Trial Outcomes & Findings for Study to Evaluate the Effect of Omeprazole on the Pharmacokinetics of SPD422 (Anagrelide Hydrochloride) in Healthy Adult Participants (NCT NCT03866434)
NCT ID: NCT03866434
Last Updated: 2021-06-15
Results Overview
Cmax of Anagrelide (SPD422) on Day 1 and Day 8 was reported. For PK outcome measures the reporting groups were split based on administration of Anagrelide alone (Day 1) and Anagrelide in combination with Omeprazole (Day 8) to provide statistical comparison in this single arm study.
COMPLETED
PHASE1
20 participants
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 and Day 8, 24 hours on Day 8
2021-06-15
Participant Flow
This study was conducted at single site in United States of America from 26 February 2019 to 10 April 2019.
A total of 20 participants were enrolled and completed the study.
Participant milestones
| Measure |
SPD422 + Omeprazole
Participants received 1 milligram (mg) of SPD422 (Anagrelide hydrochloride) (2\*0.5 mg) capsule orally on Day 1 under fasted state (10 hours prior to and until 4 hours following administration of anagrelide), followed by 40 mg of Omeprazole capsule orally once daily (prior to breakfast) on Day 2 to Day 7, followed by 1 mg of Anagrelide under fasted state in combination with Omeprazole 40 mg on Day 8.
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|---|---|
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Overall Study
STARTED
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20
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Overall Study
COMPLETED
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20
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Evaluate the Effect of Omeprazole on the Pharmacokinetics of SPD422 (Anagrelide Hydrochloride) in Healthy Adult Participants
Baseline characteristics by cohort
| Measure |
SPD422 + Omeprazole
n=20 Participants
Participants received 1 milligram (mg) of SPD422 (Anagrelide hydrochloride) (2\*0.5 mg) capsule orally on Day 1 under fasted state (10 hours prior to and until 4 hours following administration of anagrelide), followed by 40 mg of Omeprazole capsule orally once daily (prior to breakfast) on Day 2 to Day 7, followed by 1 mg of Anagrelide under fasted state in combination with Omeprazole 40 mg on Day 8.
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Age, Continuous
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32.0 years
STANDARD_DEVIATION 7.39 • n=5 Participants
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Sex: Female, Male
Female
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2 Participants
n=5 Participants
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Sex: Female, Male
Male
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18 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Hispanic or Latino
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4 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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16 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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1 Participants
n=5 Participants
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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7 Participants
n=5 Participants
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Race (NIH/OMB)
White
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12 Participants
n=5 Participants
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 and Day 8, 24 hours on Day 8Population: Pharmacokinetic (PK) set included all participants who received at least 1 dose of investigational product (anagrelide or omeprazole) and had at least 1 measurable post dose plasma concentration.
Cmax of Anagrelide (SPD422) on Day 1 and Day 8 was reported. For PK outcome measures the reporting groups were split based on administration of Anagrelide alone (Day 1) and Anagrelide in combination with Omeprazole (Day 8) to provide statistical comparison in this single arm study.
Outcome measures
| Measure |
SPD422 (Day 1)
n=20 Participants
Participants received 1 milligram (mg) of SPD422 (Anagrelide hydrochloride) (2\*0.5 mg) capsule orally on Day 1 under fasted state (10 hours prior to and until 4 hours following administration of anagrelide).
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SPD422 + Omeprazole (Day 8)
n=20 Participants
Participants received 40 mg of Omeprazole capsule orally once daily (prior to breakfast) on Day 2 to Day 7, followed by received 1 mg of Anagrelide under fasted state in combination with Omeprazole 40 mg on Day 8.
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Maximum Observed Plasma Concentration (Cmax) of Anagrelide (SPD422)
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5.028 nanogram per milliliter (ng/mL)
Standard Deviation 3.0357
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3.180 nanogram per milliliter (ng/mL)
Standard Deviation 1.6707
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PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 and Day 8, 24 hours on Day 8Population: PK set included all participants who received at least 1 dose of investigational product (anagrelide or omeprazole) and had at least 1 measurable post dose plasma concentration.
Cmax of 3-OH-Anagrelide (Active Metabolite of Anagrelide) on Day 1 and Day 8 was reported. For PK outcome measures the reporting groups were split based on administration of Anagrelide alone (Day 1) and Anagrelide in combination with Omeprazole (Day 8) to provide statistical comparison in this single arm study.
Outcome measures
| Measure |
SPD422 (Day 1)
n=20 Participants
Participants received 1 milligram (mg) of SPD422 (Anagrelide hydrochloride) (2\*0.5 mg) capsule orally on Day 1 under fasted state (10 hours prior to and until 4 hours following administration of anagrelide).
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SPD422 + Omeprazole (Day 8)
n=20 Participants
Participants received 40 mg of Omeprazole capsule orally once daily (prior to breakfast) on Day 2 to Day 7, followed by received 1 mg of Anagrelide under fasted state in combination with Omeprazole 40 mg on Day 8.
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Maximum Observed Plasma Concentration (Cmax) of 3-Hydroxy (OH)-Anagrelide (Active Metabolite of Anagrelide)
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10.30 ng/mL
Standard Deviation 3.9633
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8.341 ng/mL
Standard Deviation 2.7448
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PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 and Day 8, 24 hours on Day 8Population: PK set included all participants who received at least 1 dose of investigational product (anagrelide or omeprazole) and had at least 1 measurable post dose plasma concentration.
AUC(0-t) of Anagrelide (SPD422) in plasma on Day 1 and Day 8 was reported. For PK outcome measures the reporting groups were split based on administration of Anagrelide alone (Day 1) and Anagrelide in combination with Omeprazole (Day 8) to provide statistical comparison in this single arm study.
Outcome measures
| Measure |
SPD422 (Day 1)
n=20 Participants
Participants received 1 milligram (mg) of SPD422 (Anagrelide hydrochloride) (2\*0.5 mg) capsule orally on Day 1 under fasted state (10 hours prior to and until 4 hours following administration of anagrelide).
|
SPD422 + Omeprazole (Day 8)
n=20 Participants
Participants received 40 mg of Omeprazole capsule orally once daily (prior to breakfast) on Day 2 to Day 7, followed by received 1 mg of Anagrelide under fasted state in combination with Omeprazole 40 mg on Day 8.
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Area Under the Concentration Versus Time Curve From Zero to Last Time Point (AUC[0-t]) of Anagrelide (SPD422) in Plasma
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13.25 hour*nanogram per milliliter (h*ng/mL)
Standard Deviation 5.9297
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9.683 hour*nanogram per milliliter (h*ng/mL)
Standard Deviation 4.6171
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PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 and Day 8, 24 hours on Day 8Population: PK set included all participants who received at least 1 dose of investigational product (anagrelide or omeprazole) and had at least 1 measurable post dose plasma concentration.
AUC(0-t) of 3-OH-Anagrelide (Active Metabolite of Anagrelide) in Plasma on Day 1 and Day 8 was reported. For PK outcome measures the reporting groups were split based on administration of Anagrelide alone (Day 1) and Anagrelide in combination with Omeprazole (Day 8) to provide statistical comparison in this single arm study.
Outcome measures
| Measure |
SPD422 (Day 1)
n=20 Participants
Participants received 1 milligram (mg) of SPD422 (Anagrelide hydrochloride) (2\*0.5 mg) capsule orally on Day 1 under fasted state (10 hours prior to and until 4 hours following administration of anagrelide).
|
SPD422 + Omeprazole (Day 8)
n=20 Participants
Participants received 40 mg of Omeprazole capsule orally once daily (prior to breakfast) on Day 2 to Day 7, followed by received 1 mg of Anagrelide under fasted state in combination with Omeprazole 40 mg on Day 8.
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|---|---|---|
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Area Under the Concentration Versus Time Curve From Zero to Last Time Point (AUC[0-t]) of 3-Hydroxy (OH)-Anagrelide (Active Metabolite of Anagrelide) in Plasma
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39.51 h*ng/mL
Standard Deviation 14.946
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33.14 h*ng/mL
Standard Deviation 10.816
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PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 and Day 8, 24 hours on Day 8Population: PK set included all participants who received at least 1 dose of investigational product (anagrelide or omeprazole) and had at least 1 measurable post dose plasma concentration. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
AUC(0-infinity) of Anagrelide (SPD422) in plasma on Day 1 and Day 8 was reported. For PK outcome measures the reporting groups were split based on administration of Anagrelide alone (Day 1) and Anagrelide in combination with Omeprazole (Day 8) to provide statistical comparison in this single arm study.
Outcome measures
| Measure |
SPD422 (Day 1)
n=20 Participants
Participants received 1 milligram (mg) of SPD422 (Anagrelide hydrochloride) (2\*0.5 mg) capsule orally on Day 1 under fasted state (10 hours prior to and until 4 hours following administration of anagrelide).
|
SPD422 + Omeprazole (Day 8)
n=17 Participants
Participants received 40 mg of Omeprazole capsule orally once daily (prior to breakfast) on Day 2 to Day 7, followed by received 1 mg of Anagrelide under fasted state in combination with Omeprazole 40 mg on Day 8.
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|---|---|---|
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Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of Anagrelide (SPD422) in Plasma
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13.54 h*ng/mL
Standard Deviation 5.9951
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10.27 h*ng/mL
Standard Deviation 4.6070
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PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 and Day 8, 24 hours on Day 8Population: PK set included all participants who received at least 1 dose of investigational product (anagrelide or omeprazole) and had at least 1 measurable post dose plasma concentration. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
AUC(0-infinity) of 3-OH-Anagrelide (Active Metabolite of Anagrelide) in Plasma on Day 1 and Day 8 was reported. For PK outcome measures the reporting groups were split based on administration of Anagrelide alone (Day 1) and Anagrelide in combination with Omeprazole (Day 8) to provide statistical comparison in this single arm study.
Outcome measures
| Measure |
SPD422 (Day 1)
n=20 Participants
Participants received 1 milligram (mg) of SPD422 (Anagrelide hydrochloride) (2\*0.5 mg) capsule orally on Day 1 under fasted state (10 hours prior to and until 4 hours following administration of anagrelide).
|
SPD422 + Omeprazole (Day 8)
n=18 Participants
Participants received 40 mg of Omeprazole capsule orally once daily (prior to breakfast) on Day 2 to Day 7, followed by received 1 mg of Anagrelide under fasted state in combination with Omeprazole 40 mg on Day 8.
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|---|---|---|
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Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of 3-Hydroxy (OH)-Anagrelide (Active Metabolite of Anagrelide) in Plasma
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40.85 h*ng/mL
Standard Deviation 14.948
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35.51 h*ng/mL
Standard Deviation 11.190
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SECONDARY outcome
Timeframe: From start of study drug administration up to follow-up (up to Day 18)Population: Safety set included all participants who had taken at least 1 dose of investigational product (anagrelide or omeprazole) and had at least 1 post dose safety assessment.
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily had a causal relationship with this treatment. An AE was considered a TEAE if it started on or after dosing on Day 1 or if it started before dosing on Day 1 but increased in severity on or after dosing on Day 1 through the end of the study. Number of participants with TEAEs and TESAEs were reported.
Outcome measures
| Measure |
SPD422 (Day 1)
n=20 Participants
Participants received 1 milligram (mg) of SPD422 (Anagrelide hydrochloride) (2\*0.5 mg) capsule orally on Day 1 under fasted state (10 hours prior to and until 4 hours following administration of anagrelide).
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SPD422 + Omeprazole (Day 8)
Participants received 40 mg of Omeprazole capsule orally once daily (prior to breakfast) on Day 2 to Day 7, followed by received 1 mg of Anagrelide under fasted state in combination with Omeprazole 40 mg on Day 8.
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Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Treatment Emergent Adverse Events (TEAEs)
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9 Participants
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—
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Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Treatment Emergent Serious Adverse Events (TESAEs)
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0 Participants
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—
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Adverse Events
SPD422 + Omeprazole
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
SPD422 + Omeprazole
n=20 participants at risk
Participants received 1 milligram (mg) of SPD422 (Anagrelide hydrochloride) (2\*0.5 mg) capsule orally on Day 1 under fasted state (10 hours prior to and until 4 hours following administration of anagrelide), followed by 40 mg of Omeprazole capsule orally once daily (prior to breakfast) on Day 2 to Day 7, followed by 1 mg of Anagrelide under fasted state in combination with Omeprazole 40 mg on Day 8.
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Gastrointestinal disorders
Nausea
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20.0%
4/20 • Number of events 4 • From start of study drug administration up to follow-up (up to Day 18)
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Gastrointestinal disorders
Vomiting
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10.0%
2/20 • Number of events 2 • From start of study drug administration up to follow-up (up to Day 18)
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Nervous system disorders
Headache
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35.0%
7/20 • Number of events 11 • From start of study drug administration up to follow-up (up to Day 18)
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Psychiatric disorders
Insomnia
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5.0%
1/20 • Number of events 1 • From start of study drug administration up to follow-up (up to Day 18)
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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