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Trial record 7 of 231 for:    "essential thrombocythemia"

The Pharmacokinetics of Anagrelide in Elderly and Young Patients With Essential Thrombocythaemia (ET)

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ClinicalTrials.gov Identifier: NCT00413634
Recruitment Status : Completed
First Posted : December 20, 2006
Results First Posted : June 2, 2009
Last Update Posted : June 12, 2014
Sponsor:
Information provided by:
Shire

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Essential Thrombocythaemia
Intervention Drug: anagrelide hydrochloride
Enrollment 24
Recruitment Details Patients were between 18-50 years (young) and 65 or older (elderly) with a diagnosis of essential thrombocythemia (ET) and receiving a stable dose of anagrelide <=5mg/day for at least 4 weeks.
Pre-assignment Details The study comprised four phases: Screening (patients take their normal regimen of anagrelide), a run-in period (patients divided their normal anagrelide daily dose equally into two daily doses), Pharmacokinetics (PK) sampling day (patients take normal morning dose), and follow-up (patients were contacted by phone 30 days after PK visit).
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description Anagrelide hydrochloride in ages 18-50 years Anagrelide hydrochloride in ages 65 and older
Period Title: Overall Study
Started 12 12
Completed 12 12
Not Completed 0 0
Arm/Group Title Agrylin (Young) Agrylin (Elderly) Total
Hide Arm/Group Description Anagrelide hydrochloride in ages 18-50 years Anagrelide hydrochloride in ages 65 and older Total of all reporting groups
Overall Number of Baseline Participants 12 12 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 24 participants
<=18 years
0
   0.0%
0
   0.0%
0.0
Between 18 and 65 years
12
 100.0%
0
   0.0%
12.0
>=65 years
0
   0.0%
12
 100.0%
12.0
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 12 participants 24 participants
39.2  (8.4) 69.2  (3.0) 54.2  (16.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 24 participants
Female
9
  75.0%
8
  66.7%
17.0
Male
3
  25.0%
4
  33.3%
7.0
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 24 participants
Germany 5 10 15
United Kingdom 2 1 3
Spain 1 1 2
Sweden 2 0 2
Serbia 2 0 2
1.Primary Outcome
Title Maximum Plasma Concentration (Cmax) of Agrylin
Hide Description [Not Specified]
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population (defined as all patients with post-dose drug concentration data)
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Anagrelide hydrochloride in ages 18-50 years
Anagrelide hydrochloride in ages 65 and older
Overall Number of Participants Analyzed 12 12
Geometric Mean (Standard Deviation)
Unit of Measure: ng/ml
2.66  (0.99) 3.63  (1.44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Agrylin (Young), Agrylin (Elderly)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.092
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
2.Primary Outcome
Title Time of Maximum Plasma Concentration (Tmax) of Agrylin
Hide Description [Not Specified]
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Anagrelide hydrochloride in ages 18-50 years
Anagrelide hydrochloride in ages 65 and older
Overall Number of Participants Analyzed 12 12
Geometric Mean (Standard Deviation)
Unit of Measure: hours
1.11  (0.39) 1.14  (0.91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Agrylin (Young), Agrylin (Elderly)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.857
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
3.Primary Outcome
Title Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Agrylin
Hide Description [Not Specified]
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Anagrelide hydrochloride in ages 18-50 years
Anagrelide hydrochloride in ages 65 and older
Overall Number of Participants Analyzed 12 12
Geometric Mean (Standard Deviation)
Unit of Measure: ng.h/ml
6.4  (2.4) 10.3  (4.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Agrylin (Young), Agrylin (Elderly)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
4.Primary Outcome
Title Terminal Half-life (T 1/2) of Agrylin
Hide Description [Not Specified]
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Anagrelide hydrochloride in ages 18-50 years
Anagrelide hydrochloride in ages 65 and older
Overall Number of Participants Analyzed 12 12
Geometric Mean (Standard Deviation)
Unit of Measure: hours
1.3  (0.4) 1.4  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Agrylin (Young), Agrylin (Elderly)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.378
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
5.Primary Outcome
Title Total Clearance (CL/F) of Agrylin
Hide Description [Not Specified]
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Anagrelide hydrochloride in ages 18-50 years
Anagrelide hydrochloride in ages 65 and older
Overall Number of Participants Analyzed 12 12
Geometric Mean (Standard Deviation)
Unit of Measure: L/h
156  (73) 97  (70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Agrylin (Young), Agrylin (Elderly)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
6.Primary Outcome
Title Volume of Distribution (Vz/F) of Agrylin
Hide Description [Not Specified]
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Anagrelide hydrochloride in ages 18-50 years
Anagrelide hydrochloride in ages 65 and older
Overall Number of Participants Analyzed 12 12
Geometric Mean (Standard Deviation)
Unit of Measure: L
286  (125) 195  (137)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Agrylin (Young), Agrylin (Elderly)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
7.Primary Outcome
Title Cmax of Active Metabolite
Hide Description An active metabolite has therapeutic activity similar to the parent compound and must be considered in therapeutic pharmacokinetics.
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Active metabolite of Agrylin (BCH24426) in ages 18-50
Active metabolite of Agrylin (BCH24426) in ages 65 and older
Overall Number of Participants Analyzed 12 12
Geometric Mean (Standard Deviation)
Unit of Measure: ng/ml
7.26  (3.74) 4.19  (3.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Agrylin (Young), Agrylin (Elderly)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
8.Primary Outcome
Title Tmax of Active Metabolite
Hide Description [Not Specified]
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Active metabolite of Agrylin (BCH24426) in ages 18-50
Active metabolite of Agrylin (BCH24426) in ages 65 and older
Overall Number of Participants Analyzed 12 12
Geometric Mean (Standard Deviation)
Unit of Measure: hours
0.92  (0.26) 1.04  (0.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Agrylin (Young), Agrylin (Elderly)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.557
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
9.Primary Outcome
Title AUC of Active Metabolite
Hide Description [Not Specified]
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Active metabolite of Agrylin (BCH24426) in ages 18-50
Active metabolite of Agrylin (BCH24426) in ages 65 and older
Overall Number of Participants Analyzed 12 12
Geometric Mean (Standard Deviation)
Unit of Measure: ng.h/ml
27.6  (10.9) 17.4  (14.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Agrylin (Young), Agrylin (Elderly)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
10.Primary Outcome
Title T 1/2 of Active Metabolite
Hide Description [Not Specified]
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Active metabolite of Agrylin (BCH24426) in ages 18-50
Active metabolite of Agrylin (BCH24426) in ages 65 and older
Overall Number of Participants Analyzed 12 12
Geometric Mean (Standard Deviation)
Unit of Measure: hours
2.7  (0.5) 3.5  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Agrylin (Young), Agrylin (Elderly)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
11.Primary Outcome
Title CL/F of Active Metabolite
Hide Description [Not Specified]
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Active metabolite of Agrylin (BCH24426) in ages 18-50
Active metabolite of Agrylin (BCH24426) in ages 65 and older
Overall Number of Participants Analyzed 12 12
Geometric Mean (Standard Deviation)
Unit of Measure: L/h
36  (16) 57  (27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Agrylin (Young), Agrylin (Elderly)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
12.Primary Outcome
Title Vz/F of Active Metabolite
Hide Description [Not Specified]
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Active metabolite of Agrylin (BCH24426) in ages 18-50
Active metabolite of Agrylin (BCH24426) in ages 65 and older
Overall Number of Participants Analyzed 12 12
Geometric Mean (Standard Deviation)
Unit of Measure: L
139  (86) 277  (203)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Agrylin (Young), Agrylin (Elderly)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
13.Secondary Outcome
Title Platelet Count
Hide Description Platelet counts in patients with ET receiving Agrylin
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population (defined as all patients who received study treatment)
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Anagrelide hydrochloride in ages 18-50 years
Anagrelide hydrochloride in ages 65 and older
Overall Number of Participants Analyzed 12 12
Mean (Standard Deviation)
Unit of Measure: x 1,000,000,000/L
Baseline 488.8  (167.4) 548.5  (278.7)
2 hours post-dose 487.9  (168.1) 539.2  (258.6)
12 hours post-dose 473.2  (146.0) 540.3  (263.6)
14.Secondary Outcome
Title Heart Rate
Hide Description Heart rates in patients with ET receiving Agrylin
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Anagrelide hydrochloride in ages 18-50 years
Anagrelide hydrochloride in ages 65 and older
Overall Number of Participants Analyzed 12 12
Mean (Standard Deviation)
Unit of Measure: beats/min
Baseline 74.0  (9.6) 70.3  (8.4)
0.5 hours post-dose 72.4  (8.9) 77.7  (13.5)
1 hour post-dose 75.8  (5.5) 80.6  (11.7)
1.5 hours post-dose 78.1  (7.7) 82.7  (12.9)
2 hours post-dose 74.3  (7.0) 81.2  (13.8)
4 hours post-dose 75.0  (5.5) 74.7  (13.7)
6 hours post-dose 75.9  (8.6) 76.9  (11.4)
8 hours post-dose 75.5  (6.7) 76.3  (10.1)
12 hours post-dose 73.2  (6.0) 71.9  (8.1)
15.Secondary Outcome
Title Systolic Blood Pressure
Hide Description Systolic blood pressures in patients with ET receiving Agrylin
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Anagrelide hydrochloride in ages 18-50 years
Anagrelide hydrochloride in ages 65 and older
Overall Number of Participants Analyzed 12 12
Mean (Standard Deviation)
Unit of Measure: mmHg
Baseline 122.2  (9.6) 154.3  (19.6)
0.5 hours post-dose 122.7  (12.9) 145.2  (20.3)
1.0 hours post-dose 121.8  (11.7) 143.7  (21.8)
1.5 hours post-dose 122.3  (11.6) 140.1  (17.7)
2 hours post-dose 121.3  (12.3) 139.9  (19.8)
4 hours post-dose 122.2  (13.6) 133.7  (18.1)
6 hours post-dose 120.2  (16.1) 141.8  (19.5)
8 hours post-dose 123.6  (14.5) 136.3  (24.3)
12 hours post-dose 124.7  (13.6) 159.8  (28.6)
16.Secondary Outcome
Title Diastolic Blood Pressure
Hide Description Diastolic blood pressures in patients with ET receiving Agrylin
Time Frame over 1 day
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description:
Anagrelide hydrochloride in ages 18-50 years
Anagrelide hydrochloride in ages 65 and older
Overall Number of Participants Analyzed 12 12
Mean (Standard Deviation)
Unit of Measure: mmHg
Baseline 76.9  (7.5) 81.4  (10.3)
0.5 hours post-dose 74.8  (7.3) 75.2  (9.9)
1 hour post-dose 72.4  (6.6) 72.6  (7.5)
1.5 hours post-dose 72.8  (6.7) 71.6  (9.5)
2 hours post-dose 71.3  (7.9) 72.8  (7.1)
4 hours post-dose 76.2  (6.0) 73.0  (9.5)
6 hours post-dose 73.4  (10.0) 71.3  (7.6)
8 hours post-dose 76.3  (6.2) 75.0  (11.3)
12 hours post-dose 76.3  (9.1) 84.2  (12.4)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Agrylin (Young) Agrylin (Elderly)
Hide Arm/Group Description Anagrelide hydrochloride in ages 18-50 years Anagrelide hydrochloride in ages 65 and older
All-Cause Mortality
Agrylin (Young) Agrylin (Elderly)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Agrylin (Young) Agrylin (Elderly)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/12 (0.00%)      0/12 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Agrylin (Young) Agrylin (Elderly)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/12 (25.00%)      0/12 (0.00%)    
Infections and infestations     
Nasopharyngitis *  1/12 (8.33%)  1 0/12 (0.00%)  0
Urinary tract infection *  1/12 (8.33%)  1 0/12 (0.00%)  0
Nervous system disorders     
Headache *  1/12 (8.33%)  1 0/12 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Epistaxis *  1/12 (8.33%)  1 0/12 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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: Timothy Whitaker, M.D.
Organization: Shire
Responsible Party: Timothy Whitaker, M.D., Shire
ClinicalTrials.gov Identifier: NCT00413634     History of Changes
Other Study ID Numbers: SPD422-203
2004-004058-20 ( EudraCT Number )
First Submitted: December 19, 2006
First Posted: December 20, 2006
Results First Submitted: March 5, 2009
Results First Posted: June 2, 2009
Last Update Posted: June 12, 2014