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Bosutinib For Autosomal Dominant Polycystic Kidney Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01233869
First received: October 28, 2010
Last updated: February 10, 2016
Last verified: February 2016
Results First Received: August 26, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Polycystic Kidney, Autosomal Dominant
Interventions: Drug: Bosutinib
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
172 participants were enrolled in this study, of which 169 received at least 1 dose of study treatment.

Reporting Groups
  Description
Bosutinib 200 mg/Day 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.
Bosutinib 400 mg/Day 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.
Bosutinib 400/200 mg/Day 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.
Placebo 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.

Participant Flow for 3 periods

Period 1:   Initial Treatment Period (24 Months)
    Bosutinib 200 mg/Day     Bosutinib 400 mg/Day     Bosutinib 400/200 mg/Day     Placebo  
STARTED     58     31     24     56  
COMPLETED     34     3     22     34  
NOT COMPLETED     24     28     2     22  
Death                 1                 0                 0                 0  
Adverse Event                 9                 17                 0                 3  
Not Related to Study Drug                 14                 11                 2                 19  

Period 2:   Washout Period 30 Days
    Bosutinib 200 mg/Day     Bosutinib 400 mg/Day     Bosutinib 400/200 mg/Day     Placebo  
STARTED     34     3     22     34  
COMPLETED     34     3     22     34  
NOT COMPLETED     0     0     0     0  

Period 3:   Extended Treatment Period (46 Months)
    Bosutinib 200 mg/Day     Bosutinib 400 mg/Day     Bosutinib 400/200 mg/Day     Placebo  
STARTED     34     3     22     34  
COMPLETED     20     0     17     18  
NOT COMPLETED     14     3     5     16  
Lost to Follow-up                 0                 0                 0                 1  
Withdrawal by Subject                 10                 3                 5                 11  
Unspecified                 3                 0                 0                 3  
Adverse Event                 1                 0                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety population included all participants who received at least 1 dose of study medication.

Reporting Groups
  Description
Bosutinib 200 mg/Day 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.
Bosutinib 400 mg/Day 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.
Bosutinib 400/200 mg/Day 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.
Placebo 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 Total of all reporting groups

Baseline Measures
    Bosutinib 200 mg/Day     Bosutinib 400 mg/Day     Bosutinib 400/200 mg/Day     Placebo     Total  
Number of Participants  
[units: participants]
  58     31     24     56     169  
Age  
[units: years]
Mean (Standard Deviation)
  37.9  (8.0)     41.3  (4.9)     36.4  (7.8)     38.5  (7.4)     38.5  (7.4)  
Gender  
[units: participants]
         
Female     28     14     15     35     92  
Male     30     17     9     21     77  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline (CFB) in Total Kidney Volume (TKV) at Month 25   [ Time Frame: Baseline and Month 25 (end of Initial Treatment Period Visit [ITPV]) ]

2.  Secondary:   Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 24, 25 and Early Termination   [ Time Frame: Baseline, Month 12, Month 24, Month 25 (end of ITPV), and early termination ]

3.  Secondary:   Time to First Occurrence or Worsening of Hypertension   [ Time Frame: Baseline up to Month 25 (end of ITPV) ]

4.  Secondary:   Time to First Occurrence or Worsening of Back and/or Flank Pain   [ Time Frame: Baseline up to Month 25 (end of ITPV) ]

5.  Secondary:   Time to First Occurrence of Gross Hematuria   [ Time Frame: Baseline up to Month 25 (end of ITPV) ]

6.  Secondary:   Time to First Occurrence of Proteinuria   [ Time Frame: Baseline up to Month 25 (end of ITPV) ]

7.  Secondary:   Time to First Occurrence of End-Stage Renal Disease (ESRD) Requiring Dialysis >=56 Days   [ Time Frame: Baseline up to Month 25 (end of ITPV) ]

8.  Secondary:   Number of Participants With High Blood Urea Nitrogen (BUN) Levels   [ Time Frame: Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV) ]

9.  Secondary:   Number of Participants With High Serum Creatinine (SCr) Levels   [ Time Frame: Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV) ]

10.  Secondary:   Maximum Observed Plasma Concentration (Cmax) of Bosutinib   [ 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) ]

11.  Secondary:   Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bosutinib   [ 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) ]

12.  Secondary:   Area Under the Concentration-Time Profile From Time 0 to the Dosing Interval (AUCtau) of Bosutinib   [ 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) ]

13.  Secondary:   Lowest Concentration Observed During the Dosing Interval (Cmin) of Bosutinib   [ Time Frame: Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose) ]

14.  Secondary:   Apparent Oral Clearance (CL/F) of Bosutinib   [ Time Frame: Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose) ]

15.  Secondary:   Apparent Volume of Distribution (Vz/F) of Bosutinib   [ 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) ]

16.  Secondary:   Terminal Elimination Half-Life (t1/2) of Bosutinib   [ 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) ]

17.  Secondary:   Observed Accumulation Ratio (Rac) of Bosutinib   [ Time Frame: Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose) ]

18.  Secondary:   Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25   [ Time Frame: Baseline and end of ITPV (Month 25) ]

19.  Other Pre-specified:   Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)   [ Time Frame: Baseline up to 30 days after last study drug administration ]

20.  Other Pre-specified:   Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern   [ Time Frame: Baseline up to 30 days after last study drug administration ]

21.  Other Pre-specified:   Number of Participants With Potentially Clinically Significant Vital Signs Findings   [ Time Frame: Baseline up to 30 days after last study drug administration ]

22.  Other Pre-specified:   Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings   [ Time Frame: Baseline up to 30 days after last study drug administration ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com



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 )
Study First Received: October 28, 2010
Results First Received: August 26, 2015
Last Updated: February 10, 2016
Health Authority: United States: Food and Drug Administration