title	Measurements
	BG0007 BG0015 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in QTcF

Change from baseline in QTcF at 30 minutes (msec)

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

Posted

Least Squares Mean

95% Confidence Interval

msec

30 min

change from baseline

Participants

ID	Title	Description
OG000	Moxifloxacin	Moxiflxacin 400 mg (open label)
OG001	Placebo	Selumetinib placebo (3 capsules)
OG002	Selumetinib	Selumetinib 75mg bs (3x25mg capsules)

Units	Counts
Participants	OG00050 OG00149 OG00250
change from baseline	OG000

Title

Denominators

Categories

Title	Measurements
	OG0002.0(0.5 to 3.5) OG001-4.1(-5.6 to -2.5) OG002-4.2(-5.7 to -2.7)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002	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.	Mixed Models Analysis				Mean Difference (Final Values)	-0.2			2-Sided	90	-1.8	1.5				Yes	Non-Inferiority or Equivalence	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.

Primary

Change From Baseline in QTcF

Change from baseline in QTcF at 1 hour (msec)

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

Posted

Least Squares Mean

95% Confidence Interval

msec

1 hour

change from baseline

Participants

ID	Title	Description
OG000	Moxifloxacin	Moxiflxacin 400 mg (open label)
OG001	Placebo	Selumetinib placebo (3 capsules)
OG002	Selumetinib	Selumetinib 75mg bs (3x25mg capsules)

Units	Counts
Participants	OG000

Primary

Change From Baseline in QTcF

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

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

Posted

Least Squares Mean

95% Confidence Interval

msec

1 hour 30 min

change from baseline

Participants

ID	Title	Description
OG000	Moxifloxacin	Moxiflxacin 400 mg (open label)
OG001	Placebo	Selumetinib placebo (3 capsules)
OG002	Selumetinib	Selumetinib 75mg bs (3x25mg capsules)

Units	Counts
Participants	OG000

Primary

Change From Baseline in QTcF

Change from baseline in QTcF at 2 hours (msec)

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

Posted

Least Squares Mean

95% Confidence Interval

msec

2 hours

change from baseline

Participants

ID	Title	Description
OG000	Moxifloxacin	Moxiflxacin 400 mg (open label)
OG001	Placebo	Selumetinib placebo (3 capsules)
OG002	Selumetinib	Selumetinib 75mg bs (3x25mg capsules)

Units	Counts
Participants	OG000

Primary

Change From Baseline in QTcF

Change from baseline in QTcF at 3 hours (msec)

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

Posted

Least Squares Mean

95% Confidence Interval

msec

3 hours

change from baseline

Participants

ID	Title	Description
OG000	Moxifloxacin	Moxiflxacin 400 mg (open label)
OG001	Placebo	Selumetinib placebo (3 capsules)
OG002	Selumetinib	Selumetinib 75mg bs (3x25mg capsules)

Units	Counts
Participants	OG000

Primary

Change From Baseline in QTcF

Change from baseline in QTcF at 4 hours (msec)

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

Posted

Least Squares Mean

95% Confidence Interval

msec

4 hours

change from baseline

Participants

ID	Title	Description
OG000	Moxifloxacin	Moxiflxacin 400 mg (open label)
OG001	Placebo	Selumetinib placebo (3 capsules)
OG002	Selumetinib	Selumetinib 75mg bs (3x25mg capsules)

Units	Counts
Participants	OG000

Primary

Change From Baseline in QTcF

Change from baseline in QTcF at 6 hours (msec)

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

Posted

Least Squares Mean

95% Confidence Interval

msec

6 hours

change from baseline

Participants

ID	Title	Description
OG000	Moxifloxacin	Moxiflxacin 400 mg (open label)
OG001	Placebo	Selumetinib placebo (3 capsules)
OG002	Selumetinib	Selumetinib 75mg bs (3x25mg capsules)

Units	Counts
Participants	OG000

Primary

Change From Baseline in QTcF

Change from baseline in QTcF at 8 hours (msec)

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

Posted

Least Squares Mean

95% Confidence Interval

msec

8 hours

change from baseline

Participants

ID	Title	Description
OG000	Moxifloxacin	Moxiflxacin 400 mg (open label)
OG001	Placebo	Selumetinib placebo (3 capsules)
OG002	Selumetinib	Selumetinib 75mg bs (3x25mg capsules)

Units	Counts
Participants	OG000

Primary

Change From Baseline in QTcF

Change from baseline in QTcF at 12 hours (msec)

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

Posted

Least Squares Mean

95% Confidence Interval

msec

12 hours

change from baseline

Participants

ID	Title	Description
OG000	Moxifloxacin	Moxiflxacin 400 mg (open label)
OG001	Placebo	Selumetinib placebo (3 capsules)
OG002	Selumetinib	Selumetinib 75mg bs (3x25mg capsules)

Units	Counts
Participants	OG000

Primary

Change From Baseline in QTcF

Change from baseline in QTcF at 24 hours (msec)

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

Posted

Least Squares Mean

95% Confidence Interval

msec

24 hours

change from baseline

Participants

ID	Title	Description
OG000	Moxifloxacin	Moxiflxacin 400 mg (open label)
OG001	Placebo	Selumetinib placebo (3 capsules)
OG002	Selumetinib	Selumetinib 75mg bs (3x25mg capsules)

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Selumetinib	Selumetinib 75mg bs (3x25mg capsules)	0	51	5	51
EG001	Moxifloxacin	Moxiflxacin 400 mg (open label)	0	51	5	51
EG002	Placebo	Selumetinib placebo (3 capsules)	1	50	4	50

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Hemorrhoids	Gastrointestinal disorders		Systematic Assessment		EG0000 affected51 at risk EG0010 affected51 at risk EG0021 affected50 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Headache	Nervous system disorders	Systematic Assessment	EG0003 affected51 at risk EG0011 affected51 at risk EG0020 affected50 at risk
Disturbance in attention	Nervous system disorders	Systematic Assessment	EG0000 affected51 at risk EG0011 affected51 at risk EG0020 affected50 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0000 affected51 at risk EG0011 affected51 at risk EG0020 affected50 at risk
Dyspepsia	Gastrointestinal disorders	Systematic Assessment	EG0000 affected51 at risk EG0011 affected51 at risk EG0020 affected50 at risk
Rectal hemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0000 affected51 at risk EG0011 affected51 at risk EG0020 affected50 at risk
Hypersensitivity	Immune system disorders	Systematic Assessment	EG0000 affected51 at risk EG0010 affected51 at risk EG0021 affected50 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected51 at risk EG0010 affected51 at risk EG0021 affected50 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected51 at risk EG0010 affected51 at risk EG0021 affected50 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected51 at risk EG0011 affected51 at risk EG0020 affected50 at risk
Insomnia	Psychiatric disorders	Systematic Assessment	EG0001 affected51 at risk EG0010 affected51 at risk EG0020 affected50 at risk
Blister	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected51 at risk EG0010 affected51 at risk EG0020 affected50 at risk
Skin irritation	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected51 at risk EG0010 affected51 at risk EG0021 affected50 at risk

Ancestor Terms

ID	Term
D024841	Fluoroquinolones
D042462	4-Quinolones
D015363	Quinolones
D011804	Quinolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002	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.	Mixed Models Analysis				Mean Difference (Final Values)	-0.4			2-Sided	90	-2.0	1.3				Yes	Non-Inferiority or Equivalence	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.
OG000 OG001	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.	Mixed Models Analysis				Mean Difference (Final Values)	9.2			2-Sided	90	7.6	10.8				Yes	Non-Inferiority or Equivalence	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.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002	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.	Mixed Models Analysis				Mean Difference (Final Values)	0.9			2-Sided	90	-0.7	2.5				Yes	Non-Inferiority or Equivalence	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.
OG000 OG001	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.	Mixed Models Analysis				Mean Difference (Final Values)	9.9			2-Sided	90	8.3	11.5				Yes	Non-Inferiority or Equivalence	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.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002	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.	Mixed Models Analysis				Mean Difference (Final Values)	0.4			2-Sided	90	-1.2	2.0				Yes	Non-Inferiority or Equivalence	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.
OG000	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.	Mixed Models Analysis				Mean Difference (Final Values)	10.1			2-Sided	90	8.5	11.8				Yes	Non-Inferiority or Equivalence	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.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002	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.	Mixed Models Analysis				Mean Difference (Final Values)	-0.2			2-Sided	90	-1.8	1.5				Yes	Non-Inferiority or Equivalence	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.
OG000 OG001	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.	Mixed Models Analysis				Mean Difference (Final Values)	11.9				90	10.3	13.6				Yes	Non-Inferiority or Equivalence	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.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002	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.	Mixed Models Analysis				Mean Difference (Final Values)	-1.5			2-Sided	90	-3.1	0.2				Yes	Non-Inferiority or Equivalence	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.
OG000 OG001	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.	Mixed Models Analysis				Mean Difference (Final Values)	10.8			2-Sided	90	9.2	12.5				Yes	Non-Inferiority or Equivalence	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.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002	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.	Mixed Models Analysis				Mean Difference (Final Values)	-1.8			2-Sided	90	-3.4	-0.1				Yes	Non-Inferiority or Equivalence	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.
OG000 OG001	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.	Mixed Models Analysis				Mean Difference (Final Values)	8.8			2-Sided	90	7.1	10.4				Yes	Non-Inferiority or Equivalence	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.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002	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.	Mixed Models Analysis				Mean Difference (Final Values)	-1.3			2-Sided	90	-2.9	0.4				Yes	Non-Inferiority or Equivalence	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.
OG000 OG001	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.	Mixed Models Analysis				Mean Difference (Final Values)	8.9			2-Sided	90	7.2	10.5				Yes	Non-Inferiority or Equivalence	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.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002	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.	Mixed Models Analysis				Mean Difference (Final Values)	-4.7			2-Sided	90	-6.4	-3.1				Yes	Non-Inferiority or Equivalence	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.
OG000 OG001	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.	Mixed Models Analysis				Mean Difference (Final Values)	7.6			2-Sided	90	6.0	9.3				Yes	Non-Inferiority or Equivalence	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.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002	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.	Mixed Models Analysis				Mean Difference (Final Values)	-2.5			2-Sided	90	-4.1	-0.9				Yes	Non-Inferiority or Equivalence	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.
OG000 OG001	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.	Mixed Models Analysis				Mean Difference (Final Values)	4.0			2-Sided	90	2.4	5.7				Yes	Non-Inferiority or Equivalence	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.