Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Randomised, Open-label Study of Ponatinib Versus Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase Following Resistance to Imatinib

    Summary
    EudraCT number
    		 2015-001318-92
    Trial protocol
    		 BE   HU   DE   GB   NL   ES   DK   CZ   PT   FR   AT   PL  
    Global end of trial date
    19 Jan 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Nov 2021
    First version publication date
    13 Nov 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    AP24534-15-303
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02627677
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Takeda
    Sponsor organisation address
    95 Hayden Avenue, Lexington, United States, MA 02421
    Public contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Scientific contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Jan 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Jan 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main objective of the study was to demonstrate the efficacy of ponatinib administered at 2 starting doses (30 and 15 mg once daily [QD]) compared to nilotinib administered at 400 mg twice daily (BID) in participants with chronic phase-chronic myeloid leukemia (CP-CML) who are resistant to imatinib, as measured by major molecular response (MMR) by 12 months.
    Protection of trial subjects
    All the participants were required to read and sign the informed consent form (ICF).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Jan 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 3
    Country: Number of subjects enrolled
    Russian Federation: 32
    Country: Number of subjects enrolled
    Austria: 1
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Hungary: 1
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Czechia: 2
    Worldwide total number of subjects
    44
    EEA total number of subjects
    8
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    38
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants took part in the study at 90 investigative sites in Austria, Canada, Czechia, France, Hungary, Italy, Korea, and Russia from 31 December 2015 to 20 January 2021

    Pre-assignment
    Screening details
    		 Participants with a diagnosis of chronic phase-chronic myeloid leukemia were enrolled and randomised at a ratio of 1:2:1 to receive ponatinib 30 mg and ponatinib 15 mg compared with nilotinib 400 mg.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort A: Ponatinib 30 mg
    Arm description
    		 Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ponatinib 30 mg QD
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ponatinib 30 mg, taken orally once daily.

    Arm title
    		 Cohort B: Ponatinib 15 mg
    Arm description
    		 Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ponatinib 15 mg QD
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ponatinib 15 mg, taken orally once daily.

    Arm title
    		 Cohort C: Nilotinib 400 mg
    Arm description
    		 Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Nilotinib 400 mg BID
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Nilotinib 400 mg, taken orally twice daily.

    Number of subjects in period 1
    		Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Started
    11
    21
    12
    Completed
    0
    0
    0
    Not completed
    11
    21
    12
         Physician decision
    -
    -
    2
         Adverse event (not progressive disease)
    1
    4
    1
         Pregnancy
    -
    1
    -
         Withdrawal by Subject
    2
    1
    1
         Study Terminated by Sponsor
    5
    10
    6
         Progressive disease
    1
    3
    -
         Lost to follow-up
    -
    -
    1
         Reason not Specified
    -
    -
    1
         Lack of efficacy
    1
    2
    -
         Randomised but not Treated
    1
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort A: Ponatinib 30 mg
    Reporting group description
    		 Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.

    Reporting group title
    Cohort B: Ponatinib 15 mg
    Reporting group description
    		 Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.

    Reporting group title
    Cohort C: Nilotinib 400 mg
    Reporting group description
    		 Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.

    Reporting group values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg Total
    Number of subjects
    		 11 21 12
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 43.7 ( 17.43 ) 44.7 ( 15.53 ) 54.3 ( 13.23 ) -
    Gender categorical
    Units: Subjects
        Male
    		 7 10 6 23
        Female
    		 3 11 6 20
        Not recorded
    		 1 0 0 1
    Race (NIH/OMB)
    Units: Subjects
        Asian
    		 2 4 1 7
        White
    		 7 16 10 33
        Unknown or Not Reported
    		 1 1 1 3
        Not recorded
    		 1 0 0 1
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 0 1 1
        Not Hispanic or Latino
    		 10 21 11 42
        Not recorded
    		 1 0 0 1
    Height
    Number analysed is the number of participants with data available for Height at Baseline. Height (n=10, 21, 11)
    Units: cm
        arithmetic mean (standard deviation)
    		 172.9 ( 9.62 ) 169.4 ( 9.35 ) 168.8 ( 9.17 ) -
    Body Mass Index (BMI)
    BMI is calculated as weight (kg) divided by square of height (m^2). Number analysed is the number of participants with data available with BMI at Baseline. BMI (n=10, 21, 11)
    Units: kg/m^2
        arithmetic mean (standard deviation)
    		 25.90 ( 5.870 ) 25.35 ( 4.974 ) 25.18 ( 4.442 ) -
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 77.50 ( 18.335 ) 72.72 ( 15.213 ) 70.94 ( 14.711 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Cohort A: Ponatinib 30 mg
    Reporting group description
    		 Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.

    Reporting group title
    Cohort B: Ponatinib 15 mg
    Reporting group description
    		 Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.

    Reporting group title
    Cohort C: Nilotinib 400 mg
    Reporting group description
    		 Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.

    Subject analysis set title
    Cohort A: Ponatinib 30 mg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.

    Subject analysis set title
    Cohort B: Ponatinib 15 mg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.

    Subject analysis set title
    Cohort C: Nilotinib 400 mg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.

    Primary: Percentage of Participants with Major Molecular Response (MMR) Rate

    		Close Top of page
    End point title
    		 Percentage of Participants with Major Molecular Response (MMR) Rate [1]
    End point description
    MMR is defined as the percentage of participants achieving a ratio of ≤0.1% Breakpoint Cluster Region-Abelson (BCR ABL) to ABL transcripts on the international scale (≤0.1% BCR-ABL/ABL[IS]) at any time within 12 months after randomisation. Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis.
    End point type
    Primary
    End point timeframe
    Up to 12 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics are reported for this outcome measure.
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    10
    21
    11
    Units: percentage of participants
        number (confidence interval 95%)
    40.0 (12.2 to 73.8)
    33.3 (14.6 to 57.0)
    45.5 (16.7 to 76.6)
    No statistical analyses for this end point

    Primary: Percentage of Participants with Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs)

    		Close Top of page
    End point title
    		 Percentage of Participants with Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) [2]
    End point description
    TE-AOE: event with initial onset date on/after 1st dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on/after 1st dose date. TE-VTE: vascular occlusive event with initial onset date on/after 1st dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on/after 1st dose date. AE: any untoward medical occurrence in participant administered pharmaceutical product; untoward medical occurrence does not necessarily have causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization/prolongation of existing hospitalization, results in persistent/incapacity, is congenital anomaly/birth defect/is medically important event. Safety Population: all participants who have received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    From first dose up to 30 days post last dose (Up to approximately 46 months)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics are reported for this outcome measure.
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    10
    21
    12
    Units: percentage of participants
    number (not applicable)
        TE-AOE
    0
    4.8
    8.3
        TE-VOEs
    0
    0
    0
        AEs
    100
    95.2
    100
        SAEs
    40.0
    14.3
    16.7
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Major Cytogenetic Response (MCyR) Rates

    		 Close Top of page
    End point title
    		 Percentage of Participants with Major Cytogenetic Response (MCyR) Rates
    End point description
    MCyR was the percentage of participants achieving Complete cytogenetic response (CCyR: defined as 0% Philadelphia chromosome-positive [Ph+] metaphases by cytogenetic analysis of bone marrow) or Partial Cytogenetic Response (PCyR: defined as >0% to 35% Ph+ metaphases by cytogenetic analysis of bone marrow) at any time within 12 months after randomisation. Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    10
    21
    11
    Units: percentage of participants
        number (confidence interval 95%)
    50.0 (18.7 to 81.3)
    60.0 (36.1 to 80.9)
    50.0 (21.1 to 78.9)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Complete Cytogenetic Response (CCyR) Rates

    		 Close Top of page
    End point title
    		 Percentage of Participants with Complete Cytogenetic Response (CCyR) Rates
    End point description
    CCyR rate was defined as the percentage of participants achieving CCyR up to 12 months after randomisation. CCyR is defined as 0% Philadelphia chromosome-positive [Ph+] metaphases by cytogenetic analysis of bone marrow. Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    10
    21
    12
    Units: percentage of participants
        number (confidence interval 95%)
    40.0 (12.2 to 73.8)
    55.0 (31.5 to 76.9)
    50.0 (21.1 to 78.9)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Molecular Response (MR) Rate

    		Close Top of page
    End point title
    		 Percentage of Participants with Molecular Response (MR) Rate
    End point description
    Molecular response rate is defined as percentage of participants achieving MR2: Molecular response with 2-log reduction (defined as ≤1% BCR-ABL[IS]), MMR: Major molecular responder, MR4 (defined as ≤0.01% BCR-ABL[IS]), and MR4.5 (defined as ≤0.0032% BCR-ABL[IS]) after randomisation. Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis.
    End point type
    Secondary
    End point timeframe
    From Month 3 to every 3 months up to 48 months
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    10
    21
    11
    Units: percentage of participants
    number (not applicable)
        MR2 - Month 3
    70.0
    38.1
    45.5
        MR2 - Month 6
    60.0
    57.1
    54.5
        MR2 - Month 9
    50.0
    52.4
    45.5
        MR2 - Month 12
    50.0
    52.4
    54.5
        MR2 - Month 15
    50.0
    52.4
    54.5
        MR2 - Month 18
    50.0
    47.6
    54.5
        MR2 - Month 21
    50.0
    52.4
    45.5
        MR2 - Month 24
    50.0
    47.6
    54.5
        MR2 - Month 27
    50.0
    42.9
    54.5
        MR2 - Month 30
    50.0
    38.1
    45.5
        MR2 - Month 33
    30.0
    33.3
    27.3
        MR2 - Month 36
    50.0
    33.3
    36.4
        MR2 - Month 39
    20.0
    14.3
    18.2
        MR2 - Month 42
    10.0
    9.5
    9.1
        MR2 - Month 45
    10.0
    14.3
    9.1
        MR2 - Month 48
    10.0
    4.8
    9.1
        MR3/MMR - Month 3
    30.0
    4.8
    18.2
        MR3/MMR - Month 6
    30.0
    28.6
    36.4
        MR3/MMR - Month 9
    30.0
    28.6
    45.5
        MR3/MMR - Month 12
    40.0
    33.3
    45.5
        MR3/MMR - Month 15
    40.0
    28.6
    45.5
        MR3/MMR - Month 18
    40.0
    38.1
    45.5
        MR3/MMR - Month 21
    40.0
    33.3
    45.5
        MR3/MMR - Month 24
    40.0
    33.3
    45.5
        MR3/MMR - Month 27
    40.0
    33.3
    45.5
        MR3/MMR - Month 30
    40.0
    33.3
    45.5
        MR3/MMR - Month 33
    20.0
    28.6
    27.3
        MR3/MMR - Month 36
    40.0
    28.6
    36.4
        MR3/MMR - Month 39
    20.0
    14.3
    18.2
        MR3/MMR - Month 42
    10.0
    9.5
    9.1
        MR3/MMR - Month 45
    10.0
    9.5
    9.1
        MR3/MMR - Month 48
    10.0
    4.8
    9.1
        MR4 - Month 3
    0.0
    0.0
    0.0
        MR4 - Month 6
    20.0
    14.3
    9.1
        MR4 - Month 9
    10.0
    9.5
    18.2
        MR4 - Month 12
    10.0
    9.5
    27.3
        MR4 - Month 15
    10.0
    19.0
    27.3
        MR4 - Month 18
    20.0
    23.8
    27.3
        MR4 - Month 21
    20.0
    9.5
    36.4
        MR4 - Month 24
    10.0
    19.0
    36.4
        MR4 - Month 27
    20.0
    19.0
    36.4
        MR4 - Month 30
    20.0
    14.3
    36.4
        MR4 - Month 33
    0.0
    14.3
    9.1
        MR4 - Month 36
    10.0
    19.0
    27.3
        MR4 - Month 39
    20.0
    4.8
    18.2
        MR4 - Month 42
    10.0
    0.0
    9.1
        MR4 - Month 45
    10.0
    4.8
    9.1
        MR4 - Month 48
    10.0
    0.0
    9.1
        MR4.5 - Month 3
    0.0
    0.0
    0.0
        MR4.5 - Month 6
    20.0
    0.0
    0.0
        MR4.5 - Month 9
    0.0
    4.8
    9.1
        MR4.5 - Month 12
    0.0
    4.8
    18.2
        MR4.5 - Month 15
    10.0
    4.8
    9.1
        MR4.5 - Month 18
    10.0
    9.5
    9.1
        MR4.5 - Month 21
    10.0
    9.5
    27.3
        MR4.5 - Month 24
    10.0
    4.8
    18.2
        MR4.5 - Month 27
    10.0
    14.3
    18.2
        MR4.5 - Month 30
    10.0
    4.8
    27.3
        MR4.5 - Month 33
    0.0
    4.8
    0.0
        MR4.5 - Month 36
    10.0
    9.5
    18.2
        MR4.5 - Month 39
    10.0
    4.8
    18.2
        MR4.5 - Month 42
    10.0
    0.0
    9.1
        MR4.5 - Month 45
    10.0
    0.0
    9.1
        MR4.5 - Month 48
    0.0
    0.0
    9.1
    No statistical analyses for this end point

    Secondary: Percentage of Participants with MR1

    		Close Top of page
    End point title
    		 Percentage of Participants with MR1
    End point description
    MR1 was defined as the percentage of participants achieving a ratio of ≤10% BCR ABL to ABL transcripts on the international scale at 3 months. Safety Population includes all participants who have received at least 1 dose of study drug, with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Month 3
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    10
    21
    11
    Units: percentage of participants
        number (not applicable)
    70.0
    66.7
    63.6
    No statistical analyses for this end point

    Secondary: Time to Response

    		 Close Top of page
    End point title
    		 Time to Response
    End point description
    Time to MMR defined as the interval between the randomisation date and the first date at which the criteria for response was met. MMR was defined as <=0.1% BCR-ABL. Safety Population includes all participants who have received at least 1 dose of study drug. Only responders were analyzed for this outcome measure. 99999 indicates that the upper limit of confidence interval (CI) was not estimable due to less number of participants with event.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    5
    9
    5
    Units: months
        median (confidence interval 95%)
    3.07 (3.0 to 99999)
    6.29 (3.0 to 18.1)
    6.07 (3.0 to 99999)
    No statistical analyses for this end point

    Secondary: Duration of response

    		Close Top of page
    End point title
    		 Duration of response
    End point description
    Duration of response defined as the interval between the first assessment at which the criteria for response was met until the earliest date at which loss of response occurs, or the criteria for progression was met. Safety Population includes all participants who have received at least 1 dose of study drug. 99999 indicates that the median, lower limit and upper limit of CI were not estimable due to less number of participants with event.
    End point type
    Secondary
    End point timeframe
    Up to approximately 60 months
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    10
    21
    12
    Units: months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (3.0 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Progression-free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression-free Survival (PFS)
    End point description
    Progression-free survival (PFS) defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression was met (progression to AP- or BP CML), or death due to any cause, censored at the last response assessment. Safety Population includes all participants who have received at least 1 dose of study drug. 99999 indicates that the median, lower limit and upper limit of CI were not estimable due to less number of participants with event.
    End point type
    Secondary
    End point timeframe
    Up to end of study (approximately 60 months)
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    10
    21
    12
    Units: months
        median (confidence interval 95%)
    99999 (8.0 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Overall Survival

    		Close Top of page
    End point title
    		 Overall Survival
    End point description
    Overall survival (OS) defined as the interval between the first dose date of study treatment and date of death due to any cause, censored at the last contact date to be alive. Safety Population includes all participants who have received at least 1 dose of study drug. 99999 indicates that the median, lower limit and upper limit of CI were not estimable due to less number of participants with event.
    End point type
    Secondary
    End point timeframe
    Up to end of study (approximately 60 months)
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    10
    21
    12
    Units: months
        median (confidence interval 95%)
    99999 (18.5 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Achieved/Maintained Complete Hematologic Response (CHR)

    		 Close Top of page
    End point title
    		 Percentage of Participants who Achieved/Maintained Complete Hematologic Response (CHR)
    End point description
    CHR rate is defined as the percentage of participants achieving CHR at any time after initiation of study treatment. CHR is defined as achieving all of the following measurements: White blood cells (WBC) ≤ institutional upper limit of normal (ULN); Platelets <450 x 10^9/L; No blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; Basophils in peripheral blood <5%; No extramedullary involvement (including no hepatomegaly or splenomegaly). Safety Population includes all participants who have received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    3 months after the first dose of study treatment
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    10
    21
    12
    Units: percentage of participants
        median (confidence interval 95%)
    60.0 (26.2 to 87.8)
    81.0 (58.1 to 94.6)
    50.0 (21.1 to 78.9)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption

    		 Close Top of page
    End point title
    		 Percentage of Participants with Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption
    End point description
    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Safety Population includes all participants who have received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    From first dose up to end of treatment (Up to approximately 45 months)
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    10
    21
    12
    Units: percentage of participants
    number (not applicable)
        TEAEs Leading to Treatment Discontinuation
    10.0
    23.8
    25.0
        TEAEs Leading to Dose Reduction
    40.0
    19.0
    33.3
        TEAEs Leading to Dose Interruption
    70.0
    38.1
    41.7
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Progression to Accelerated Phase (AP) or Blast Phase (BP)-CML

    		 Close Top of page
    End point title
    		 Percentage of Participants with Progression to Accelerated Phase (AP) or Blast Phase (BP)-CML
    End point description
    Progression to AP is defined as: >=15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*10^9 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP-CML is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
    End point type
    Secondary
    End point timeframe
    Up to end of study (Up to approximately 60 months)
    End point values
    		 Cohort A: Ponatinib 30 mg Cohort B: Ponatinib 15 mg Cohort C: Nilotinib 400 mg
    Number of subjects analysed
    0 [3]
    0 [4]
    0 [5]
    Units: participants
    Notes
    [3] - As the study was terminated, data was not collected ad analyzed for this outcome measure.
    [4] - As the study was terminated, data was not collected ad analyzed for this outcome measure.
    [5] - As the study was terminated, data was not collected ad analyzed for this outcome measure.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months)
    Adverse event reporting additional description
    At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes participants who have received at least 1 dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Cohort A: Ponatinib 30 mg
    Reporting group description
    		 Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.

    Reporting group title
    Cohort C: Nilotinib 400 mg
    Reporting group description
    		 Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.

    Reporting group title
    Cohort B: Ponatinib 15 mg
    Reporting group description
    		 Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.

    Serious adverse events
    		 Cohort A: Ponatinib 30 mg Cohort C: Nilotinib 400 mg Cohort B: Ponatinib 15 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 10 (40.00%)
    2 / 12 (16.67%)
    3 / 21 (14.29%)
         number of deaths (all causes)
    1
    0
    1
         number of deaths resulting from adverse events
    Investigations
    Platelet count decreased
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femoral neck fracture
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial flutter
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Pancreatitis acute
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonia aspiration
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort A: Ponatinib 30 mg Cohort C: Nilotinib 400 mg Cohort B: Ponatinib 15 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 10 (100.00%)
    12 / 12 (100.00%)
    20 / 21 (95.24%)
    Vascular disorders
    Essential hypertension
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Hypertension
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 12 (8.33%)
    2 / 21 (9.52%)
         occurrences all number
    4
    1
    8
    Peripheral artery stenosis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Fatigue
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 12 (25.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    4
    1
    Asthenia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Influenza like illness
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Bronchial obstruction
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Cough
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Pulmonary artery dilatation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Throat irritation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 10 (30.00%)
    2 / 12 (16.67%)
    1 / 21 (4.76%)
         occurrences all number
    14
    2
    4
    Blood cholesterol increased
         subjects affected / exposed
    2 / 10 (20.00%)
    3 / 12 (25.00%)
    2 / 21 (9.52%)
         occurrences all number
    2
    4
    2
    Platelet count decreased
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 12 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    12
    0
    7
    Lipase increased
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 12 (16.67%)
    1 / 21 (4.76%)
         occurrences all number
    1
    4
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 10 (20.00%)
    2 / 12 (16.67%)
    0 / 21 (0.00%)
         occurrences all number
    10
    2
    0
    Platelet count increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    2
    0
    1
    Weight increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    3
    0
    1
    Blood bilirubin increased
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    1
    4
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Blood magnesium decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Blood phosphorus decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Blood triglycerides increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    5
    0
    0
    N-terminal prohormone brain natriuretic peptide increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    2
    0
    Weight decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    1
    Procedural pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    1
    Paternal exposure timing unspecified
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Thermal burn
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Cardiac disorders
    Left ventricular hypertrophy
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Pericardial effusion
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    1
    1
    0
    Sinus arrhythmia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Atrial fibrillation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Dilatation atrial
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Right atrial hypertrophy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Right ventricular dilatation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Headache
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    1
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    5 / 10 (50.00%)
    2 / 12 (16.67%)
    5 / 21 (23.81%)
         occurrences all number
    24
    13
    27
    Anaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 12 (0.00%)
    3 / 21 (14.29%)
         occurrences all number
    11
    0
    4
    Neutropenia
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 12 (16.67%)
    3 / 21 (14.29%)
         occurrences all number
    10
    15
    7
    Anaemia folate deficiency
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Thrombocytosis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    2
    Splenic lesion
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Eye disorders
    Retinal vascular disorder
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    1
    Periorbital oedema
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Cataract
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    1
    Vomiting
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    2
    1
    0
    Nausea
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    2 / 21 (9.52%)
         occurrences all number
    0
    1
    2
    Constipation
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Dental caries
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Gastritis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Pancreatitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Hepatobiliary disorders
    Hepatitis toxic
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Ocular icterus
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Rash
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Rash maculo-papular
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    0
    0
    2
    Dermatitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Rash papular
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    1
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    4 / 21 (19.05%)
         occurrences all number
    1
    2
    5
    Arthralgia
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    4 / 21 (19.05%)
         occurrences all number
    0
    3
    4
    Pain in extremity
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    3 / 21 (14.29%)
         occurrences all number
    2
    1
    4
    Musculoskeletal pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    1 / 21 (4.76%)
         occurrences all number
    0
    2
    1
    Spinal pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatitis viral
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Ear infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    2
    0
    Pharyngitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 21 (0.00%)
         occurrences all number
    0
    1
    0
    Metabolism and nutrition disorders
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    2 / 21 (9.52%)
         occurrences all number
    1
    0
    2
    Diabetes mellitus
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Hyperlipidaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    0 / 21 (0.00%)
         occurrences all number
    0
    2
    0
    Hyperglycaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    0
    1
    Hypophosphataemia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Mar 2016
    Amendment 2: Imposed more stringent and detailed guidelines for contraception requirements of participants on the study. Excluded participants with hypersensitivity to the ponatinib or nilotinib active substances or to any of their inactive ingredients. Added Hepatitis B virus serology as a screening requirement. Increased the blood count and lipase monitoring frequency (additional screens on Day 15 during Cycle 2 and Cycle 3) in adherence to the ponatinib Investigator's Brochure. Changed statistical testing scheme to use Bonferroni procedure rather than Hochberg procedure to adjust for comparisons of Cohorts A and B to Cohort C. Updated the Schedule of Events to allow another option (brain natriuretic peptide testing) for sites unable to perform N-terminal pro-brain natriuretic peptide testing. Added requirements for an eye exam at screening and throughout treatment period as clinically indicated. Provided guidance for ocular toxicity. Corrected dose modification for nilotinib for Grade 3 peripheral vascular arterial events, QT interval corrected (Fridericia) (QTcF) prolongation and amylase/lipase elevations. Updated sponsor contact information.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    This study was terminated due to operational feasibility and not due to any safety concerns.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun Apr 28 05:35:29 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA