Efficacy, Safety, Tolerability and Pharmacokinetics (PK) of Nilotinib (AMN107) in Pulmonary Arterial Hypertension (PAH)

This study has been terminated.
(Study was terminated due to serious adverse event (SAE))
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01179737
First received: August 3, 2010
Last updated: January 14, 2014
Last verified: January 2014
Results First Received: January 14, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Pulmonary Arterial Hypertension
Interventions: Drug: Nilotinib
Drug: Placebo to nilotinib

  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
23 participants were enrolled into the study (15 in cohort 1; 8 in cohort 2) 8 participants completed cohort 1 and 6 of these participants moved into cohort 1expansion. Of the 5 participants that completed Cohort 1 expansion; 3 participants went into an Extension. None of the participants completed treatment as trial was terminated

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized 6:1 ratio to nilotinib and placebo

Reporting Groups
  Description
Cohort 1: Nilotinib Participants were assigned to receive nilotinib 50 mg during 14 days, followed by 150 mg during 14 days, followed by 300 mg during 140 days.
Cohort 1: Placebo Participants were assigned to receive placebo to nilotinib to match 50 mg and 150 mg capsules during 168 days.
Cohort 2: Nilotinib Particibants were assigned to receive nilotinib 300 mg during 168 days
Cohort 2: Placebo Particibants were assigned to receive placebo to match 50mg and / or 150mg capsules during 168 days

Participant Flow for 3 periods

Period 1:   Cohort 1 & Cohort 2
    Cohort 1: Nilotinib     Cohort 1: Placebo     Cohort 2: Nilotinib     Cohort 2: Placebo  
STARTED     12     3 [1]   4     4  
COMPLETED     7     1     0     0  
NOT COMPLETED     5     2     4     4  
Adverse Event                 3                 1                 1                 0  
Withdrew consent                 2                 0                 0                 0  
Administrative problems                 0                 0                 2                 4  
Death                 0                 0                 1                 0  
Withdrew consent without EOS 1 visit                 0                 1                 0                 0  
[1] One patient was missing the end of study evaluation

Period 2:   Cohort 1 & Cohort 2 Expansion
    Cohort 1: Nilotinib     Cohort 1: Placebo     Cohort 2: Nilotinib     Cohort 2: Placebo  
STARTED     5 [1]   1     0     0  
COMPLETED     4     1     0     0  
NOT COMPLETED     1     0     0     0  
Death                 1                 0                 0                 0  
[1] 2 participants did not enroll in extension

Period 3:   Extension
    Cohort 1: Nilotinib     Cohort 1: Placebo     Cohort 2: Nilotinib     Cohort 2: Placebo  
STARTED     3 [1]   0 [2]   0     0  
COMPLETED     0     0     0     0  
NOT COMPLETED     3     0     0     0  
The study was terminated                 3                 0                 0                 0  
[1] Two patients did not enrol in the extension
[2] One patient did not enrol in the extension



  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.
an end of study evaluation was only available for 14 of these patients

Reporting Groups
  Description
Cohort 1: Nilotinib Participants were assigned to receive nilotinib 50 mg during 14 days, followed by 150 mg during 14 days, followed by 300 mg during 140 days.
Cohort 1: Placebo Participants were assigned to receive placebo to nilotinib to match 50 mg and 150 mg capsules during 168 days.
Cohort 2: Nilotinib Particibants were assigned to receive nilotinib 300 mg during 168 days
Cohort 2: Placebo Particibants were assigned to receive placebo to match 50mg and / or 150mg capsules during 168 days
Total Total of all reporting groups

Baseline Measures
    Cohort 1: Nilotinib     Cohort 1: Placebo     Cohort 2: Nilotinib     Cohort 2: Placebo     Total  
Number of Participants  
[units: participants]
  12     3     4     4     23  
Age  
[units: Years]
Mean ± Standard Deviation
  52  ± 13.1     60  ± 6.1     31  ± 14.6     33  ± 10.2     32  ± 11.8  
Gender  
[units: Participants]
         
Female     10     3     4     3     20  
Male     2     0     0     1     3  



  Outcome Measures
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1.  Primary:   Change in Pulmonary Vascular Resistance (PVR)   [ Time Frame: 168 days ]

2.  Secondary:   Change in Six-Minute Walk Distance (6MWD) From Baseline   [ Time Frame: Baseline, 168 ]

3.  Secondary:   Total Number of Adverse Events and Serious Adverse Events   [ Time Frame: 168 days ]


  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharnaceuticals
phone: 862-778-8300
e-mail: trialandresults.registries@novartis.com


No publications provided


Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01179737     History of Changes
Obsolete Identifiers: NCT01531270
Other Study ID Numbers: CAMN107X2201, 2010-019883-36
Study First Received: August 3, 2010
Results First Received: January 14, 2014
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Korea: Korea FDA
Germany: Ministry of Health
Switzerland: Swissmedic
Singapore: Health Sciences Authority
Italy: The Italian Medicines Agency
Hungary: Institutional Ethics Committee