Trial Outcomes & Findings for The Pharmacokinetics of Anagrelide in Elderly and Young Patients With Essential Thrombocythaemia (ET) (NCT NCT00413634)
NCT ID: NCT00413634
Last Updated: 2021-06-29
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
24 participants
Primary outcome timeframe
over 1 day
Results posted on
2021-06-29
Participant Flow
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.
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).
Participant milestones
| Measure |
Agrylin (Young)
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
12
|
|
Overall Study
COMPLETED
|
12
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Pharmacokinetics of Anagrelide in Elderly and Young Patients With Essential Thrombocythaemia (ET)
Baseline characteristics by cohort
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Age, Continuous
|
39.2 years
STANDARD_DEVIATION 8.4 • n=5 Participants
|
69.2 years
STANDARD_DEVIATION 3.0 • n=7 Participants
|
54.2 years
STANDARD_DEVIATION 16.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
5 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
Serbia
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: over 1 dayPopulation: PK population (defined as all patients with post-dose drug concentration data)
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Agrylin
|
2.66 ng/ml
Standard Deviation 0.99
|
3.63 ng/ml
Standard Deviation 1.44
|
PRIMARY outcome
Timeframe: over 1 dayPopulation: PK population
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of Agrylin
|
1.11 hours
Standard Deviation 0.39
|
1.14 hours
Standard Deviation 0.91
|
PRIMARY outcome
Timeframe: over 1 dayPopulation: PK population
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Agrylin
|
6.4 ng.h/ml
Standard Deviation 2.4
|
10.3 ng.h/ml
Standard Deviation 4.0
|
PRIMARY outcome
Timeframe: over 1 dayPopulation: PK population
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Terminal Half-life (T 1/2) of Agrylin
|
1.3 hours
Standard Deviation 0.4
|
1.4 hours
Standard Deviation 0.3
|
PRIMARY outcome
Timeframe: over 1 dayPopulation: PK population
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Total Clearance (CL/F) of Agrylin
|
156 L/h
Standard Deviation 73
|
97 L/h
Standard Deviation 70
|
PRIMARY outcome
Timeframe: over 1 dayPopulation: PK population
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Volume of Distribution (Vz/F) of Agrylin
|
286 L
Standard Deviation 125
|
195 L
Standard Deviation 137
|
PRIMARY outcome
Timeframe: over 1 dayPopulation: PK population
An active metabolite has therapeutic activity similar to the parent compound and must be considered in therapeutic pharmacokinetics.
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Cmax of Active Metabolite
|
7.26 ng/ml
Standard Deviation 3.74
|
4.19 ng/ml
Standard Deviation 3.47
|
PRIMARY outcome
Timeframe: over 1 dayPopulation: PK population
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Tmax of Active Metabolite
|
0.92 hours
Standard Deviation 0.26
|
1.04 hours
Standard Deviation 0.99
|
PRIMARY outcome
Timeframe: over 1 dayPopulation: PK population
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
AUC of Active Metabolite
|
27.6 ng.h/ml
Standard Deviation 10.9
|
17.4 ng.h/ml
Standard Deviation 14.8
|
PRIMARY outcome
Timeframe: over 1 dayPopulation: PK population
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
T 1/2 of Active Metabolite
|
2.7 hours
Standard Deviation 0.5
|
3.5 hours
Standard Deviation 1.1
|
PRIMARY outcome
Timeframe: over 1 dayPopulation: PK population
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
CL/F of Active Metabolite
|
36 L/h
Standard Deviation 16
|
57 L/h
Standard Deviation 27
|
PRIMARY outcome
Timeframe: over 1 dayPopulation: PK population
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Vz/F of Active Metabolite
|
139 L
Standard Deviation 86
|
277 L
Standard Deviation 203
|
SECONDARY outcome
Timeframe: over 1 dayPopulation: Safety population (defined as all patients who received study treatment)
Platelet counts in patients with ET receiving Agrylin
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Platelet Count
Baseline
|
488.8 x 1,000,000,000/L
Standard Deviation 167.4
|
548.5 x 1,000,000,000/L
Standard Deviation 278.7
|
|
Platelet Count
2 hours post-dose
|
487.9 x 1,000,000,000/L
Standard Deviation 168.1
|
539.2 x 1,000,000,000/L
Standard Deviation 258.6
|
|
Platelet Count
12 hours post-dose
|
473.2 x 1,000,000,000/L
Standard Deviation 146.0
|
540.3 x 1,000,000,000/L
Standard Deviation 263.6
|
SECONDARY outcome
Timeframe: over 1 dayPopulation: Safety population
Heart rates in patients with ET receiving Agrylin
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Heart Rate
Baseline
|
74.0 beats/min
Standard Deviation 9.6
|
70.3 beats/min
Standard Deviation 8.4
|
|
Heart Rate
0.5 hours post-dose
|
72.4 beats/min
Standard Deviation 8.9
|
77.7 beats/min
Standard Deviation 13.5
|
|
Heart Rate
1 hour post-dose
|
75.8 beats/min
Standard Deviation 5.5
|
80.6 beats/min
Standard Deviation 11.7
|
|
Heart Rate
1.5 hours post-dose
|
78.1 beats/min
Standard Deviation 7.7
|
82.7 beats/min
Standard Deviation 12.9
|
|
Heart Rate
2 hours post-dose
|
74.3 beats/min
Standard Deviation 7.0
|
81.2 beats/min
Standard Deviation 13.8
|
|
Heart Rate
4 hours post-dose
|
75.0 beats/min
Standard Deviation 5.5
|
74.7 beats/min
Standard Deviation 13.7
|
|
Heart Rate
6 hours post-dose
|
75.9 beats/min
Standard Deviation 8.6
|
76.9 beats/min
Standard Deviation 11.4
|
|
Heart Rate
8 hours post-dose
|
75.5 beats/min
Standard Deviation 6.7
|
76.3 beats/min
Standard Deviation 10.1
|
|
Heart Rate
12 hours post-dose
|
73.2 beats/min
Standard Deviation 6.0
|
71.9 beats/min
Standard Deviation 8.1
|
SECONDARY outcome
Timeframe: over 1 dayPopulation: Safety population
Systolic blood pressures in patients with ET receiving Agrylin
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Systolic Blood Pressure
Baseline
|
122.2 mmHg
Standard Deviation 9.6
|
154.3 mmHg
Standard Deviation 19.6
|
|
Systolic Blood Pressure
0.5 hours post-dose
|
122.7 mmHg
Standard Deviation 12.9
|
145.2 mmHg
Standard Deviation 20.3
|
|
Systolic Blood Pressure
1.0 hours post-dose
|
121.8 mmHg
Standard Deviation 11.7
|
143.7 mmHg
Standard Deviation 21.8
|
|
Systolic Blood Pressure
1.5 hours post-dose
|
122.3 mmHg
Standard Deviation 11.6
|
140.1 mmHg
Standard Deviation 17.7
|
|
Systolic Blood Pressure
2 hours post-dose
|
121.3 mmHg
Standard Deviation 12.3
|
139.9 mmHg
Standard Deviation 19.8
|
|
Systolic Blood Pressure
4 hours post-dose
|
122.2 mmHg
Standard Deviation 13.6
|
133.7 mmHg
Standard Deviation 18.1
|
|
Systolic Blood Pressure
6 hours post-dose
|
120.2 mmHg
Standard Deviation 16.1
|
141.8 mmHg
Standard Deviation 19.5
|
|
Systolic Blood Pressure
8 hours post-dose
|
123.6 mmHg
Standard Deviation 14.5
|
136.3 mmHg
Standard Deviation 24.3
|
|
Systolic Blood Pressure
12 hours post-dose
|
124.7 mmHg
Standard Deviation 13.6
|
159.8 mmHg
Standard Deviation 28.6
|
SECONDARY outcome
Timeframe: over 1 dayPopulation: Safety population
Diastolic blood pressures in patients with ET receiving Agrylin
Outcome measures
| Measure |
Agrylin (Young)
n=12 Participants
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 Participants
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Diastolic Blood Pressure
Baseline
|
76.9 mmHg
Standard Deviation 7.5
|
81.4 mmHg
Standard Deviation 10.3
|
|
Diastolic Blood Pressure
0.5 hours post-dose
|
74.8 mmHg
Standard Deviation 7.3
|
75.2 mmHg
Standard Deviation 9.9
|
|
Diastolic Blood Pressure
1 hour post-dose
|
72.4 mmHg
Standard Deviation 6.6
|
72.6 mmHg
Standard Deviation 7.5
|
|
Diastolic Blood Pressure
1.5 hours post-dose
|
72.8 mmHg
Standard Deviation 6.7
|
71.6 mmHg
Standard Deviation 9.5
|
|
Diastolic Blood Pressure
2 hours post-dose
|
71.3 mmHg
Standard Deviation 7.9
|
72.8 mmHg
Standard Deviation 7.1
|
|
Diastolic Blood Pressure
4 hours post-dose
|
76.2 mmHg
Standard Deviation 6.0
|
73.0 mmHg
Standard Deviation 9.5
|
|
Diastolic Blood Pressure
6 hours post-dose
|
73.4 mmHg
Standard Deviation 10.0
|
71.3 mmHg
Standard Deviation 7.6
|
|
Diastolic Blood Pressure
8 hours post-dose
|
76.3 mmHg
Standard Deviation 6.2
|
75.0 mmHg
Standard Deviation 11.3
|
|
Diastolic Blood Pressure
12 hours post-dose
|
76.3 mmHg
Standard Deviation 9.1
|
84.2 mmHg
Standard Deviation 12.4
|
Adverse Events
Agrylin (Young)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Agrylin (Elderly)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Agrylin (Young)
n=12 participants at risk
Anagrelide hydrochloride in ages 18-50 years
|
Agrylin (Elderly)
n=12 participants at risk
Anagrelide hydrochloride in ages 65 and older
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
|
Infections and infestations
Urinary tract infection
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
Additional Information
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