Trial Outcomes & Findings for First In Human, Phase 1 Study of AG013736 In Patients With Solid Tumors (NCT NCT01469052)
NCT ID: NCT01469052
Last Updated: 2012-03-26
Results Overview
MTD is defined as the dose level at which "no more than 1 of 6 participants experience dose-limiting toxicity (DLT) following de-escalation from the maximum administered dose (MAD)." DLT includes grade (Gr) 2 or greater gastrointestinal toxicities, Gr 3 anemia, nonhematological toxicities (excluding nausea, vomiting, and diarrhea) or Gr 4 neutropenia, thrombocytopenia and inability to resume axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
36 participants
Primary outcome timeframe
Baseline up to Day 28
Results posted on
2012-03-26
Participant Flow
Participant milestones
| Measure |
Cohort 1: Axitinib (10 mg QD + 10 mg/20mg/30mg BID), Fed
Single dose of axitinib (AG-013736) 10 milligram (mg) tablet orally once daily (QD) followed by 30 mg single dose after 48 hours. Axitinib (AG-013736) 10 mg/ 20 mg/ 30 mg tablet orally twice daily (BID) in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 2: Axitinib 20 mg BID, Fed
Axitinib (AG-013736) 20 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 3: Axitinib 5 mg BID, Fed
Axitinib (AG-013736) 5 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 4: Axitinib 15 mg QD, Fed
Axitinib (AG-013736) 15 mg tablet orally QD in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 5: Axitinib 5 mg BID, Fasted
Axitinib (AG-013736) 5 mg tablet orally BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted
Axitinib (AG-013736) 2 mg tablet orally BID on the first day of dosing followed by 5 mg BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
4
|
6
|
6
|
8
|
6
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
4
|
6
|
5
|
8
|
6
|
Reasons for withdrawal
| Measure |
Cohort 1: Axitinib (10 mg QD + 10 mg/20mg/30mg BID), Fed
Single dose of axitinib (AG-013736) 10 milligram (mg) tablet orally once daily (QD) followed by 30 mg single dose after 48 hours. Axitinib (AG-013736) 10 mg/ 20 mg/ 30 mg tablet orally twice daily (BID) in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 2: Axitinib 20 mg BID, Fed
Axitinib (AG-013736) 20 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 3: Axitinib 5 mg BID, Fed
Axitinib (AG-013736) 5 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 4: Axitinib 15 mg QD, Fed
Axitinib (AG-013736) 15 mg tablet orally QD in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 5: Axitinib 5 mg BID, Fasted
Axitinib (AG-013736) 5 mg tablet orally BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted
Axitinib (AG-013736) 2 mg tablet orally BID on the first day of dosing followed by 5 mg BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
3
|
0
|
2
|
0
|
1
|
|
Overall Study
Progressive disease
|
3
|
0
|
5
|
3
|
7
|
2
|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
0
|
0
|
0
|
2
|
|
Overall Study
Moved to rollover protocol
|
1
|
0
|
1
|
0
|
0
|
1
|
|
Overall Study
Other
|
0
|
1
|
0
|
0
|
1
|
0
|
Baseline Characteristics
First In Human, Phase 1 Study of AG013736 In Patients With Solid Tumors
Baseline characteristics by cohort
| Measure |
Cohort 1: Axitinib (10 mg QD + 10 mg/20mg/30mg BID), Fed
n=6 Participants
Single dose of axitinib (AG-013736) 10 mg tablet orally QD followed by 30 mg single dose after 48 hours. Axitinib (AG-013736) 10 mg/ 20 mg/ 30 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 2: Axitinib 20 mg BID, Fed
n=4 Participants
Axitinib (AG-013736) 20 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 3: Axitinib 5 mg BID, Fed
n=6 Participants
Axitinib (AG-013736) 5 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 4: Axitinib 15 mg QD, Fed
n=6 Participants
Axitinib (AG-013736) 15 mg tablet orally QD in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 5: Axitinib 5 mg BID, Fasted
n=8 Participants
Axitinib (AG-013736) 5 mg tablet orally BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted
n=6 Participants
Axitinib (AG-013736) 2 mg tablet orally BID on the first day of dosing followed by 5 mg BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age Continuous
|
53.83 Years
STANDARD_DEVIATION 8.75 • n=93 Participants
|
58.50 Years
STANDARD_DEVIATION 4.80 • n=4 Participants
|
55.00 Years
STANDARD_DEVIATION 7.27 • n=27 Participants
|
56.00 Years
STANDARD_DEVIATION 9.44 • n=483 Participants
|
54.88 Years
STANDARD_DEVIATION 7.95 • n=36 Participants
|
64.17 Years
STANDARD_DEVIATION 10.01 • n=10 Participants
|
56.86 Years
STANDARD_DEVIATION 8.53 • n=115 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
5 Participants
n=36 Participants
|
3 Participants
n=10 Participants
|
20 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
3 Participants
n=36 Participants
|
3 Participants
n=10 Participants
|
16 Participants
n=115 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Day 28Population: Analysis population included all enrolled participants who received at least one dose of the study drug.
MTD is defined as the dose level at which "no more than 1 of 6 participants experience dose-limiting toxicity (DLT) following de-escalation from the maximum administered dose (MAD)." DLT includes grade (Gr) 2 or greater gastrointestinal toxicities, Gr 3 anemia, nonhematological toxicities (excluding nausea, vomiting, and diarrhea) or Gr 4 neutropenia, thrombocytopenia and inability to resume axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.
Outcome measures
| Measure |
All Treated Participants
n=36 Participants
All participants of Cohorts 1 to 6 received oral doses of axitinib (AG-013736) (10 mg and 15 mg, QD; 2 mg, 5 mg, 10 mg, 20 mg and 30 mg, BID) tablet in fed or fasted state in cycles of 4 weeks, up to 8 cycles.
|
Cohort 2: Axitinib 20 mg BID, Fed
Axitinib (AG-013736) 20 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 3: Axitinib 5 mg BID, Fed
Axitinib (AG-013736) 5 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 4: Axitinib 15 mg QD, Fed
Axitinib (AG-013736) 15 mg tablet orally QD in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 5: Axitinib 5 mg BID, Fasted
Axitinib (AG-013736) 5 mg tablet orally BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted
Axitinib (AG-013736) 2 mg tablet orally BID on the first day of dosing followed by 5 mg BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
|---|---|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD)
|
5 mg BID
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours (hrs) post-dose on Day (D) 1 and 15 of Cycle (C) 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)Population: Analysis population included all enrolled participants who received at least one dose of the study drug.'n' signifies those participants evaluated for this measure at specific time point for each cohort respectively.
Outcome measures
| Measure |
All Treated Participants
n=6 Participants
All participants of Cohorts 1 to 6 received oral doses of axitinib (AG-013736) (10 mg and 15 mg, QD; 2 mg, 5 mg, 10 mg, 20 mg and 30 mg, BID) tablet in fed or fasted state in cycles of 4 weeks, up to 8 cycles.
|
Cohort 2: Axitinib 20 mg BID, Fed
n=4 Participants
Axitinib (AG-013736) 20 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 3: Axitinib 5 mg BID, Fed
n=6 Participants
Axitinib (AG-013736) 5 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 4: Axitinib 15 mg QD, Fed
n=6 Participants
Axitinib (AG-013736) 15 mg tablet orally QD in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 5: Axitinib 5 mg BID, Fasted
n=8 Participants
Axitinib (AG-013736) 5 mg tablet orally BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted
n=6 Participants
Axitinib (AG-013736) 2 mg tablet orally BID on the first day of dosing followed by 5 mg BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
|---|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
Day 29 (n= 4, 3, 5, 5, 7, 6)
|
76.25 Nanogram/milliliter (ng/mL)
Standard Deviation 67.86
|
69.14 Nanogram/milliliter (ng/mL)
Standard Deviation 103.14
|
26.44 Nanogram/milliliter (ng/mL)
Standard Deviation 17.28
|
60.11 Nanogram/milliliter (ng/mL)
Standard Deviation 103.76
|
43.28 Nanogram/milliliter (ng/mL)
Standard Deviation 41.41
|
60.48 Nanogram/milliliter (ng/mL)
Standard Deviation 29.10
|
|
Maximum Observed Plasma Concentration (Cmax)
Day 1 (n= 6, 4, 6, 5, 8, 6)
|
144.48 Nanogram/milliliter (ng/mL)
Standard Deviation 73.90
|
97.81 Nanogram/milliliter (ng/mL)
Standard Deviation 89.96
|
20.71 Nanogram/milliliter (ng/mL)
Standard Deviation 9.48
|
88.16 Nanogram/milliliter (ng/mL)
Standard Deviation 84.93
|
22.21 Nanogram/milliliter (ng/mL)
Standard Deviation 34.88
|
19.75 Nanogram/milliliter (ng/mL)
Standard Deviation 17.95
|
|
Maximum Observed Plasma Concentration (Cmax)
Day 15 (n= 6, 3, 5, 6, 6, 6)
|
130.91 Nanogram/milliliter (ng/mL)
Standard Deviation 60.23
|
94.75 Nanogram/milliliter (ng/mL)
Standard Deviation 110.81
|
28.68 Nanogram/milliliter (ng/mL)
Standard Deviation 8.33
|
67.08 Nanogram/milliliter (ng/mL)
Standard Deviation 42.50
|
51.82 Nanogram/milliliter (ng/mL)
Standard Deviation 31.21
|
52.24 Nanogram/milliliter (ng/mL)
Standard Deviation 53.87
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)Population: Analysis population included all enrolled participants who received at least one dose of the study drug. 'n' signifies those participants evaluated for this measure at specific time point for each cohort respectively.
Outcome measures
| Measure |
All Treated Participants
n=6 Participants
All participants of Cohorts 1 to 6 received oral doses of axitinib (AG-013736) (10 mg and 15 mg, QD; 2 mg, 5 mg, 10 mg, 20 mg and 30 mg, BID) tablet in fed or fasted state in cycles of 4 weeks, up to 8 cycles.
|
Cohort 2: Axitinib 20 mg BID, Fed
n=4 Participants
Axitinib (AG-013736) 20 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 3: Axitinib 5 mg BID, Fed
n=6 Participants
Axitinib (AG-013736) 5 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 4: Axitinib 15 mg QD, Fed
n=6 Participants
Axitinib (AG-013736) 15 mg tablet orally QD in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 5: Axitinib 5 mg BID, Fasted
n=8 Participants
Axitinib (AG-013736) 5 mg tablet orally BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted
n=6 Participants
Axitinib (AG-013736) 2 mg tablet orally BID on the first day of dosing followed by 5 mg BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
|---|---|---|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Day 1 (n= 6, 4, 6, 5, 8, 6)
|
2.00 hr
Interval 1.0 to 4.0
|
4.04 hr
Interval 2.0 to 8.03
|
4.00 hr
Interval 1.0 to 4.08
|
2.05 hr
Interval 1.98 to 4.0
|
1.52 hr
Interval 0.5 to 4.0
|
1.01 hr
Interval 1.0 to 4.0
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Day 15 (n= 6, 3, 5, 6, 6, 6)
|
3.00 hr
Interval 1.0 to 4.0
|
3.95 hr
Interval 2.08 to 4.05
|
2.00 hr
Interval 1.0 to 4.22
|
4.00 hr
Interval 2.0 to 11.83
|
1.01 hr
Interval 0.98 to 2.03
|
1.51 hr
Interval 0.98 to 4.0
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Day 29 (n= 4, 3, 5, 5, 7, 6)
|
3.44 hr
Interval 0.0 to 4.03
|
4.13 hr
Interval 1.0 to 11.98
|
2.00 hr
Interval 1.0 to 4.0
|
3.50 hr
Interval 2.0 to 8.97
|
1.00 hr
Interval 0.5 to 4.02
|
2.01 hr
Interval 0.98 to 4.0
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)Population: Analysis population included all enrolled participants who received at least one dose of the study drug. 'n' signifies those participants evaluated for this measure at specific time point for each cohort respectively.
AUC (0-12)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-12).
Outcome measures
| Measure |
All Treated Participants
n=6 Participants
All participants of Cohorts 1 to 6 received oral doses of axitinib (AG-013736) (10 mg and 15 mg, QD; 2 mg, 5 mg, 10 mg, 20 mg and 30 mg, BID) tablet in fed or fasted state in cycles of 4 weeks, up to 8 cycles.
|
Cohort 2: Axitinib 20 mg BID, Fed
n=4 Participants
Axitinib (AG-013736) 20 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 3: Axitinib 5 mg BID, Fed
n=6 Participants
Axitinib (AG-013736) 5 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 4: Axitinib 15 mg QD, Fed
n=6 Participants
Axitinib (AG-013736) 15 mg tablet orally QD in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 5: Axitinib 5 mg BID, Fasted
n=8 Participants
Axitinib (AG-013736) 5 mg tablet orally BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted
n=6 Participants
Axitinib (AG-013736) 2 mg tablet orally BID on the first day of dosing followed by 5 mg BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
|---|---|---|---|---|---|---|
|
Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)]
Day 1 (n= 6, 4, 6, 5, 8, 6)
|
692.47 ng*hr/mL
Interval 363.89 to 1317.76
|
564.56 ng*hr/mL
Interval 100.47 to 3172.37
|
88.62 ng*hr/mL
Interval 60.05 to 130.8
|
473.26 ng*hr/mL
Interval 162.59 to 1377.58
|
68.73 ng*hr/mL
Interval 29.84 to 158.34
|
61.92 ng*hr/mL
Interval 19.33 to 198.31
|
|
Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)]
Day 15 (n= 6, 3, 5, 6, 6, 6)
|
793.89 ng*hr/mL
Interval 372.39 to 1692.48
|
485.52 ng*hr/mL
Interval 15.97 to 14760.66
|
130.57 ng*hr/mL
Interval 77.24 to 220.72
|
380.56 ng*hr/mL
Interval 161.49 to 896.8
|
126.25 ng*hr/mL
Interval 50.65 to 314.7
|
218.05 ng*hr/mL
Interval 81.21 to 585.47
|
|
Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)]
Day 29 (n= 4, 3, 5, 5, 7, 6)
|
456.53 ng*hr/mL
Interval 98.07 to 2125.11
|
441.50 ng*hr/mL
Interval 19.51 to 9989.18
|
144.13 ng*hr/mL
Interval 66.74 to 311.24
|
377.86 ng*hr/mL
Interval 104.98 to 1360.02
|
126.08 ng*hr/mL
Interval 55.72 to 285.29
|
253.45 ng*hr/mL
Interval 127.21 to 504.96
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)Population: Analysis population included all enrolled participants who received at least one dose of the study drug. 'n' signifies those participants evaluated for this measure at specific time point for each cohort respectively.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Outcome measures
| Measure |
All Treated Participants
n=6 Participants
All participants of Cohorts 1 to 6 received oral doses of axitinib (AG-013736) (10 mg and 15 mg, QD; 2 mg, 5 mg, 10 mg, 20 mg and 30 mg, BID) tablet in fed or fasted state in cycles of 4 weeks, up to 8 cycles.
|
Cohort 2: Axitinib 20 mg BID, Fed
n=4 Participants
Axitinib (AG-013736) 20 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 3: Axitinib 5 mg BID, Fed
n=6 Participants
Axitinib (AG-013736) 5 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 4: Axitinib 15 mg QD, Fed
n=6 Participants
Axitinib (AG-013736) 15 mg tablet orally QD in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 5: Axitinib 5 mg BID, Fasted
n=8 Participants
Axitinib (AG-013736) 5 mg tablet orally BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted
n=6 Participants
Axitinib (AG-013736) 2 mg tablet orally BID on the first day of dosing followed by 5 mg BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
|---|---|---|---|---|---|---|
|
Apparent Oral Clearance (CL/F)
Day 1 (n= 6, 4, 6, 5, 8, 6)
|
19.80 Liter/hr (L/hr)
Interval 9.14 to 42.87
|
30.82 Liter/hr (L/hr)
Interval 5.0 to 189.99
|
53.17 Liter/hr (L/hr)
Interval 35.99 to 78.55
|
29.04 Liter/hr (L/hr)
Interval 10.34 to 81.59
|
71.82 Liter/hr (L/hr)
Interval 31.26 to 165.04
|
30.27 Liter/hr (L/hr)
Interval 8.95 to 102.37
|
|
Apparent Oral Clearance (CL/F)
Day 15 (n= 6, 3, 5, 6, 6, 6)
|
18.82 Liter/hr (L/hr)
Interval 8.9 to 39.78
|
32.69 Liter/hr (L/hr)
Interval 2.8 to 381.94
|
38.29 Liter/hr (L/hr)
Interval 22.65 to 64.73
|
30.61 Liter/hr (L/hr)
Interval 11.26 to 83.23
|
39.05 Liter/hr (L/hr)
Interval 15.38 to 99.13
|
22.93 Liter/hr (L/hr)
Interval 8.54 to 61.57
|
|
Apparent Oral Clearance (CL/F)
Day 29 (n= 4, 2, 5, 5, 7, 6)
|
27.32 Liter/hr (L/hr)
Interval 8.35 to 89.42
|
18.82 Liter/hr (L/hr)
Interval 0.0 to
The upper limit of Confidence interval was not estimable since only 2 participants were evaluable.
|
34.69 Liter/hr (L/hr)
Interval 16.06 to 74.91
|
31.07 Liter/hr (L/hr)
Interval 7.11 to 135.74
|
38.51 Liter/hr (L/hr)
Interval 16.66 to 89.02
|
19.73 Liter/hr (L/hr)
Interval 9.9 to 39.31
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)Population: Analysis population included all enrolled participants who received at least one dose of the study drug. 'n' signifies those participants evaluated for this measure at specific time point for each cohort respectively.
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Outcome measures
| Measure |
All Treated Participants
n=6 Participants
All participants of Cohorts 1 to 6 received oral doses of axitinib (AG-013736) (10 mg and 15 mg, QD; 2 mg, 5 mg, 10 mg, 20 mg and 30 mg, BID) tablet in fed or fasted state in cycles of 4 weeks, up to 8 cycles.
|
Cohort 2: Axitinib 20 mg BID, Fed
n=4 Participants
Axitinib (AG-013736) 20 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 3: Axitinib 5 mg BID, Fed
n=6 Participants
Axitinib (AG-013736) 5 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 4: Axitinib 15 mg QD, Fed
n=6 Participants
Axitinib (AG-013736) 15 mg tablet orally QD in fed state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 5: Axitinib 5 mg BID, Fasted
n=8 Participants
Axitinib (AG-013736) 5 mg tablet orally BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted
n=6 Participants
Axitinib (AG-013736) 2 mg tablet orally BID on the first day of dosing followed by 5 mg BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles.
|
|---|---|---|---|---|---|---|
|
Plasma Decay Half-Life (t1/2)
Day 29 (n= 3, 2, 5, 3, 6, 6)
|
6.11 hr
Standard Deviation 4.23
|
3.94 hr
Standard Deviation 2.65
|
2.78 hr
Standard Deviation 0.80
|
2.16 hr
Standard Deviation 0.79
|
3.03 hr
Standard Deviation 0.74
|
3.33 hr
Standard Deviation 0.90
|
|
Plasma Decay Half-Life (t1/2)
Day 1 (n= 6, 3, 5, 5, 5, 4)
|
3.09 hr
Standard Deviation 1.00
|
3.29 hr
Standard Deviation 1.86
|
2.31 hr
Standard Deviation 0.64
|
3.08 hr
Standard Deviation 0.97
|
1.86 hr
Standard Deviation 0.44
|
3.77 hr
Standard Deviation 1.60
|
|
Plasma Decay Half-Life (t1/2)
Day 15 (n= 5, 3, 5, 4, 5, 6)
|
5.20 hr
Standard Deviation 3.12
|
3.17 hr
Standard Deviation 1.71
|
2.22 hr
Standard Deviation 0.34
|
2.48 hr
Standard Deviation 0.68
|
2.01 hr
Standard Deviation 1.23
|
5.78 hr
Standard Deviation 6.33
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)Population: The actual mean values were not reported in the fed and fasted state because the food effect evaluation was conducted across different dose groups and hence it was not appropriate to report overall mean values in different doses as PK parameters change with dose.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)Population: The actual mean values were not reported in the fed and fasted state because the food effect evaluation was conducted across different dose groups and hence it was not appropriate to report overall mean values in different doses as PK parameters change with dose.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)Population: The actual mean values were not reported in the fed and fasted state because the food effect evaluation was conducted across different dose groups and hence it was not appropriate to report overall mean values in different doses as PK parameters change with dose.
AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)Population: The actual mean values were not reported in the fed and fasted state because the food effect evaluation was conducted across different dose groups and hence it was not appropriate to report overall mean values in different doses as PK parameters change with dose.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)Population: The actual mean values were not reported in the fed and fasted state because the food effect evaluation was conducted across different dose groups and hence it was not appropriate to report overall mean values in different doses as PK parameters change with dose.
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Outcome measures
Outcome data not reported
Adverse Events
All Treated Participants
Serious events: 12 serious events
Other events: 36 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Treated Participants
n=36 participants at risk
All participants of Cohorts 1 to 6 received oral doses of axitinib (AG-013736) (10 mg and 15 mg, QD; 2 mg, 5 mg, 10 mg, 20 mg and 30 mg, BID) tablet in fed or fasted state in cycles of 4 weeks, up to 8 cycles.
|
|---|---|
|
Gastrointestinal disorders
Dysphagia
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Pain
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Dehydration
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Cardiac disorders
Cardiac arrest
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Cardiac disorders
Myocardial infarction
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Cardiac disorders
Supraventricular tachycardia
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Cardiac disorders
Tachycardia
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Eye disorders
Eye pain
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Faecaloma
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Mesenteric vein thrombosis
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Oral pain
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Pancreatitis
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Stomatitis
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Pyrexia
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Convulsion
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Apnoea
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
2.8%
1/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Vascular disorders
Hypertension
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
Other adverse events
| Measure |
All Treated Participants
n=36 participants at risk
All participants of Cohorts 1 to 6 received oral doses of axitinib (AG-013736) (10 mg and 15 mg, QD; 2 mg, 5 mg, 10 mg, 20 mg and 30 mg, BID) tablet in fed or fasted state in cycles of 4 weeks, up to 8 cycles.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Cardiac disorders
Tachycardia
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Abdominal distension
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Abdominal pain
|
11.1%
4/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Constipation
|
33.3%
12/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
9/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Dry mouth
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Dyspepsia
|
13.9%
5/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Nausea
|
38.9%
14/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Oral pain
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
8.3%
3/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Retching
|
8.3%
3/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Stomatitis
|
11.1%
4/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Vomiting
|
27.8%
10/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Asthenia
|
11.1%
4/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Chest pain
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Fatigue
|
44.4%
16/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Non-cardiac chest pain
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Oedema peripheral
|
16.7%
6/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Pyrexia
|
8.3%
3/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Thirst
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Infection
|
8.3%
3/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Urinary tract infection
|
11.1%
4/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Weight decreased
|
16.7%
6/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
47.2%
17/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Dehydration
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
8.3%
3/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
19.4%
7/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
6/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
8.3%
3/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
11.1%
4/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
11.1%
4/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Depressed level of consciousness
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Dizziness
|
16.7%
6/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Headache
|
33.3%
12/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Psychiatric disorders
Anxiety
|
11.1%
4/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Psychiatric disorders
Depression
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Psychiatric disorders
Insomnia
|
11.1%
4/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Renal and urinary disorders
Dysuria
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Renal and urinary disorders
Proteinuria
|
8.3%
3/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
6/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
19.4%
7/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
30.6%
11/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
8.3%
3/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
8.3%
3/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Vascular disorders
Hypertension
|
50.0%
18/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Dysphagia
|
13.9%
5/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Flatulence
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Oral discomfort
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Alanine aminotransferase increased
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Aspartate aminotransferase increased
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
8.3%
3/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.6%
2/36
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER