Trial Outcomes & Findings for Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC) (NCT NCT01650805)

Last Updated: 2014-11-17

Results Overview

A ratio of reverse transcribed transcript of BCR-ABL to ABL ≤ 0.1% on the international scale, measured by real-time quantitative polymerase chain reaction.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

307 participants

Primary outcome timeframe

12 months after first dose

Results posted on

2014-11-17

Participant Flow

A total of 307 subjects were enrolled (ponatinib patients: 155; imatinib patients: 152). Patients were randomized in a 1:1 fashion to receive either ponatinib or imatinib.

Participant milestones

Participant milestones
Measure	Ponatinib ponatinib: 45 mg tablet, taken orally once daily	Imatinib imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Overall Study STARTED	155	152
Overall Study COMPLETED	154	152
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ponatinib ponatinib: 45 mg tablet, taken orally once daily	Imatinib imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ponatinib n=155 Participants ponatinib: 45 mg tablet, taken orally once daily	Imatinib n=152 Participants imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily	Total n=307 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	119 Participants n=93 Participants	116 Participants n=4 Participants	235 Participants n=27 Participants
Age, Categorical >=65 years	36 Participants n=93 Participants	36 Participants n=4 Participants	72 Participants n=27 Participants
Age, Continuous	51.9 years STANDARD_DEVIATION 15.66 • n=93 Participants	51.2 years STANDARD_DEVIATION 15.19 • n=4 Participants	51.5 years STANDARD_DEVIATION 15.41 • n=27 Participants
Sex: Female, Male Female	58 Participants n=93 Participants	60 Participants n=4 Participants	118 Participants n=27 Participants
Sex: Female, Male Male	97 Participants n=93 Participants	92 Participants n=4 Participants	189 Participants n=27 Participants
Region of Enrollment Portugal	0 participants n=93 Participants	2 participants n=4 Participants	2 participants n=27 Participants
Region of Enrollment United States	48 participants n=93 Participants	34 participants n=4 Participants	82 participants n=27 Participants
Region of Enrollment Hong Kong	4 participants n=93 Participants	1 participants n=4 Participants	5 participants n=27 Participants
Region of Enrollment Taiwan	3 participants n=93 Participants	2 participants n=4 Participants	5 participants n=27 Participants
Region of Enrollment Finland	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Region of Enrollment Spain	16 participants n=93 Participants	9 participants n=4 Participants	25 participants n=27 Participants
Region of Enrollment Italy	15 participants n=93 Participants	14 participants n=4 Participants	29 participants n=27 Participants
Region of Enrollment United Kingdom	6 participants n=93 Participants	12 participants n=4 Participants	18 participants n=27 Participants
Region of Enrollment France	14 participants n=93 Participants	21 participants n=4 Participants	35 participants n=27 Participants
Region of Enrollment Czech Republic	1 participants n=93 Participants	3 participants n=4 Participants	4 participants n=27 Participants
Region of Enrollment Canada	16 participants n=93 Participants	13 participants n=4 Participants	29 participants n=27 Participants
Region of Enrollment Poland	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants
Region of Enrollment Belgium	3 participants n=93 Participants	2 participants n=4 Participants	5 participants n=27 Participants
Region of Enrollment Singapore	1 participants n=93 Participants	11 participants n=4 Participants	12 participants n=27 Participants
Region of Enrollment Australia	1 participants n=93 Participants	6 participants n=4 Participants	7 participants n=27 Participants
Region of Enrollment Netherlands	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants
Region of Enrollment Germany	11 participants n=93 Participants	12 participants n=4 Participants	23 participants n=27 Participants
Region of Enrollment New Zealand	4 participants n=93 Participants	4 participants n=4 Participants	8 participants n=27 Participants
Region of Enrollment Sweden	6 participants n=93 Participants	2 participants n=4 Participants	8 participants n=27 Participants
Region of Enrollment Korea, Republic of	3 participants n=93 Participants	2 participants n=4 Participants	5 participants n=27 Participants
Region of Enrollment Switzerland	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants

PRIMARY outcome

Timeframe: 12 months after first dose

Population: Patients with 12 month assessment (due to early termination of the study, none of the endpoints could be evaluated as planned).

A ratio of reverse transcribed transcript of BCR-ABL to ABL ≤ 0.1% on the international scale, measured by real-time quantitative polymerase chain reaction.

Outcome measures

Outcome measures
Measure	Ponatinib n=10 Participants ponatinib: 45 mg tablet, taken orally once daily	Imatinib n=13 Participants imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Major Molecular Response (MMR) Rate at 12 Months	8 participants	5 participants

SECONDARY outcome

Timeframe: 5 years after first dose

To compare the efficacy of ponatinib with imatinib, as measured by MMR rate, at 5 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 months after first dose

Population: Patients with 3 month assessment

To compare the proportion of patients achieving a ratio of \<10% BCR-ABL to ABL transcript levels at 3 months, as measured by the international scale (\<10% BCR-ABL\^IS), in patients administered ponatinib versus those administered imatinib

Outcome measures

Outcome measures
Measure	Ponatinib n=109 Participants ponatinib: 45 mg tablet, taken orally once daily	Imatinib n=114 Participants imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
<10% BCR-ABL^IS Rate	103 participants	77 participants

SECONDARY outcome

Timeframe: 12 months after first dose

Population: Patients with 12 month assessment

The percentage of Ph+ metaphases in bone marrow (peripheral blood may not be used), with a review of a minimum of 20 metaphases. Responses are defined as follows: Complete (CCyR): 0% Ph+ metaphases.

Outcome measures

Outcome measures
Measure	Ponatinib n=5 Participants ponatinib: 45 mg tablet, taken orally once daily	Imatinib n=7 Participants imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Complete Cytogenetic Response (CCyR) Rate	5 participants	6 participants

SECONDARY outcome

Timeframe: Up to 8 years after the last patient's first dose

To compare, according to treatment with ponatinib versus imatinib, progression-free survival

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 8 years after the last patient's first dose

To compare, according to treatment with ponatinib versus imatinib, overall survival

Outcome measures

Outcome data not reported

Adverse Events

Ponatinib 45 mg

Serious events: 49 serious events

Other events: 145 other events

Deaths: 0 deaths

Imatinib 400 mg

Serious events: 13 serious events

Other events: 144 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Maureen Conlan, Senior Medical Director

ARIAD Pharmaceuticals, Inc.

Phone: 1-617-621-2316

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Ponatinib 45 mg n=154 participants at risk ponatinib: 45 mg tablet, taken orally once daily	Imatinib 400 mg n=152 participants at risk imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	1.3% 2/154 • Number of events 2 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Cardiac disorders ANGINA PECTORIS	1.3% 2/154 • Number of events 2 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Cardiac disorders ATRIAL FIBRILLATION	1.9% 3/154 • Number of events 3 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Cardiac disorders CARDIAC ARREST	0.00% 0/154 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.66% 1/152 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Cardiac disorders CARDIAC FAILURE	1.3% 2/154 • Number of events 4 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Cardiac disorders CORONARY ARTERY DISEASE	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Cardiac disorders MYOPERICARDITIS	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Cardiac disorders PERICARDIAL EFFUSION	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Ear and labyrinth disorders VERTIGO POSITIONAL	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.66% 1/152 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Eye disorders EYE PAIN	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Eye disorders PHOTOPHOBIA	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Eye disorders RETINAL VEIN THROMBOSIS	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders ABDOMINAL PAIN	1.3% 2/154 • Number of events 3 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders NAUSEA	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders PANCREATITIS	3.2% 5/154 • Number of events 5 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders SMALL INTESTINAL OBSTRUCTION	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders VOMITING	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
General disorders NON-CARDIAC CHEST PAIN	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
General disorders OEDEMA PERIPHERAL	0.00% 0/154 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.66% 1/152 • Number of events 2 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
General disorders PYREXIA	1.3% 2/154 • Number of events 2 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.66% 1/152 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
General disorders SYSTEMIC INFLAMMATORY RESPONSE SYNDROME	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Hepatobiliary disorders CHOLECYSTITIS	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Hepatobiliary disorders HEPATITIS	0.00% 0/154 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.66% 1/152 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations BACTERIAL PYELONEPHRITIS	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations CERVICITIS	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations DISSEMINATED TUBERCULOSIS	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations DIVERTICULITIS	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations HEPATITIS B	0.00% 0/154 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.66% 1/152 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations HERPES ZOSTER	0.00% 0/154 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.66% 1/152 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations LUNG INFECTION	0.00% 0/154 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.66% 1/152 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations PARAINFLUENZAE VIRUS INFECTION	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations PARASPINAL ABSCESS	0.00% 0/154 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.66% 1/152 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations PERICOLIC ABSCESS	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations PNEUMONIA	1.3% 2/154 • Number of events 3 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.66% 1/152 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations PYELONEPHRITIS	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations RESPIRATORY TRACT INFECTION	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations SEPSIS	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations VESTIBULAR NEURONITIS	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations VIRAL UPPER RESPIRATORY TRACT INFECTION	0.00% 0/154 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.66% 1/152 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Injury, poisoning and procedural complications COMPRESSION FRACTURE	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.00% 0/152 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.

Other adverse events
Measure	Ponatinib 45 mg n=154 participants at risk ponatinib: 45 mg tablet, taken orally once daily	Imatinib 400 mg n=152 participants at risk imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Blood and lymphatic system disorders ANAEMIA	8.4% 13/154 • Number of events 15 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	7.9% 12/152 • Number of events 14 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Eye disorders DRY EYE	6.5% 10/154 • Number of events 10 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	2.0% 3/152 • Number of events 3 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Eye disorders EYELID OEDEMA	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	8.6% 13/152 • Number of events 13 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Eye disorders PERIORBITAL OEDEMA	0.65% 1/154 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	21.7% 33/152 • Number of events 37 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders ABDOMINAL DISCOMFORT	6.5% 10/154 • Number of events 11 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	3.3% 5/152 • Number of events 5 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders ABDOMINAL PAIN	35.1% 54/154 • Number of events 69 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	9.9% 15/152 • Number of events 15 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders CONSTIPATION	26.6% 41/154 • Number of events 48 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	2.0% 3/152 • Number of events 3 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders DIARRHOEA	13.0% 20/154 • Number of events 28 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	27.0% 41/152 • Number of events 54 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders DRY MOUTH	7.1% 11/154 • Number of events 11 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	3.3% 5/152 • Number of events 5 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders DYSPEPSIA	4.5% 7/154 • Number of events 7 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	5.9% 9/152 • Number of events 10 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders NAUSEA	22.1% 34/154 • Number of events 44 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	34.2% 52/152 • Number of events 58 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Gastrointestinal disorders VOMITING	11.0% 17/154 • Number of events 18 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	18.4% 28/152 • Number of events 30 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
General disorders ASTHENIA	3.9% 6/154 • Number of events 6 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	7.9% 12/152 • Number of events 14 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
General disorders CHILLS	6.5% 10/154 • Number of events 12 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	3.9% 6/152 • Number of events 6 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
General disorders FATIGUE	20.8% 32/154 • Number of events 37 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	19.7% 30/152 • Number of events 35 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
General disorders OEDEMA PERIPHERAL	9.1% 14/154 • Number of events 15 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	14.5% 22/152 • Number of events 24 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
General disorders PAIN	5.8% 9/154 • Number of events 10 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	1.3% 2/152 • Number of events 2 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
General disorders PYREXIA	16.9% 26/154 • Number of events 31 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	3.9% 6/152 • Number of events 8 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	3.2% 5/154 • Number of events 5 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	8.6% 13/152 • Number of events 16 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Investigations ALANINE AMINOTRANSFERASE INCREASED	13.0% 20/154 • Number of events 29 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	1.3% 2/152 • Number of events 3 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Investigations AMYLASE INCREASED	9.1% 14/154 • Number of events 20 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	0.66% 1/152 • Number of events 1 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	11.7% 18/154 • Number of events 24 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	3.9% 6/152 • Number of events 7 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Investigations BLOOD ALKALINE PHOSPHATASE INCREASED	9.1% 14/154 • Number of events 20 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	3.3% 5/152 • Number of events 5 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Investigations LIPASE INCREASED	26.6% 41/154 • Number of events 68 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	7.2% 11/152 • Number of events 13 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Investigations NEUTROPHIL COUNT DECREASED	5.2% 8/154 • Number of events 15 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	11.2% 17/152 • Number of events 34 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Investigations PLATELET COUNT DECREASED	23.4% 36/154 • Number of events 65 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	13.8% 21/152 • Number of events 37 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Investigations WEIGHT DECREASED	5.8% 9/154 • Number of events 11 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	1.3% 2/152 • Number of events 2 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Investigations WHITE BLOOD CELL COUNT DECREASED	3.2% 5/154 • Number of events 5 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	5.9% 9/152 • Number of events 11 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Metabolism and nutrition disorders DECREASED APPETITE	11.7% 18/154 • Number of events 20 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	4.6% 7/152 • Number of events 8 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Metabolism and nutrition disorders HYPERTRIGLYCERIDAEMIA	8.4% 13/154 • Number of events 14 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	4.6% 7/152 • Number of events 8 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Musculoskeletal and connective tissue disorders ARTHRALGIA	18.8% 29/154 • Number of events 33 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	15.1% 23/152 • Number of events 29 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Musculoskeletal and connective tissue disorders BACK PAIN	7.1% 11/154 • Number of events 13 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	3.9% 6/152 • Number of events 7 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Musculoskeletal and connective tissue disorders BONE PAIN	8.4% 13/154 • Number of events 19 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	7.9% 12/152 • Number of events 16 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	7.1% 11/154 • Number of events 12 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	34.2% 52/152 • Number of events 62 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	6.5% 10/154 • Number of events 11 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	2.6% 4/152 • Number of events 4 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Musculoskeletal and connective tissue disorders MYALGIA	26.0% 40/154 • Number of events 44 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	17.8% 27/152 • Number of events 31 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	12.3% 19/154 • Number of events 19 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	7.9% 12/152 • Number of events 15 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Nervous system disorders DIZZINESS	9.7% 15/154 • Number of events 21 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	5.9% 9/152 • Number of events 11 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Nervous system disorders HEADACHE	32.5% 50/154 • Number of events 61 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	13.2% 20/152 • Number of events 27 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Nervous system disorders LETHARGY	1.9% 3/154 • Number of events 3 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.	6.6% 10/152 • Number of events 12 • Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.