Ponatinib in Participants With Resistant Chronic Phase Ch... | NCT02467270 | Trialant
NCT02467270
Sponsor
Takeda
Status
Completed
Last Update Posted
Mar 17, 2026Actual
Enrollment
283Actual
Phase
Phase 2
Conditions
Myeloid Leukemia, Chronic, Chronic Phase
Interventions
Ponatinib
Countries
United States
Argentina
Australia
Canada
Chile
Czechia
Denmark
France
Germany
Hong Kong
Italy
Poland
Portugal
Russia
Singapore
South Korea
Spain
Sweden
Switzerland
Taiwan
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02467270
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
AP24534-14-203
Secondary IDs
ID
Type
Description
Link
2014-001617-12
EudraCT Number
15/LO/1192
Registry Identifier
NRES
U1111-1238-0007
Other Grant/Funding Number
WHO
2024-514516-27-00
EU Trial (CTIS) Number
Brief Title
Ponatinib in Participants With Resistant Chronic Phase Chronic Myeloid Leukemia (CP-CML) to Characterize the Efficacy and Safety of a Range of Doses
Official Title
A Randomized, Open-label, Phase 2 Trial of Ponatinib in Patients With Resistant Chronic Phase Chronic Myeloid Leukemia to Characterize the Efficacy and Safety of a Range of Doses
Acronym
OPTIC
Organization
TakedaINDUSTRY
Status Module
Record Verification Date
Mar 2026
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jul 13, 2015Actual
Primary Completion Date
Apr 29, 2020Actual
Completion Date
Apr 23, 2025Actual
First Submitted Date
Jun 2, 2015
First Submission Date that Met QC Criteria
Jun 5, 2015
First Posted Date
Jun 10, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Apr 14, 2021
Results First Submitted that Met QC Criteria
May 18, 2021
Results First Posted Date
Jun 14, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Mar 13, 2026
Last Update Posted Date
Mar 17, 2026Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
TakedaINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this study is to characterize the efficacy of ponatinib administered in 3 starting doses (45 mg, 30 mg, and 15 mg daily) in participants with CP-CML who are resistant to prior tyrosine-kinase inhibitor (TKI) therapy or have T315I mutation, as measured by <=1 % Breakpoint Cluster Region-Abelson Transcript Level using International Scale (BCR-ABL1IS) at 12 months.
Detailed Description
The drug being tested in this study is ponatinib. This study will characterize the safety and efficacy of ponatinib over a range of 3 starting doses.
The study will enroll 276 participants in 3 cohorts and each cohort will have 92 participants. All the participants will be randomized to receive once-daily oral administration of 1 of 3 starting doses of ponatinib:
Cohort A: 45 mg ponatinib tablet
Cohort B: 30 mg ponatinib tablet
Cohort C: 15 mg ponatinib tablet
The study is designed to consist of 2 periods: 24-cycle Main treatment period and optional treatment continuation period. Participants will be treated with their randomized dose of study drug in the Main Treatment Period until the occurrence of at least one of the following: absence of CHR by 3 months, absence of MCyR at 12 months, absence of <=1% BCR-ABL1IS at 12 months, loss of <=1% BCR-ABL1IS development of intolerance, or completion of all 24 cycles of treatment (whichever occurs first). Following completion of approximately 5 years or following early withdrawal, participants may enter into an optional treatment continuation period.
This multi-center trial will be conducted in the United States, United Kingdom, Republic of Korea, Spain, France, Taiwan, Australia, Canada, Italy, Chile, Japan, Germany, Argentina, Poland, Czech Republic, Denmark, Hong Kong, Portugal, Russia, Singapore, Switzerland, and Sweden. The overall time to participate in this study is approximately 96 months. Participants will make a final visit to the clinic approximately 30 days after the last dose of study treatment.
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Drug: Ponatinib
Treatment Period: Cohort B: Ponatinib 30 mg
Experimental
Participants received ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Drug: Ponatinib
Treatment Period: Cohort C: Ponatinib 15 mg
Experimental
Participants received ponatinib 15 mg orally once daily in each 28 day Cycle.
Drug: Ponatinib
Close-out Period: Cohort A: Ponatinib 45 mg
Experimental
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Drug: Ponatinib
Close-out Period: Cohort B: Ponatinib 30 mg
Experimental
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Ponatinib
Drug
Tablet, taken orally once daily.
Close-out Period: Cohort A: Ponatinib 45 mg
Close-out Period: Cohort B: Ponatinib 30 mg
Close-out Period: Cohort C: Ponatinib 15 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percentage of Participants With Molecular Response (MR2: <=1% Breakpoint Cluster Region-Abelson Transcript Level) as Measured by the International Scale (BCR-ABL1IS) at Month 12
MR2 was defined as a ratio of reverse transcribed transcript of BCR-ABL to ABL <=1% Breakpoint Cluster Region-Abelson Transcript Level as measured by the International Scale (BCR-ABL1IS), equivalent to a 2-log reduction in transcript.
12 months after the first dose of study treatment
Secondary Outcomes
Measure
Description
Time Frame
Percentage of Participants With Major Molecular Response (MMR/MR3)
MMR/MR3 was defined as a ratio of reverse transcribed transcript of BCR-ABL to ABL ≤0.1% on the international scale (equivalent to a 3-log reduction in transcript).
12, 24 and 60 months after the first dose of study treatment
Percentage of Participants With Major Cytogenetic Response (MCyR)
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Have chronic phase-chronic myelogenous leukemia/chronic myeloid leukemia (CP-CML) and have received at least two prior tyrosine kinase inhibitor (TKI) therapies and have demonstrated resistance to treatment OR have documented history of presence of T315I mutation after receiving any number of prior TKI.
o] The diagnosis of chronic myeloid leukemia (CML) will be made using standard hematopathologic and cytogenetic criteria; CP-CML will be defined by all of the following: i <15% blasts in bone marrow ii <30% blasts plus promyelocytes in bone marrow iii <20% basophils in peripheral blood. iv >= 100*10^9/liter (L) platelets (>=100,000/mm^3). v No evidence of extramedullary disease except hepatosplenomegaly vi No prior diagnosis of AP-CML, and BP-CML o] Cytogenetic assessment at screening must demonstrate the BCR-ABL1 fusion by presence of the t(9;22) Philadelphia chromosome.
i Variant translocations are only allowed provided they meet inclusion criterion 1d.
o] Resistance to prior TKI therapy is defined as follows (participants must meet at least 1 criterion): i Three months after the initiation of prior TKI therapy: No cytogenetic response (>95% Ph+) or failure to achieve CHR or new mutation ii Six months after the initiation of prior TKI therapy: BCR-ABL1IS >10% and/or Ph+ >65% or new mutation iii Twelve months after the initiation of prior TKI therapy: BCR ABL1IS >10% and/or Ph+ >35% or new mutation iv At any time after the initiation of prior TKI therapy, the development of a new BCR-ABL1 kinase domain mutation(s) v At any time after the initiation of prior TKI therapy, the development of new clonal evolution vi At any time after the initiation of prior TKI therapy, the loss of CHR, or CCyR, or the confirmed loss of MMR in 2 consecutive tests, one of which has a BCR-ABL1IS transcript level of >=1% or new mutation o] >1% of BCR-ABL1IS as shown by real-time polymerase chain reaction
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Have adequate renal function as defined by the following criterion:
o] Serum creatinine <=1.5*ULN for institution o] Estimated creatinine clearance >=30 milliliter per minute (mL/min) (Cockcroft-Gault formula)
Have adequate hepatic function as defined by the following criteria:
o] Total serum bilirubin <=1.5*ULN, unless due to Gilbert's syndrome o] Alanine transaminase (ALT) <=2.5*ULN, or <=5*ULN if leukemic infiltration of the liver is present o] Aspartate transaminase (AST) <=2.5*ULN, or <=5*ULN if leukemic infiltration of the liver is present
Have normal pancreatic status as defined by the following criterion:
o] Serum lipase and amylase <=1.5*ULN
Have normal QT interval corrected (Frederica) (QTcF) interval on screening electrocardiogram (ECG) evaluation, defined as QTcF of <=450 milliseconds (ms) in males or <=470 ms in females.
Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
Agree to use a highly effective form of contraception with sexual partners from randomization through at least 4 months after the end of treatment (for female and male participants who are fertile).
Provide written informed consent.
Be willing and able to comply with scheduled visits and study procedures.
Have recovered from toxicities related to prior anticancer therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 grade <=1.
Exclusion Criteria:
Have used any approved TKIs or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is longer, prior to receiving study drug.
Received interferon, cytarabine, or immunotherapy within 14 days, or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of ponatinib, or have not recovered (>grade 1 by NCI CTCAE, version 4.0) from AEs (except alopecia), due to agents previously administered.
Have undergone autologous or allogeneic stem cell transplant <60 days prior to receiving the first dose of ponatinib; have any evidence of ongoing graft-versus-host disease (GVHD) or GVHD requiring immunosuppressive therapy.
Are being considered for hematopoietic stem cell transplant (HSCT) within 6-12 months of enrollment (note: ponatinib is not to be used as a bridge to HSCT in this trial).
Are taking medications with a known risk of Torsades de Pointes.
Have previously been treated with ponatinib.
Have active CNS disease as evidenced by cytology or pathology; in the absence of clinical CNS disease, lumbar puncture is not required. History itself of CNS involvement is not exclusionary if CNS has been cleared with a documented negative lumbar puncture.
Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
o] Any history of myocardial infarction (MI), unstable angina, cerebrovascular accident, or Transient Ischemic Attack (TIA) o] Any history of peripheral vascular infarction, including visceral infarction o] Any revascularization procedure, including the placement of a stent o] Congestive heart failure (CHF) (New York Heart Association [NYHA] class III or IV) within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal, per local institutional standards, within 6 months prior to enrollment o] History of clinically significant (as determined by the treating physician) atrial arrhythmia or any history of ventricular arrhythmia o] Venous thromboembolism, including deep venous thrombosis or pulmonary embolism, within 6 months prior to enrollment
Have uncontrolled hypertension (that is, >150 and >90 for systolic blood pressure (SBP) and diastolic blood pressure (DBP) respectively). Participants with hypertension should be under treatment at study entry to ensure blood pressure control. Those requiring 3 or more antihypertensive medications should be discussed with the medical monitor.
Have poorly controlled diabetes defined as HbA1c values of >7.5%. Participants with preexisting, well-controlled diabetes are not excluded.
Have a significant bleeding disorder unrelated to CML.
Have a history of alcohol abuse.
Have a history of either acute pancreatitis within 1 year of study enrollment or of chronic pancreatitis.
Have malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drug.
Have a history of another malignancy, other than cervical cancer in situ or basal cell or squamous cell carcinoma of the skin; the exception is if participants have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy.
Are pregnant or lactating.
Have undergone major surgery (with the exception of minor surgical procedures, such as catheter placement or BM biopsy) within 14 days prior to first dose of ponatinib.
Have an active infection which requires intravenous antibiotics.
Have a known history of human immunodeficiency virus infection; testing is not required in the absence of prior documentation or known history.
Have any condition or illness that, in the opinion of the investigator, would compromise participant safety or interfere with the evaluation of the drug.
Have hypersensitivity to the ponatinib active substance or to any of its inactive ingredients.
Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Types
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame
Not provided
Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Participants with chronic phase-chronic myelogenous leukemia(CP-CML) who received at least 2 prior tyrosine kinase inhibitor(TKI) therapies were enrolled in 1:1:1 ratio in 3 cohorts:ponatinib:45 milligrams(mg)(Cohort A);30mg(Cohort B);or 15mg(Cohort C). Participants who started at 45/30mg received mandatory dose reduction of their daily dose to 15mg upon achievement of less than equal to (≤)1% breakpoint cluster region-Abelson 1 transcript level as measured by International Scale (BCR-ABL1IS).
Recruitment Details
Participants took part in the study at 61 investigative sites globally from 13 July 2015 to 23 April 2025.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
FG001
Treatment Period: Cohort B: Ponatinib 30 mg
Periods
Title
Milestones
Reasons Not Completed
Treatment Period (60 Months)
Type
Comment
Milestone Data
STARTED
Due to limitation during the electronic data capture for participants, the reason for discontinuation from the study was not available and hence reason for discontinuation from study treatment for the participants has been added to this section.
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Apr 7, 2021
Feb 2, 2026
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Belgium
China
Finland
Japan
Norway
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Participants received ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Drug: Ponatinib
Close-out Period: Cohort C: Ponatinib 15 mg
Experimental
Participants received ponatinib 15 mg orally once daily in each 28 day Cycle.
MCyR was defined as percentage of participants with complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). Cytogenetic response is the percentage of Philadelphia chromosome positive (Ph+) metaphases in bone marrow (BM). Response is further defined as MCyR: CCyR or PCyR, where CCyR: 0% Ph + metaphases; PCyR: >0 to 35% Ph + metaphases.
12 months after the first dose of study treatment
Duration of Major Molecular Response (MMR/MR3)
Duration of MMR/MR3 was defined as the interval between the first assessment at which the criteria for <=0.1% MMR were met until the earliest date at which loss of <=0.1% MMR occurred, or the criteria for progression were met. Progression to accelerated phase (AP) was 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*109 platelets per liter (/L) in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to blast phase (BP) was defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
Baseline up to approximately 8.9 years
Percentage of Participants With Adjusted Incidence Rates for Treatment Emergent Arterial Occlusive Events (AOEs), Venous Thrombotic Events (VTEs), Adverse Events (AEs), and Serious AEs (SAEs)
Percentage of participants with adjusted incidence rates who developed AOEs and VTEs were categorized according to arterial occlusive events and venous thrombotic events. AE is any untoward medical occurrence in participant administered medicinal investigational drug. Untoward medical occurrence does not necessarily have to have causal relationship with treatment. SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is congenital anomaly/birth defect/is medically important event that may not be immediately life-threatening/result in death or hospitalization, but may jeopardize participant/may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.
From first dose up to 30 days after last dose of the study drug (up to approximately 9.8 years)
Percentage of Participants With Complete Cytogenetic Response (CCyR)
Cytogenetic response was defined as the percentage of Ph+ metaphases in bone marrow (peripheral blood may not be used), with a review of a minimum of 20 metaphases. CCyR was defined as 0% Ph+ metaphases.
Month 12
Percentage of Participants With Molecular Response 4 (MR4) and Molecular Response 4.5 (MR4.5)
MR4 was defined as <=0.01% BCR-ABL1IS. MR 4.5was defined as <=0.0032% BCR-ALB1IS. MR4 and MR4.5 by each time point means the best outcome up to each time point after randomization.
Up to approximately 9.5 years
Percentage of Participants With Molecular Response 1 (MR1)
MR1 was defined as percentage of participants achieving a ratio of <=10% Breakpoint Cluster Region-Abelson (BCR-ABL1) transcripts on the international scale. MR1 is molecular response with 1-log reduction in transcript.
3 months after the first dose of study treatment
Percentage of Participants With Complete Hematologic Response (CHR)
CHR was defined as achieving all of the following measurements: white blood cells (WBC) <= institutional upper limit of normal (ULN), platelets less than (<)450,000 per cubic millimeter (/mm^3), no blasts or promyelocytes in peripheral blood, <5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood <5%, and no extramedullary involvement (including no hepatomegaly or splenomegaly).
3 months after the first dose of study treatment
Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption
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.
Up to approximately 9.8 years
Kaplan-Meier Estimate of Duration of Response (DOR) of <=1% BCR-ABL1 IS (MR2) at Months 12 and 24
DOR (≤1% BCR-ABL1IS) is defined as interval between first assessment at which criteria for ≤1% BCR-ABL1IS are met until earliest date at which loss of ≤1% BCR-ABL1IS occurs, or criteria for progression accelerated phase (AP) or blast Phase (BP) of chronic myeloid leukemia (CML) are met. Loss of ≤1% BCR-ABL1IS is an increase to >1% of BCR-ABL1IS. Progression to AP: ≥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*109 platelets per liter in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP: ≥30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly. Kaplan-Meier method was used for analysis of percentage of participants who achieved DOR of 12 and 24 months.
12 and 24 months after the first dose of study treatment
Kaplan-Meier Estimate of Duration of Response (DOR) of Major Molecular Response (MMR/MR3)
Duration of MMR/MR3 is defined as interval between first assessment at which criteria for MMR are met until earliest date at which loss of MMR occurs, or criteria for progression (progression to AP or BP of CML) are met. Participants remaining in MMR will be censored at last date at which criteria for MMR are met. Loss of MMR is an increase to >0.1% of BCR-ABL1IS. Progression to AP: >= 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*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly. Kaplan-Meier method was used for analysis of percentage of participants who achieved DOR of 12 and 24 months.
12 and 24 months after the first dose of study treatment
Duration of Response in MR2 Responders
Duration of response in "responders" was defined as any participants who achieved ≤1% BCR-ABL1IS (MR2) at any time during the study. Responders were defined as those participants who met all of the following: were randomized and treated, responded at 12 months after the initiation of study treatment, and underwent baseline polymerase chain reaction (PCR) assessment.
Baseline up to approximately 8.9 years
Time to Response (MR2)
Time to response was defined as the time interval from the date of the first dose of the study drug until the initial observation of CR or PR for participants with confirmed CR/PR. Response was defined as any participants who achieved ≤1% BCR-ABL1IS (MR2) at any time during the study. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. CR for non-target lesion: Disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis) and normalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the Baseline sum diameters.
Baseline up to approximately 5 years
Percentage of Participants With Progression to Accelerated Phase (AP)-Chronic Myeloid Leukemia (CML) or Blast Phase (BP)-CML
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*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
From first dose date of study treatment up to approximately 8.9 years
Progression-free Survival (PFS)
PFS was defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression were met (progression to the AP or BP of CML), or death due to any cause, censored at the last response assessment. Progression to AP was 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*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP was defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
Up to approximately 8.9 years
Overall Survival (OS)
OS was defined as the interval between the first dose of study treatment and death due to any cause, censored at the last contact date when the participant was alive.
Up to approximately 8.9 years
Indianapolis
Indiana
46237
United States
University of Maryland Medical Center
Baltimore
Maryland
21201
United States
Michigan Medicine
Ann Arbor
Michigan
48109
United States
Barbara Ann Karmanos Cancer Institute
Detroit
Michigan
48201
United States
University of Minnesota Medical School
Minneapolis
Minnesota
55455
United States
University of Nebraska Medical Center
Omaha
Nebraska
68198
United States
Hackensack University Medical Center
Hackensack
New Jersey
07601
United States
Memorial Sloan-Kettering Cancer Center - New York
New York
New York
10065
United States
NewYork-Presbyterian Weill Cornell Medical Center
New York
New York
10065
United States
Duke University Medical Center
Durham
North Carolina
27710
United States
Cleveland Clinic Taussig Cancer Institute Main Campus
Cleveland
Ohio
44195
United States
Oregon Health and Science University
Portland
Oregon
97239
United States
Abramson Cancer Center
Philadelphia
Pennsylvania
19104
United States
MD Anderson Cancer Center
Houston
Texas
77030
United States
University of Utah Huntsman Cancer Institute
Salt Lake City
Utah
84112
United States
Fundaleu
Ciudad Autonoma de Buenos Aires
Buenos Aires
C1114AAN
Argentina
Hospital General de Agudo Jose Maria Ramos Mejia
Ciudad Autonoma de Buenos Aires
Buenos Aires
C1221ADC
Argentina
Hospital Italiano La Plata
La Plata
Buenos Aires
B1900AXI
Argentina
Royal North Shore Hospital
Saint Leonards
New South Wales
2065
Australia
Royal Adelaide Hospital
Adelaide
South Australia
5000
Australia
Princess Margaret Hospital - Toronto
Toronto
Ontario
M5G 2M9
Canada
Jewish General Hospital
Montreal
Quebec
H3T 1E2
Canada
Saskatchewan Cancer Agency
Regina
Saskatchewan
S4T 7T1
Canada
Hospital del Salvador
Providencia
Santiago Metropolitan
7500922
Chile
Centro de Investigaciones Clinicas Vina del Mar
Viña del Mar
Valparaiso
2540364
Chile
Ustav Hematologie a Krevni Transfuze Praha
Prague
Prague
12820
Czechia
Fakultni Nemocnice Olomouc
Olomouc
772 00
Czechia
Aarhus University Hospital
Aarhus C
\Aarhus
DK-8000
Denmark
Centre de Lutte Contre le Cancer - Institut Bergonie
Bordeaux
Aquitaine
33076
France
Centre Hospitalier Regional Universitaire de Lille
Lille
Hauts-de-France
59037
France
Centre Hospitalier Universitaire de Nancy Hopital de Brabois
Vandœuvre-lès-Nancy
Lorraine
54511
France
Institut Universitaire du Cancer de Toulouse Oncopole
Toulouse
Midi-pyrenees
31059
France
Center Hospitalier Universitaire d'Angers
Angers
Pays de la Loire Region
49933
France
Centre Hospitalier Universitaire de Nantes Hotel Dieu
Nantes
Pays de la Loire Region
44093
France
Centre Hospitalier Universitaire de Poitiers
Poitiers
Poitou-charentes
86021
France
Centre Hospitalier Universitaire de Nice Hopital l'Archet
Azienda Sanitaria Locale di Pescara Ospedale Civile Dello Spirito Santo
Pescara
65124
Italy
Sapienza Universita Di Roma
Roma
00161
Italy
AOUI - Ospedale Policlinico "Giambattista Rossi" di Borgo Roma
Verona
37134
Italy
Malopolskie Centrum Medyczne
Krakow
Lesser Poland Voivodeship
30-510
Poland
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
Wroclaw
Lower Silesian Voivodeship
50-367
Poland
Instytut Hematologii i Transfuzjologii
Warsaw
Masovian Voivodeship
02-776
Poland
Uniwersyteckie Centrum Kliniczne
Gdansk
Pomeranian Voivodeship
80-952
Poland
Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
Lodz
Łódź Voivodeship
93-510
Poland
Instituto Portugues de Oncologia de Lisboa Francisco Gentil
Lisbon
1090-023
Portugal
Centro Hospitalar Sao Joao
Porto
4200-319
Portugal
Rostov State Medical University
Rostov-on-Don
Rostov Oblast
344022
Russia
Chelyabinsk Regional Clinical Hospital
Chelyabinsk
454076
Russia
Kemerovo Regional Clinical Hospital
Kemerovo
650066
Russia
GBUZ Moscow Clinical Scientific Center DZM
Moscow
111123
Russia
Russian Academy of Medical Science
Moscow
125167
Russia
FGU Russian Scientific Research Institute of Hematology and Transfusiology
Saint Petersburg
191024
Russia
Almazov Federal North-West Medical Research Centre of Department of Health of Russian Federation
Saint Petersburg
197341
Russia
Samara State Medical University
Samara
443099
Russia
Saratov State Medical University
Saratov
355018
Russia
Singapore General Hospital
Singapore
169856
Singapore
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul
6591
South Korea
Hospital Regional Universitario Carlos Haya
Málaga
Andalusia
29010
Spain
Hospital Universitario de Gran Canaria Doctor Nergrin
Las Palmas de Gran Canaria
LAS Palmas
35010
Spain
Hospital Clinic i Provincial de Barcelona
Barcelona
08036
Spain
Hospital Universitario de La Princesa
Madrid
28006
Spain
Hospital Universitario Ramon Y Cajal
Madrid
28034
Spain
Hospital Clinico Universitario de Valencia
Valencia
46010
Spain
Akademiska Sjukhuset
Uppsala
751 85
Sweden
University Hospital Zurich
Zurich
8091
Switzerland
National Taiwan University Hospital
Taipei
100
Taiwan
Royal Liverpool University Hospital NHS Trust
Liverpool
England
L7 8XP
United Kingdom
King's College Hospital NHS Foundation Trust
London
England
SE5 9RS
United Kingdom
Imperial College Healthcare NHS Trust
London
England
W12 0NN
United Kingdom
Nottingham City Hospital NHS Trust
Nottingham
England
NG5 1PB
United Kingdom
Churchill Hospital
Oxford
England
OX3 7LE
United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow
Scotland
G12 0YN
United Kingdom
Derived
Cortes J, Apperley J, Lomaia E, Moiraghi B, Undurraga Sutton M, Pavlovsky C, Chuah C, Sacha T, Lipton JH, Schiffer CA, McCloskey J, Hochhaus A, Rousselot P, Rosti G, de Lavallade H, Turkina A, Rojas C, Arthur CK, Maness L, Talpaz M, Mauro M, Hall T, Lu V, Srivastava S, Deininger M. Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial. Blood. 2021 Nov 25;138(21):2042-2050. doi: 10.1182/blood.2021012082.
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
FG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
FG003
Close-out Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
FG004
Close-out Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
FG005
Close-out Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
FG00094 subjects
FG00195 subjects
FG00294 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Treated (Safety Population)
Included all participants who received at least one dose of study drug.
FG00094 subjects
FG00194 subjects
FG00294 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG00094 subjects
FG00195 subjects
FG00294 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Type
Comment
Reasons
Participants Never Treated
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Ongoing at the end of Treatment Period
FG00027 subjects
FG00117 subjects
FG00217 subjects
FG0030 subjects
FG004
Adverse Event
FG00020 subjects
FG00119 subjects
FG00217 subjects
FG0030 subjects
FG004
Progressive Disease
FG0009 subjects
FG00110 subjects
FG0027 subjects
FG0030 subjects
FG004
Death
FG0004 subjects
FG0012 subjects
FG0023 subjects
FG0030 subjects
FG004
Lack of Efficacy
FG00016 subjects
FG00122 subjects
FG00228 subjects
FG0030 subjects
FG004
Non-compliance With Study Drug
FG0000 subjects
FG0012 subjects
FG0021 subjects
FG0030 subjects
FG004
Lost to Follow-up
FG0003 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG004
Pregnancy
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Transitioned to post-trial ponatinib access
FG0005 subjects
FG0010 subjects
FG0025 subjects
FG0030 subjects
Physician Decision
FG0002 subjects
FG0019 subjects
FG0028 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0006 subjects
FG0019 subjects
FG0027 subjects
FG0030 subjects
FG004
Reason not Specified
FG0001 subjects
FG0012 subjects
FG0020 subjects
FG0030 subjects
FG004
Close-out Period (11 Months)
Type
Comment
Milestone Data
STARTED
Due to limitation during the electronic data capture for participants, the reason for discontinuation from the study was not available and hence reason for discontinuation from study treatment for the participants has been added to this section.
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00327 subjects
FG00417 subjects
FG00517 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00327 subjects
FG004
Type
Comment
Reasons
Transitioned to post-trial ponatinib access
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Safety Population included all participants who received at least one dose of study drug.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
BG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
BG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00094
BG00194
BG00294
BG003282
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
ParticipantsBG00094
ParticipantsBG00194
ParticipantsBG00294
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00094
ParticipantsBG00194
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00094
ParticipantsBG00194
ParticipantsBG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Race
ParticipantsBG00094
ParticipantsBG00194
ParticipantsBG002
Region of Enrollment
Count of Participants
Participants
Title
Denominators
Categories
Argentina
ParticipantsBG00094
ParticipantsBG00194
ParticipantsBG002
Weight
Mean
Standard Deviation
kg
Title
Denominators
Categories
ParticipantsBG00094
ParticipantsBG00194
ParticipantsBG002
Height
Number analyzed is the number of participants with data available for height at Baseline.
Mean
Standard Deviation
meter
Title
Denominators
Categories
ParticipantsBG00094
ParticipantsBG00191
ParticipantsBG002
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score
ECOG performance status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity). Only categories with data are reported.
Count of Participants
Participants
Title
Denominators
Categories
Score= 0
ParticipantsBG00094
ParticipantsBG001
Randomization Stratum
Randomization stratum is based on Age (years)/History of Hypertension, Diabetes, or Hyperlipidemia. The number in the reported categories denotes age and Yes or No indicates history of hypertension, diabetes or hyperlipidemia was present or absent. '<' indicates less than and '>=' indicates greater than equal to in the reported categories.
Count of Participants
Participants
Title
Denominators
Categories
<60/No
ParticipantsBG00094
ParticipantsBG00194
ParticipantsBG002
Time Since Diagnosis
Number analyzed is the number of participants with data available for analysis.
Mean
Standard Deviation
years
Title
Denominators
Categories
ParticipantsBG00094
ParticipantsBG00192
ParticipantsBG002
Prior Tyrosine Kinase Inhibitor (TKIs)
Count of Participants
Participants
Title
Denominators
Categories
Imatinib
ParticipantsBG00094
ParticipantsBG00194
ParticipantsBG002
Number of Prior Approved TKIs
Count of Participants
Participants
Title
Denominators
Categories
1
ParticipantsBG00094
ParticipantsBG00194
ParticipantsBG002
Mutations at Baseline
Number analyzed is the total number of participants (n=278) with data available for analysis, excluding 4 participants who did not have mutation test result at baseline (2 in Cohort A, 1 in Cohort B, 1 in Cohort C).
Count of Participants
Participants
No
Title
Denominators
Categories
No mutation detected
ParticipantsBG00092
ParticipantsBG00193
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Percentage of Participants With Molecular Response (MR2: <=1% Breakpoint Cluster Region-Abelson Transcript Level) as Measured by the International Scale (BCR-ABL1IS) at Month 12
MR2 was defined as a ratio of reverse transcribed transcript of BCR-ABL to ABL <=1% Breakpoint Cluster Region-Abelson Transcript Level as measured by the International Scale (BCR-ABL1IS), equivalent to a 2-log reduction in transcript.
The Intent-to-treat (ITT) Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (i.e., participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug.
Posted
Number
95% Confidence Interval
percentage of participants
12 months after the first dose of study treatment
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00093
OG00193
OG00291
Title
Denominators
Categories
Title
Measurements
OG00044.1(31.7 to 57.0)
OG00129.0(18.4 to 41.6)
OG00223.1(13.4 to 35.3)
Secondary
Percentage of Participants With Major Molecular Response (MMR/MR3)
MMR/MR3 was defined as a ratio of reverse transcribed transcript of BCR-ABL to ABL ≤0.1% on the international scale (equivalent to a 3-log reduction in transcript).
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured, regardless of whether they received the assigned study drug. Seven participants were randomized but excluded from the ITT population because they had atypical transcripts (transcript type other than b2a2/b3a2) and were not evaluable for BCR-ABL1IS outcome.
Posted
Number
percentage of participants
12, 24 and 60 months after the first dose of study treatment
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Secondary
Percentage of Participants With Major Cytogenetic Response (MCyR)
MCyR was defined as percentage of participants with complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). Cytogenetic response is the percentage of Philadelphia chromosome positive (Ph+) metaphases in bone marrow (BM). Response is further defined as MCyR: CCyR or PCyR, where CCyR: 0% Ph + metaphases; PCyR: >0 to 35% Ph + metaphases.
ITT Cytogenetic Population included all participants who were randomized and had a cytogenetic assessment at Baseline with ≥20 metaphases examined, regardless of whether they received the assigned study drug. Overall number of participants analyzed is the number of participants with data available for analysis.
Posted
Number
95% Confidence Interval
percentage of participants
12 months after the first dose of study treatment
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Secondary
Duration of Major Molecular Response (MMR/MR3)
Duration of MMR/MR3 was defined as the interval between the first assessment at which the criteria for <=0.1% MMR were met until the earliest date at which loss of <=0.1% MMR occurred, or the criteria for progression were met. Progression to accelerated phase (AP) was 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*109 platelets per liter (/L) in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to blast phase (BP) was defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (i.e., participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug. Overall number of participants analyzed is the number of participants with MR3.
Posted
Median
95% Confidence Interval
months
Baseline up to approximately 8.9 years
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Secondary
Percentage of Participants With Adjusted Incidence Rates for Treatment Emergent Arterial Occlusive Events (AOEs), Venous Thrombotic Events (VTEs), Adverse Events (AEs), and Serious AEs (SAEs)
Percentage of participants with adjusted incidence rates who developed AOEs and VTEs were categorized according to arterial occlusive events and venous thrombotic events. AE is any untoward medical occurrence in participant administered medicinal investigational drug. Untoward medical occurrence does not necessarily have to have causal relationship with treatment. SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is congenital anomaly/birth defect/is medically important event that may not be immediately life-threatening/result in death or hospitalization, but may jeopardize participant/may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.
Safety Population included all participants who received at least 1 dose of study drug.
Posted
Number
percentage of participants
From first dose up to 30 days after last dose of the study drug (up to approximately 9.8 years)
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Secondary
Percentage of Participants With Complete Cytogenetic Response (CCyR)
Cytogenetic response was defined as the percentage of Ph+ metaphases in bone marrow (peripheral blood may not be used), with a review of a minimum of 20 metaphases. CCyR was defined as 0% Ph+ metaphases.
ITT Cytogenetic Population included all participants who were randomized and had a cytogenetic assessment at Baseline with ≥20 metaphases examined, regardless of whether they received the assigned study drug. Overall number of participants analyzed is the number of participants with data available for analysis.
Posted
Number
percentage of participants
Month 12
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Secondary
Percentage of Participants With Molecular Response 4 (MR4) and Molecular Response 4.5 (MR4.5)
MR4 was defined as <=0.01% BCR-ABL1IS. MR 4.5was defined as <=0.0032% BCR-ALB1IS. MR4 and MR4.5 by each time point means the best outcome up to each time point after randomization.
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (i.e., participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug.
Posted
Number
95% Confidence Interval
percentage of participants
Up to approximately 9.5 years
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Secondary
Percentage of Participants With Molecular Response 1 (MR1)
MR1 was defined as percentage of participants achieving a ratio of <=10% Breakpoint Cluster Region-Abelson (BCR-ABL1) transcripts on the international scale. MR1 is molecular response with 1-log reduction in transcript.
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (i.e., participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug.
Posted
Number
percentage of participants
3 months after the first dose of study treatment
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Secondary
Percentage of Participants With Complete Hematologic Response (CHR)
CHR was defined as achieving all of the following measurements: white blood cells (WBC) <= institutional upper limit of normal (ULN), platelets less than (<)450,000 per cubic millimeter (/mm^3), no blasts or promyelocytes in peripheral blood, <5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood <5%, and no extramedullary involvement (including no hepatomegaly or splenomegaly).
The analysis included all randomized participant who had been on study for at least 3 months, including the following defined as non-CHR: a) Any participant with end of treatment/early termination (EOT/ET) before 3 months, b) Any participant with CHR not evaluable or with no CHR results at 3 months, and c) Failed to achieve/maintain CHR at Month 3.
Posted
Number
95% Confidence Interval
percentage of participants
3 months after the first dose of study treatment
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Secondary
Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption
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 included all participants who received at least 1 dose of study drug.
Posted
Number
percentage of participants
Up to approximately 9.8 years
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Secondary
Kaplan-Meier Estimate of Duration of Response (DOR) of <=1% BCR-ABL1 IS (MR2) at Months 12 and 24
DOR (≤1% BCR-ABL1IS) is defined as interval between first assessment at which criteria for ≤1% BCR-ABL1IS are met until earliest date at which loss of ≤1% BCR-ABL1IS occurs, or criteria for progression accelerated phase (AP) or blast Phase (BP) of chronic myeloid leukemia (CML) are met. Loss of ≤1% BCR-ABL1IS is an increase to >1% of BCR-ABL1IS. Progression to AP: ≥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*109 platelets per liter in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP: ≥30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly. Kaplan-Meier method was used for analysis of percentage of participants who achieved DOR of 12 and 24 months.
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (i.e., participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug. Overall number of participants analyzed is the number of participants with MR2. Number analyzed is the number of participants with data available for analysis at the specified time point.
Posted
Number
95% Confidence Interval
percentage of participants
12 and 24 months after the first dose of study treatment
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Secondary
Kaplan-Meier Estimate of Duration of Response (DOR) of Major Molecular Response (MMR/MR3)
Duration of MMR/MR3 is defined as interval between first assessment at which criteria for MMR are met until earliest date at which loss of MMR occurs, or criteria for progression (progression to AP or BP of CML) are met. Participants remaining in MMR will be censored at last date at which criteria for MMR are met. Loss of MMR is an increase to >0.1% of BCR-ABL1IS. Progression to AP: >= 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*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly. Kaplan-Meier method was used for analysis of percentage of participants who achieved DOR of 12 and 24 months.
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (i.e., participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug. Overall number of participants analyzed is the number of participants with MR3. Number analyzed is the number of participants with data available for analysis at the specified time point.
Posted
Number
95% Confidence Interval
percentage of participants
12 and 24 months after the first dose of study treatment
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Secondary
Duration of Response in MR2 Responders
Duration of response in "responders" was defined as any participants who achieved ≤1% BCR-ABL1IS (MR2) at any time during the study. Responders were defined as those participants who met all of the following: were randomized and treated, responded at 12 months after the initiation of study treatment, and underwent baseline polymerase chain reaction (PCR) assessment.
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (i.e., participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug. Overall number of participants analyzed is the number of participants with MR2.
Posted
Median
95% Confidence Interval
months
Baseline up to approximately 8.9 years
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Secondary
Time to Response (MR2)
Time to response was defined as the time interval from the date of the first dose of the study drug until the initial observation of CR or PR for participants with confirmed CR/PR. Response was defined as any participants who achieved ≤1% BCR-ABL1IS (MR2) at any time during the study. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. CR for non-target lesion: Disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis) and normalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the Baseline sum diameters.
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (i.e., participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug. Overall number of participants analyzed is the number of participants with MR2.
Posted
Median
95% Confidence Interval
months
Baseline up to approximately 5 years
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Secondary
Percentage of Participants With Progression to Accelerated Phase (AP)-Chronic Myeloid Leukemia (CML) or Blast Phase (BP)-CML
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*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
All randomized participants were included in the analysis.
Posted
Number
percentage of participants
From first dose date of study treatment up to approximately 8.9 years
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Secondary
Progression-free Survival (PFS)
PFS was defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression were met (progression to the AP or BP of CML), or death due to any cause, censored at the last response assessment. Progression to AP was 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*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP was defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
All randomized participants were included in the analysis.
Posted
Median
95% Confidence Interval
months
Up to approximately 8.9 years
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Secondary
Overall Survival (OS)
OS was defined as the interval between the first dose of study treatment and death due to any cause, censored at the last contact date when the participant was alive.
All randomized participants were included in the analysis.
Posted
Median
95% Confidence Interval
months
Up to approximately 8.9 years
ID
Title
Description
OG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Time Frame
From first dose up to 30 days after last dose of the study drug (up to approximately 9.8 years)
Description
All Cause Mortality: All randomized participants were assessed for all-cause mortality. Serious and Non-serious adverse events: Safety Population included all participants who received at least 1 dose of study drug and were assessed for serious and non-serious adverse events.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Treatment Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
19
94
38
94
93
94
EG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
16
95
33
94
90
94
EG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
14
94
39
94
90
94
EG003
Close-out Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
0
27
1
27
19
27
EG004
Close-out Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
0
17
3
17
16
17
EG005
Close-out Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
0
17
0
17
13
17
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal pain
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG0030 affected27 at risk
EG0040 affected17 at risk
EG0050 affected17 at risk
Abdominal pain upper
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Acute coronary syndrome
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0012 affected94 at risk
EG0020 affected94 at risk
EG003
Acute hepatic failure
Hepatobiliary disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0021 affected94 at risk
EG003
Acute myocardial infarction
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Adenocarcinoma gastric
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Adenocarcinoma of colon
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Age-related macular degeneration
Eye disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Alcoholic pancreatitis
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA 28.0
Systematic Assessment
EG0003 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Angina pectoris
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Angina unstable
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Appendicitis
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Arterial thrombosis
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0013 affected94 at risk
EG0021 affected94 at risk
EG003
Atrial flutter
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Blast crisis in myelogenous leukaemia
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Bone marrow failure
Blood and lymphatic system disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
COVID-19
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Cardiac arrest
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Cardio-respiratory arrest
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0022 affected94 at risk
EG003
Cerebral haematoma
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Cerebral infarction
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0021 affected94 at risk
EG003
Cerebral ischaemia
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Cerebral vascular occlusion
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Coeliac artery stenosis
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Diabetic foot infection
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0012 affected94 at risk
EG0020 affected94 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Erythema multiforme
Skin and subcutaneous tissue disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Facial nerve disorder
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Fatigue
General disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0011 affected94 at risk
EG0022 affected94 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
General physical health deterioration
General disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Haematemesis
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Headache
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Hepatic function abnormal
Hepatobiliary disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Hepatobiliary disease
Hepatobiliary disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Hepatotoxicity
Hepatobiliary disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Hypertension
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Hypertensive crisis
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Infection
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Influenza
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Influenza like illness
General disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Intermenstrual bleeding
Reproductive system and breast disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Ischaemic stroke
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0012 affected94 at risk
EG0022 affected94 at risk
EG003
Lipase increased
Investigations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Loss of consciousness
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Malignant melanoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Meningitis
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Mesenteric vascular insufficiency
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Middle cerebral artery stroke
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Myocardial ischaemia
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0011 affected94 at risk
EG0023 affected94 at risk
EG003
Neutropenic sepsis
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Obstructive pancreatitis
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Pancreatitis acute
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Pancytopenia
Blood and lymphatic system disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0021 affected94 at risk
EG003
Papilloedema
Eye disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Pericarditis
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Platelet count decreased
Investigations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0023 affected94 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Pyrexia
General disorders
MedDRA 28.0
Systematic Assessment
EG0004 affected94 at risk
EG0011 affected94 at risk
EG0021 affected94 at risk
EG003
Rash erythematous
Skin and subcutaneous tissue disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Rash pruritic
Skin and subcutaneous tissue disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Renal artery stenosis
Renal and urinary disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Renal colic
Renal and urinary disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Retinal vein thrombosis
Eye disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Seizure
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Sepsis
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0012 affected94 at risk
EG0020 affected94 at risk
EG003
Small intestinal haemorrhage
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Splenomegaly
Blood and lymphatic system disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Subclavian artery stenosis
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Subdural haematoma
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Sudden death
General disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 28.0
Systematic Assessment
EG0005 affected94 at risk
EG0012 affected94 at risk
EG0025 affected94 at risk
EG003
Thrombotic stroke
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Thyroiditis
Endocrine disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Tibia fracture
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Tooth abscess
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Tooth infection
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Tumour lysis syndrome
Metabolism and nutrition disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Uterine polyp
Reproductive system and breast disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Ventricular tachycardia
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Vertebrobasilar stroke
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal pain
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG00011 affected94 at risk
EG00111 affected94 at risk
EG00210 affected94 at risk
EG0030 affected27 at risk
EG0040 affected17 at risk
EG0050 affected17 at risk
Abdominal pain upper
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0008 affected94 at risk
EG00111 affected94 at risk
EG0023 affected94 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 28.0
Systematic Assessment
EG00025 affected94 at risk
EG0019 affected94 at risk
EG00221 affected94 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA 28.0
Systematic Assessment
EG0003 affected94 at risk
EG0015 affected94 at risk
EG0025 affected94 at risk
EG003
Amylase increased
Investigations
MedDRA 28.0
Systematic Assessment
EG0005 affected94 at risk
EG0015 affected94 at risk
EG0022 affected94 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA 28.0
Systematic Assessment
EG00022 affected94 at risk
EG00119 affected94 at risk
EG00217 affected94 at risk
EG003
Aortic arteriosclerosis
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Aortic dilatation
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Aortic valve stenosis
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Arteriosclerosis
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0021 affected94 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 28.0
Systematic Assessment
EG00012 affected94 at risk
EG00123 affected94 at risk
EG00215 affected94 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 28.0
Systematic Assessment
EG00016 affected94 at risk
EG0016 affected94 at risk
EG00214 affected94 at risk
EG003
Asthenia
General disorders
MedDRA 28.0
Systematic Assessment
EG0006 affected94 at risk
EG0018 affected94 at risk
EG0023 affected94 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 28.0
Systematic Assessment
EG0008 affected94 at risk
EG00115 affected94 at risk
EG0027 affected94 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA 28.0
Systematic Assessment
EG0006 affected94 at risk
EG0015 affected94 at risk
EG0028 affected94 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0013 affected94 at risk
EG0023 affected94 at risk
EG003
Blood cholesterol increased
Investigations
MedDRA 28.0
Systematic Assessment
EG0006 affected94 at risk
EG0014 affected94 at risk
EG0026 affected94 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0016 affected94 at risk
EG0021 affected94 at risk
EG003
Blood triglycerides increased
Investigations
MedDRA 28.0
Systematic Assessment
EG0006 affected94 at risk
EG0011 affected94 at risk
EG0022 affected94 at risk
EG003
Blood uric acid increased
Investigations
MedDRA 28.0
Systematic Assessment
EG0003 affected94 at risk
EG0011 affected94 at risk
EG0021 affected94 at risk
EG003
Brachiocephalic arteriosclerosis
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Bronchitis viral
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Bundle branch block right
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
C-reactive protein increased
Investigations
MedDRA 28.0
Systematic Assessment
EG0004 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
COVID-19
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0009 affected94 at risk
EG0019 affected94 at risk
EG0024 affected94 at risk
EG003
Carotid arteriosclerosis
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Carotid artery stenosis
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0012 affected94 at risk
EG0023 affected94 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG00013 affected94 at risk
EG00111 affected94 at risk
EG00214 affected94 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 28.0
Systematic Assessment
EG0007 affected94 at risk
EG0012 affected94 at risk
EG0023 affected94 at risk
EG003
Cystitis noninfective
Renal and urinary disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Defect conduction intraventricular
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Depression
Psychiatric disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Dermatitis
Skin and subcutaneous tissue disorders
MedDRA 28.0
Systematic Assessment
EG0006 affected94 at risk
EG0014 affected94 at risk
EG0021 affected94 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0005 affected94 at risk
EG0014 affected94 at risk
EG0029 affected94 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0006 affected94 at risk
EG0018 affected94 at risk
EG0022 affected94 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA 28.0
Systematic Assessment
EG00011 affected94 at risk
EG0017 affected94 at risk
EG0024 affected94 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0017 affected94 at risk
EG0025 affected94 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 28.0
Systematic Assessment
EG0005 affected94 at risk
EG0014 affected94 at risk
EG0023 affected94 at risk
EG003
Early repolarisation syndrome
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Endometriosis
Reproductive system and breast disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Essential hypertension
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Fatigue
General disorders
MedDRA 28.0
Systematic Assessment
EG00010 affected94 at risk
EG0017 affected94 at risk
EG0025 affected94 at risk
EG003
Folliculitis
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0005 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0012 affected94 at risk
EG0021 affected94 at risk
EG003
Glaucoma
Eye disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Glycosylated haemoglobin increased
Investigations
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0012 affected94 at risk
EG0023 affected94 at risk
EG003
Headache
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG00019 affected94 at risk
EG00121 affected94 at risk
EG00220 affected94 at risk
EG003
Hepatitis toxic
Hepatobiliary disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0012 affected94 at risk
EG0020 affected94 at risk
EG003
Hypercholesterolaemia
Metabolism and nutrition disorders
MedDRA 28.0
Systematic Assessment
EG0005 affected94 at risk
EG0015 affected94 at risk
EG0028 affected94 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 28.0
Systematic Assessment
EG0006 affected94 at risk
EG00111 affected94 at risk
EG0029 affected94 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0012 affected94 at risk
EG0025 affected94 at risk
EG003
Hyperlipidaemia
Metabolism and nutrition disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Hypertension
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG00031 affected94 at risk
EG00138 affected94 at risk
EG00227 affected94 at risk
EG003
Hypertriglyceridaemia
Metabolism and nutrition disorders
MedDRA 28.0
Systematic Assessment
EG00015 affected94 at risk
EG00110 affected94 at risk
EG0029 affected94 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 28.0
Systematic Assessment
EG0004 affected94 at risk
EG0011 affected94 at risk
EG0026 affected94 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 28.0
Systematic Assessment
EG0003 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Inguinal hernia
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 28.0
Systematic Assessment
EG0005 affected94 at risk
EG0015 affected94 at risk
EG0023 affected94 at risk
EG003
Intermittent claudication
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Keratopathy
Eye disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Left atrial dilatation
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0012 affected94 at risk
EG0021 affected94 at risk
EG003
Left ventricular dysfunction
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0003 affected94 at risk
EG0011 affected94 at risk
EG0021 affected94 at risk
EG003
Left ventricular hypertrophy
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0003 affected94 at risk
EG0013 affected94 at risk
EG0020 affected94 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA 28.0
Systematic Assessment
EG0004 affected94 at risk
EG0016 affected94 at risk
EG0027 affected94 at risk
EG003
Lipase increased
Investigations
MedDRA 28.0
Systematic Assessment
EG00024 affected94 at risk
EG00119 affected94 at risk
EG00214 affected94 at risk
EG003
Madarosis
Skin and subcutaneous tissue disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Mitral valve incompetence
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0015 affected94 at risk
EG0020 affected94 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 28.0
Systematic Assessment
EG0003 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 28.0
Systematic Assessment
EG0008 affected94 at risk
EG0018 affected94 at risk
EG00212 affected94 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0004 affected94 at risk
EG0016 affected94 at risk
EG0023 affected94 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0008 affected94 at risk
EG0019 affected94 at risk
EG0028 affected94 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 28.0
Systematic Assessment
EG00029 affected94 at risk
EG00123 affected94 at risk
EG00224 affected94 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0015 affected94 at risk
EG0022 affected94 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 28.0
Systematic Assessment
EG0008 affected94 at risk
EG0019 affected94 at risk
EG0028 affected94 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0013 affected94 at risk
EG0020 affected94 at risk
EG003
Peripheral arterial occlusive disease
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Peripheral artery stenosis
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Peripheral vascular disorder
Vascular disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Platelet count decreased
Investigations
MedDRA 28.0
Systematic Assessment
EG00011 affected94 at risk
EG0019 affected94 at risk
EG00211 affected94 at risk
EG003
Pulmonary valve incompetence
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0003 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Pyrexia
General disorders
MedDRA 28.0
Systematic Assessment
EG00017 affected94 at risk
EG0017 affected94 at risk
EG00210 affected94 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 28.0
Systematic Assessment
EG00013 affected94 at risk
EG0019 affected94 at risk
EG0023 affected94 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA 28.0
Systematic Assessment
EG0006 affected94 at risk
EG0017 affected94 at risk
EG0024 affected94 at risk
EG003
Rash papular
Skin and subcutaneous tissue disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0015 affected94 at risk
EG0021 affected94 at risk
EG003
Renal artery stenosis
Renal and urinary disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0020 affected94 at risk
EG003
Respiratory tract infection viral
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0005 affected94 at risk
EG0013 affected94 at risk
EG0025 affected94 at risk
EG003
Skin mass
Skin and subcutaneous tissue disorders
MedDRA 28.0
Systematic Assessment
EG0000 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 28.0
Systematic Assessment
EG00040 affected94 at risk
EG00136 affected94 at risk
EG00236 affected94 at risk
EG003
Transaminases increased
Investigations
MedDRA 28.0
Systematic Assessment
EG0003 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Tremor
Nervous system disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0011 affected94 at risk
EG0020 affected94 at risk
EG003
Tricuspid valve incompetence
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0012 affected94 at risk
EG0020 affected94 at risk
EG003
Type 2 diabetes mellitus
Metabolism and nutrition disorders
MedDRA 28.0
Systematic Assessment
EG0001 affected94 at risk
EG0010 affected94 at risk
EG0021 affected94 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0007 affected94 at risk
EG0014 affected94 at risk
EG0026 affected94 at risk
EG003
Ventricular extrasystoles
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0012 affected94 at risk
EG0021 affected94 at risk
EG003
Vision blurred
Eye disorders
MedDRA 28.0
Systematic Assessment
EG0002 affected94 at risk
EG0015 affected94 at risk
EG0021 affected94 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0004 affected94 at risk
EG0018 affected94 at risk
EG0025 affected94 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00093
OG00193
OG00291
Title
Denominators
Categories
12 Months
Title
Measurements
OG00017.2
OG00120.4
OG00216.5
24 Months
Title
Measurements
OG00024.7
OG00115.1
OG00219.8
60 Months
Title
Measurements
OG00046.2
OG00129.0
OG00224.2
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00091
OG00190
OG00289
Title
Denominators
Categories
Title
Measurements
OG00048.4(37.7 to 59.1)
OG00130.0(20.8 to 40.6)
OG00243.8(33.3 to 54.7)
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00045
OG00128
OG00224
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)Median and 95% confidence interval (CI) were not available due to censoring.
OG001NA(27.3 to NA)Median and upper limit of 95% CI were not available due to censoring.
OG002NA(NA to NA)Median and 95% CI were not available due to censoring.
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
OG003
Close-out Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG004
Close-out Period: Cohort B: Ponatinib 30 mg
Ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG005
Close-out Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00094
OG00194
OG00294
OG00327
OG00417
OG00517
Title
Denominators
Categories
AOEs
Title
Measurements
OG00013.8
OG0019.6
OG0025.3
OG0033.7
OG00411.8
OG0050
VTEs
Title
Measurements
OG0001.1
OG0011.1
OG0021.1
OG003
AEs
Title
Measurements
OG000100.0
OG00197.9
OG00297.9
OG003
SAEs
Title
Measurements
OG00040.4
OG00135.1
OG00241.5
OG003
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00091
OG00190
OG00289
Title
Denominators
Categories
Title
Measurements
OG00034.1
OG00118.9
OG00229.2
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00093
OG00193
OG00291
Title
Denominators
Categories
MR4: 3 Months
Title
Measurements
OG0001.1(0.0 to 5.8)
OG0011.1(0.0 to 5.8)
OG0020(0.0 to 4.0)
MR4: 6 Months
Title
Measurements
OG0003.2(0.7 to 9.1)
OG0012.2(0.3 to 7.6)
OG0023.3(0.7 to 9.3)
MR4: 9 Months
Title
Measurements
OG0005.4(1.8 to 12.1)
OG0018.6(3.8 to 16.2)
OG0025.5(1.8 to 12.4)
MR4: 12 Months
Title
Measurements
OG0006.5(2.4 to 13.5)
OG0019.7(4.5 to 17.6)
OG0027.7(3.1 to 15.2)
MR4: 15 Months
Title
Measurements
OG0006.5(2.4 to 13.5)
OG0019.7(4.5 to 17.6)
OG0028.8(3.9 to 16.6)
MR4: 18 Months
Title
Measurements
OG0007.5(3.1 to 14.9)
OG0019.7(4.5 to 17.6)
OG00212.1(6.2 to 20.6)
MR4: 21 Months
Title
Measurements
OG0007.5(3.1 to 14.9)
OG00111.8(6.1 to 20.2)
OG00212.1(6.2 to 20.6)
MR4: 24 Months
Title
Measurements
OG00010.8(5.3 to 18.9)
OG00112.9(6.8 to 21.5)
OG00212.1(6.2 to 20.6)
MR4: 27 Months
Title
Measurements
OG00011.8(6.1 to 20.2)
OG00115.1(8.5 to 24.0)
OG00213.2(7.0 to 21.9)
MR4: 30 Months
Title
Measurements
OG00012.9(6.8 to 21.5)
OG00115.1(8.5 to 24.0)
OG00213.2(7.0 to 21.9)
MR4: 33 Months
Title
Measurements
OG00016.1(9.3 to 25.2)
OG00115.1(8.5 to 24.0)
OG00213.2(7.0 to 21.9)
MR4: 36 Months
Title
Measurements
OG00018.3(11.0 to 27.6)
OG00115.1(8.5 to 24.0)
OG00214.3(7.8 to 23.2)
MR4: 39 Months
Title
Measurements
OG00019.4(11.9 to 28.9)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4: 42 Months
Title
Measurements
OG00019.4(11.9 to 28.9)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4: 45 Months
Title
Measurements
OG00019.4(11.9 to 28.9)
OG00116.1(9.3 to 25.2)
OG00218.7(11.3 to 28.2)
MR4: 48 Months
Title
Measurements
OG00020.4(12.8 to 30.1)
OG00116.1(9.3 to 25.2)
OG00218.7(11.3 to 28.2)
MR4: 51 Months
Title
Measurements
OG00021.5(13.7 to 31.2)
OG00117.2(10.2 to 26.4)
OG00218.7(11.3 to 28.2)
MR4: 54 Months
Title
Measurements
OG00021.5(13.7 to 31.2)
OG00117.2(10.2 to 26.4)
OG00218.7(11.3 to 28.2)
MR4: 57 Months
Title
Measurements
OG00021.5(13.7 to 31.2)
OG00118.3(11.0 to 27.6)
OG00218.7(11.3 to 28.2)
MR4: 60 Months
Title
Measurements
OG00023.7(15.5 to 33.6)
OG00118.3(11.0 to 27.6)
OG00218.7(11.3 to 28.2)
MR4: 63 Months
Title
Measurements
OG00023.7(15.5 to 33.6)
OG00118.3(11.0 to 27.6)
OG00218.7(11.3 to 28.2)
MR4: 66 Months
Title
Measurements
OG00024.7(16.4 to 34.8)
OG00119.4(11.9 to 28.9)
OG00218.7(11.3 to 28.2)
MR4: 69 Months
Title
Measurements
OG00024.7(16.4 to 34.8)
OG00119.4(11.9 to 28.9)
OG00218.7(11.3 to 28.2)
MR4: 72 Months
Title
Measurements
OG00024.7(16.4 to 34.8)
OG00119.4(11.9 to 28.9)
OG00218.7(11.3 to 28.2)
MR4: 75 Months
Title
Measurements
OG00024.7(16.4 to 34.8)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 78 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 81 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 84 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 87 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 90 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 93 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 96 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 99 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 102 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 105 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 108 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 111 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4: 114 Months
Title
Measurements
OG00025.8(17.3 to 35.9)
OG00119.4(11.9 to 28.9)
OG00219.8(12.2 to 29.4)
MR4.5: 3 Months
Title
Measurements
OG0001.1(0.0 to 5.8)
OG0010(0.0 to 3.9)
OG0020(0.0 to 4.0)
MR4.5: 6 Months
Title
Measurements
OG0001.1(0.0 to 5.8)
OG0011.1(0.0 to 5.8)
OG0020(0.0 to 4.0)
MR4.5: 9 Months
Title
Measurements
OG0002.2(0.3 to 7.6)
OG0013.2(0.7 to 9.1)
OG0022.2(0.3 to 7.7)
MR4.5: 12 Months
Title
Measurements
OG0004.3(1.2 to 10.6)
OG0016.5(2.4 to 13.5)
OG0022.2(0.3 to 7.7)
MR4.5: 15 Months
Title
Measurements
OG0004.3(1.2 to 10.6)
OG0017.5(3.1 to 14.9)
OG0023.3(0.7 to 9.3)
MR4.5: 18 Months
Title
Measurements
OG0005.4(1.8 to 12.1)
OG0017.5(3.1 to 14.9)
OG0024.4(1.2 to 10.9)
MR4.5: 21 Months
Title
Measurements
OG0005.4(1.8 to 12.1)
OG0017.5(3.1 to 14.9)
OG0026.6(2.5 to 13.8)
MR4.5: 24 Months
Title
Measurements
OG0005.4(1.8 to 12.1)
OG0018.6(3.8 to 16.2)
OG0028.8(3.9 to 16.6)
MR4.5: 27 Months
Title
Measurements
OG0005.4(1.8 to 12.1)
OG0018.6(3.8 to 16.2)
OG0028.8(3.9 to 16.6)
MR4.5: 30 Months
Title
Measurements
OG0006.5(2.4 to 13.5)
OG0018.6(3.8 to 16.2)
OG0029.9(4.6 to 17.9)
MR4.5: 33 Months
Title
Measurements
OG0006.5(2.4 to 13.5)
OG0018.6(3.8 to 16.2)
OG0029.9(4.6 to 17.9)
MR4.5: 36 Months
Title
Measurements
OG00011.8(6.1 to 20.2)
OG0019.7(4.5 to 17.6)
OG00211.0(5.4 to 19.3)
MR4.5: 39 Months
Title
Measurements
OG00011.8(6.1 to 20.2)
OG0019.7(4.5 to 17.6)
OG00212.1(6.2 to 20.6)
MR4.5: 42 Months
Title
Measurements
OG00011.8(6.1 to 20.2)
OG00110.8(5.3 to 18.9)
OG00213.2(7.0 to 21.9)
MR4.5: 45 Months
Title
Measurements
OG00011.8(6.1 to 20.2)
OG00110.8(5.3 to 18.9)
OG00215.4(8.7 to 24.5)
MR4.5: 48 Months
Title
Measurements
OG00011.8(6.1 to 20.2)
OG00110.8(5.3 to 18.9)
OG00215.4(8.7 to 24.5)
MR4.5: 51 Months
Title
Measurements
OG00011.8(6.1 to 20.2)
OG00112.9(6.8 to 21.5)
OG00215.4(8.7 to 24.5)
MR4.5: 54 Months
Title
Measurements
OG00012.9(6.8 to 21.5)
OG00112.9(6.8 to 21.5)
OG00215.4(8.7 to 24.5)
MR4.5: 57 Months
Title
Measurements
OG00012.9(6.8 to 21.5)
OG00114.0(7.7 to 22.7)
OG00215.4(8.7 to 24.5)
MR4.5: 60 Months
Title
Measurements
OG00012.9(6.8 to 21.5)
OG00114.0(7.7 to 22.7)
OG00215.4(8.7 to 24.5)
MR4.5: 63 Months
Title
Measurements
OG00012.9(6.8 to 21.5)
OG00115.1(8.5 to 24.0)
OG00215.4(8.7 to 24.5)
MR4.5: 66 Months
Title
Measurements
OG00012.9(6.8 to 21.5)
OG00115.1(8.5 to 24.0)
OG00215.4(8.7 to 24.5)
MR4.5: 69 Months
Title
Measurements
OG00012.9(6.8 to 21.5)
OG00115.1(8.5 to 24.0)
OG00216.5(9.5 to 25.7)
MR4.5: 72 Months
Title
Measurements
OG00014.0(7.7 to 22.7)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 75 Months
Title
Measurements
OG00014.0(7.7 to 22.7)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 78 Months
Title
Measurements
OG00014.0(7.7 to 22.7)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 81 Months
Title
Measurements
OG00014.0(7.7 to 22.7)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 84 Months
Title
Measurements
OG00015.1(8.5 to 24.0)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 87 Months
Title
Measurements
OG00015.1(8.5 to 24.0)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 90 Months
Title
Measurements
OG00015.1(8.5 to 24.0)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 93 Months
Title
Measurements
OG00015.1(8.5 to 24.0)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 96 Months
Title
Measurements
OG00015.1(8.5 to 24.0)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 99 Months
Title
Measurements
OG00015.1(8.5 to 24.0)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 102 Months
Title
Measurements
OG00015.1(8.5 to 24.0)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 105 Months
Title
Measurements
OG00015.1(8.5 to 24.0)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 108 Months
Title
Measurements
OG00015.1(8.5 to 24.0)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 111 Months
Title
Measurements
OG00015.1(8.5 to 24.0)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
MR4.5: 114 Months
Title
Measurements
OG00015.1(8.5 to 24.0)
OG00115.1(8.5 to 24.0)
OG00217.6(10.4 to 27.0)
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00093
OG00193
OG00291
Title
Denominators
Categories
Title
Measurements
OG00052.7
OG00144.1
OG00242.9
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00094
OG00195
OG00294
Title
Denominators
Categories
Title
Measurements
OG00087.2(78.8 to 93.2)
OG00181.1(71.7 to 88.4)
OG00281.9(72.6 to 89.1)
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
OG003
Close-out Period: Cohort A: Ponatinib 45 mg
Participants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG004
Close-out Period: Cohort B: Ponatinib 30 mg
Ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG005
Close-out Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00094
OG00194
OG00294
OG00327
OG00417
OG00517
Title
Denominators
Categories
TEAEs Leading to Treatment Discontinuation
Title
Measurements
OG00024.5
OG00119.1
OG00220.2
OG0033.7
OG0040
OG0050
TEAEs Leading to Dose Reduction
Title
Measurements
OG00051.1
OG00139.4
OG00234.0
OG003
TEAEs Leading to Dose Interruption
Title
Measurements
OG00080.9
OG00168.1
OG00266.0
OG003
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00056
OG00138
OG00236
Title
Denominators
Categories
Month 12
ParticipantsOG00052
ParticipantsOG00135
ParticipantsOG00233
Title
Measurements
OG00079.13(64.5 to 88.3)
OG00179.20(61.2 to 89.5)
OG00290.10(72.4 to 96.7)
Month 24
ParticipantsOG00056
ParticipantsOG00138
ParticipantsOG00236
Title
Measurements
OG000
OG001
Treatment Period: Cohort B: Ponatinib 30 mg
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00045
OG00128
OG00224
Title
Denominators
Categories
Month 12
ParticipantsOG00032
ParticipantsOG00124
ParticipantsOG00221
Title
Measurements
OG00088.97(69.5 to 96.3)
OG00193.33(61.3 to 99.0)
OG00294.74(68.1 to 99.2)
Month 24
ParticipantsOG00045
ParticipantsOG00128
ParticipantsOG00224
Title
Measurements
OG000
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00056
OG00138
OG00236
Title
Denominators
Categories
Title
Measurements
OG000NA(61.5 to NA)Median and upper limit of 95% CI were not available due to censoring.
OG001NA(NA to NA)Median and 95% CI were not available due to censoring.
OG002NA(NA to NA)Median and 95% CI were not available due to censoring.
Participants received ponatinib 30 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00056
OG00138
OG00236
Title
Denominators
Categories
Title
Measurements
OG0006.00(5.8 to 6.1)
OG0013.11(3.0 to 6.0)
OG0026.18(3.1 to 14.5)
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00094
OG00195
OG00294
Title
Denominators
Categories
Progressed to AP-CML
Title
Measurements
OG00011.7
OG00111.6
OG00213.8
Progressed to BP-CML
Title
Measurements
OG0003.2
OG0011.1
OG0022.1
OG002
Treatment Period: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily in each 28-day cycle.
Units
Counts
Participants
OG00094
OG00195
OG00294
Title
Denominators
Categories
Title
Measurements
OG000NA(63.5 to NA)Median and upper limit of 95% CI were not available due to censoring.
OG00175.04(45.0 to NA)Upper limit of 95% CI was not available due to censoring.
OG002NA(45.8 to NA)Median and upper limit of 95% CI were not available due to censoring.
Units
Counts
Participants
OG00094
OG00195
OG00294
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)Median and 95% CI were not available due to censoring.
OG001NA(NA to NA)Median and 95% CI were not available due to censoring.
OG002NA(NA to NA)Median and 95% CI were not available due to censoring.