Amendment 1: The protocol was amended to allow for additional safety monitoring, provide necessary clarifications and ensure alignment with the core protocol CQTI571A2301. To implement additional safety monitoring, three additional visits were added to the protocol changing the 6- month interval visits to 3-month intervals.

Amendment 2: The protocol was amended to clarify the exclusion criterion for male and female contraception requirements and to specify an end date for the study.

Amendment 3: The protocol was amended to unblind patients and site staff to the QTI571 dose strength and allow for patients to administer open-label study medication. This planned amendment followed the database lock and unblinding of the treatment assignments in the core protocol CQTI571A2301. Prior to this amendment, extension study medication was supplied in a blinded fashion to patients to prevent knowledge of the QTI571 dose level. This was done in order to maintain the blinding of the core protocol CQTI571A2301. Following this database lock, it is no longer necessary to have patients administer placebo study medication and maintain blinding in the extension study. In addition, the requirements for restarting study drug after a drop in platelets was amended. At the request of the French Health Authority, a specific country requirement was added, wherein, patients in this country can only resume when platelet count is above 75,000/mm3, even though the baseline count may have been lower. This requirement was implemented globally however has come to be overly restrictive for many patients in other countries whose platelet count was below the restart requirement at baseline. Since this requirement was only specific to France, the protocol will now allow patients in other countries to be restarted on drug when the platelet count has returned to baseline levels if less than 75,000/mm3 at study start.

Amendment 4: The protocol was amended to obtain survival follow-up information on extension patients and core protocol CQTI571A2301 patients who did not enroll in the extension study. This information is being collected for additional safety monitoring of all patients involved in the core and extension trials. Survival follow-up information will be collected every six months after the patients’ last study visit for up to 3 years up until the time of study database lock for this extension protocol.

Amendment 5: The protocol was amended to clarify the process for the collection of survival follow-up information from subjects in the United States only, as per local regulations. This information is being collected for additional safety monitoring of all patients involved in the core and extension trials. Survival follow-up information will be collected every six months after the patients’ last study visit for up to 3 years up until the time of study database lock for this extension protocol. Local regulations in the United States also permit obtaining publically available survival information without patient consent. Survival information will be collected from public databases, in the United States only, for subjects whose consent can not be obtained.

Amendment 6: The protocol was amended to update language regarding the packaging of the study drug by removing the specifics of open-label study drug provided in 140-tablet bottles. This change will allow for alternative packaging to be used in this study. In addition text was deleted if not pertinent to a section, referred to in previous sections or not relevant to provide in the protocol.

Amendment 7: The protocol was amended to extend the study duration by one additional year, thereby changing the overall study duration to four years for the approximate 74 ongoing patients out of 144 patients enrolled. This extension in study duration will consist of two additional visits of 6-month frequency with reduced assessments. A physical exam, echocardiogram, and dipstick urine test will not be required as part of the new study visits. Additionally, NTproBNP lab assessment, six-minute walk test and Borg Scale will be performed at one of the 2 new study visits only. Following 3 years of study treatment with imatinib, patients are considered stable and echocardiography will not be required except for the final study visit. The echocardiogram should be performed as clinically indicated as part of standard of care. The assessment schedule and other relevant protocol sections have been updated accordingly. Extending the study by one additional year will allow patients to continue to participate in this extension study and avoid treatment interruption. The protocol stated co-medications that are inhibitors, inducers or substrates of CYP3A4 and CYP2D6 should be used with caution. A statement was added in this amendment to also avoid grapefruit juice and other foods that inhibit CYP3A4 while taking imatinib as these foods may increase the plasma concentration of imatinib.

Amendment 8: The protocol was amended to revise the information on concomitant use of imatinib and oral vitamin K antagonists in PAH patients. This is based on updated information on the risk of bleeding events, especially subdural hematoma, and the need for these events to receive careful evaluation in PAH patients – as the risk of subdural hematoma is increased in patients taking imatinib and oral vitamin K antagonists concomitantly.