Trial Outcomes & Findings for Study to Assess the Effect of AZD9291 on the Blood Levels of Rosuvastatin, in Patients With EGFRm+ Non-small Cell Lung Cancer (NCT NCT02317016)
NCT ID: NCT02317016
Last Updated: 2018-07-31
Results Overview
Rate and extent of absorption of rosuvastatin by assessment of Cmax. Single rosuvastatin doses were first without, then with AZD9291 (Day 1 \[Period 1\] and Day 32 \[Period 3\], respectively).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
44 participants
Primary outcome timeframe
Blood samples collected on Days 1 and 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours post rosuvastatin dose in Part A.
Results posted on
2018-07-31
Participant Flow
First patient enrolled: 10 March 2015; Last Subject Last Visit Part A: 11 July 2015 and Part B: 11 July 2016. Study performed at 14 sites across North America and Western Europe. Part A assessed effect of AZD9291 on PK of rosuvastatin following multiple oral dosing; Part B allowed subjects further access to AZD9291 and additional safety data.
Participant milestones
| Measure |
Rosuvastatin and AZD9291 (Part A); AZD9291 Alone (Part B)
In Part A of the study, sequential treatments of rosuvastatin alone, followed by AZD9291 alone, followed by rosuvastatin + AZD9291. Each patient received 20 mg single oral doses of rosuvastatin on Day 1 and Day 32, and 80 mg oral doses of AZD9291 tablets once daily for 31 days (Days 4 to 34).
In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.
|
|---|---|
|
Part A: Day 1-3 (Rosuvastatin Alone)
STARTED
|
44
|
|
Part A: Day 1-3 (Rosuvastatin Alone)
COMPLETED
|
44
|
|
Part A: Day 1-3 (Rosuvastatin Alone)
NOT COMPLETED
|
0
|
|
Part A: Day 4-31 (AZD9291 Alone)
STARTED
|
44
|
|
Part A: Day 4-31 (AZD9291 Alone)
COMPLETED
|
43
|
|
Part A: Day 4-31 (AZD9291 Alone)
NOT COMPLETED
|
1
|
|
Part A: Day 32-34 (Rosuvastatin+AZD9291)
STARTED
|
43
|
|
Part A: Day 32-34 (Rosuvastatin+AZD9291)
COMPLETED
|
41
|
|
Part A: Day 32-34 (Rosuvastatin+AZD9291)
NOT COMPLETED
|
2
|
|
Part B: Day 35 to End Part B (AZD9291)
STARTED
|
42
|
|
Part B: Day 35 to End Part B (AZD9291)
COMPLETED
|
11
|
|
Part B: Day 35 to End Part B (AZD9291)
NOT COMPLETED
|
31
|
Reasons for withdrawal
| Measure |
Rosuvastatin and AZD9291 (Part A); AZD9291 Alone (Part B)
In Part A of the study, sequential treatments of rosuvastatin alone, followed by AZD9291 alone, followed by rosuvastatin + AZD9291. Each patient received 20 mg single oral doses of rosuvastatin on Day 1 and Day 32, and 80 mg oral doses of AZD9291 tablets once daily for 31 days (Days 4 to 34).
In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.
|
|---|---|
|
Part A: Day 4-31 (AZD9291 Alone)
Adverse Event
|
1
|
|
Part A: Day 32-34 (Rosuvastatin+AZD9291)
Condition under investigation worsened
|
1
|
|
Part A: Day 32-34 (Rosuvastatin+AZD9291)
Death
|
1
|
|
Part B: Day 35 to End Part B (AZD9291)
Condition under investigation worsened
|
23
|
|
Part B: Day 35 to End Part B (AZD9291)
Adverse Event
|
1
|
|
Part B: Day 35 to End Part B (AZD9291)
Withdrawal by Subject
|
2
|
|
Part B: Day 35 to End Part B (AZD9291)
Death
|
5
|
Baseline Characteristics
Study to Assess the Effect of AZD9291 on the Blood Levels of Rosuvastatin, in Patients With EGFRm+ Non-small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Rosuvastatin and AZD9291 (Part A); AZD9291 Alone (Part B)
n=44 Participants
In Part A of the study, sequential treatments of rosuvastatin alone, followed by AZD9291 alone, followed by rosuvastatin + AZD9291. Each patient received 20 mg single oral doses of rosuvastatin on Day 1 and Day 32, and 80 mg oral doses of AZD9291 tablets once daily for 31 days (Days 4 to 34).
In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.
|
|---|---|
|
Age, Continuous
|
61.5 years
STANDARD_DEVIATION 11.37 • n=5 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
41 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Blood samples collected on Days 1 and 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours post rosuvastatin dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Rate and extent of absorption of rosuvastatin by assessment of Cmax. Single rosuvastatin doses were first without, then with AZD9291 (Day 1 \[Period 1\] and Day 32 \[Period 3\], respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=42 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
n=39 Participants
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of Maximum Plasma Concentration (Cmax) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291
|
13.96 nanogram per millilitre (ng/mL)
Geometric Coefficient of Variation 66.7
|
24.03 nanogram per millilitre (ng/mL)
Geometric Coefficient of Variation 70.5
|
PRIMARY outcome
Timeframe: Blood samples collected on Days 1 and 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours post rosuvastatin dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Rate and extent of absorption of rosuvastatin by assessment of AUC from time zero extrapolated to infinity. Single rosuvastatin doses were first without, then with AZD9291 (Day 1; Period 1 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=31 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
n=32 Participants
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of AUC From Time Zero Extrapolated to Infinity for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291
|
139.1 ng * h o u r per mL (ng*h/mL )
Geometric Coefficient of Variation 49.0
|
185.7 ng * h o u r per mL (ng*h/mL )
Geometric Coefficient of Variation 60.9
|
SECONDARY outcome
Timeframe: Blood samples collected on Days 1 and 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours post rosuvastatin dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Rate and extent of absorption of rosuvastatin by assessment of tmax. Single rosuvastatin doses were first without, then with AZD9291 (Day 1; Period 1 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=42 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
n=39 Participants
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of Time to Maximum Plasma Concentration (Tmax) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291
|
2.05 h
Interval 0.48 to 5.95
|
2.07 h
Interval 0.47 to 6.0
|
SECONDARY outcome
Timeframe: Blood samples collected on Days 1 and 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours post rosuvastatin dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Rate and extent of absorption of rosuvastatin by assessment of AUC0-t. Single rosuvastatin doses were first without, then with AZD9291 (Day 1; Period 1 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=42 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
n=37 Participants
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration at Time "t" (AUC0-t) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291
|
130.6 ng*h/mL
Geometric Coefficient of Variation 51.1
|
183.7 ng*h/mL
Geometric Coefficient of Variation 58.3
|
SECONDARY outcome
Timeframe: Blood samples collected on Days 1 and 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours post rosuvastatin dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Rate and extent of absorption of rosuvastatin by assessment of CL/F. Single rosuvastatin doses were first without, then with AZD9291 (Day 1; Period 1 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=31 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
n=32 Participants
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of Apparent Plasma Clearance (CL/F) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291
|
143.8 Litre / h (L/h)
Geometric Coefficient of Variation 49.0
|
107.7 Litre / h (L/h)
Geometric Coefficient of Variation 60.9
|
SECONDARY outcome
Timeframe: Blood samples collected on Days 1 and 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours post rosuvastatin dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Rate and extent of absorption of rosuvastatin by assessment of Vz/F. Single rosuvastatin doses were first without, then with AZD9291 (Day 1; Period 1 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=31 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
n=32 Participants
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of Apparent Volume of Distribution (Vz/F) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291
|
3890 L
Geometric Coefficient of Variation 65.0
|
2874 L
Geometric Coefficient of Variation 77.9
|
SECONDARY outcome
Timeframe: Blood samples collected on Days 1 and 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours post rosuvastatin dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Rate and extent of absorption of rosuvastatin by assessment of t1/2(lambda\_z). Single rosuvastatin doses were first without, then with AZD9291 (Day 1; Period 1 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=31 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
n=32 Participants
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of Terminal Elimination Half-life (t1/2[lambda_z]) for Rosuvastatin After a Single Dose Alone and in Combination With AZD9291
|
18.75 h
Geometric Coefficient of Variation 29.5
|
18.51 h
Geometric Coefficient of Variation 37.4
|
SECONDARY outcome
Timeframe: Blood samples collected pre-dose on Days 11, 18, and 25 and on Day 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post AZD9291 dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Rate and extent of absorption for AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of AUCtau. AZD9291 doses were first without, then with rosuvastatin (Days 4 to 31; Period 2 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=37 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUCtau) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together
AZD9291 AUCtau
|
15800 nanomolar * h (nM*h)
Geometric Coefficient of Variation 45.0
|
—
|
|
Assessment of Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUCtau) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together
AZ5104 AUCtau
|
1655 nanomolar * h (nM*h)
Geometric Coefficient of Variation 62.1
|
—
|
|
Assessment of Area Under the Plasma Concentration-time Curve During the Dosing Interval (AUCtau) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together
AZ7550 AUCtau
|
1418 nanomolar * h (nM*h)
Geometric Coefficient of Variation 44.7
|
—
|
SECONDARY outcome
Timeframe: Blood samples collected pre-dose on Days 11, 18, and 25 and on Day 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post AZD9291 dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Rate and extent of absorption for AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of Css,max after multiple dosing. AZD9291 doses were first without, then with rosuvastatin (Days 4 to 31; Period 2 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=37 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of Maximum Plasma Concentration at Steady State (Css,Max) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together
AZD9291 Css,max
|
897.9 nM
Geometric Coefficient of Variation 47.2
|
—
|
|
Assessment of Maximum Plasma Concentration at Steady State (Css,Max) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together
AZ5104 Css,max
|
86.20 nM
Geometric Coefficient of Variation 60.3
|
—
|
|
Assessment of Maximum Plasma Concentration at Steady State (Css,Max) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together
AZ7550 Css,max
|
73.73 nM
Geometric Coefficient of Variation 47.3
|
—
|
SECONDARY outcome
Timeframe: Blood samples collected pre-dose on Days 11, 18, and 25 and on Day 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post AZD9291 dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Rate and extent of absorption for AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of tss,max after multiple dosing. AZD9291 doses were first without, then with rosuvastatin (Days 4 to 31; Period 2 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=37 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of Time to Reach Maximum Plasma Concentration at Steady State (Tss,Max) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together
AZD9291 tss,max
|
5.00 h
Interval 2.0 to 8.17
|
—
|
|
Assessment of Time to Reach Maximum Plasma Concentration at Steady State (Tss,Max) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together
AZ5104 tss,max
|
5.00 h
Interval 0.5 to 24.33
|
—
|
|
Assessment of Time to Reach Maximum Plasma Concentration at Steady State (Tss,Max) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together
AZ7550 tss,max
|
5.05 h
Interval 1.5 to 12.05
|
—
|
SECONDARY outcome
Timeframe: Blood samples collected pre-dose on Days 11, 18, and 25 and on Day 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post AZD9291 dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Rate and extent of absorption for AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of Css,min over the dosing interval. AZD9291 doses were first without, then with rosuvastatin (Days 4 to 31; Period 2 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=37 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of Minimum Plasma Concentration at Steady State (Css,Min) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together
AZD9291 Css,min
|
485.6 nM
Geometric Coefficient of Variation 47.3
|
—
|
|
Assessment of Minimum Plasma Concentration at Steady State (Css,Min) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together
AZ5104 Css, min
|
54.60 nM
Geometric Coefficient of Variation 63.6
|
—
|
|
Assessment of Minimum Plasma Concentration at Steady State (Css,Min) for AZD9291, and AZ5104 and AZ7550 (Metabolites) Following Administration of AZD9291 and Rosuvastatin Together
AZ7550 Css, min
|
46.46 nM
Geometric Coefficient of Variation 46.3
|
—
|
SECONDARY outcome
Timeframe: Blood samples collected pre-dose on Days 11, 18, and 25 and on Day 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post AZD9291 dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Rate and extent of absorption for AZD9291 by assessment of CLss/F after multiple dosing. AZD9291 doses were first without, then with rosuvastatin (Days 4 to 31; Period 2 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=37 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of Apparent Plasma Clearance at Steady State (CLss/F) for AZD9291 Following Administration of AZD9291 and Rosuvastatin Together
|
10.14 L/h
Geometric Coefficient of Variation 45.0
|
—
|
SECONDARY outcome
Timeframe: Blood samples collected pre-dose on Days 11, 18, and 25 and on Day 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post AZD9291 dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Assessment of MRCss,max for AZ5104 and AZ7550 (calculated as AZ5104 to AZD9291 and AZ7550 to AZD9291) after multiple dosing. AZD9291 doses were first without, then with rosuvastatin (Days 4 to 31; Period 2 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=37 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of the Metabolite to Parent Ratios of Css,Max (MRCss,Max) for AZ5104 and AZ7550 Following Administration of AZD9291 and Rosuvastatin Together
AZ5104 Css,max / AZD9291 Css,max
|
0.09599 Ratio
Geometric Coefficient of Variation 28.2
|
—
|
|
Assessment of the Metabolite to Parent Ratios of Css,Max (MRCss,Max) for AZ5104 and AZ7550 Following Administration of AZD9291 and Rosuvastatin Together
AZ7550 Css,max / AZD9291 Css,max
|
0.08212 Ratio
Geometric Coefficient of Variation 31.7
|
—
|
SECONDARY outcome
Timeframe: Blood samples collected pre-dose on Days 11, 18, and 25 and on Day 32 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post AZD9291 dose in Part A.Population: The PK analysis set included all dosed patients who had at least 1 quantifiable plasma concentration collected post-dose without any important deviations or events that would exclude the patient.
Assessment of MRAUCtau for AZ5104 and AZ7550 (calculated as AZ5104 to AZD9291 and AZ7550 to AZD9291) after multiple dosing. AZD9291 doses were first without, then with rosuvastatin (Days 4 to 31; Period 2 and Day 32; Period 3, respectively).
Outcome measures
| Measure |
Rosuvastatin Alone (Period 1 [Day 1])
n=37 Participants
Rosuvastatin 20 mg single oral dose on Day 1 (Part A). Rosuvastatin was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose.
|
AZD9291 + Rosuvastatin (Period 3 [Day 32])
Steady state AZD9291 80 mg in combination with rosuvastatin 20 mg single oral dose on Day 32 (Part A). The Day 32 treatment (AZD9291 plus rosuvastatin) could occur within a window of ±2 days. Treatment was administered fasted from at least 2 hours before dosing to at least 2 hours after dosing. Water was allowed as desired except for 1 hour before and after dose. Previously, patients had received AZD9291 80 mg once daily for 28 days during Period 2 (Days 4 to 31), and after Day 32 in Period 3 (Days 33 and 34) patients also received AZD9291 80 mg once daily doses.
|
|---|---|---|
|
Assessment of the Metabolite to Parent Ratios of AUCtau (MRAUCtau) for AZ5104 and AZ7550 Following Administration of AZD9291 and Rosuvastatin Together
AZ7550 AUCtau / AZD9291 AUCtau
|
0.08971 Ratio
Geometric Coefficient of Variation 33.6
|
—
|
|
Assessment of the Metabolite to Parent Ratios of AUCtau (MRAUCtau) for AZ5104 and AZ7550 Following Administration of AZD9291 and Rosuvastatin Together
AZ5104 AUCtau / AZD9291 AUCtau
|
0.1048 Ratio
Geometric Coefficient of Variation 28.1
|
—
|
Adverse Events
Overall Safety Population
Serious events: 7 serious events
Other events: 40 other events
Deaths: 0 deaths
Part A Safety Population
Serious events: 2 serious events
Other events: 34 other events
Deaths: 0 deaths
Part B Safety Population
Serious events: 6 serious events
Other events: 29 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Overall Safety Population
n=44 participants at risk
Parts A and B of the study combined.
|
Part A Safety Population
n=44 participants at risk
In Part A of the study, each patient received 80 mg oral doses of AZD9291 tablets once daily for 31 days (Days 4 to 34) and single 20 mg oral doses of rosuvastatin on Day 1 and Day 32.
|
Part B Safety Population
n=42 participants at risk
In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.
|
|---|---|---|---|
|
Investigations
Blood creatine phosphokinase increased
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
0.00%
0/42 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Investigations
Transaminases increased
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
0.00%
0/44 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.4%
1/42 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
0.00%
0/44 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.4%
1/42 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
General disorders
Fatigue
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
0.00%
0/44 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.4%
1/42 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Infections and infestations
Pneumonia
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
0.00%
0/44 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.4%
1/42 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Infections and infestations
Pneumonia pseudomonal
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
0.00%
0/44 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.4%
1/42 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Nervous system disorders
Transient ischaemic attack
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
0.00%
0/44 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.4%
1/42 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
0.00%
0/44 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.4%
1/42 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.3%
1/44 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.4%
1/42 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
Other adverse events
| Measure |
Overall Safety Population
n=44 participants at risk
Parts A and B of the study combined.
|
Part A Safety Population
n=44 participants at risk
In Part A of the study, each patient received 80 mg oral doses of AZD9291 tablets once daily for 31 days (Days 4 to 34) and single 20 mg oral doses of rosuvastatin on Day 1 and Day 32.
|
Part B Safety Population
n=42 participants at risk
In Part B of the study, each patient received 80 mg oral AZD9291 tablet formulation once daily, for the duration of their participation.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
9.1%
4/44 • Number of events 6 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
6.8%
3/44 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.8%
2/42 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Gastrointestinal disorders
Constipation
|
13.6%
6/44 • Number of events 7 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
9.1%
4/44 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
7.1%
3/42 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Gastrointestinal disorders
Diarrhoea
|
29.5%
13/44 • Number of events 27 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
20.5%
9/44 • Number of events 12 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
21.4%
9/42 • Number of events 15 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Gastrointestinal disorders
Vomiting
|
6.8%
3/44 • Number of events 5 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.5%
2/44 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.8%
2/42 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
General disorders
Fatigue
|
18.2%
8/44 • Number of events 9 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
11.4%
5/44 • Number of events 5 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
7.1%
3/42 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Investigations
Blood creatine phosphokinase increased
|
6.8%
3/44 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
0.00%
0/44 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
7.1%
3/42 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.6%
6/44 • Number of events 9 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.5%
2/44 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
11.9%
5/42 • Number of events 7 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Ear and labyrinth disorders
Vertigo
|
6.8%
3/44 • Number of events 5 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.5%
2/44 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
7.1%
3/42 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Eye disorders
Dry eye
|
6.8%
3/44 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
0.00%
0/44 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
7.1%
3/42 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Gastrointestinal disorders
Abdominal pain
|
6.8%
3/44 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.5%
2/44 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.8%
2/42 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Gastrointestinal disorders
Nausea
|
15.9%
7/44 • Number of events 8 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
9.1%
4/44 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
7.1%
3/42 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Gastrointestinal disorders
Stomatitis
|
6.8%
3/44 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
7.1%
3/42 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
General disorders
Asthenia
|
20.5%
9/44 • Number of events 12 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
9.1%
4/44 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
16.7%
7/42 • Number of events 8 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
General disorders
Pyrexia
|
13.6%
6/44 • Number of events 7 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
6.8%
3/44 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
9.5%
4/42 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
General disorders
Xerosis
|
6.8%
3/44 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.8%
2/42 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Infections and infestations
Paronychia
|
13.6%
6/44 • Number of events 11 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
11.9%
5/42 • Number of events 10 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Infections and infestations
Rhinitis
|
9.1%
4/44 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.5%
2/44 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.8%
2/42 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Infections and infestations
Urinary tract infection
|
9.1%
4/44 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
6.8%
3/44 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.4%
1/42 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Metabolism and nutrition disorders
Decreased appetite
|
36.4%
16/44 • Number of events 19 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
20.5%
9/44 • Number of events 9 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
21.4%
9/42 • Number of events 10 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.6%
6/44 • Number of events 6 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
9.1%
4/44 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.8%
2/42 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
11.4%
5/44 • Number of events 5 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
0.00%
0/44 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
11.9%
5/42 • Number of events 5 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
11.4%
5/44 • Number of events 5 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
9.1%
4/44 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.4%
1/42 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
11.4%
5/44 • Number of events 5 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
9.1%
4/44 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.4%
1/42 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
11.4%
5/44 • Number of events 5 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
6.8%
3/44 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.8%
2/42 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Nervous system disorders
Headache
|
13.6%
6/44 • Number of events 8 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.5%
2/44 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
9.5%
4/42 • Number of events 6 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Psychiatric disorders
Insomnia
|
9.1%
4/44 • Number of events 5 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.5%
2/44 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.8%
2/42 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
11/44 • Number of events 15 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
9.1%
4/44 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
19.0%
8/42 • Number of events 11 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
27.3%
12/44 • Number of events 12 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
18.2%
8/44 • Number of events 8 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
9.5%
4/42 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.8%
3/44 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.8%
2/42 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
11.4%
5/44 • Number of events 6 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.5%
2/44 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
9.5%
4/42 • Number of events 4 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
13.6%
6/44 • Number of events 8 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.3%
1/44 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
11.9%
5/42 • Number of events 7 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
6.8%
3/44 • Number of events 3 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
4.5%
2/44 • Number of events 2 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
2.4%
1/42 • Number of events 1 • Approximately 1 month for Part A; up to approximately 14 months for Part B and approximately 15 months for Overall (Parts A and B combined).
Part A: Adverse events (AEs) collected from day of first dose until day prior to first dose in Part B (Day 35), 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).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
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Restriction type: OTHER