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Trial record 96 of 205 for:    SPORANOX I.V. OR ITRACONAZOLE OR ONMEL OR SPORANOX-PULSE OR Sporanos OR R 51,211 OR SPORANOX

Study to Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of AZD9291, in Patients With EGFR Positive Non-small Cell Lung Cancer. Patients Will be Chosen From Those Who Have Already Been Prescribed an EGFR TKI Medicine (Such as Iressa or Tarceva)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02157883
Recruitment Status : Active, not recruiting
First Posted : June 6, 2014
Results First Posted : April 14, 2016
Last Update Posted : February 5, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Conditions Advanced Non Small Cell Lung Cancer
Advanced (Inoperable) Non Small Cell Lung Cancer
Interventions Procedure: Pharmacokinetic sampling
Drug: AZD9291
Drug: Itraconazole
Enrollment 39
Recruitment Details First subject enrolled: 6 November 2014; Last Subject Last Visit Part A: 3 April 2015 and Part B: 31 March 2016. Study performed at 15 sites across Asia, North America and Western Europe. Part A assessed effect of multiple doses of itraconazole on PK of AZD9291; Part B allowed subjects further access to AZD9291 and provided additional safety data.
Pre-assignment Details The 39 patients started Period 1 and received treatment.
Arm/Group Title AZD9291 and Itraconozole (Part A); AZD9291 Alone (Part B)
Hide Arm/Group Description

In Part A of the study, sequential treatments of AZD9291 alone (including a washout) followed by AZD9291+itraconazole. Each patient received single 80 mg oral doses of AZD9291 tablets on Days 1 and 10, and in addition received itraconazole capsules 200 mg twice daily on Days 6 to 18.

In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.

Period Title: Part A: Day 1-5 (AZD9291 Alone)
Started 39
Completed 39
Not Completed 0
Period Title: Part A: Day 6-18 (AZD9291+Itraconozole)
Started 39
Completed 38
Not Completed 1
Reason Not Completed
Adverse Event             1
Period Title: Part B: Day 19 to End Part B (AZD9291)
Started 38
Completed 16
Not Completed 22
Reason Not Completed
Adverse Event             3
Disease progression             15
Withdrawal by Subject             1
Death             3
Arm/Group Title AZD9291 and Itraconozole (Part A); AZD9291 Alone (Part B)
Hide Arm/Group Description

In Part A of the study, sequential treatments of AZD9291 alone (including a washout) followed by AZD9291+itraconazole. Each patient received single 80 mg oral doses of AZD9291 tablets on Days 1 and 10, and in addition received itraconazole capsules 200 mg twice daily on Days 6 to 18.

In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.

Overall Number of Baseline Participants 39
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 39 participants
58.8  (10.73)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants
Female
27
  69.2%
Male
12
  30.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants
American Indian or Alaska Native
0
   0.0%
Asian
29
  74.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
10
  25.6%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Cmax of AZD9291
Hide Description Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration
Time Frame Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration >10% of Cmax).
Arm/Group Title AZD9291 Alone AZD9291+Itraconazole
Hide Arm/Group Description:
Single oral dose of 80mg AZD9291 on Day 1
Single oral dose 80mg AZD9291 on Day 10, itraconazole 200mg twice daily dosing on Days 6-18
Overall Number of Participants Analyzed 34 30
Geometric Mean (Full Range)
Unit of Measure: nM
242.5
(88.8 to 704)
201.7
(78.2 to 676)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD9291 Alone, AZD9291+Itraconazole
Comments Study sized so experiment-wise power for the upper bound of the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being below 200% was 90% (95% for each parameter). Within patient CV assumed to be 34%. A 50% increase in exposure was also assumed.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Upper bound of the 90% CIs below 200%.
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 79.87
Confidence Interval (2-Sided) 90%
73.15 to 87.21
Estimation Comments AZD9291+itraconazole / AZD9291 alone. Results based on linear mixed-effects model with treatment as fixed effect and patient as a random effect.
2.Primary Outcome
Title AUC of AZD9291
Hide Description Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to infinity
Time Frame Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration >10% of Cmax).
Arm/Group Title AZD9291 Alone AZD9291+Itraconazole
Hide Arm/Group Description:
Single oral dose of 80mg AZD9291 on Day 1
Single oral dose 80mg AZD9291 on Day 10, itraconazole 200mg twice daily dosing on Days 6-18
Overall Number of Participants Analyzed 33 30
Geometric Mean (Full Range)
Unit of Measure: nM*h
13520
(6510 to 40400)
17090
(7130 to 59600)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD9291 Alone, AZD9291+Itraconazole
Comments Study sized so experiment-wise power for the upper bound of the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being below 200% was 90% (95% for each parameter). Within patient CV assumed to be 34%. A 50% increase in exposure was also assumed.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Upper bound of the 90% CIs below 200%.
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 124.17
Confidence Interval (2-Sided) 90%
114.61 to 134.53
Estimation Comments AZD9291+itraconazole / AZD9291 alone. Results based on linear mixed-effects model with treatment as fixed effect and patient as a random effect.
3.Secondary Outcome
Title AUC(0-120) of AZD9291
Hide Description Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to 120 hours
Time Frame Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration >10% of Cmax).
Arm/Group Title AZD9291 Alone AZD9291+Itraconazole
Hide Arm/Group Description:
Single oral dose of 80mg AZD9291 on Day 1
Single oral dose 80mg AZD9291 on Day 10, itraconazole 200mg twice daily dosing on Days 6-18
Overall Number of Participants Analyzed 34 31
Geometric Mean (Full Range)
Unit of Measure: nM*h
10280
(4980 to 27500)
11370
(5100 to 37500)
4.Secondary Outcome
Title AUC(0-t) of AZD9291
Hide Description Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration curve from time zero to last quantifiable dose
Time Frame Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration >10% of Cmax).
Arm/Group Title AZD9291 Alone AZD9291+Itraconazole
Hide Arm/Group Description:
Single oral dose of 80mg AZD9291 on Day 1
Single oral dose 80mg AZD9291 on Day 10, itraconazole 200mg twice daily dosing on Days 6-18
Overall Number of Participants Analyzed 34 31
Geometric Mean (Full Range)
Unit of Measure: nM*h
12260
(6090 to 33600)
14520
(6280 to 49600)
5.Secondary Outcome
Title Tmax of AZD9291
Hide Description Pharmacokinetics of AZD9291 by assessment of time to Cmax
Time Frame Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration >10% of Cmax).
Arm/Group Title AZD9291 Alone AZD9291+Itraconazole
Hide Arm/Group Description:
Single oral dose of 80mg AZD9291 on Day 1
Single oral dose 80mg AZD9291 on Day 10, itraconazole 200mg twice daily dosing on Days 6-18
Overall Number of Participants Analyzed 34 30
Median (Full Range)
Unit of Measure: hours
4.00
(2.03 to 11.87)
6.04
(3.00 to 72.00)
6.Secondary Outcome
Title t1/2 of AZD9291
Hide Description Pharmacokinetics of AZD9291 by assessment of the terminal half-life
Time Frame Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration >10% of Cmax).
Arm/Group Title AZD9291 Alone AZD9291+Itraconazole
Hide Arm/Group Description:
Single oral dose of 80mg AZD9291 on Day 1
Single oral dose 80mg AZD9291 on Day 10, itraconazole 200mg twice daily dosing on Days 6-18
Overall Number of Participants Analyzed 34 30
Geometric Mean (Full Range)
Unit of Measure: hours
61.05
(38.7 to 131)
78.36
(56.3 to 150)
7.Secondary Outcome
Title CL/F of AZD9291
Hide Description Rate and extent of absorption of AZD9291 by assessment of apparent clearance following oral administration
Time Frame Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration >10% of Cmax).
Arm/Group Title AZD9291 Alone AZD9291+Itraconazole
Hide Arm/Group Description:
Single oral dose of 80mg AZD9291 on Day 1
Single oral dose 80mg AZD9291 on Day 10, itraconazole 200mg twice daily dosing on Days 6-18
Overall Number of Participants Analyzed 33 30
Geometric Mean (Full Range)
Unit of Measure: L/h
11.84
(3.96 to 24.6)
9.368
(2.69 to 22.5)
8.Secondary Outcome
Title Vz/F of AZD9291
Hide Description Rate and extent of absorption of AZD9291 by assessment of the apprarent volume of distribution
Time Frame Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose concentration >10% of Cmax).
Arm/Group Title AZD9291 Alone AZD9291+Itraconazole
Hide Arm/Group Description:
Single oral dose of 80mg AZD9291 on Day 1
Single oral dose 80mg AZD9291 on Day 10, itraconazole 200mg twice daily dosing on Days 6-18
Overall Number of Participants Analyzed 33 30
Geometric Mean (Full Range)
Unit of Measure: L
1019
(491 to 2310)
1059
(344 to 2630)
9.Secondary Outcome
Title Cmax of AZ5104
Hide Description Pharmacokinetics of AZ5104 (metabolite to AZD9291) by assessment of maximum plasma AZ5104 concentration
Time Frame Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose AZ5104 concentration >20% of Cmax).
Arm/Group Title AZD9291 Alone AZD9291+Itraconazole
Hide Arm/Group Description:
Single oral dose of 80mg AZD9291 on Day 1
Single oral dose 80mg AZD9291 on Day 10, itraconazole 200mg twice daily dosing on Days 6-18
Overall Number of Participants Analyzed 34 16
Geometric Mean (Full Range)
Unit of Measure: nM
8.568
(2.36 to 23.4)
5.746
(2.15 to 15.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD9291 Alone, AZD9291+Itraconazole
Comments Study sized so experiment-wise power for the upper bound of the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being below 200% was 90% (95% for each parameter). Within patient CV assumed to be 34%. A 50% increase in exposure was also assumed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 75.87
Confidence Interval (2-Sided) 90%
64.18 to 89.69
Estimation Comments AZD9291+itraconazole / AZD9291 alone. No pre-specified margins for equivalence test for metabolites, but analysed for consistency with AZD9291 analysis.
10.Secondary Outcome
Title AUC of AZ5104
Hide Description Pharmacokinetics of AZ5104 (metabolite to AZD9291) by assessment of area under the plasma concentration time curve from zero to infinity
Time Frame Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and excluding Period 2 data for patients meeting carry-over exclusion criterion (defined as Period 2 pre-dose AZ5104 concentration >20% of Cmax).
Arm/Group Title AZD9291 Alone AZD9291+Itraconazole
Hide Arm/Group Description:
Single oral dose of 80mg AZD9291 on Day 1
Single oral dose 80mg AZD9291 on Day 10, itraconazole 200mg twice daily dosing on Days 6-18
Overall Number of Participants Analyzed 31 15
Geometric Mean (Full Range)
Unit of Measure: nM*h
1155
(367 to 4360)
941.4
(337 to 2620)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD9291 Alone, AZD9291+Itraconazole
Comments Study sized so experiment-wise power for the upper bound of the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being below 200% was 90% (95% for each parameter). Within patient CV assumed to be 34%. A 50% increase in exposure was also assumed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 108.25
Confidence Interval (2-Sided) 90%
94.36 to 124.19
Estimation Comments AZD9291+itraconazole / AZD9291 alone. No pre-specified margins for equivalence test for metabolites, but analysed for consistency with AZD9291 analysis.
11.Secondary Outcome
Title Cmax of AZ7550
Hide Description Pharmacokinetics of AZ7550 (metabolite to AZD9291) by assessment of maximum plasma AZ7550 concentration
Time Frame Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations/violations and including Period 2 data (since all patients met carry over criteria of Period 2 pre-dose AZ7550 concentration >20% of Cmax).
Arm/Group Title AZD9291 Alone AZD9291+Itraconazole
Hide Arm/Group Description:
Single oral dose of 80mg AZD9291 on Day 1
Single oral dose 80mg AZD9291 on Day 10, itraconazole 200mg twice daily dosing on Days 6-18
Overall Number of Participants Analyzed 34 33
Geometric Mean (Full Range)
Unit of Measure: nM
4.321
(1.64 to 11.7)
1.897
(0.659 to 5.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD9291 Alone, AZD9291+Itraconazole
Comments Study sized so experiment-wise power for the upper bound of the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being below 200% was 90% (95% for each parameter). Within patient CV assumed to be 34%. A 50% increase in exposure was also assumed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 44.33
Confidence Interval (2-Sided) 90%
39.94 to 49.21
Estimation Comments AZD9291+itraconazole / AZD9291 alone. No pre-specified margins for equivalence test for metabolites, but analysed for consistency with AZD9291 analysis.
12.Secondary Outcome
Title AUC of AZ7550
Hide Description Pharmacokinetics of AZ7550 (metabolite to AZD9291) by assessment of area under the plasma concentration time curve from zero to infinity
Time Frame Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of AZD9291 and had sufficient postdose PK assessments to determine outcome measure without important protocol deviations, where AUC possible to calculate, and including Period 2 data (all patients met carry over criteria of Period 2 pre-dose AZ7550 concentration >20% of Cmax).
Arm/Group Title AZD9291 Alone AZD9291+Itraconazole
Hide Arm/Group Description:
Single oral dose of 80mg AZD9291 on Day 1
Single oral dose 80mg AZD9291 on Day 10, itraconazole 200mg twice daily dosing on Days 6-18
Overall Number of Participants Analyzed 33 19
Geometric Mean (Full Range)
Unit of Measure: nM*h
624.1
(210 to 1700)
292.1
(158 to 578)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD9291 Alone, AZD9291+Itraconazole
Comments Study sized so experiment-wise power for the upper bound of the 90% CIs of geometric mean ratios for both AUC and Cmax of AZD9291 being below 200% was 90% (95% for each parameter). Within patient CV assumed to be 34%. A 50% increase in exposure was also assumed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 49.02
Confidence Interval (2-Sided) 90%
43.70 to 54.99
Estimation Comments AZD9291+itraconazole / AZD9291 alone. No pre-specified margins for equivalence test for metabolites, but analysed for consistency with AZD9291 analysis.
Time Frame Approximately 3 weeks for Part A; up to approximately 15.5 months for Part B and approximately 16 months for Overall (Parts A and B combined).
Adverse Event Reporting Description Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 19), or until 30 days after last dose if discontinued in Part A. Part B: AEs collected from day of first dose in Part B until 30 days after last dose, or until last dose in Part B for those entering continued access phase (CAP).
 
Arm/Group Title Overall Safety Population Part A Safety Population Part B Safety Population
Hide Arm/Group Description Parts A and B of the study combined. In Part A of the study, each patient received a single 80 mg oral AZD9291 tablet dose in each of 2 treatment periods (AZD9291 dosing on Days 1 and 10). Patients additionally received itraconazole 200 mg twice daily dosing from Days 6 to 18. In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.
All-Cause Mortality
Overall Safety Population Part A Safety Population Part B Safety Population
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Overall Safety Population Part A Safety Population Part B Safety Population
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/39 (30.77%)      3/39 (7.69%)      9/38 (23.68%)    
Gastrointestinal disorders       
Gastric ulcer  1  1/39 (2.56%)  1 0/39 (0.00%)  0 1/38 (2.63%)  1
Infections and infestations       
Influenza  1  1/39 (2.56%)  1 0/39 (0.00%)  0 1/38 (2.63%)  1
Metapneumovirus infection  1 [1]  1/39 (2.56%)  1 0/39 (0.00%)  0 1/38 (2.63%)  1
Pneumonia  1  3/39 (7.69%)  3 1/39 (2.56%)  1 2/38 (5.26%)  2
Respiratory syncytial virus infection  1  1/39 (2.56%)  1 1/39 (2.56%)  1 0/38 (0.00%)  0
Urinary tract infection  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Investigations       
Hepatic enzyme increased  1  2/39 (5.13%)  2 1/39 (2.56%)  1 1/38 (2.63%)  1
Respiratory, thoracic and mediastinal disorders       
Bronchopleural fistula  1 [1]  1/39 (2.56%)  1 0/39 (0.00%)  0 1/38 (2.63%)  1
Pulmonary embolism  1  1/39 (2.56%)  1 0/39 (0.00%)  0 1/38 (2.63%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
[1]
Death
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Overall Safety Population Part A Safety Population Part B Safety Population
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   39/39 (100.00%)      24/39 (61.54%)      38/38 (100.00%)    
Blood and lymphatic system disorders       
Anaemia  1  6/39 (15.38%)  6 1/39 (2.56%)  1 5/38 (13.16%)  5
Thrombocytopenia  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Ear and labyrinth disorders       
Tinnitus  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Gastrointestinal disorders       
Abdominal distension  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Abdominal pain  1  3/39 (7.69%)  5 3/39 (7.69%)  4 1/38 (2.63%)  1
Constipation  1  8/39 (20.51%)  9 2/39 (5.13%)  2 6/38 (15.79%)  7
Diarrhoea  1  15/39 (38.46%)  17 2/39 (5.13%)  2 13/38 (34.21%)  15
Dry mouth  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Dyspepsia  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Mouth ulceration  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Nausea  1  14/39 (35.90%)  18 7/39 (17.95%)  8 10/38 (26.32%)  10
Oesophageal pain  1  2/39 (5.13%)  3 1/39 (2.56%)  1 2/38 (5.26%)  2
Stomatitis  1  5/39 (12.82%)  5 0/39 (0.00%)  0 5/38 (13.16%)  5
Vomiting  1  10/39 (25.64%)  15 6/39 (15.38%)  8 6/38 (15.79%)  7
General disorders       
Fatigue  1  12/39 (30.77%)  13 3/39 (7.69%)  3 9/38 (23.68%)  10
Influenza like illness  1  3/39 (7.69%)  3 0/39 (0.00%)  0 3/38 (7.89%)  3
Non-cardiac chest pain  1  3/39 (7.69%)  3 1/39 (2.56%)  1 2/38 (5.26%)  2
Oedema peripheral  1  4/39 (10.26%)  5 2/39 (5.13%)  2 3/38 (7.89%)  3
Infections and infestations       
Herpes zoster  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Paronychia  1  8/39 (20.51%)  9 0/39 (0.00%)  0 8/38 (21.05%)  9
Pneumonia  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Upper respiratory tract infection  1  5/39 (12.82%)  5 1/39 (2.56%)  1 4/38 (10.53%)  4
Urinary tract infection  1  4/39 (10.26%)  5 1/39 (2.56%)  1 4/38 (10.53%)  4
Investigations       
Alanine aminotransferase increased  1  4/39 (10.26%)  8 0/39 (0.00%)  0 4/38 (10.53%)  8
Aspartate aminotransferase increased  1  4/39 (10.26%)  9 0/39 (0.00%)  0 4/38 (10.53%)  9
Blood alkaline phosphatase increased  1  3/39 (7.69%)  4 0/39 (0.00%)  0 3/38 (7.89%)  4
Blood creatine increased  1  2/39 (5.13%)  3 0/39 (0.00%)  0 2/38 (5.26%)  3
Electrocardiogram QT prolonged  1  3/39 (7.69%)  4 1/39 (2.56%)  1 3/38 (7.89%)  3
Neutrophil count decreased  1  2/39 (5.13%)  3 0/39 (0.00%)  0 2/38 (5.26%)  3
Metabolism and nutrition disorders       
Decreased appetite  1  12/39 (30.77%)  12 1/39 (2.56%)  1 11/38 (28.95%)  11
Diabetes mellitus  1  2/39 (5.13%)  2 1/39 (2.56%)  1 1/38 (2.63%)  1
Hyperkalaemia  1  4/39 (10.26%)  4 1/39 (2.56%)  1 3/38 (7.89%)  3
Hypocalcaemia  1  2/39 (5.13%)  2 1/39 (2.56%)  1 1/38 (2.63%)  1
Hyponatraemia  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Musculoskeletal and connective tissue disorders       
Arthralgia  1  4/39 (10.26%)  4 0/39 (0.00%)  0 4/38 (10.53%)  4
Back pain  1  4/39 (10.26%)  4 0/39 (0.00%)  0 4/38 (10.53%)  4
Muscle spasms  1  3/39 (7.69%)  3 0/39 (0.00%)  0 3/38 (7.89%)  3
Musculoskeletal chest pain  1  3/39 (7.69%)  3 0/39 (0.00%)  0 3/38 (7.89%)  3
Musculoskeletal pain  1  4/39 (10.26%)  4 0/39 (0.00%)  0 4/38 (10.53%)  4
Myalgia  1  2/39 (5.13%)  2 1/39 (2.56%)  1 1/38 (2.63%)  1
Pain in extremity  1  3/39 (7.69%)  3 1/39 (2.56%)  1 2/38 (5.26%)  2
Nervous system disorders       
Dizziness  1  7/39 (17.95%)  9 4/39 (10.26%)  4 3/38 (7.89%)  5
Headache  1  7/39 (17.95%)  9 1/39 (2.56%)  1 6/38 (15.79%)  8
Psychiatric disorders       
Anxiety  1  4/39 (10.26%)  4 1/39 (2.56%)  1 3/38 (7.89%)  3
Depressed mood  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Renal and urinary disorders       
Dysuria  1  3/39 (7.69%)  3 0/39 (0.00%)  0 3/38 (7.89%)  3
Respiratory, thoracic and mediastinal disorders       
Cough  1  6/39 (15.38%)  8 3/39 (7.69%)  3 4/38 (10.53%)  5
Dyspnoea  1  4/39 (10.26%)  4 0/39 (0.00%)  0 4/38 (10.53%)  4
Haemoptysis  1  4/39 (10.26%)  4 0/39 (0.00%)  0 4/38 (10.53%)  4
Oropharyngeal pain  1  2/39 (5.13%)  3 0/39 (0.00%)  0 2/38 (5.26%)  3
Productive cough  1  3/39 (7.69%)  3 0/39 (0.00%)  0 3/38 (7.89%)  3
Rhinorrhoea  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Skin and subcutaneous tissue disorders       
Dermatitis acneiform  1  3/39 (7.69%)  3 0/39 (0.00%)  0 3/38 (7.89%)  3
Dry skin  1  4/39 (10.26%)  4 0/39 (0.00%)  0 4/38 (10.53%)  4
Pruritus  1  5/39 (12.82%)  6 1/39 (2.56%)  1 4/38 (10.53%)  5
Rash  1  2/39 (5.13%)  2 1/39 (2.56%)  1 1/38 (2.63%)  1
Rash macular  1  2/39 (5.13%)  2 0/39 (0.00%)  0 2/38 (5.26%)  2
Skin fissures  1  3/39 (7.69%)  3 0/39 (0.00%)  0 3/38 (7.89%)  3
Vascular disorders       
Deep vein thrombosis  1  2/39 (5.13%)  2 1/39 (2.56%)  1 1/38 (2.63%)  1
Hypertension  1  3/39 (7.69%)  3 1/39 (2.56%)  1 2/38 (5.26%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
At end of Part B, the CAP allowed patients to continue receiving AZD9291 if still deriving clinical benefit. No clinical data was databased during the CAP; thus AE data is presented to end of Part B only.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Principal Investigator (PI) agrees to collaborate on the contents and formation of any publication and to pay due consideration to comments and opinions offered. AstraZeneca have 30 days for final manuscript review and may require that submission for publication be delayed in order to file patent application.
Results Point of Contact
Name/Title: Dr Karen So
Organization: AstraZeneca
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02157883     History of Changes
Other Study ID Numbers: D5160C00012
2014-001557-16 ( EudraCT Number )
First Submitted: June 5, 2014
First Posted: June 6, 2014
Results First Submitted: March 15, 2016
Results First Posted: April 14, 2016
Last Update Posted: February 5, 2019