Advanced Solid Malignancies
Conditions
Keywords
Phase I, cancer, advanced solid malignancies, dose escalation, AZD2014, mTor kinase inhibitor, safety, pharmacokinetics
Brief summary
The main purpose of the study is to establish a safe dose of the drug by providing information on any potential side effects this drug may cause and collecting data about how a patient's cancer responds to the drug. The study will also assess the blood levels and action of AZD2014 in the body over a period of time and will indicate whether the drug has an effect on the types of cancer the patients have.
Interventions
DRUGAZD2014
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.
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 150 Years
Healthy volunteers
No
Inclusion criteria
* Histological or cytological confirmation of a solid, malignant tumour that is refractory to standard therapies or for which no standard therapies exist * At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by computerised tomography (CT) magnetic resonance imaging (MRI) or plain X-ray and is suitable for repeated assessment * World Health Organisation performance status 0-2 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
Exclusion criteria
* Patients with severe laboratory abnormalities for haematology, liver or renal function. Also treatment with any haemopoietic growth factors are not allowed within two weeks prior to first dose of study drug * Patients with abnormal fasting glucose, type I or uncontrolled type II diabetes * Patients with severe cardiac condition of ischemia, impaired ventricular function and arrhythmias, evidence of severe or uncontrolled systemic or current unstable or uncompensated respiratory or cardiac conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | Up to 21 days from first multiple dose | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) Single Dose | Following Single Dose up to 12, 24 or 48 hours post 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) |
| Area Under the Curve (AUC) Single Dose | Following Single Dose up to 12, 24 or 48 hours post 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) |
| Maximum Concentration (Cmax) at Steady State | Multiple dosing to steady state (up to 12 or 48 hours post dose) | 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) |
| Area Under the Curve (AUC) at Steady State | Multiple dosing to steady state (up to 12 or 48 hours post dose) | 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) |
| Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | Pre dose through to 12 hours post 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) |
| Urine PK - Fraction Dose Excreted (fe(0-12)) at Steady State | Pre dose through to 24 hours post dose | 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) |
| Urine PK - Renal Clearance (Renal CL) Single Dose | Pre dose through to 24 hours post 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) |
| Best Objective Response | Assessed every 8 weeks until progression or withdrawal, whichever came first, estimated to be up to 4 months | 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 |
| Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | predose and 2 hours after a single dose | Phosphorylation levels of 4EBP1 from peripheral blood mononuclear cell (Patients with undetectable values at baseline have been excluded) |
| Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | predose and 2 hours after a single dose | Phosphorylation levels of AKT from PRP (Patients with undetectable values at baseline have been excluded) |
| Partial Metabolic Response (PMR), Cycle 1 | Cycle 1 Day 8 | 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) |
| Partial Metabolic Response (PMR), Cycle 2 | Cycle 2 Day 8 | 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) |
| Complete Metabolic Response (CMR), Cycle 1 | Cycle 1 Day 8 | 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) |
| Complete Metabolic Response (CMR), Cycle 2 | Cycle 2 Day 8 | 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) |
| Urine PK - Renal Clearance (Renal CL) at Steady State | Pre dose through to 24 hours post 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) |
Countries
United Kingdom
Participant flow
Recruitment details
First Subject In: 30th December 2009 Last Subject Last visit: 18th August 2014 2 sites located in the UK Number of participants analyzed in Dose Limiting Toxicity (DLT) outcome measure are patients evaluable for DLT assessment Note - in the Clinical Study Report, combined groups are discussed (e.g. Part A 125mg BD Int and Part B 125mg BD tab Int)
Pre-assignment details
A total of 172 patients were enrolled. 135 of these patients passed screening assessments and were dosed
Participants by arm
| Arm | Count |
|---|---|
| Part A 25mg BD Soln Cont Continuous BD dosing | 6 |
| Part A 50mg BD Soln Cont Continuous BD dosing | 8 |
| Part B 50mg BD Soln Cont Continuous BD dosing | 33 |
| Part B Fed/Fasted 50mg BD Tab Cont Continuous BD dosing | 18 |
| Part A 75mg QD Soln Cont Continuous QD dosing | 3 |
| Part A 125mg QD Soln Cont Continuous QD dosing | 5 |
| Part A 100mg QD Tab Cont Continuous QD dosing | 8 |
| Part A 125mg QD Tab Cont Continuous QD dosing | 3 |
| Part A 175mg QD Tab Cont Continuous QD dosing | 7 |
| Part A 100mg BD Tab Int Intermittent BD dosing | 3 |
| Part A 125mg BD Tab Int Intermittent BD dosing | 7 |
| Part A 170mg BD Tab Int Intermittent BD dosing | 8 |
| Part A 225mg BD Tab Int Intermittent BD dosing | 8 |
| Part B 125mg BD Tab Int Intermittent BD dosing | 6 |
| Part B 170mg BD Tab Int Intermittent BD dosing | 3 |
| Part A 70mg BD Soln Cont Continuous BD dosing | 5 |
| Part A 100mg BD Soln Cont Continuous BD dosing | 4 |
| Total | 135 |
Baseline characteristics
| Characteristic | Part A 25mg BD Soln Cont | Part A 50mg BD Soln Cont | Part B 50mg BD Soln Cont | Part B Fed/Fasted 50mg BD Tab Cont | Part A 75mg QD Soln Cont | Part A 125mg QD Soln Cont | Part A 100mg QD Tab Cont | Part A 125mg QD Tab Cont | Part A 175mg QD Tab Cont | Part A 100mg BD Tab Int | Part A 125mg BD Tab Int | Part A 170mg BD Tab Int | Part A 225mg BD Tab Int | Part B 125mg BD Tab Int | Part B 170mg BD Tab Int | Part A 70mg BD Soln Cont | Part A 100mg BD Soln Cont | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.2 Years STANDARD_DEVIATION 15.8 | 58.3 Years STANDARD_DEVIATION 14.1 | 57.2 Years STANDARD_DEVIATION 10.3 | 58.6 Years STANDARD_DEVIATION 14.2 | 51.7 Years STANDARD_DEVIATION 11.5 | 50.0 Years STANDARD_DEVIATION 16.1 | 59.4 Years STANDARD_DEVIATION 11 | 51.3 Years STANDARD_DEVIATION 18.9 | 65.6 Years STANDARD_DEVIATION 9.8 | 59.0 Years STANDARD_DEVIATION 18.7 | 67.3 Years STANDARD_DEVIATION 7.9 | 57.6 Years STANDARD_DEVIATION 5.4 | 53.8 Years STANDARD_DEVIATION 9.9 | 54.2 Years STANDARD_DEVIATION 14.2 | 42.7 Years STANDARD_DEVIATION 9 | 47.4 Years STANDARD_DEVIATION 14.8 | 50.0 Years STANDARD_DEVIATION 8.2 | 56.9 Years STANDARD_DEVIATION 12.3 |
| Sex: Female, Male Female | 2 Participants | 8 Participants | 22 Participants | 8 Participants | 2 Participants | 4 Participants | 6 Participants | 2 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 6 Participants | 5 Participants | 3 Participants | 3 Participants | 2 Participants | 88 Participants |
| Sex: Female, Male Male | 4 Participants | 0 Participants | 11 Participants | 10 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 0 Participants | 3 Participants | 4 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 8 / 8 | 5 / 5 | 3 / 3 | 7 / 7 | 6 / 6 | 8 / 8 | 5 / 5 | 3 / 3 | 3 / 3 | 7 / 7 | 8 / 8 | 8 / 8 | 32 / 33 | 9 / 9 | 9 / 9 | 6 / 6 | 3 / 3 |
| serious Total, serious adverse events | 1 / 4 | 4 / 8 | 0 / 5 | 2 / 3 | 4 / 7 | 5 / 6 | 0 / 8 | 2 / 5 | 1 / 3 | 1 / 3 | 3 / 7 | 3 / 8 | 6 / 8 | 11 / 33 | 4 / 9 | 3 / 9 | 3 / 6 | 2 / 3 |
Outcome results
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
Time frame: Up to 21 days from first multiple dose
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A 25mg BD Soln Cont | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 50mg BD Soln Cont | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 75mg QD Soln Cont | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 125mg QD Soln Cont | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 100mg QD Tab Cont | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 125mg QD Tab Cont | Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
| Part A 175mg QD Tab Cont | Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
| Part A 100mg BD Tab Int | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 125mg BD Tab Int | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 170mg BD Tab Int | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 225mg BD Tab Int | Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
| Part B 125mg BD Tab Int | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part B 170mg BD Tab Int | Number of Participants With Dose Limiting Toxicities (DLTs) | 3 Participants |
| Part A 70mg BD Soln Cont | Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
| Part A 100mg BD Soln Cont | Number of Participants With Dose Limiting Toxicities (DLTs) | 4 Participants |
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)
Time frame: Multiple dosing to steady state (up to 12 or 48 hours post dose)
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A 25mg BD Soln Cont | Area Under the Curve (AUC) at Steady State | 2984 ng*h/mL | Geometric Coefficient of Variation 78.71 |
| Part A 50mg BD Soln Cont | Area Under the Curve (AUC) at Steady State | 6436 ng*h/mL | Geometric Coefficient of Variation 57.04 |
| Part B 50mg BD Soln Cont | Area Under the Curve (AUC) at Steady State | 7532 ng*h/mL | Geometric Coefficient of Variation 120.5 |
| Part A 75mg QD Soln Cont | Area Under the Curve (AUC) at Steady State | NA ng*h/mL | — |
| Part A 125mg QD Soln Cont | Area Under the Curve (AUC) at Steady State | NA ng*h/mL | — |
| Part A 100mg QD Tab Cont | Area Under the Curve (AUC) at Steady State | 17230 ng*h/mL | Geometric Coefficient of Variation 64.89 |
| Part A 100mg BD Tab Int | Area Under the Curve (AUC) at Steady State | 77690 ng*h/mL | Geometric Coefficient of Variation 41.93 |
| Part A 125mg BD Tab Int | Area Under the Curve (AUC) at Steady State | 78150 ng*h/mL | Geometric Coefficient of Variation 73.52 |
| Part A 170mg BD Tab Int | Area Under the Curve (AUC) at Steady State | 177100 ng*h/mL | Geometric Coefficient of Variation 79.93 |
| Part A 225mg BD Tab Int | Area Under the Curve (AUC) at Steady State | 380200 ng*h/mL | Geometric Coefficient of Variation 52.06 |
| Part B 125mg BD Tab Int | Area Under the Curve (AUC) at Steady State | 89530 ng*h/mL | Geometric Coefficient of Variation 27.06 |
| Part B 170mg BD Tab Int | Area Under the Curve (AUC) at Steady State | NA ng*h/mL | — |
| Part A 70mg BD Soln Cont | Area Under the Curve (AUC) at Steady State | NA ng*h/mL | — |
| Part B 50mg BD Tablet Fasted | Area Under the Curve (AUC) at Steady State | 5275 ng*h/mL | Geometric Coefficient of Variation 53.17 |
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)
Time frame: Following Single Dose up to 12, 24 or 48 hours post dose
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A 25mg BD Soln Cont | Area Under the Curve (AUC) Single Dose | 1640 ng*h/mL | Geometric Coefficient of Variation 51.92 |
| Part A 50mg BD Soln Cont | Area Under the Curve (AUC) Single Dose | 5308 ng*h/mL | Geometric Coefficient of Variation 63.35 |
| Part B 50mg BD Soln Cont | Area Under the Curve (AUC) Single Dose | 3520 ng*h/mL | Geometric Coefficient of Variation 81.37 |
| Part A 75mg QD Soln Cont | Area Under the Curve (AUC) Single Dose | 8866 ng*h/mL | Geometric Coefficient of Variation 50.78 |
| Part A 125mg QD Soln Cont | Area Under the Curve (AUC) Single Dose | 20790 ng*h/mL | Geometric Coefficient of Variation 39.4 |
| Part A 100mg QD Tab Cont | Area Under the Curve (AUC) Single Dose | 11160 ng*h/mL | Geometric Coefficient of Variation 64.18 |
| Part A 125mg QD Tab Cont | Area Under the Curve (AUC) Single Dose | 23450 ng*h/mL | Geometric Coefficient of Variation 24 |
| Part A 175mg QD Tab Cont | Area Under the Curve (AUC) Single Dose | 31670 ng*h/mL | Geometric Coefficient of Variation 61.45 |
| Part A 100mg BD Tab Int | Area Under the Curve (AUC) Single Dose | 11850 ng*h/mL | Geometric Coefficient of Variation 11.29 |
| Part A 125mg BD Tab Int | Area Under the Curve (AUC) Single Dose | 8364 ng*h/mL | Geometric Coefficient of Variation 118.6 |
| Part A 170mg BD Tab Int | Area Under the Curve (AUC) Single Dose | 18630 ng*h/mL | Geometric Coefficient of Variation 74.75 |
| Part A 225mg BD Tab Int | Area Under the Curve (AUC) Single Dose | 33840 ng*h/mL | Geometric Coefficient of Variation 60.95 |
| Part B 125mg BD Tab Int | Area Under the Curve (AUC) Single Dose | 15390 ng*h/mL | Geometric Coefficient of Variation 50.33 |
| Part B 170mg BD Tab Int | Area Under the Curve (AUC) Single Dose | 30030 ng*h/mL | Geometric Coefficient of Variation 14.13 |
| Part A 70mg BD Soln Cont | Area Under the Curve (AUC) Single Dose | 8967 ng*h/mL | Geometric Coefficient of Variation 32.54 |
| Part A 100mg BD Soln Cont | Area Under the Curve (AUC) Single Dose | 9671 ng*h/mL | Geometric Coefficient of Variation 65.88 |
| Part B 50mg BD Tablet Fasted | Area Under the Curve (AUC) Single Dose | 3690 ng*h/mL | Geometric Coefficient of Variation 98.07 |
| Part B 50mg BD Tablet Fed | Area Under the Curve (AUC) Single Dose | 3411 ng*h/mL | Geometric Coefficient of Variation 66.71 |
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
Time frame: Assessed every 8 weeks until progression or withdrawal, whichever came first, estimated to be up to 4 months
Population: Efficacy analysis set - Patients who received at least 1 dose of AZD2014 and have a baseline tumour assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A 25mg BD Soln Cont | Best Objective Response | Responders | 0 Participants |
| Part A 25mg BD Soln Cont | Best Objective Response | Non-responders | 6 Participants |
| Part A 25mg BD Soln Cont | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 2 Participants |
| Part A 50mg BD Soln Cont | Best Objective Response | Non-responders | 8 Participants |
| Part A 50mg BD Soln Cont | Best Objective Response | Responders | 0 Participants |
| Part A 50mg BD Soln Cont | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 1 Participants |
| Part B 50mg BD Soln Cont | Best Objective Response | Non-responders | 31 Participants |
| Part B 50mg BD Soln Cont | Best Objective Response | Responders | 2 Participants |
| Part B 50mg BD Soln Cont | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 12 Participants |
| Part B Fed/Fasted 50mg BD Tab Cont | Best Objective Response | Responders | 0 Participants |
| Part B Fed/Fasted 50mg BD Tab Cont | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 7 Participants |
| Part B Fed/Fasted 50mg BD Tab Cont | Best Objective Response | Non-responders | 18 Participants |
| Part A 75mg QD Soln Cont | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 1 Participants |
| Part A 75mg QD Soln Cont | Best Objective Response | Non-responders | 3 Participants |
| Part A 75mg QD Soln Cont | Best Objective Response | Responders | 0 Participants |
| Part A 125mg QD Soln Cont | Best Objective Response | Non-responders | 5 Participants |
| Part A 125mg QD Soln Cont | Best Objective Response | Responders | 0 Participants |
| Part A 125mg QD Soln Cont | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 1 Participants |
| Part A 100mg QD Tab Cont | Best Objective Response | Non-responders | 8 Participants |
| Part A 100mg QD Tab Cont | Best Objective Response | Responders | 0 Participants |
| Part A 100mg QD Tab Cont | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 4 Participants |
| Part A 125mg QD Tab Cont | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 0 Participants |
| Part A 125mg QD Tab Cont | Best Objective Response | Responders | 0 Participants |
| Part A 125mg QD Tab Cont | Best Objective Response | Non-responders | 3 Participants |
| Part A 175mg QD Tab Cont | Best Objective Response | Non-responders | 7 Participants |
| Part A 175mg QD Tab Cont | Best Objective Response | Responders | 0 Participants |
| Part A 175mg QD Tab Cont | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 1 Participants |
| Part A 100mg BD Tab Int | Best Objective Response | Responders | 0 Participants |
| Part A 100mg BD Tab Int | Best Objective Response | Non-responders | 3 Participants |
| Part A 100mg BD Tab Int | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 0 Participants |
| Part A 125mg BD Tab Int | Best Objective Response | Non-responders | 7 Participants |
| Part A 125mg BD Tab Int | Best Objective Response | Responders | 0 Participants |
| Part A 125mg BD Tab Int | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 3 Participants |
| Part A 170mg BD Tab Int | Best Objective Response | Responders | 0 Participants |
| Part A 170mg BD Tab Int | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 2 Participants |
| Part A 170mg BD Tab Int | Best Objective Response | Non-responders | 8 Participants |
| Part A 225mg BD Tab Int | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 1 Participants |
| Part A 225mg BD Tab Int | Best Objective Response | Non-responders | 8 Participants |
| Part A 225mg BD Tab Int | Best Objective Response | Responders | 0 Participants |
| Part B 125mg BD Tab Int | Best Objective Response | Non-responders | 6 Participants |
| Part B 125mg BD Tab Int | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 1 Participants |
| Part B 125mg BD Tab Int | Best Objective Response | Responders | 0 Participants |
| Part B 170mg BD Tab Int | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 0 Participants |
| Part B 170mg BD Tab Int | Best Objective Response | Non-responders | 3 Participants |
| Part B 170mg BD Tab Int | Best Objective Response | Responders | 0 Participants |
| Part A 70mg BD Soln Cont | Best Objective Response | Responders | 0 Participants |
| Part A 70mg BD Soln Cont | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 2 Participants |
| Part A 70mg BD Soln Cont | Best Objective Response | Non-responders | 5 Participants |
| Part A 100mg BD Soln Cont | Best Objective Response | Stable disease ≥8 wks (a subset of non-responders) | 0 Participants |
| Part A 100mg BD Soln Cont | Best Objective Response | Responders | 0 Participants |
| Part A 100mg BD Soln Cont | Best Objective Response | Non-responders | 4 Participants |
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)
Time frame: Cycle 1 Day 8
Population: Efficacy analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A 25mg BD Soln Cont | Complete Metabolic Response (CMR), Cycle 1 | 0 Participants |
| Part A 50mg BD Soln Cont | Complete Metabolic Response (CMR), Cycle 1 | 0 Participants |
| Part B 50mg BD Soln Cont | Complete Metabolic Response (CMR), Cycle 1 | 0 Participants |
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)
Time frame: Cycle 2 Day 8
Population: Efficacy analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A 25mg BD Soln Cont | Complete Metabolic Response (CMR), Cycle 2 | 0 Participants |
| Part A 50mg BD Soln Cont | Complete Metabolic Response (CMR), Cycle 2 | 0 Participants |
| Part B 50mg BD Soln Cont | Complete Metabolic Response (CMR), Cycle 2 | 0 Participants |
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)
Time frame: Multiple dosing to steady state (up to 12 or 48 hours post dose)
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A 25mg BD Soln Cont | Maximum Concentration (Cmax) at Steady State | 746.9 ng/mL | Geometric Coefficient of Variation 72.42 |
| Part A 50mg BD Soln Cont | Maximum Concentration (Cmax) at Steady State | 1822 ng/mL | Geometric Coefficient of Variation 38.78 |
| Part B 50mg BD Soln Cont | Maximum Concentration (Cmax) at Steady State | 1704 ng/mL | Geometric Coefficient of Variation 85.92 |
| Part A 75mg QD Soln Cont | Maximum Concentration (Cmax) at Steady State | NA ng/mL | — |
| Part A 125mg QD Soln Cont | Maximum Concentration (Cmax) at Steady State | 5517 ng/mL | Geometric Coefficient of Variation 29.14 |
| Part A 100mg QD Tab Cont | Maximum Concentration (Cmax) at Steady State | 2730 ng/mL | Geometric Coefficient of Variation 47.23 |
| Part A 100mg BD Tab Int | Maximum Concentration (Cmax) at Steady State | 3258 ng/mL | Geometric Coefficient of Variation 25.2 |
| Part A 125mg BD Tab Int | Maximum Concentration (Cmax) at Steady State | 3534 ng/mL | Geometric Coefficient of Variation 25.08 |
| Part A 170mg BD Tab Int | Maximum Concentration (Cmax) at Steady State | 7557 ng/mL | Geometric Coefficient of Variation 38.19 |
| Part A 225mg BD Tab Int | Maximum Concentration (Cmax) at Steady State | 11400 ng/mL | Geometric Coefficient of Variation 24.23 |
| Part B 125mg BD Tab Int | Maximum Concentration (Cmax) at Steady State | 5649 ng/mL | Geometric Coefficient of Variation 27.38 |
| Part B 170mg BD Tab Int | Maximum Concentration (Cmax) at Steady State | NA ng/mL | — |
| Part A 70mg BD Soln Cont | Maximum Concentration (Cmax) at Steady State | NA ng/mL | — |
| Part B 50mg BD Tablet Fasted | Maximum Concentration (Cmax) at Steady State | 1162 ng/mL | Geometric Coefficient of Variation 46.37 |
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)
Time frame: Following Single Dose up to 12, 24 or 48 hours post dose
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A 25mg BD Soln Cont | Maximum Concentration (Cmax) Single Dose | 435 ng/mL | Geometric Coefficient of Variation 41.98 |
| Part A 50mg BD Soln Cont | Maximum Concentration (Cmax) Single Dose | 1313 ng/mL | Geometric Coefficient of Variation 43.62 |
| Part B 50mg BD Soln Cont | Maximum Concentration (Cmax) Single Dose | 1089 ng/mL | Geometric Coefficient of Variation 62.43 |
| Part A 75mg QD Soln Cont | Maximum Concentration (Cmax) Single Dose | 1476 ng/mL | Geometric Coefficient of Variation 78.18 |
| Part A 125mg QD Soln Cont | Maximum Concentration (Cmax) Single Dose | 4046 ng/mL | Geometric Coefficient of Variation 22.46 |
| Part A 100mg QD Tab Cont | Maximum Concentration (Cmax) Single Dose | 2048 ng/mL | Geometric Coefficient of Variation 47.26 |
| Part A 125mg QD Tab Cont | Maximum Concentration (Cmax) Single Dose | 2989 ng/mL | Geometric Coefficient of Variation 20.69 |
| Part A 175mg QD Tab Cont | Maximum Concentration (Cmax) Single Dose | 3251 ng/mL | Geometric Coefficient of Variation 54.69 |
| Part A 100mg BD Tab Int | Maximum Concentration (Cmax) Single Dose | 1868 ng/mL | Geometric Coefficient of Variation 32.82 |
| Part A 125mg BD Tab Int | Maximum Concentration (Cmax) Single Dose | 1826 ng/mL | Geometric Coefficient of Variation 62.99 |
| Part A 170mg BD Tab Int | Maximum Concentration (Cmax) Single Dose | 3293 ng/mL | Geometric Coefficient of Variation 74.44 |
| Part A 225mg BD Tab Int | Maximum Concentration (Cmax) Single Dose | 5223 ng/mL | Geometric Coefficient of Variation 39.53 |
| Part B 125mg BD Tab Int | Maximum Concentration (Cmax) Single Dose | 2849 ng/mL | Geometric Coefficient of Variation 61.7 |
| Part B 170mg BD Tab Int | Maximum Concentration (Cmax) Single Dose | 4395 ng/mL | Geometric Coefficient of Variation 14.92 |
| Part A 70mg BD Soln Cont | Maximum Concentration (Cmax) Single Dose | 2382 ng/mL | Geometric Coefficient of Variation 38.8 |
| Part A 100mg BD Soln Cont | Maximum Concentration (Cmax) Single Dose | 2787 ng/mL | Geometric Coefficient of Variation 71.97 |
| Part B 50mg BD Tablet Fasted | Maximum Concentration (Cmax) Single Dose | 856.3 ng/mL | Geometric Coefficient of Variation 73.47 |
| Part B 50mg BD Tablet Fed | Maximum Concentration (Cmax) Single Dose | 643.7 ng/mL | Geometric Coefficient of Variation 54.1 |
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)
Time frame: Cycle 1 Day 8
Population: Efficacy analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A 25mg BD Soln Cont | Partial Metabolic Response (PMR), Cycle 1 | 0 Participants |
| Part A 50mg BD Soln Cont | Partial Metabolic Response (PMR), Cycle 1 | 0 Participants |
| Part B 50mg BD Soln Cont | Partial Metabolic Response (PMR), Cycle 1 | 4 Participants |
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)
Time frame: Cycle 2 Day 8
Population: Efficacy analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A 25mg BD Soln Cont | Partial Metabolic Response (PMR), Cycle 2 | 0 Participants |
| Part A 50mg BD Soln Cont | Partial Metabolic Response (PMR), Cycle 2 | 0 Participants |
| Part B 50mg BD Soln Cont | Partial Metabolic Response (PMR), Cycle 2 | 5 Participants |
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)
Time frame: predose and 2 hours after a single dose
Population: Efficacy analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A 50mg BD Soln Cont | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -47.422 Percent change |
| Part B 50mg BD Soln Cont | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -31.067 Percent change |
| Part B Fed/Fasted 50mg BD Tab Cont | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -21.710 Percent change |
| Part A 75mg QD Soln Cont | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -78.760 Percent change |
| Part A 125mg QD Soln Cont | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -74.053 Percent change |
| Part A 100mg QD Tab Cont | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -66.855 Percent change |
| Part A 125mg QD Tab Cont | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -68.966 Percent change |
| Part A 175mg QD Tab Cont | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -82.249 Percent change |
| Part A 100mg BD Tab Int | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -57.317 Percent change |
| Part A 125mg BD Tab Int | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -76.977 Percent change |
| Part A 170mg BD Tab Int | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -67.275 Percent change |
| Part A 225mg BD Tab Int | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -55.847 Percent change |
| Part B 125mg BD Tab Int | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -42.632 Percent change |
| Part B 170mg BD Tab Int | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -64.855 Percent change |
| Part A 70mg BD Soln Cont | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -57.143 Percent change |
| Part A 100mg BD Soln Cont | Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose | -62.775 Percent change |
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)
Time frame: predose and 2 hours after a single dose
Population: Efficacy analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A 25mg BD Soln Cont | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -63.633 Percent change |
| Part A 50mg BD Soln Cont | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -76.202 Percent change |
| Part B 50mg BD Soln Cont | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -65.375 Percent change |
| Part B Fed/Fasted 50mg BD Tab Cont | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -62.942 Percent change |
| Part A 75mg QD Soln Cont | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -67.349 Percent change |
| Part A 125mg QD Soln Cont | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -82.737 Percent change |
| Part A 100mg QD Tab Cont | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -76.364 Percent change |
| Part A 125mg QD Tab Cont | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -49.476 Percent change |
| Part A 175mg QD Tab Cont | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -86.422 Percent change |
| Part A 100mg BD Tab Int | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -57.326 Percent change |
| Part A 125mg BD Tab Int | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -63.350 Percent change |
| Part A 170mg BD Tab Int | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -62.839 Percent change |
| Part A 225mg BD Tab Int | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -85.376 Percent change |
| Part B 125mg BD Tab Int | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -92.031 Percent change |
| Part B 170mg BD Tab Int | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -66.958 Percent change |
| Part A 70mg BD Soln Cont | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -90.374 Percent change |
| Part A 100mg BD Soln Cont | Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose | -88.343 Percent change |
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)
Time frame: Pre dose through to 24 hours post dose
Population: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A 75mg QD Soln Cont | Urine PK - Fraction Dose Excreted (fe(0-12)) at Steady State | NA Percent concentration | — |
| Part A 125mg QD Soln Cont | Urine PK - Fraction Dose Excreted (fe(0-12)) at Steady State | 0.9056 Percent concentration | Standard Deviation 0.6456 |
| Part A 100mg QD Tab Cont | Urine PK - Fraction Dose Excreted (fe(0-12)) at Steady State | 1.026 Percent concentration | Standard Deviation 0.3658 |
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)
Time frame: Pre dose through to 12 hours post dose
Population: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A 25mg BD Soln Cont | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | 0.3709 Percent concentration | Standard Deviation 0.2953 |
| Part A 50mg BD Soln Cont | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | 0.5459 Percent concentration | Standard Deviation 0.4828 |
| Part A 75mg QD Soln Cont | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | NA Percent concentration | — |
| Part A 125mg QD Soln Cont | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | 0.7094 Percent concentration | Standard Deviation 0.3569 |
| Part A 100mg QD Tab Cont | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | 0.7728 Percent concentration | Standard Deviation 0.4854 |
| Part A 175mg QD Tab Cont | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | 0.8344 Percent concentration | Standard Deviation 0.569 |
| Part A 125mg BD Tab Int | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | 0.8991 Percent concentration | Standard Deviation 0.735 |
| Part A 170mg BD Tab Int | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | 0.4744 Percent concentration | Standard Deviation 0.2252 |
| Part A 225mg BD Tab Int | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | 1.106 Percent concentration | Standard Deviation 0.8091 |
| Part B 125mg BD Tab Int | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | NA Percent concentration | — |
| Part B 170mg BD Tab Int | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | NA Percent concentration | — |
| Part A 70mg BD Soln Cont | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | 0.3288 Percent concentration | Standard Deviation 0.1359 |
| Part A 100mg BD Soln Cont | Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose | 0.7680 Percent concentration | Standard Deviation 0.7217 |
Secondary
Urine PK - Renal Clearance (Renal CL) at Steady State
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)
Time frame: Pre dose through to 24 hours post dose
Population: PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A 25mg BD Soln Cont | Urine PK - Renal Clearance (Renal CL) at Steady State | 0.03702 L/h | Standard Deviation 0.02688 |
| Part A 50mg BD Soln Cont | Urine PK - Renal Clearance (Renal CL) at Steady State | 0.04242 L/h | Standard Deviation 0.01126 |
| Part A 70mg BD Soln Cont | Urine PK - Renal Clearance (Renal CL) at Steady State | NA L/h | — |
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)
Time frame: Pre dose through to 24 hours post dose
Population: PK analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A 25mg BD Soln Cont | Urine PK - Renal Clearance (Renal CL) Single Dose | 0.07304 L/h | Standard Deviation 0.07247 |
| Part A 50mg BD Soln Cont | Urine PK - Renal Clearance (Renal CL) Single Dose | 0.03994 L/h | Standard Deviation 0.02933 |
| Part A 75mg QD Soln Cont | Urine PK - Renal Clearance (Renal CL) Single Dose | NA L/h | — |
| Part A 125mg QD Soln Cont | Urine PK - Renal Clearance (Renal CL) Single Dose | 0.04338 L/h | Standard Deviation 0.009039 |
| Part A 100mg QD Tab Cont | Urine PK - Renal Clearance (Renal CL) Single Dose | 0.07526 L/h | Standard Deviation 0.03353 |
| Part A 175mg QD Tab Cont | Urine PK - Renal Clearance (Renal CL) Single Dose | 0.08576 L/h | Standard Deviation 0.02948 |
| Part A 125mg BD Tab Int | Urine PK - Renal Clearance (Renal CL) Single Dose | 0.1081 L/h | Standard Deviation 0.01434 |
| Part A 170mg BD Tab Int | Urine PK - Renal Clearance (Renal CL) Single Dose | 0.06049 L/h | Standard Deviation 0.05774 |
| Part A 225mg BD Tab Int | Urine PK - Renal Clearance (Renal CL) Single Dose | 0.07377 L/h | Standard Deviation 0.05802 |
| Part B 125mg BD Tab Int | Urine PK - Renal Clearance (Renal CL) Single Dose | NA L/h | — |
| Part B 170mg BD Tab Int | Urine PK - Renal Clearance (Renal CL) Single Dose | NA L/h | — |
| Part A 70mg BD Soln Cont | Urine PK - Renal Clearance (Renal CL) Single Dose | 0.03083 L/h | Standard Deviation 0.01394 |
| Part A 100mg BD Soln Cont | Urine PK - Renal Clearance (Renal CL) Single Dose | 0.09813 L/h | Standard Deviation 0.04768 |