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Bosutinib For Autosomal Dominant Polycystic Kidney Disease

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ClinicalTrials.gov Identifier: NCT01233869
Recruitment Status : Completed
First Posted : November 3, 2010
Results First Posted : October 28, 2015
Last Update Posted : March 11, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Polycystic Kidney, Autosomal Dominant
Interventions Drug: Bosutinib
Drug: Placebo
Enrollment 172
Recruitment Details  
Pre-assignment Details 172 participants were enrolled in this study, of which 169 received at least 1 dose of study treatment.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months. Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group. Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months. Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Period Title: Initial Treatment Period (24 Months)
Started 58 31 24 56
Completed 34 3 22 34
Not Completed 24 28 2 22
Reason Not Completed
Death             1             0             0             0
Adverse Event             9             17             0             3
Not Related to Study Drug             14             11             2             19
Period Title: Washout Period 30 Days
Started 34 3 22 34
Completed 34 3 22 34
Not Completed 0 0 0 0
Period Title: Extended Treatment Period (46 Months)
Started 34 3 22 34
Completed 20 0 17 18
Not Completed 14 3 5 16
Reason Not Completed
Lost to Follow-up             0             0             0             1
Withdrawal by Subject             10             3             5             11
Other             3             0             0             3
Adverse Event             1             0             0             1
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo Total
Hide Arm/Group Description Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months. Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group. Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months. Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months. Total of all reporting groups
Overall Number of Baseline Participants 58 31 24 56 169
Hide Baseline Analysis Population Description
The safety population included all participants who received at least 1 dose of study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 58 participants 31 participants 24 participants 56 participants 169 participants
37.9  (8.0) 41.3  (4.9) 36.4  (7.8) 38.5  (7.4) 38.5  (7.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 31 participants 24 participants 56 participants 169 participants
Female
28
  48.3%
14
  45.2%
15
  62.5%
35
  62.5%
92
  54.4%
Male
30
  51.7%
17
  54.8%
9
  37.5%
21
  37.5%
77
  45.6%
1.Primary Outcome
Title Change From Baseline (CFB) in Total Kidney Volume (TKV) at Month 25
Hide Description TKV was measured by centrally evaluated Magnetic Resonance Imaging (MRI).
Time Frame Baseline and Month 25 (end of Initial Treatment Period Visit [ITPV])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The modified intent-to-treat (mITT) population included all participants who were randomized and received at least 2-weeks' worth of treatment and have at least 1 follow-up MRI assessment that was preceded by a 1-month washout of the study drug; n=the number of participants analyzed at that time point in the respective arms.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 27 6 21 33
Mean (Standard Deviation)
Unit of Measure: centimeter cube (cm^3)
Baseline (n=27,6,21,33) 1686.38  (944.30) 1418.96  (629.34) 1487.48  (531.96) 1670.33  (640.69)
CFB at Month 25 (n=23,3,20,30) 85.05  (231.09) 102.45  (257.30) -6.18  (119.79) 175.36  (191.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bosutinib 200 mg/Day, Bosutinib 400 mg/Day, Bosutinib 400/200 mg/Day, Placebo
Comments Statistical Analysis 1 is comparison of annualized rate of kidney enlargement: placebo versus pooled bosutinib.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 3.86
Confidence Interval (2-Sided) 95%
2.02 to 5.74
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bosutinib 200 mg/Day, Bosutinib 400/200 mg/Day
Comments Statistical Analysis 2 is comparison of annualized rate of kidney enlargement: bosutinib 200 mg/day versus bosutinib 400/200 mg/day.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1234
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 1.83
Confidence Interval (2-Sided) 95%
-0.50 to 4.22
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bosutinib 200 mg/Day, Placebo
Comments Statistical Analysis 3 is comparison of annualized rate of kidney enlargement: placebo versus bosutinib 200 mg/day.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0050
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 3.06
Confidence Interval (2-Sided) 95%
0.93 to 5.23
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Bosutinib 400 mg/Day, Placebo
Comments Statistical Analysis 4 is comparison of annualized rate of kidney enlargement: placebo versus bosutinib 400 mg/day.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1336
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 3.41
Confidence Interval (2-Sided) 95%
-1.03 to 8.05
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Bosutinib 400/200 mg/Day, Placebo
Comments Statistical Analysis 5 is comparison of annualized rate of kidney enlargement: placebo versus bosutinib 400/200 mg/day.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 4.95
Confidence Interval (2-Sided) 95%
2.65 to 7.30
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 24, 25 and Early Termination
Hide Description eGFR was centrally evaluated. Glomerular filtration rate (GFR) is an index of kidney function that describes the flow of filtered fluid through the kidney. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. Month 25 is the end of the ITPV.
Time Frame Baseline, Month 12, Month 24, Month 25 (end of ITPV), and early termination
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mITT population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment; n=the number of participants analyzed at that time point in the respective arms.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24 56
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m^2
CFB at Month 12 (n=26,4,21,31) -6.38  (11.60) -7.56  (11.27) -11.52  (10.86) 1.30  (9.71)
CFB at Month 24 (n=23,3,20,30) -8.47  (15.02) -21.59  (13.74) -13.16  (13.41) -7.95  (12.91)
CFB at End of ITPV (n=23,3,20,30) -5.00  (10.78) -13.24  (12.45) -9.92  (14.55) -2.74  (18.01)
CFB at Early Termination (n=6,3,1,4) -11.91  (8.79) 0.78  (4.83) -10.24 [1]   (NA) -2.75  (21.35)
[1]
Standard deviation (SD) was not calculated as only 1 participant was analyzed.
3.Secondary Outcome
Title Time to First Occurrence or Worsening of Hypertension
Hide Description The time to first occurrence or worsening of hypertension was observed (defined as the need for increased dose of or need for additional anti-hypertensive medication). The numbers presented correspond to the very first occurrence or worsening of hypertension in that treatment group.
Time Frame Baseline up to Month 25 (end of ITPV)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mITT-2 population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment (elimination of 1-month washout requirement).
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24 56
Measure Type: Number
Unit of Measure: days
15 180 90 30
4.Secondary Outcome
Title Time to First Occurrence or Worsening of Back and/or Flank Pain
Hide Description The time to first occurrence or worsening of back and/or flank pain was observed (defined as initial onset of polycystic kidney disease [PKD]-related chronic back and/or flank pain; initiation of pain medication treatment for PKD-related chronic back and/or flank pain; addition of a pain medicine for treatment of PKD-related chronic back and/or flank pain; increase in dose of pain medication for treatment of PKD-related chronic back and/or flank pain). The numbers presented correspond to the very first occurrence or worsening of back and/or flank pain in that treatment group.
Time Frame Baseline up to Month 25 (end of ITPV)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mITT-2 population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment (elimination of 1-month washout requirement).
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24 56
Measure Type: Number
Unit of Measure: days
30 30 270 15
5.Secondary Outcome
Title Time to First Occurrence of Gross Hematuria
Hide Description Gross hematuria is the presence of blood in the urine (defined as pink, red, or cola-colored urine due to the presence of red blood cells). The numbers presented correspond to the very first occurrence of gross hematuria in that treatment group.
Time Frame Baseline up to Month 25 (end of ITPV)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mITT-2 population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment (elimination of 1-month washout requirement).
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24 56
Measure Type: Number
Unit of Measure: days
330 180 180 45
6.Secondary Outcome
Title Time to First Occurrence of Proteinuria
Hide Description Proteinuria is the presence of an excess of serum proteins in the urine, which may be an early sign of kidney disease. The numbers presented correspond to the very first occurrence of proteinuria in that treatment group.
Time Frame Baseline up to Month 25 (end of ITPV)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mITT-2 population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment (elimination of 1-month washout requirement).
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24 56
Measure Type: Number
Unit of Measure: days
360 NA [1]  270 540
[1]
No proteinuria events were observed.
7.Secondary Outcome
Title Time to First Occurrence of End-Stage Renal Disease (ESRD) Requiring Dialysis >=56 Days
Hide Description ESRD is when the kidneys permanently fail to work at a level needed for daily life. No participants developed ESRD during the treatment period, therefore the analysis of the onset of ESRD requiring ≥56 days of dialysis was not performed.
Time Frame Baseline up to Month 25 (end of ITPV)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mITT-2 population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment (elimination of 1-month washout requirement).
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24 56
Measure Type: Number
Unit of Measure: days
NA [1]  NA [1]  NA [1]  NA [1] 
[1]
No participants developed ESRD during the treatment period, therefore the analysis of the onset of ESRD requiring ≥56 days of dialysis was not performed.
8.Secondary Outcome
Title Number of Participants With High Blood Urea Nitrogen (BUN) Levels
Hide Description A BUN test can reveal how well the kidneys are working by measuring the amount of urea nitrogen in the blood. A high BUN level (>1.3 times the upper limit of normal) may suggest that the kidneys are not working properly. Month 25 is the end of the ITPV.
Time Frame Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study drug.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24 56
Measure Type: Number
Unit of Measure: participants
Day 15 0 0 2 0
Month 6 0 0 0 0
Month 12 0 0 0 0
Month 18 0 0 0 0
Month 24 0 0 1 0
End of ITPV 0 0 2 0
9.Secondary Outcome
Title Number of Participants With High Serum Creatinine (SCr) Levels
Hide Description A SCr test can reveal how well the kidneys are working by measuring the amount of urea nitrogen in the blood. A high SCr level (>1.3 times the upper limit of normal) may suggest that the kidneys are not working properly. Month 25 is the end of the ITPV.
Time Frame Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study drug.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24 56
Measure Type: Number
Unit of Measure: participants
Day 15 0 1 0 0
Month 6 0 0 0 0
Month 12 0 0 0 1
Month 18 0 0 0 0
Month 24 0 1 1 1
End of ITPV 0 0 0 1
10.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Bosutinib
Hide Description [Not Specified]
Time Frame Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest; n=the number of participants analyzed at that time point in the respective arms.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
Day 1 (n=58,31,24)
32.61
(53%)
74.87
(47%)
84.57
(56%)
Day 15 (n=58,16,22)
68.72
(43%)
127.90
(28%)
155.00
(31%)
11.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bosutinib
Hide Description [Not Specified]
Time Frame Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest; n=the number of participants analyzed at that time point in the respective arms.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24
Median (Full Range)
Unit of Measure: hours
Day 1 (n=58,31,24)
3.00
(1.00 to 24.00)
3.00
(2.80 to 23.80)
4.86
(1.00 to 5.25)
Day 15 (n=58,16,22)
3.95
(0.00 to 25.60)
3.00
(1.00 to 8.00)
5.00
(1.00 to 8.12)
12.Secondary Outcome
Title Area Under the Concentration-Time Profile From Time 0 to the Dosing Interval (AUCtau) of Bosutinib
Hide Description Area under the concentration-time profile from time 0 to time tau, the dosing interval, where tau=24 hours.
Time Frame Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest; n=the number of participants analyzed at that time point in the respective arms.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Day 1 (n=58,30,24)
437
(48%)
1040
(49%)
1149
(50%)
Day 15 (n=58,16,22)
1059
(45%)
2052
(36%)
2384
(34%)
13.Secondary Outcome
Title Lowest Concentration Observed During the Dosing Interval (Cmin) of Bosutinib
Hide Description [Not Specified]
Time Frame Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Overall Number of Participants Analyzed 58 16 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
25.15
(49%)
19.60
(20880%)
50.67
(50%)
14.Secondary Outcome
Title Apparent Oral Clearance (CL/F) of Bosutinib
Hide Description 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.
Time Frame Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Overall Number of Participants Analyzed 58 16 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/hr
188.8
(45%)
195.0
(36%)
167.8
(34%)
15.Secondary Outcome
Title Apparent Volume of Distribution (Vz/F) of Bosutinib
Hide Description Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Time Frame Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest. There was no sufficient data to well-characterize the terminal phase, therefore Vz/F was not reported.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
16.Secondary Outcome
Title Terminal Elimination Half-Life (t1/2) of Bosutinib
Hide Description t1/2 is the time measured for the plasma concentration to decrease by one half.
Time Frame Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest. There was no sufficient data to well-characterize the terminal phase, therefore t1/2 was not reported.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
17.Secondary Outcome
Title Observed Accumulation Ratio (Rac) of Bosutinib
Hide Description Observed accumulation ratio (Rac) was calculated as AUC from time 0 to 24 hours (Day 15) divided by AUC from time 0 to 24 hours (Day 1).
Time Frame Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Overall Number of Participants Analyzed 58 16 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
2.452
(36%)
2.280
(42%)
2.075
(41%)
18.Secondary Outcome
Title Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25
Hide Description The KDQoL-36 is a 36-item questionnaire on kidney disease-specific measure of patient-reported quality of life with 5 subscales: physical and mental functioning (items 1-12); burden of kidney disease subscale (items 13-16); symptoms and problems (items 17-28); effects of kidney disease on daily life subscale (items 29-36). The raw scores are transformed linearly to a range of 0 to 100, with higher scores indicating better quality of life.
Time Frame Baseline and end of ITPV (Month 25)
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Hide Analysis Population Description
The mITT-2 population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment (elimination of 1-month washout); n=the number of participants analyzed in the respective arms.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 42 9 24 43
Mean (Standard Deviation)
Unit of Measure: units on a scale
Burden of Disease: Baseline (n=42,9,24,43) 84.23  (18.48) 84.722  (20.99) 79.43  (24.97) 74.86  (30.21)
Burden of Disease: CFB Month 25 (n=32,3,22,34) -2.54  (15.70) -2.08  (9.55) 0.57  (15.90) 1.84  (19.13)
Kidney Disease Effects: Baseline (n=42,9,24,43) 93.30  (8.58) 92.01  (11.06) 91.54  (11.53) 90.41  (14.10)
Kidney Disease Effects: CFB Month 25; n=32,3,22,34 1.07  (5.48) 3.13  (5.41) -0.57  (9.72) 3.22  (9.50)
SF-12 Mental Health: Baseline (n=42,9,24,43) 54.31  (6.39) 51.11  (12.87) 50.19  (9.28) 51.33  (8.58)
SF-12 Mental Health: CFB Month 25 (n=32,3,22,34) -1.50  (5.87) 6.55  (6.30) 1.34  (7.35) 0.12  (10.25)
SF-12 Physical Health: Baseline (n=42,9,24,43) 50.52  (6.93) 51.78  (6.40) 49.64  (8.35) 47.17  (10.93)
SF-12 Physical Health: CFB Month 25 (n=32,3,22,34) -0.28  (5.81) -7.59  (7.63) -2.33  (8.16) 2.32  (8.34)
Symptoms/Problems: Baseline (n=42,9,24,43) 93.13  (6.96) 93.69  (7.35) 90.72  (9.31) 90.86  (9.29)
Symptoms/Problems: CFB Month 25 (n=32,3,22,34) -2.42  (7.21) -8.33  (9.19) -3.75  (8.04) 0.27  (9.31)
19.Other Pre-specified Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
Time Frame Baseline up to 30 days after last study drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study drug.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24 56
Measure Type: Number
Unit of Measure: participants
AEs 56 30 23 51
SAEs 12 4 6 5
20.Other Pre-specified Outcome
Title Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern
Hide Description The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, RBC morphology, platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen [BUN], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (coagulation panel, circulating immune complex, and complement activation).
Time Frame Baseline up to 30 days after last study drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study drug.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24 56
Measure Type: Number
Unit of Measure: participants
53 20 23 43
21.Other Pre-specified Outcome
Title Number of Participants With Potentially Clinically Significant Vital Signs Findings
Hide Description Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine/sitting pulse rate <40 or >120 beats per minute (bpm), standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) of >=30 millimeters of mercury (mm Hg) change from baseline in same posture or SBP <90 mm Hg, diastolic blood pressure (DBP) >=20 mmHg change from baseline in same posture or DBP <50 mm Hg.
Time Frame Baseline up to 30 days after last study drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study drug; n=the number of participants analyzed in the respective arms.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24 56
Measure Type: Number
Unit of Measure: participants
Supine SBP <90 mm Hg (n=2,2,1,4) 0 0 0 0
Sitting SBP <90 mm Hg (n=58,29,24,54) 0 0 1 0
Supine DBP <50 mm Hg (n=2,2,1,4) 0 0 0 0
Sitting DBP <50 mm Hg (n=58,29,24,54) 0 1 1 0
Supine Pulse Rate <40 or >120 bpm(n=2,2,1,4) 0 0 0 0
Sitting Pulse Rate <40 or >120 bpm (n=58,29,24,54) 1 0 0 0
Supine SBP ≥30 mm Hg Decrease (n=2,2,1,4) 0 0 1 0
Sitting SBP ≥30 mm Hg Decrease (n=58,29,24,54) 2 1 2 2
Supine DBP ≥20 mm Hg Decrease (n=2,2,1,4) 0 0 1 0
Sitting DBP ≥20 mm Hg Decrease (n=58,29,24,54) 12 3 3 5
Supine SBP ≥30 mm Hg Increase (n=2,2,1,4) 0 0 0 0
Sitting SBP ≥30 mm Hg Increase (n=58,29,24,54) 3 1 3 3
Supine DBP ≥20 mm Hg Increase (n=2,2,1,4) 0 0 0 0
Sitting DBP ≥20 mm Hg Increase (n=58,29,24,54) 5 3 5 5
22.Other Pre-specified Outcome
Title Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Hide Description ECGs were centrally evaluated. ECG parameters included PR interval, QRS interval, and corrected QT interval using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval greater than or equal to (≥)300 milliseconds (msec) or ≥25% increase when baseline is greater than (>)200 msec and ≥50% increase when baseline is less than or equal to (≤)200 msec; QRS interval ≥200 msec or ≥25%/50% increase from baseline; and QTcF ≥450 msec or ≥30 msec increase.
Time Frame Baseline up to 30 days after last study drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study drug; n=the number of participants analyzed in the respective arms.
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description:
Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.
Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.
Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Overall Number of Participants Analyzed 58 31 24 56
Measure Type: Number
Unit of Measure: participants
PR Interval ≥300 msec (n=58,31,24,56) 0 0 0 0
QRS Complex ≥200 msec (n=58,31,24,56) 0 0 0 0
QTcF Interval 450-<480 msec (n=58,31,24,56) 3 2 0 6
QTcF Interval 480-<500 msec (n=58,31,24,56) 0 0 0 0
QTcF Interval ≥500 msec (n=58,31,24,56) 0 0 0 0
PR Interval ≥25/50% Increase (n=57,28,23,52) 0 0 0 0
QRS Complex ≥25/50% Increase (n=57,28,23,52) 0 0 0 0
QTcF Interval 30-<60 msec Increase (n=57,28,23,52) 4 1 1 5
QTcF Interval ≥60 msec Increase (n=57,28,23,52) 0 0 0 0
Time Frame Baseline up to 30 days after last study drug administration
Adverse Event Reporting Description 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 participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
 
Arm/Group Title Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Hide Arm/Group Description Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months. Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group. Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months. Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
All-Cause Mortality
Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/58 (20.69%)   4/31 (12.90%)   6/24 (25.00%)   5/56 (8.93%) 
Blood and lymphatic system disorders         
Anaemia * 1  0/58 (0.00%)  0/31 (0.00%)  1/24 (4.17%)  0/56 (0.00%) 
Cardiac disorders         
Ventricular extrasystoles * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Gastrointestinal disorders         
Abdominal pain * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Peptic ulcer * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Subileus * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Hepatobiliary disorders         
Hepatitis acute * 1  0/58 (0.00%)  1/31 (3.23%)  0/24 (0.00%)  0/56 (0.00%) 
Infections and infestations         
Appendicitis * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Gastroenteritis * 1  0/58 (0.00%)  1/31 (3.23%)  0/24 (0.00%)  0/56 (0.00%) 
Hepatitis C * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  1/56 (1.79%) 
Pneumonia * 1  0/58 (0.00%)  1/31 (3.23%)  0/24 (0.00%)  0/56 (0.00%) 
Pyelonephritis acute * 1  0/58 (0.00%)  0/31 (0.00%)  1/24 (4.17%)  0/56 (0.00%) 
Renal cyst infection * 1  0/58 (0.00%)  0/31 (0.00%)  0/24 (0.00%)  1/56 (1.79%) 
Sepsis * 1  2/58 (3.45%)  0/31 (0.00%)  1/24 (4.17%)  0/56 (0.00%) 
Urinary tract infection * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Investigations         
Alanine aminotransferase increased * 1  2/58 (3.45%)  1/31 (3.23%)  0/24 (0.00%)  0/56 (0.00%) 
Amylase increased * 1  0/58 (0.00%)  1/31 (3.23%)  0/24 (0.00%)  0/56 (0.00%) 
Aspartate aminotransferase increased * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Lipase increased * 1  0/58 (0.00%)  1/31 (3.23%)  0/24 (0.00%)  0/56 (0.00%) 
Musculoskeletal and connective tissue disorders         
Osteonecrosis * 1  0/58 (0.00%)  0/31 (0.00%)  0/24 (0.00%)  1/56 (1.79%) 
Sacroiliitis * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Spondylitis * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Nervous system disorders         
Intracranial aneurysm * 1  0/58 (0.00%)  0/31 (0.00%)  1/24 (4.17%)  0/56 (0.00%) 
Syncope * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Psychiatric disorders         
Insomnia * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Psychosomatic disease * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Renal and urinary disorders         
Calculus ureteric * 1  0/58 (0.00%)  0/31 (0.00%)  1/24 (4.17%)  0/56 (0.00%) 
Haematuria * 1  0/58 (0.00%)  0/31 (0.00%)  0/24 (0.00%)  1/56 (1.79%) 
Renal cyst haemorrhage * 1  1/58 (1.72%)  1/31 (3.23%)  1/24 (4.17%)  0/56 (0.00%) 
Renal cyst ruptured * 1  0/58 (0.00%)  1/31 (3.23%)  0/24 (0.00%)  1/56 (1.79%) 
Renal failure acute * 1  0/58 (0.00%)  1/31 (3.23%)  0/24 (0.00%)  0/56 (0.00%) 
Renal haemorrhage * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Reproductive system and breast disorders         
Cervix disorder * 1  0/28 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/35 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (v17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bosutinib 200 mg/Day Bosutinib 400 mg/Day Bosutinib 400/200 mg/Day Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   56/58 (96.55%)   30/31 (96.77%)   23/24 (95.83%)   50/56 (89.29%) 
Blood and lymphatic system disorders         
Anaemia * 1  7/58 (12.07%)  4/31 (12.90%)  5/24 (20.83%)  2/56 (3.57%) 
Eosinophilia * 1  3/58 (5.17%)  0/31 (0.00%)  1/24 (4.17%)  0/56 (0.00%) 
Cardiac disorders         
Pericardial effusion * 1  2/58 (3.45%)  1/31 (3.23%)  2/24 (8.33%)  0/56 (0.00%) 
Gastrointestinal disorders         
Abdominal distension * 1  3/58 (5.17%)  2/31 (6.45%)  2/24 (8.33%)  3/56 (5.36%) 
Abdominal pain * 1  4/58 (6.90%)  8/31 (25.81%)  2/24 (8.33%)  7/56 (12.50%) 
Abdominal pain upper * 1  5/58 (8.62%)  7/31 (22.58%)  8/24 (33.33%)  5/56 (8.93%) 
Constipation * 1  2/58 (3.45%)  2/31 (6.45%)  1/24 (4.17%)  1/56 (1.79%) 
Diarrhoea * 1  26/58 (44.83%)  26/31 (83.87%)  18/24 (75.00%)  11/56 (19.64%) 
Dyspepsia * 1  6/58 (10.34%)  2/31 (6.45%)  3/24 (12.50%)  3/56 (5.36%) 
Gastrooesophageal reflux disease * 1  0/58 (0.00%)  0/31 (0.00%)  0/24 (0.00%)  3/56 (5.36%) 
Nausea * 1  21/58 (36.21%)  15/31 (48.39%)  13/24 (54.17%)  9/56 (16.07%) 
Vomiting * 1  6/58 (10.34%)  11/31 (35.48%)  9/24 (37.50%)  4/56 (7.14%) 
General disorders         
Asthenia * 1  1/58 (1.72%)  1/31 (3.23%)  3/24 (12.50%)  1/56 (1.79%) 
Chest pain * 1  1/58 (1.72%)  2/31 (6.45%)  0/24 (0.00%)  0/56 (0.00%) 
Fatigue * 1  4/58 (6.90%)  8/31 (25.81%)  2/24 (8.33%)  6/56 (10.71%) 
Influenza-like illness * 1  2/58 (3.45%)  1/31 (3.23%)  3/24 (12.50%)  6/56 (10.71%) 
Oedema peripheral * 1  2/58 (3.45%)  1/31 (3.23%)  1/24 (4.17%)  3/56 (5.36%) 
Pain * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  3/56 (5.36%) 
Pyrexia * 1  2/58 (3.45%)  3/31 (9.68%)  2/24 (8.33%)  1/56 (1.79%) 
Hepatobiliary disorders         
Hepatocellular injury * 1  3/58 (5.17%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Immune system disorders         
Hypersensitivity * 1  2/58 (3.45%)  1/31 (3.23%)  0/24 (0.00%)  3/56 (5.36%) 
Infections and infestations         
Bronchitis * 1  3/58 (5.17%)  2/31 (6.45%)  2/24 (8.33%)  3/56 (5.36%) 
Cystitis * 1  0/58 (0.00%)  0/31 (0.00%)  3/24 (12.50%)  1/56 (1.79%) 
Gastroenteritis viral * 1  0/58 (0.00%)  0/31 (0.00%)  1/24 (4.17%)  3/56 (5.36%) 
Influenza * 1  2/58 (3.45%)  0/31 (0.00%)  1/24 (4.17%)  3/56 (5.36%) 
Nasopharyngitis * 1  12/58 (20.69%)  3/31 (9.68%)  8/24 (33.33%)  8/56 (14.29%) 
Pharyngitis * 1  0/58 (0.00%)  0/31 (0.00%)  3/24 (12.50%)  4/56 (7.14%) 
Rhinitis * 1  2/58 (3.45%)  0/31 (0.00%)  2/24 (8.33%)  2/56 (3.57%) 
Sinusitis * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  3/56 (5.36%) 
Upper respiratory tract infection * 1  6/58 (10.34%)  4/31 (12.90%)  7/24 (29.17%)  7/56 (12.50%) 
Urinary tract infection * 1  8/58 (13.79%)  2/31 (6.45%)  2/24 (8.33%)  8/56 (14.29%) 
Vaginal infection * 1  1/28 (3.57%)  0/14 (0.00%)  0/15 (0.00%)  3/35 (8.57%) 
Viral infection * 1  2/58 (3.45%)  0/31 (0.00%)  1/24 (4.17%)  3/56 (5.36%) 
Vulvovaginal mycotic infection * 1  1/28 (3.57%)  0/14 (0.00%)  1/15 (6.67%)  1/35 (2.86%) 
Injury, poisoning and procedural complications         
Excoriation * 1  3/58 (5.17%)  0/31 (0.00%)  1/24 (4.17%)  0/56 (0.00%) 
Investigations         
Alanine aminotransferase increased * 1  18/58 (31.03%)  16/31 (51.61%)  12/24 (50.00%)  4/56 (7.14%) 
Amylase increased * 1  2/58 (3.45%)  4/31 (12.90%)  3/24 (12.50%)  1/56 (1.79%) 
Aspartate aminotransferase increased * 1  17/58 (29.31%)  11/31 (35.48%)  6/24 (25.00%)  3/56 (5.36%) 
Blood creatine phosphokinase increased * 1  11/58 (18.97%)  3/31 (9.68%)  6/24 (25.00%)  5/56 (8.93%) 
Blood creatinine increased * 1  2/58 (3.45%)  1/31 (3.23%)  2/24 (8.33%)  2/56 (3.57%) 
Blood lactate dehydrogenase increased * 1  0/58 (0.00%)  2/31 (6.45%)  0/24 (0.00%)  0/56 (0.00%) 
Blood phosphorus decreased * 1  0/58 (0.00%)  2/31 (6.45%)  0/24 (0.00%)  0/56 (0.00%) 
Gamma-glutamyltransferase increased * 1  4/58 (6.90%)  0/31 (0.00%)  0/24 (0.00%)  0/56 (0.00%) 
Haemoglobin decreased * 1  0/58 (0.00%)  0/31 (0.00%)  2/24 (8.33%)  0/56 (0.00%) 
Lipase increased * 1  5/58 (8.62%)  6/31 (19.35%)  6/24 (25.00%)  3/56 (5.36%) 
Weight increased * 1  0/58 (0.00%)  2/31 (6.45%)  3/24 (12.50%)  0/56 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite * 1  2/58 (3.45%)  4/31 (12.90%)  4/24 (16.67%)  0/56 (0.00%) 
Hypophosphataemia * 1  2/58 (3.45%)  0/31 (0.00%)  2/24 (8.33%)  1/56 (1.79%) 
Musculoskeletal and connective tissue disorders         
Arthralgia * 1  5/58 (8.62%)  0/31 (0.00%)  1/24 (4.17%)  5/56 (8.93%) 
Back pain * 1  9/58 (15.52%)  2/31 (6.45%)  1/24 (4.17%)  8/56 (14.29%) 
Flank pain * 1  10/58 (17.24%)  5/31 (16.13%)  0/24 (0.00%)  5/56 (8.93%) 
Muscle spasms * 1  3/58 (5.17%)  1/31 (3.23%)  0/24 (0.00%)  3/56 (5.36%) 
Musculoskeletal pain * 1  3/58 (5.17%)  1/31 (3.23%)  2/24 (8.33%)  2/56 (3.57%) 
Myalgia * 1  0/58 (0.00%)  0/31 (0.00%)  0/24 (0.00%)  3/56 (5.36%) 
Pain in extremity * 1  1/58 (1.72%)  0/31 (0.00%)  0/24 (0.00%)  3/56 (5.36%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Uterine leiomyoma * 1  0/28 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/35 (0.00%) 
Nervous system disorders         
Dizziness * 1  7/58 (12.07%)  2/31 (6.45%)  4/24 (16.67%)  3/56 (5.36%) 
Dysgeusia * 1  0/58 (0.00%)  2/31 (6.45%)  0/24 (0.00%)  0/56 (0.00%) 
Headache * 1  9/58 (15.52%)  3/31 (9.68%)  2/24 (8.33%)  12/56 (21.43%) 
Psychiatric disorders         
Insomnia * 1  3/58 (5.17%)  1/31 (3.23%)  0/24 (0.00%)  1/56 (1.79%) 
Renal and urinary disorders         
Haematuria * 1  4/58 (6.90%)  3/31 (9.68%)  1/24 (4.17%)  4/56 (7.14%) 
Proteinuria * 1  1/58 (1.72%)  0/31 (0.00%)  2/24 (8.33%)  3/56 (5.36%) 
Renal failure acute * 1  2/58 (3.45%)  1/31 (3.23%)  2/24 (8.33%)  0/56 (0.00%) 
Reproductive system and breast disorders         
Amenorrhoea * 1  0/28 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/35 (0.00%) 
Cervical dysplasia * 1  0/28 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/35 (0.00%) 
Menorrhagia * 1  1/28 (3.57%)  0/14 (0.00%)  1/15 (6.67%)  1/35 (2.86%) 
Metrorrhagia * 1  1/28 (3.57%)  0/14 (0.00%)  1/15 (6.67%)  0/35 (0.00%) 
Ovarian cyst * 1  0/28 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  1/35 (2.86%) 
Vaginal inflammation * 1  0/28 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  1/35 (2.86%) 
Respiratory, thoracic and mediastinal disorders         
Cough * 1  2/58 (3.45%)  3/31 (9.68%)  3/24 (12.50%)  4/56 (7.14%) 
Oropharyngeal pain * 1  5/58 (8.62%)  2/31 (6.45%)  1/24 (4.17%)  2/56 (3.57%) 
Skin and subcutaneous tissue disorders         
Acne * 1  4/58 (6.90%)  0/31 (0.00%)  0/24 (0.00%)  1/56 (1.79%) 
Alopecia * 1  2/58 (3.45%)  1/31 (3.23%)  3/24 (12.50%)  3/56 (5.36%) 
Dermatitis allergic * 1  2/58 (3.45%)  0/31 (0.00%)  2/24 (8.33%)  0/56 (0.00%) 
Pruritis * 1  1/58 (1.72%)  2/31 (6.45%)  1/24 (4.17%)  1/56 (1.79%) 
Rash maculo-papular * 1  0/58 (0.00%)  2/31 (6.45%)  0/24 (0.00%)  0/56 (0.00%) 
Vascular disorders         
Hypertension * 1  8/58 (13.79%)  3/31 (9.68%)  5/24 (20.83%)  9/56 (16.07%) 
Hypotension * 1  1/58 (1.72%)  0/31 (0.00%)  3/24 (12.50%)  0/56 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (v17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01233869     History of Changes
Other Study ID Numbers: B1871019
3160A7-2211 ( Other Identifier: Alias Study Number )
2010-023017-65 ( EudraCT Number )
First Submitted: October 28, 2010
First Posted: November 3, 2010
Results First Submitted: August 26, 2015
Results First Posted: October 28, 2015
Last Update Posted: March 11, 2016