Trial Outcomes & Findings for French Observational Xagrid (FOX) Study In Adult Patients With Essential Thrombocythemia (NCT NCT01192347)

NCT ID: NCT01192347

Last Updated: 2021-06-14

Results Overview

Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when Anagrelide Hydrochloride treatment was initiated, using the following variables: •Withdrawal of previous cytoreductive therapy: -Before: if a stop date of previous cytoreductive therapy was prior to the date of Anagrelide Hydrochloride initiation -After: if a stop date of previous cytoreductive therapy was between the first administration and the last administration of Anagrelide Hydrochloride during the follow-up -Not Withdrawn: in all other cases

• Recruitment status: COMPLETED
• Target enrollment: 177 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2021-06-14

Participant Flow

177 subjects were enrolled, but 2 never received Anagrelide Hydrochloride (Xagrid) and were excluded from the trial (n = 175).

Participant milestones

Measure	Anagrelide Hydrochloride The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Overall Study STARTED	175
Overall Study COMPLETED	163
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Measure	Anagrelide Hydrochloride The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Overall Study Death	3
Overall Study Lost to Follow-up	3
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	1
Overall Study Suspected serious adverse drug reaction	1
Overall Study Patient seen in different hospital	1
Overall Study Patient not visiting hospital regularly	1
Overall Study Patient did not show up for visits	1

Baseline Characteristics

French Observational Xagrid (FOX) Study In Adult Patients With Essential Thrombocythemia

Baseline characteristics by cohort

Measure	Anagrelide Hydrochloride n=175 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Age, Continuous	67.0 years STANDARD_DEVIATION 15.4 • n=93 Participants
Age, Customized <=60 years	42 Participants n=93 Participants
Age, Customized >60 years	133 Participants n=93 Participants
Sex: Female, Male Female	108 Participants n=93 Participants
Sex: Female, Male Male	67 Participants n=93 Participants
Region of Enrollment France	175 Participants n=93 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Full Analysis Set (FAS) comprised all enrolled patients for whom Anagrelide Hydrochloride therapy was initiated. Subjects who had not taken any previous cytoreductive therapy other than Anagrelide Hydrochloride were excluded from the FAS.

Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when Anagrelide Hydrochloride treatment was initiated, using the following variables: •Withdrawal of previous cytoreductive therapy: -Before: if a stop date of previous cytoreductive therapy was prior to the date of Anagrelide Hydrochloride initiation -After: if a stop date of previous cytoreductive therapy was between the first administration and the last administration of Anagrelide Hydrochloride during the follow-up -Not Withdrawn: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=115 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Percentage of Subjects With Continuation of Anagrelide Hydrochloride at 6 Months: Withdrawal of Previous Cytoreductive Therapy Before Anagrelide Hydrochloride Initiation	81.7 percentage of subjects Interval 73.5 to 88.3

PRIMARY outcome

Timeframe: 6 months

Population: Full Analysis Set (FAS) comprised all enrolled patients for whom Anagrelide Hydrochloride therapy was initiated. Subjects who had not taken any previous cytoreductive therapy other than Anagrelide Hydrochloride were excluded from the FAS.

Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when Anagrelide Hydrochloride treatment was initiated, using the following variables: •Withdrawal of previous cytoreductive therapy: -Before: if a stop date of previous cytoreductive therapy was prior to the date of Anagrelide Hydrochloride initiation -After: if a stop date of previous cytoreductive therapy was between the first administration and the last administration of Anagrelide Hydrochloride during the follow-up -Not Withdrawn: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=39 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Percentage of Subjects With Continuation of Anagrelide Hydrochloride at 6 Months: Withdrawal of Previous Cytoreductive Therapy After Anagrelide Hydrochloride Initiation	94.9 percentage of subjects Interval 82.7 to 99.4

PRIMARY outcome

Timeframe: 6 months

Population: Full Analysis Set (FAS) comprised all enrolled patients for whom Anagrelide Hydrochloride therapy was initiated. Subjects who had not taken any previous cytoreductive therapy other than Anagrelide Hydrochloride were excluded from the FAS.

Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when Anagrelide Hydrochloride treatment was initiated, using the following variables: •Withdrawal of previous cytoreductive therapy: -Before: if a stop date of previous cytoreductive therapy was prior to the date of Anagrelide Hydrochloride initiation -After: if a stop date of previous cytoreductive therapy was between the first administration and the last administration of Anagrelide Hydrochloride during the follow-up -Not Withdrawn: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=16 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Percentage of Subjects With Continuation of Anagrelide Hydrochloride at 6 Months: No Withdrawal of Previous Cytoreductive Therapy	81.3 percentage of subjects Interval 54.4 to 96.0

PRIMARY outcome

Timeframe: 6 months

Population: Full Analysis Set (FAS) comprised all enrolled patients for whom Anagrelide Hydrochloride therapy was initiated. Subjects who had not taken any previous cytoreductive therapy other than Anagrelide Hydrochloride were excluded from the FAS.

Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when XAGRID treatment was initiated, using the following variables: •Initiation of XAGRID dosing consistent with the Summary of Product Characteristics (SmPC): •Consistent if: -The starting dose was <=1 mg/day, AND -Any increase in dose was no more than 0.5mg/day, AND -Any increase in dose was made at least 7 days after first initiation or at least 7 days after any previous modification (up or down), AND -The maximum dose did not exceed 10 mg/day at any stage. •Inconsistent: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=133 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Percentage of Subjects With Continuation of Anagrelide Hydrochloride at 6 Months: When the Dosing Was Consistent With the Summary of Product Characteristics (SmPC)	83.5 percentage of subjects Interval 76.0 to 89.3

PRIMARY outcome

Timeframe: 6 months

Population: Full Analysis Set (FAS) comprised all enrolled patients for whom Anagrelide Hydrochloride therapy was initiated. Subjects who had not taken any previous cytoreductive therapy other than Anagrelide Hydrochloride were excluded from the FAS.

Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when XAGRID treatment was initiated, using the following variables: •Initiation of XAGRID dosing consistent with the Summary of Product Characteristics (SmPC): •Consistent if: -The starting dose was <=1 mg/day, AND -Any increase in dose was no more than 0.5mg/day, AND -Any increase in dose was made at least 7 days after first initiation or at least 7 days after any previous modification (up or down), AND -The maximum dose did not exceed 10 mg/day at any stage. •Inconsistent: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=37 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Percentage of Subjects With Continuation of Anagrelide Hydrochloride at 6 Months: When the Dosing Was Inconsistent With the Summary of Product Characteristics (SmPC)	89.2 percentage of subjects Interval 74.6 to 97.0

PRIMARY outcome

Timeframe: 6 months

Population: Full Analysis Set (FAS) comprised all enrolled patients for whom Anagrelide Hydrochloride therapy was initiated. Subjects who had not taken any previous cytoreductive therapy other than Anagrelide Hydrochloride were excluded from the FAS.

Full response is a platelet count of <400x10^9/L. Partial response is a platelet count between 400-600x10^9/L or a platelet count reduction of 200x10^9. Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when Anagrelide Hydrochloride treatment was initiated, using the following variables: •Withdrawal of previous cytoreductive therapy: -Before: if a stop date of previous cytoreductive therapy was prior to the date of Anagrelide Hydrochloride initiation -After: if a stop date of previous cytoreductive therapy was between the first administration and the last administration of Anagrelide Hydrochloride during the follow-up -Not Withdrawn: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=115 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Percentage of Subjects Achieving Platelet Target Response: Withdrawal of Previous Cytoreductive Therapy Before Anagrelide Hydrochloride Initiation Full response	41.7 percentage of subjects Interval 32.6 to 51.3
Percentage of Subjects Achieving Platelet Target Response: Withdrawal of Previous Cytoreductive Therapy Before Anagrelide Hydrochloride Initiation Partial response	25.2 percentage of subjects Interval 17.6 to 34.2

PRIMARY outcome

Timeframe: 6 months

Population: Full Analysis Set (FAS) comprised all enrolled patients for whom Anagrelide Hydrochloride therapy was initiated. Subjects who had not taken any previous cytoreductive therapy other than Anagrelide Hydrochloride were excluded from the FAS.

Full response is a platelet count of <400x10^9/L. Partial response is a platelet count between 400-600x10^9/L or a platelet count reduction of 200x10^9. Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when Anagrelide Hydrochloride treatment was initiated, using the following variables: •Withdrawal of previous cytoreductive therapy: -Before: if a stop date of previous cytoreductive therapy was prior to the date of Anagrelide Hydrochloride initiation -After: if a stop date of previous cytoreductive therapy was between the first administration and the last administration of Anagrelide Hydrochloride during the follow-up -Not Withdrawn: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=39 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Percentage of Subjects Achieving Platelet Target Response: Withdrawal of Previous Cytoreductive Therapy After Anagrelide Hydrochloride Initiation Full response	48.7 percentage of subjects Interval 32.4 to 65.2
Percentage of Subjects Achieving Platelet Target Response: Withdrawal of Previous Cytoreductive Therapy After Anagrelide Hydrochloride Initiation Partial response	38.5 percentage of subjects Interval 23.4 to 55.4

PRIMARY outcome

Timeframe: 6 months

Population: Full Analysis Set (FAS) comprised all enrolled patients for whom Anagrelide Hydrochloride therapy was initiated. Subjects who had not taken any previous cytoreductive therapy other than Anagrelide Hydrochloride were excluded from the FAS.

Full response is a platelet count of <400x10^9/L. Partial response is a platelet count between 400-600x10^9/L or a platelet count reduction of 200x10^9. Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when Anagrelide Hydrochloride treatment was initiated, using the following variables: •Withdrawal of previous cytoreductive therapy: -Before: if a stop date of previous cytoreductive therapy was prior to the date of Anagrelide Hydrochloride initiation -After: if a stop date of previous cytoreductive therapy was between the first administration and the last administration of Anagrelide Hydrochloride during the follow-up -Not Withdrawn: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=16 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Percentage of Subjects Achieving Platelet Target Response: No Withdrawal of Previous Cytoreductive Therapy Full response	25.0 percentage of subjects Interval 7.3 to 52.4
Percentage of Subjects Achieving Platelet Target Response: No Withdrawal of Previous Cytoreductive Therapy Partial response	31.3 percentage of subjects Interval 11.0 to 58.7

PRIMARY outcome

Timeframe: 6 months

Population: Full Analysis Set (FAS) comprised all enrolled patients for whom Anagrelide Hydrochloride therapy was initiated. Subjects who had not taken any previous cytoreductive therapy other than Anagrelide Hydrochloride were excluded from the FAS.

Full response is a platelet count of <400x10^9/L. Partial response is a platelet count between 400-600x10^9/L or a platelet count reduction of 200x10^9. Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when XAGRID treatment was initiated, using the following variables: •Initiation of XAGRID dosing consistent with the Summary of Product Characteristics (SmPC): •Consistent if: -The starting dose was <=1 mg/day, AND -Any increase in dose was no more than 0.5mg/day, AND -Any increase in dose was made at least 7 days after first initiation or at least 7 days after any previous modification (up or down), AND -The maximum dose did not exceed 10 mg/day at any stage. •Inconsistent: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=133 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Percentage of Subjects Achieving Platelet Target Response: When the Dosing Was Consistent With the Summary of Product Characteristics (SmPC) Full response	44.4 percentage of subjects Interval 35.8 to 53.2
Percentage of Subjects Achieving Platelet Target Response: When the Dosing Was Consistent With the Summary of Product Characteristics (SmPC) Partial response	30.8 percentage of subjects Interval 23.1 to 39.4

PRIMARY outcome

Timeframe: 6 months

Population: Full Analysis Set (FAS) comprised all enrolled patients for whom Anagrelide Hydrochloride therapy was initiated. Subjects who had not taken any previous cytoreductive therapy other than Anagrelide Hydrochloride were excluded from the FAS.

Full response is a platelet count of <400x10^9/L. Partial response is a platelet count between 400-600x10^9/L or a platelet count reduction of 200x10^9. Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when XAGRID treatment was initiated, using the following variables: •Initiation of XAGRID dosing consistent with the Summary of Product Characteristics (SmPC): •Consistent if: -The starting dose was <=1 mg/day, AND -Any increase in dose was no more than 0.5mg/day, AND -Any increase in dose was made at least 7 days after first initiation or at least 7 days after any previous modification (up or down), AND -The maximum dose did not exceed 10 mg/day at any stage. •Inconsistent: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=37 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Percentage of Subjects Achieving Platelet Target Response: When the Dosing Was Inconsistent With the Summary of Product Characteristics (SmPC) Full response	32.4 percentage of subjects Interval 18.0 to 49.8
Percentage of Subjects Achieving Platelet Target Response: When the Dosing Was Inconsistent With the Summary of Product Characteristics (SmPC) Partial response	21.6 percentage of subjects Interval 9.8 to 38.2

SECONDARY outcome

Timeframe: 6 months

Population: Safety Set comprised all subjects who had taken at least 1 dose of Anagrelide Hydrochloride and had at least 1 post-baseline safety assessment documented.

Outcome measures

Measure	Anagrelide Hydrochloride n=175 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Percentage of Subjects With Anagrelide Hydrochloride Starting Doses 0.3 mg/day	0.6 percentage of subjects
Percentage of Subjects With Anagrelide Hydrochloride Starting Doses 0.5 mg/day	41.1 percentage of subjects
Percentage of Subjects With Anagrelide Hydrochloride Starting Doses 1.0 mg/day	52.6 percentage of subjects
Percentage of Subjects With Anagrelide Hydrochloride Starting Doses 1.3 mg/day	0.6 percentage of subjects
Percentage of Subjects With Anagrelide Hydrochloride Starting Doses 1.5 mg/day	5.1 percentage of subjects

SECONDARY outcome

Timeframe: 6 months

Population: Safety Set comprised all subjects who had taken at least 1 dose of Anagrelide Hydrochloride and had at least 1 post-baseline safety assessment documented.

Outcome measures

Measure	Anagrelide Hydrochloride n=175 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Number of Subjects With Anagrelide Hydrochloride Titration Modifcations- First Modification Only -0.5 mg/day	7 participants
Number of Subjects With Anagrelide Hydrochloride Titration Modifcations- First Modification Only -0.2 mg/day	2 participants
Number of Subjects With Anagrelide Hydrochloride Titration Modifcations- First Modification Only -1.0 mg/day	1 participants
Number of Subjects With Anagrelide Hydrochloride Titration Modifcations- First Modification Only No change	26 participants
Number of Subjects With Anagrelide Hydrochloride Titration Modifcations- First Modification Only +0.2 mg/day	1 participants
Number of Subjects With Anagrelide Hydrochloride Titration Modifcations- First Modification Only +0.5 mg/day	109 participants
Number of Subjects With Anagrelide Hydrochloride Titration Modifcations- First Modification Only +1.0 mg/day	12 participants
Number of Subjects With Anagrelide Hydrochloride Titration Modifcations- First Modification Only +1.2 mg/day	1 participants
Number of Subjects With Anagrelide Hydrochloride Titration Modifcations- First Modification Only Dose interruption	9 participants
Number of Subjects With Anagrelide Hydrochloride Titration Modifcations- First Modification Only Discontinued therapy	7 participants

SECONDARY outcome

Timeframe: 6 months

Population: Safety Set comprised all subjects who had taken at least 1 dose of Anagrelide Hydrochloride and had at least 1 post-baseline safety assessment documented.

Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when Anagrelide Hydrochloride treatment was initiated, using the following variables: •Withdrawal of previous cytoreductive therapy: -Before: if a stop date of previous cytoreductive therapy was prior to the date of Anagrelide Hydrochloride initiation -After: if a stop date of previous cytoreductive therapy was between the first administration and the last administration of Anagrelide Hydrochloride during the follow-up -Not Withdrawn: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=115 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Summary of Adverse Drug Reactions (ADR): Withdrawal of Previous Cytoreductive Therapy Before Anagrelide Hydrochloride Initiation ADR	44.3 percentage of subjects
Summary of Adverse Drug Reactions (ADR): Withdrawal of Previous Cytoreductive Therapy Before Anagrelide Hydrochloride Initiation Serious ADR	5.2 percentage of subjects
Summary of Adverse Drug Reactions (ADR): Withdrawal of Previous Cytoreductive Therapy Before Anagrelide Hydrochloride Initiation ADR leading to stopping Xagrid	16.5 percentage of subjects

SECONDARY outcome

Timeframe: 6 months

Population: Safety Set comprised all subjects who had taken at least 1 dose of Anagrelide Hydrochloride and had at least 1 post-baseline safety assessment documented.

Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when Anagrelide Hydrochloride treatment was initiated, using the following variables: •Withdrawal of previous cytoreductive therapy: -Before: if a stop date of previous cytoreductive therapy was prior to the date of Anagrelide Hydrochloride initiation -After: if a stop date of previous cytoreductive therapy was between the first administration and the last administration of Anagrelide Hydrochloride during the follow-up -Not Withdrawn: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=39 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Summary of Adverse Drug Reactions: Withdrawal of Previous Cytoreductive Therapy After Anagrelide Hydrochloride Initiation ADR	51.3 percentage of subjects
Summary of Adverse Drug Reactions: Withdrawal of Previous Cytoreductive Therapy After Anagrelide Hydrochloride Initiation Serious ADR	2.6 percentage of subjects
Summary of Adverse Drug Reactions: Withdrawal of Previous Cytoreductive Therapy After Anagrelide Hydrochloride Initiation ADR leading to stopping Xagrid	15.4 percentage of subjects

SECONDARY outcome

Timeframe: 6 months

Population: Safety Set comprised all subjects who had taken at least 1 dose of Anagrelide Hydrochloride and had at least 1 post-baseline safety assessment documented.

Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when Anagrelide Hydrochloride treatment was initiated, using the following variables: •Withdrawal of previous cytoreductive therapy: -Before: if a stop date of previous cytoreductive therapy was prior to the date of Anagrelide Hydrochloride initiation -After: if a stop date of previous cytoreductive therapy was between the first administration and the last administration of Anagrelide Hydrochloride during the follow-up -Not Withdrawn: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=16 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Summary of Adverse Drug Reactions: No Withdrawal of Previous Cytoreductive Therapy ADR	37.5 percentage of subjects
Summary of Adverse Drug Reactions: No Withdrawal of Previous Cytoreductive Therapy Serious ADR	6.3 percentage of subjects
Summary of Adverse Drug Reactions: No Withdrawal of Previous Cytoreductive Therapy ADR leading to stopping Xagrid	12.5 percentage of subjects

SECONDARY outcome

Timeframe: 6 months

Population: Safety Set comprised all subjects who had taken at least 1 dose of Anagrelide Hydrochloride and had at least 1 post-baseline safety assessment documented.

Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when XAGRID treatment was initiated, using the following variables: •Initiation of XAGRID dosing consistent with the Summary of Product Characteristics (SmPC): •Consistent if: -The starting dose was <=1 mg/day, AND -Any increase in dose was no more than 0.5mg/day, AND -Any increase in dose was made at least 7 days after first initiation or at least 7 days after any previous modification (up or down), AND -The maximum dose did not exceed 10 mg/day at any stage. •Inconsistent: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=133 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Summary of Adverse Drug Reactions: When the Dosing Was Consistent With the Summary of Product Characteristics (SmPC) ADR	39.1 percentage of subjects
Summary of Adverse Drug Reactions: When the Dosing Was Consistent With the Summary of Product Characteristics (SmPC) Serious ADR	4.5 percentage of subjects
Summary of Adverse Drug Reactions: When the Dosing Was Consistent With the Summary of Product Characteristics (SmPC) ADR leading to stopping Xagrid	18.8 percentage of subjects

SECONDARY outcome

Timeframe: 6 months

Population: Safety Set comprised all subjects who had taken at least 1 dose of Anagrelide Hydrochloride and had at least 1 post-baseline safety assessment documented.

Patients who had taken a previous cytoreductive therapy were divided into subgroups based on the treatment regimens used when XAGRID treatment was initiated, using the following variables: •Initiation of XAGRID dosing consistent with the Summary of Product Characteristics (SmPC): •Consistent if: -The starting dose was <=1 mg/day, AND -Any increase in dose was no more than 0.5mg/day, AND -Any increase in dose was made at least 7 days after first initiation or at least 7 days after any previous modification (up or down), AND -The maximum dose did not exceed 10 mg/day at any stage. •Inconsistent: in all other cases

Outcome measures

Measure	Anagrelide Hydrochloride n=37 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Summary of Adverse Drug Reactions: When the Dosing Was Inconsistent With the Summary of Product Characteristics (SmPC) ADR	67.6 percentage of subjects
Summary of Adverse Drug Reactions: When the Dosing Was Inconsistent With the Summary of Product Characteristics (SmPC) Serious ADR	5.4 percentage of subjects
Summary of Adverse Drug Reactions: When the Dosing Was Inconsistent With the Summary of Product Characteristics (SmPC) ADR leading to stopping Xagrid	5.4 percentage of subjects

SECONDARY outcome

Timeframe: 6 months

Population: Safety Set comprised all subjects who had taken at least 1 dose of Anagrelide Hydrochloride and had at least 1 post-baseline safety assessment documented.

Outcome measures

Measure	Anagrelide Hydrochloride n=175 Participants The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Maximum Daily Dose of Anagrelide Hydrochloride	1.5 mg/day Standard Deviation 0.6

Adverse Events

Anagrelide Hydrochloride

Serious events: 8 serious events

Other events: 81 other events

Deaths: 0 deaths

Serious adverse events

Measure	Anagrelide Hydrochloride n=175 participants at risk The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Blood and lymphatic system disorders Anemia	0.57% 1/175 • Number of events 1
Cardiac disorders Angina pectoris	0.57% 1/175 • Number of events 1
Cardiac disorders Cardiac failure	0.57% 1/175 • Number of events 1
Cardiac disorders Palpitations	0.57% 1/175 • Number of events 1
Nervous system disorders Cerebrovascular accident	0.57% 1/175 • Number of events 2
Nervous system disorders Headache	0.57% 1/175 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	0.57% 1/175 • Number of events 1
Vascular disorders Hypertensive crisis	1.1% 2/175 • Number of events 2

Other adverse events

Measure	Anagrelide Hydrochloride n=175 participants at risk The decision to initiate Anagrelide Hydrochloride and the dose prescribed was made by treating physician.
Blood and lymphatic system disorders Anemia	2.3% 4/175 • Number of events 5
Cardiac disorders Edema peripheral	2.3% 4/175 • Number of events 4
Cardiac disorders Palpitations	12.6% 22/175 • Number of events 24
Cardiac disorders Tachycardia	2.9% 5/175 • Number of events 5
Ear and labyrinth disorders Tinnitis	2.3% 4/175 • Number of events 5
Gastrointestinal disorders Abdominal pain	2.9% 5/175 • Number of events 5
Gastrointestinal disorders Diarrhea	5.7% 10/175 • Number of events 10
Gastrointestinal disorders Nausea	2.9% 5/175 • Number of events 5
General disorders Asthenia	5.7% 10/175 • Number of events 10
Nervous system disorders Headache	10.3% 18/175 • Number of events 20

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
• Publication restrictions are in place

Restriction type: OTHER