A Study of Anagrelide and Hydroxyurea in High-Risk Essential Thrombocythemia Patients
Study Details
Study Description
Brief Summary
Essential thrombocythaemia is a disorder of bone marrow, which causes too many platelets to be produced. Platelets are small cells carried around in the blood, which help form blood clots. When patients have too many platelets, there is a risk of blood clots forming unnecessarily and excessive bleeding. The aim of this study is to gain additional information on the safety profile of Anagrelide (Xagrid(r)) and Hydroxyurea (also known as hydroxycarbamide).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: A
|
Drug: Anagrelide
Anagrelide hydrochloride 0.5mg capsules;initial dose administered will be 1.0mg/day administered as 0.5mg bid. The dose will be titrated such that the total daily dose is incremented by no more than 0.5mg per week as required depending on platelet reduction versus adverse event profile.
|
Active Comparator: B
|
Drug: Hydroxyurea
Hydroxyurea is 500mg hydroxycarbamide capsules; initial dose is 1000mg/day, administered in two divided doses (500mg/dose). Dose titrated to effect to achieve a response.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time [Baseline and Month 1, 2, 3, 6, 9, 12, 18, 24, 30 and 36]
The LVEF was measured by echocardiography and considered a sufficiently sensitive measure to evaluate any changes in cardiac function.
- Platelet Count at Month 6 [Month 6]
Platelet count was evaluated.
Secondary Outcome Measures
- Change From Baseline in Platelet Counts at Month 3 and 36 [Baseline and Month 3 and 36]
Platelet count was evaluated throughout the study.
- Percentage of Participants With Complete Response [Baseline up to Month 36]
A complete response was defined as a platelet count of less than (<) 400x10^9/Liter which was confirmed over 2 consecutive visits at least 28 days apart.
- Percentage of Participants With Partial Response [Baseline up to Month 36]
A partial response is defined as a platelet count of 400-600 x 10^9/Liter and a reduction in platelet count of at least 200 x 10^9/Liter from baseline which was confirmed over 2 consecutive visits at least 28 days apart.
- Time to Complete Response [Baseline up to Month 36]
Time in days from the date of the first dose of study medication to the date of the first visit at which response was classified. If a participant did not achieve response then they were censored at their last visit in the study (Month 36 or withdrawal).
- Time to Partial Response [Baseline up to Month 36]
Time in days from the date of the first dose of study medication to the date of the first visit at which response was classified. If a participant did not achieve response then they were censored at their last visit in the study (Month 36 or withdrawal).
- Number of Participants With Thrombotic and Haemorrhagic Events [From the signing of informed consent until the last study-related visit (Month 36)]
Thrombohaemorrhagic events are a well-known complication of the underlying essential thrombocythemia (ET) and disease progression. Events such as arterial and venous thrombosis, serious haemorrhage (including gastrointestinal haemorrhage), and death from vascular causes have been reported in participants who received cytoreductive treatment.
- Change From Baseline in White Blood Cell Count Over Time [Baseline and Month 6, 12, 18, 24, 30 and 36]
White blood cell count was evaluated throughout the study.
- Change From Baseline in Red Blood Cell Count Over Time [Baseline and Month 6, 12, 18, 24, 30 and 36]
Red blood cell count was evaluated throughout the study.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Confirmed diagnosis of essential thrombocythaemia - high risk profile
-
Previously untreated with a cytoreductive agent
-
Females of childbearing potential must have a negative urine pregnancy test prior to entering the study and must agree to use effective birth control for the duration of the study
Exclusion Criteria:
-
Diagnosis of any other myeloproliferative disorder
-
Any known cause for a secondary thrombocytosis
-
Anti-coagulant and anti-aggregant therapies
-
Known or suspected heart disease
-
Left Ventricular Ejection Fraction < 55%
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University Multiprofile Hospital for Active Treatment ''Dr Georgi Stranski'' - Pleven | Pleven | Bulgaria | 5800 | |
2 | University Multiprofile Hospital for active Treatment ''Alexandrovska'' Clinic of Haematology | Sofia | Bulgaria | 1303 | |
3 | University Multiprofile Hospital for Active Treament ''Sv. Marina'' - Varna Haematology Clinic | Varna | Bulgaria | 9010 | |
4 | CHU Angers Services des Maladies du Sang | Angers | Cedex 09 | France | 49933 |
5 | Hopital Saint Louis - Centre d'Investigation Clinique | Paris | France | ||
6 | University of Debrecen Medical and Health Science Centre | Debrecen | Hungary | 4012 | |
7 | Petz Aladar County Teaching Hospital | Gyor | Hungary | 9024 | |
8 | Pandy Kalman Hospital of Bekes County | Gyula | Hungary | 5700 | |
9 | Kaposi Mor Teaching Hospital | Kaposvar | Hungary | 7400 | |
10 | Uniwersyteckie Centrum Kliniczne Katedra i Klinika Hematologii i Transplantologii | Gdansk | Poland | 80-952 | |
11 | Samodzielny Publiczny Szpital Kliniczny Nr 1 | Lublin | Poland | 21-081 | |
12 | Katedra i Klinika Onkologii i Chorob Wewnetrznych Akademii Medycznej | Warsaw | Poland | 02-097 | |
13 | Klinika Hematologii Instytut Hematologii i Transfuzjologi | Warsaw | Poland | 02-776 | |
14 | Hospitals da Universidade de Coimbra | Coimbra | Portugal | 3000-076 | |
15 | Institute for Haematology of Clinical Centre of Serbia | Belgrade | Serbia | 11000 |
Sponsors and Collaborators
- Shire
Investigators
- Study Director: Study Director, Takeda
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SPD422-403
- 2004-004061-15
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | A total of 183 participants were screened, 149 participants were randomized at 29 sites across 10 countries. Four (4) participants randomized but withdrawn prior to treatment and 1 participant not randomized but treated. |
Arm/Group Title | Anagrelide | Hydroxyurea |
---|---|---|
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. |
Period Title: Overall Study | ||
STARTED | 76 | 70 |
COMPLETED | 41 | 43 |
NOT COMPLETED | 35 | 27 |
Baseline Characteristics
Arm/Group Title | Anagrelide | Hydroxyurea | Total |
---|---|---|---|
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. | Total of all reporting groups |
Overall Participants | 76 | 70 | 146 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
52.1
(16.10)
|
52.9
(15.80)
|
52.5
(15.91)
|
Sex: Female, Male (Count of Participants) | |||
Female |
56
73.7%
|
45
64.3%
|
101
69.2%
|
Male |
20
26.3%
|
25
35.7%
|
45
30.8%
|
Outcome Measures
Title | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time |
---|---|
Description | The LVEF was measured by echocardiography and considered a sufficiently sensitive measure to evaluate any changes in cardiac function. |
Time Frame | Baseline and Month 1, 2, 3, 6, 9, 12, 18, 24, 30 and 36 |
Outcome Measure Data
Analysis Population Description |
---|
The Full Analysis Set (FAS) population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. Here, n = Number of participants analysed for specified category at the specified time points in each arm respectively. |
Arm/Group Title | Anagrelide | Hydroxyurea |
---|---|---|
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. |
Measure Participants | 73 | 68 |
Baseline |
66.4
(4.81)
|
66.9
(4.59)
|
Change from baseline at Month 1 |
0.5
(4.68)
|
-1.1
(4.73)
|
Change from baseline at Month 2 |
1.2
(5.80)
|
0
(5.03)
|
Change from baseline at Month 3 |
0.1
(5.31)
|
-0.4
(3.94)
|
Change from baseline at Month 6 |
-0.5
(5.68)
|
-0.6
(3.95)
|
Change from baseline at Month 9 |
-0.8
(4.78)
|
-1.5
(5.15)
|
Change from baseline at Month 12 |
-0.8
(6.61)
|
-0.6
(5.67)
|
Change from baseline at Month 18 |
-2.0
(5.54)
|
-1.2
(4.84)
|
Change from baseline at Month 24 |
-1.8
(6.81)
|
-1.7
(6.17)
|
Change from baseline at Month 30 |
-1.8
(5.84)
|
-0.2
(5.38)
|
Change from baseline at Month 36 |
-1.7
(6.55)
|
-0.6
(5.46)
|
Title | Platelet Count at Month 6 |
---|---|
Description | Platelet count was evaluated. |
Time Frame | Month 6 |
Outcome Measure Data
Analysis Population Description |
---|
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. Here, N = Number of participants analysed in each arm for this outcome measure. |
Arm/Group Title | Anagrelide | Hydroxyurea |
---|---|---|
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. |
Measure Participants | 60 | 58 |
Mean (Standard Deviation) [10^9 platelets per liter] |
418.6
(135.96)
|
396.0
(144.07)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Anagrelide, Hydroxyurea |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
Comments | Noninferiority of anagrelide could be concluded if lower limit of 95% Confidence Interval for the difference between treatment groups (Hydroxyurea - Anagrelide) was > -100 x 10^9/Liter. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Least Square Mean |
Estimated Value | -100.5 | |
Confidence Interval |
(2-Sided) 95% -179.42 to -21.49 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 39.93 |
|
Estimation Comments |
Title | Change From Baseline in Platelet Counts at Month 3 and 36 |
---|---|
Description | Platelet count was evaluated throughout the study. |
Time Frame | Baseline and Month 3 and 36 |
Outcome Measure Data
Analysis Population Description |
---|
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded with last observation carried forward (LOCF). Here, n=number of participants analysed for specified category at specified time points in each arm respectively. |
Arm/Group Title | Anagrelide | Hydroxyurea |
---|---|---|
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. |
Measure Participants | 73 | 68 |
Change from baseline at Month 3 |
575.3
(36.11)
|
462.2
(37.54)
|
Change from baseline at Month 36 |
531.0
(42.14)
|
462.8
(43.81)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Anagrelide, Hydroxyurea |
---|---|---|
Comments | Month 3 | |
Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
Comments | Noninferiority of anagrelide could be concluded if lower limit of 95% Confidence Interval for the difference between treatment groups (Hydroxyurea - Anagrelide) was > -100 x 10^9/Liter. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Least Square Mean |
Estimated Value | -113.1 | |
Confidence Interval |
(2-Sided) 95% -187.40 to -38.83 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 37.56 |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Anagrelide, Hydroxyurea |
---|---|---|
Comments | Month 36 | |
Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
Comments | Noninferiority of anagrelide could be concluded if lower limit of 95% Confidence Interval for the difference between treatment groups (Hydroxyurea - Anagrelide) was > -100 x 10^9/Liter. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Least Square Mean |
Estimated Value | -68.3 | |
Confidence Interval |
(2-Sided) 95% -154.95 to 18.43 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 43.83 |
|
Estimation Comments |
Title | Percentage of Participants With Complete Response |
---|---|
Description | A complete response was defined as a platelet count of less than (<) 400x10^9/Liter which was confirmed over 2 consecutive visits at least 28 days apart. |
Time Frame | Baseline up to Month 36 |
Outcome Measure Data
Analysis Population Description |
---|
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. |
Arm/Group Title | Anagrelide | Hydroxyurea |
---|---|---|
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. |
Measure Participants | 73 | 68 |
Number [percenatge of participants] |
58.9
77.5%
|
58.8
84%
|
Title | Percentage of Participants With Partial Response |
---|---|
Description | A partial response is defined as a platelet count of 400-600 x 10^9/Liter and a reduction in platelet count of at least 200 x 10^9/Liter from baseline which was confirmed over 2 consecutive visits at least 28 days apart. |
Time Frame | Baseline up to Month 36 |
Outcome Measure Data
Analysis Population Description |
---|
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. |
Arm/Group Title | Anagrelide | Hydroxyurea |
---|---|---|
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. |
Measure Participants | 73 | 68 |
Number [percentage of participants] |
21.9
28.8%
|
27.9
39.9%
|
Title | Time to Complete Response |
---|---|
Description | Time in days from the date of the first dose of study medication to the date of the first visit at which response was classified. If a participant did not achieve response then they were censored at their last visit in the study (Month 36 or withdrawal). |
Time Frame | Baseline up to Month 36 |
Outcome Measure Data
Analysis Population Description |
---|
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. |
Arm/Group Title | Anagrelide | Hydroxyurea |
---|---|---|
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. |
Measure Participants | 73 | 68 |
Median (95% Confidence Interval) [days] |
177.0
|
123.0
|
Title | Time to Partial Response |
---|---|
Description | Time in days from the date of the first dose of study medication to the date of the first visit at which response was classified. If a participant did not achieve response then they were censored at their last visit in the study (Month 36 or withdrawal). |
Time Frame | Baseline up to Month 36 |
Outcome Measure Data
Analysis Population Description |
---|
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. |
Arm/Group Title | Anagrelide | Hydroxyurea |
---|---|---|
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. |
Measure Participants | 73 | 68 |
Median (95% Confidence Interval) [days] |
61.0
|
47.0
|
Title | Number of Participants With Thrombotic and Haemorrhagic Events |
---|---|
Description | Thrombohaemorrhagic events are a well-known complication of the underlying essential thrombocythemia (ET) and disease progression. Events such as arterial and venous thrombosis, serious haemorrhage (including gastrointestinal haemorrhage), and death from vascular causes have been reported in participants who received cytoreductive treatment. |
Time Frame | From the signing of informed consent until the last study-related visit (Month 36) |
Outcome Measure Data
Analysis Population Description |
---|
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. |
Arm/Group Title | Anagrelide | Hydroxyurea |
---|---|---|
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. |
Measure Participants | 73 | 68 |
Number [participants] |
30
39.5%
|
16
22.9%
|
Title | Change From Baseline in White Blood Cell Count Over Time |
---|---|
Description | White blood cell count was evaluated throughout the study. |
Time Frame | Baseline and Month 6, 12, 18, 24, 30 and 36 |
Outcome Measure Data
Analysis Population Description |
---|
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. Here, n = Number of participants analysed for specified category at the specified time points in each arm respectively. |
Arm/Group Title | Anagrelide | Hydroxyurea |
---|---|---|
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. |
Measure Participants | 73 | 68 |
Baseline |
9.13
(2.159)
|
10.20
(3.491)
|
Change from baseline at Month 6 |
-0.38
(4.257)
|
-5.02
(2.525)
|
Change from baseline at Month 12 |
-1.00
(2.001)
|
-4.79
(2.779)
|
Change from baseline at Month 18 |
-1.18
(2.184)
|
-4.46
(2.664)
|
Change from baseline at Month 24 |
-1.24
(2.283)
|
-4.82
(2.692)
|
Change from baseline at Month 30 |
-1.00
(2.316)
|
-4.59
(3.391)
|
Change from baseline at Month 36 |
-1.63
(2.234)
|
-4.46
(3.312)
|
Title | Change From Baseline in Red Blood Cell Count Over Time |
---|---|
Description | Red blood cell count was evaluated throughout the study. |
Time Frame | Baseline and Month 6, 12, 18, 24, 30 and 36 |
Outcome Measure Data
Analysis Population Description |
---|
The FAS population included all randomized participants who received at least 1 dose of study medication and who had a pretreatment and at least 1 post baseline LVEF measurement recorded. Here, n = Number of participants analysed for specified category at the specified time points in each arm respectively. |
Arm/Group Title | Anagrelide | Hydroxyurea |
---|---|---|
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. |
Measure Participants | 73 | 68 |
Baseline |
4.757
(0.5897)
|
4.787
(0.6002)
|
Change from baseline at Month 6 |
-0.227
(0.4134)
|
-1.467
(0.6563)
|
Change from baseline at Month 12 |
-0.246
(0.4292)
|
-1.398
(0.5744)
|
Change from baseline at Month 18 |
-0.225
(0.4224)
|
-1.323
(0.7278)
|
Change from baseline at Month 24 |
-0.299
(0.5811)
|
-1.281
(0.7219)
|
Change from baseline at Month 30 |
-0.295
(0.5713)
|
-1.339
(0.6509)
|
Change from baseline at Month 36 |
-0.366
(0.4328)
|
-1.362
(0.6586)
|
Adverse Events
Time Frame | From the signing of informed consent until the last study-related visit (Month 36) | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Anagrelide | Hydroxyurea | ||
Arm/Group Description | Participants received Anagrelide hydrochloride 1.0 milligram (mg) per day administered orally as 0.5 mg capsule twice daily (bid) for 1 week. Then the dose was titrated such that the total daily dose is incremented by no more than 0.5 mg in any 1 week and the recommended maximum single dose could not exceed 2.5 mg as required depending on platelet reduction versus adverse event profile. Total daily dosage was not exceed 10 mg. Participants followed for up to 3 years. | Participants received Hydroxyurea as 1000 mg per day administered orally as 500 mg capsule twice daily and dose titrated to effect to achieve a response. Participants followed for up to 3 years. | ||
All Cause Mortality |
||||
Anagrelide | Hydroxyurea | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Anagrelide | Hydroxyurea | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 17/76 (22.4%) | 13/70 (18.6%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Iron deficiency anaemia | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Pancytopenia | 0/76 (0%) | 0 | 1/70 (1.4%) | 1 |
Cardiac disorders | ||||
Angina unstable | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Left ventricular failure | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Tachycardia | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Gastrointestinal disorders | ||||
Anal fistula | 0/76 (0%) | 0 | 1/70 (1.4%) | 2 |
Crohn's disease | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Gastrointestinal haemorrhage | 0/76 (0%) | 0 | 1/70 (1.4%) | 1 |
Inguinal hernia | 0/76 (0%) | 0 | 1/70 (1.4%) | 1 |
Upper gastrointestinal haemorrhage | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
General disorders | ||||
Asthenia | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Sudden death | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Infections and infestations | ||||
Ear infection | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Laryngitis | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Sepsis | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Injury, poisoning and procedural complications | ||||
Foot fracture | 0/76 (0%) | 0 | 1/70 (1.4%) | 1 |
Traumatic amputation | 0/76 (0%) | 0 | 1/70 (1.4%) | 1 |
Traumatic haematoma | 1/76 (1.3%) | 2 | 0/70 (0%) | 0 |
Metabolism and nutrition disorders | ||||
Hyperglycaemia | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Type 2 diabetes mellitus | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||
Scleroderma | 0/76 (0%) | 0 | 1/70 (1.4%) | 1 |
Tendon calcification | 0/76 (0%) | 0 | 1/70 (1.4%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Adenoid cystic carcinoma | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Bladder cancer | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Breast cancer | 0/76 (0%) | 0 | 1/70 (1.4%) | 1 |
Malignant melanoma | 0/76 (0%) | 0 | 1/70 (1.4%) | 1 |
Peripheral nerve sheath tumour malignant | 0/76 (0%) | 0 | 1/70 (1.4%) | 1 |
Nervous system disorders | ||||
Aphasia | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Cerebral infarction | 1/76 (1.3%) | 2 | 0/70 (0%) | 0 |
Ischaemic stroke | 3/76 (3.9%) | 3 | 0/70 (0%) | 0 |
Neurological decompensation | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Vasculitis cerebral | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Reproductive system and breast disorders | ||||
Ovarian cyst | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||
Pulmonary embolism | 1/76 (1.3%) | 1 | 1/70 (1.4%) | 1 |
Respiratory distress | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Vascular disorders | ||||
Deep vein thrombosis | 0/76 (0%) | 0 | 1/70 (1.4%) | 1 |
Hypertensive crisis | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Peripheral artery thrombosis | 1/76 (1.3%) | 1 | 0/70 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
Anagrelide | Hydroxyurea | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 46/76 (60.5%) | 27/70 (38.6%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 4/76 (5.3%) | 6 | 8/70 (11.4%) | 9 |
Leukopenia | 1/76 (1.3%) | 1 | 7/70 (10%) | 7 |
Neutropenia | 0/76 (0%) | 0 | 5/70 (7.1%) | 8 |
Cardiac disorders | ||||
Palpitations | 18/76 (23.7%) | 29 | 0/70 (0%) | 0 |
Ear and labyrinth disorders | ||||
Vertigo | 5/76 (6.6%) | 5 | 0/70 (0%) | 0 |
Gastrointestinal disorders | ||||
Diarrhoea | 6/76 (7.9%) | 7 | 3/70 (4.3%) | 3 |
General disorders | ||||
Asthenia | 5/76 (6.6%) | 6 | 4/70 (5.7%) | 6 |
Chest pain | 4/76 (5.3%) | 7 | 1/70 (1.4%) | 1 |
Infections and infestations | ||||
Nasopharyngitis | 2/76 (2.6%) | 2 | 5/70 (7.1%) | 8 |
Pharyngitis | 2/76 (2.6%) | 2 | 6/70 (8.6%) | 8 |
Upper respiratory tract infection | 4/76 (5.3%) | 4 | 1/70 (1.4%) | 1 |
Urinary tract infection | 4/76 (5.3%) | 8 | 2/70 (2.9%) | 2 |
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 6/76 (7.9%) | 7 | 2/70 (2.9%) | 2 |
Nervous system disorders | ||||
Headache | 19/76 (25%) | 33 | 1/70 (1.4%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||
Epistaxis | 4/76 (5.3%) | 5 | 2/70 (2.9%) | 2 |
Vascular disorders | ||||
Hypertension | 9/76 (11.8%) | 12 | 1/70 (1.4%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Shire |
Phone | +1 866 842 5335 |
ClinicalTransparency@shire.com |
- SPD422-403
- 2004-004061-15