Study to Assess the Safety, Tolerability, Pharmacokinetic... | NCT01026402

ID	Type	Description	Link
2009-015244-42	EudraCT Number

Study to Assess the Safety, Tolerability, Pharmacokinetic... | NCT01026402 | Trialant

Arms/Interventions Module

Label	Type	Description	Intervention Names
AZD2014	Experimental	AZD2014 dose escalation phase in Part A and expansion phase in Part B.	Drug: AZD2014

Interventions

Name	Type	Description	Arm Group Labels	Other Names
AZD2014	Drug	Dose escalation phase: a single dose taken orally (solution or tablet) of AZD2014 on single dose day 1 (visit 2), followed by once or twice daily continuous dosing after a washout period (48 hours - 7 days) at visit 4, until discontinuation or withdrawal or Single or multiple doses taken orally (solution or tablet) of AZD2014 taken intermittently until discontinuation or withdrawal. Expansion phase: twice daily dosing from day 1 until discontinuation or withdrawal or a single dose taken orally of AZD2014 on single dose day 1 (visit 2), followed by a single dose on second single dose day 1 (visit 3) after a washout period (48 hours - 7 days) followed by once or twice daily continuous dosing after a washout period (48 hours - 7 days) at visit 4, until discontinuation or withdrawal or single or multiple doses taken orally (solution or tablet) of AZD2014 taken intermittently until discontinuation or withdrawal.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Dose Limiting Toxicities (DLTs)	Maximum Tolerated Dose (MTD) was determined by testing various doses and schedules of AZD2014 in cohorts of 3-6 evaluable patients. MTD reflects the highest dose of drug at each schedule that did not cause a DLT in >1 patient	Up to 21 days from first multiple dose

Secondary Outcomes

Measure	Description	Time Frame
Best Objective Response	Best Objective Response per Response Evaluation Criteria in Solid Tumours Criteria (RECIST) 1.1 for target and non target lesions assessed by CT, MRI or X-ray; Complete Response (CR), Disappearance of all target lesions since baseline; Partial Response (PR), At least a 30 percent decrease in the sum of diameters of target lesions; Progressive Disease (PD), At least a 20 percent increase in the sum of diameters of target lesions and an absolute increase of at least 5mm

Contacts/Locations Module

Name	Affiliation	Role
Dr. Udai Banerji	The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT	Principal Investigator
Elisabeth Oelmann	AstraZeneca	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Manchester			United Kingdom
Research Site

Arm/Group Information

ID	Title	Description
FG000	Part A 25mg BD Soln Cont	Continuous BD dosing
FG001	Part A 50mg BD Soln Cont	Continuous BD dosing
FG002	Part B 50mg BD Soln Cont	Continuous BD dosing
FG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
FG004	Part A 75mg QD Soln Cont	Continuous QD dosing
FG005	Part A 125mg QD Soln Cont	Continuous QD dosing
FG006	Part A 100mg QD Tab Cont	Continuous QD dosing
FG007	Part A 125mg QD Tab Cont	Continuous QD dosing
FG008	Part A 175mg QD Tab Cont	Continuous QD dosing
FG009	Part A 100mg BD Tab Int	Intermittent BD dosing
FG010	Part A 125mg BD Tab Int	Intermittent BD dosing
FG011	Part A 170mg BD Tab Int	Intermittent BD dosing
FG012	Part A 225mg BD Tab Int	Intermittent BD dosing
FG013	Part B 125mg BD Tab Int	Intermittent BD dosing
FG014	Part B 170mg BD Tab Int	Intermittent BD dosing
FG015	Part A 70mg BD Soln Cont	Continuous BD dosing
FG016	Part A 100mg BD Soln Cont	Continuous BD dosing

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0006 subjects FG0018 subjects FG00233 subjects FG00318 subjects FG0043 subjects FG0055 subjects FG0068 subjects FG0073 subjects FG0087 subjects FG0093 subjects FG0107 subjects FG0118 subjects FG0128 subjects FG0136 subjects FG0143 subjects FG0155 subjects FG0164 subjects
COMPLETED		FG0006 subjects FG0018 subjects FG00233 subjects FG00318 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Baseline Characteristics Module

ID	Title	Description
BG000	Part A 25mg BD Soln Cont	Continuous BD dosing
BG001	Part A 50mg BD Soln Cont	Continuous BD dosing

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

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

Number of Participants With Dose Limiting Toxicities (DLTs)

Maximum Tolerated Dose (MTD) was determined by testing various doses and schedules of AZD2014 in cohorts of 3-6 evaluable patients. MTD reflects the highest dose of drug at each schedule that did not cause a DLT in >1 patient

Safety Analysis Set - All patients that received at least 1 dose of AZD2014. This includes dosed patients who are not evaluable for dose escalation decision purposes.

Posted

Number

Participants

Up to 21 days from first multiple dose

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part A - AZD2014 100 mg BD Solution	Continuous BD dosing

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Myocardial infarction	Cardiac disorders	MedDRA 17.1	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 17.1	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Bryony Harrop	AstraZeneca	01625 582828		ClinicalTrialTransparency@astrazeneca.com

ID	Term
D009369	Neoplasms

ID	Term
C585537	vistusertib

Title

Denominators

Categories

Title	Measurements
	BG00059.2± 15.8 BG00158.3± 14.1 BG00257.2± 10.3 BG00358.6± 14.2 BG00451.7± 11.5 BG00550.0± 16.1 BG00659.4± 11.0 BG00751.3± 18.9 BG00865.6± 9.8 BG00959.0± 18.7 BG01067.3± 7.9 BG01157.6± 5.4 BG01253.8± 9.9 BG01354.2± 14.2 BG01442.7± 9.0 BG01547.4± 14.8 BG01650.0± 8.2 BG01756.9± 12.3

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0002 BG0018 BG00222 BG0038 BG0042 BG0054 BG0066 BG0072 BG0084 BG0093 BG0104 BG0114 BG0126 BG0135 BG0143 BG0153 BG0162 BG01788
Male	BG0004 BG0010 BG00211 BG00310 BG004

Group IDs	Parameter Type	Parameter Value	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001 OG015 OG016	Maximum Tolerated Dose	50	50mg twice daily continuous dosing 20 evaluable patients	No	Superiority or Other
OG004 OG005 OG006 OG007 OG008	Maximum Tolerated Dose	100	100mg once daily continuous dosing 16 evaluable patients	No	Superiority or Other
OG009 OG010 OG011 OG012 OG013 OG014	Maximum Tolerated Dose	125	125mg twice daily intermittent dosing (2 days on, 5 days off) 29 evaluable patients	No	Superiority or Other

Secondary

Best Objective Response

Best Objective Response per Response Evaluation Criteria in Solid Tumours Criteria (RECIST) 1.1 for target and non target lesions assessed by CT, MRI or X-ray; Complete Response (CR), Disappearance of all target lesions since baseline; Partial Response (PR), At least a 30 percent decrease in the sum of diameters of target lesions; Progressive Disease (PD), At least a 20 percent increase in the sum of diameters of target lesions and an absolute increase of at least 5mm

Efficacy analysis set - Patients who received at least 1 dose of AZD2014 and have a baseline tumour assessment

Posted

Number

Participants

Assessed every 8 weeks until progression or withdrawal, whichever came first, estimated to be up to 4 months

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing

Units	Counts
Participants	OG0006 OG0018 OG00233 OG003

Title

Denominators

Categories

Responders

Title	Measurements
	OG0000 OG0010 OG0022 OG003

Secondary

Maximum Concentration (Cmax) Single Dose

Maximum concentration following single dose (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

PK analysis set

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Following Single Dose up to 12, 24 or 48 hours post dose

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing
OG017	Part B 50mg BD Tablet Fasted	Continuous BD dosing
OG018	Part B 50mg BD Tablet Fed	Continuous BD dosing

Units	Counts
Participants	OG0006 OG0018 OG00219 OG003

Title

Denominators

Categories

Title	Measurements
	OG000435± 41.98 OG0011313± 43.62 OG0021089± 62.43 OG004

Secondary

Area Under the Curve (AUC) Single Dose

Area under the curve following single dose Continuous dosing - AUC parameter used Intermittent dosing - AUC(0-12) used (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

PK analysis set

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

Following Single Dose up to 12, 24 or 48 hours post dose

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing
OG017	Part B 50mg BD Tablet Fasted	Continuous BD dosing
OG018	Part B 50mg BD Tablet Fed	Continuous BD dosing

Units	Counts
Participants	OG0006 OG0018 OG00217 OG003

Title

Denominators

Categories

Title	Measurements
	OG0001640± 51.92 OG0015308± 63.35 OG0023520± 81.37 OG004

Secondary

Maximum Concentration (Cmax) at Steady State

Cmax at steady state (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

PK analysis set

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Multiple dosing to steady state (up to 12 or 48 hours post dose)

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing
OG017	Part B 50mg BD Tablet Fasted	Continuous BD dosing
OG018	Part B 50mg BD Tablet Fed	Continuous BD dosing

Units	Counts
Participants	OG0006 OG0016 OG00211 OG003

Title

Denominators

Categories

Title	Measurements
	OG000746.9± 72.42 OG0011822± 38.78 OG0021704± 85.92 OG004

Secondary

Area Under the Curve (AUC) at Steady State

AUC at steady state Continuous dosing - AUCss used Intermittent dosing - Weekly AUC used (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

PK analysis set

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

Multiple dosing to steady state (up to 12 or 48 hours post dose)

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing
OG017	Part B 50mg BD Tablet Fasted	Continuous BD dosing
OG018	Part B 50mg BD Tablet Fed	Continuous BD dosing

Units	Counts
Participants	OG0006 OG0016 OG00211 OG003

Title

Denominators

Categories

Title	Measurements
	OG0002984± 78.71 OG0016436± 57.04 OG0027532± 120.5 OG004

Secondary

Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose

Fraction dose excreted unchanged in the urine from 0-12 hours after a single dose (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

PK analysis set - A subset of Safety Analysis set who have reportable plasma concentrations and PK parameter data and who have no important protocol deviations/AEs that may impact PK

Posted

Mean

Standard Deviation

Percent concentration

Pre dose through to 12 hours post dose

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing
OG017	Part B 50mg BD Tablet Fasted	Continuous BD dosing
OG018	Part B 50mg BD Tablet Fed	Continuous BD dosing

Units	Counts
Participants	OG0005 OG0017 OG0020 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.3709± 0.2953 OG0010.5459± 0.4828 OG004NA± NAWhen there were less than 3 values, summary values were not calculated

Secondary

Urine PK - Fraction Dose Excreted (fe(0-12)) at Steady State

Fraction dose excreted unchanged in the urine from 0-12 hours after dosing (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

PK analysis set - A subset of Safety Analysis set who have reportable plasma concentrations and PK parameter data and who have no important protocol deviations/AEs that may impact PK

Posted

Mean

Standard Deviation

Percent concentration

Pre dose through to 24 hours post dose

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing
OG017	Part B 50mg BD Tablet Fasted	Continuous BD dosing
OG018	Part B 50mg BD Tablet Fed	Continuous BD dosing

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Title

Denominators

Categories

Title	Measurements
	OG004NA± NAWhen there were less than 3 values, summary values were not calculated OG0050.9056± 0.6456 OG0061.026± 0.3658

Secondary

Urine PK - Renal Clearance (Renal CL) Single Dose

Renal Clearance (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

PK analysis set

Posted

Mean

Standard Deviation

L/h

Pre dose through to 24 hours post dose

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing
OG017	Part B 50mg BD Tablet Fasted	Continuous BD dosing
OG018	Part B 50mg BD Tablet Fed	Continuous BD dosing

Units	Counts
Participants	OG0005 OG0016 OG0020 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.07304± 0.07247 OG0010.03994± 0.02933 OG004NA± NAWhen there were less than 3 values, summary values were not calculated

Secondary

Urine PK - Renal Clearance (Renal CL) at Steady State

PK analysis set

Posted

Mean

Standard Deviation

L/h

Pre dose through to 24 hours post dose

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing
OG017	Part B 50mg BD Tablet Fasted	Continuous BD dosing
OG018	Part B 50mg BD Tablet Fed	Continuous BD dosing

Units	Counts
Participants	OG0005 OG0015 OG0020 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.03702± 0.02688 OG0010.04242± 0.01126 OG015NA± NAWhen there were less than 3 values, summary values were not calculated

Secondary

Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose

Phosphorylation levels of 4EBP1 from peripheral blood mononuclear cell (Patients with undetectable values at baseline have been excluded)

Efficacy analysis set

Posted

Median

Full Range

Percent change

predose and 2 hours after a single dose

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing

Units	Counts
Participants	OG0000 OG0016 OG00213 OG003

Title

Denominators

Categories

Title	Measurements
	OG001-47.422(-94.28 to 37.28) OG002-31.067(-96.92 to -10.98) OG003-21.710(-89.58 to 33.33) OG004

Secondary

Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose

Phosphorylation levels of AKT from PRP (Patients with undetectable values at baseline have been excluded)

Efficacy analysis set

Posted

Median

Full Range

Percent change

predose and 2 hours after a single dose

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing

Units	Counts
Participants	OG0005 OG0018 OG00232 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-63.633(-89.99 to -12.15) OG001-76.202(-100.00 to 13.47) OG002-65.375(-99.99 to 2.29) OG003

Secondary

Partial Metabolic Response (PMR), Cycle 1

Partial metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)

Efficacy analysis set

Posted

Number

Participants

Cycle 1 Day 8

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing

Units	Counts
Participants	OG0006 OG0018 OG00233 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0024

Secondary

Partial Metabolic Response (PMR), Cycle 2

Partial metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)

Efficacy analysis set

Posted

Number

Participants

Cycle 2 Day 8

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing

Units	Counts
Participants	OG0006 OG0018 OG00233 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0025

Secondary

Complete Metabolic Response (CMR), Cycle 1

Complete metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)

Efficacy analysis set

Posted

Number

Participants

Cycle 1 Day 8

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing

Units	Counts
Participants	OG0006 OG0018 OG00233 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020

Secondary

Complete Metabolic Response (CMR), Cycle 2

Complete metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)

Efficacy analysis set

Posted

Number

Participants

Cycle 2 Day 8

ID	Title	Description
OG000	Part A 25mg BD Soln Cont	Continuous BD dosing
OG001	Part A 50mg BD Soln Cont	Continuous BD dosing
OG002	Part B 50mg BD Soln Cont	Continuous BD dosing
OG003	Part B Fed/Fasted 50mg BD Tab Cont	Continuous BD dosing
OG004	Part A 75mg QD Soln Cont	Continuous QD dosing
OG005	Part A 125mg QD Soln Cont	Continuous QD dosing
OG006	Part A 100mg QD Tab Cont	Continuous QD dosing
OG007	Part A 125mg QD Tab Cont	Continuous QD dosing
OG008	Part A 175mg QD Tab Cont	Continuous QD dosing
OG009	Part A 100mg BD Tab Int	Intermittent BD dosing
OG010	Part A 125mg BD Tab Int	Intermittent BD dosing
OG011	Part A 170mg BD Tab Int	Intermittent BD dosing
OG012	Part A 225mg BD Tab Int	Intermittent BD dosing
OG013	Part B 125mg BD Tab Int	Intermittent BD dosing
OG014	Part B 170mg BD Tab Int	Intermittent BD dosing
OG015	Part A 70mg BD Soln Cont	Continuous BD dosing
OG016	Part A 100mg BD Soln Cont	Continuous BD dosing

Units	Counts
Participants	OG0006 OG0018 OG00233 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020