- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03866434
Study to Evaluate the Effect of Omeprazole on the Pharmacokinetics of SPD422 (Anagrelide Hydrochloride) in Healthy Adult Participants
May 24, 2021 updated by: Shire
A Phase 1, Open-label, Single-sequence, Non-randomized, Crossover, Drug-Drug Interaction Study to Evaluate the Effect of Omeprazole on the Pharmacokinetics of SPD422 (Anagrelide Hydrochloride) in Healthy Adult Subjects
This Phase 1, open-label, single-sequence, non-randomized, multiple-dose, crossover pharmacokinetic study is a single site study in the United States and will be conducted to assess the effect of a CYP1A2 inducer (omeprazole 40 mg once daily [QD]) on the pharmacokinetics of anagrelide (1 mg) when administered concurrently in healthy participants.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Tennessee
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Knoxville, Tennessee, United States, 37920
- New Orleans Center for Clinical Research
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 45 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Participants who has given, personally signed, and dated informed consent to participate in the study, in accordance with the International Conference on Harmonization Good Clinical Practice Guideline E6 (1996) and applicable regulations, before completing any study-related procedures.
- Age 18-45 years inclusive at the time of consent. The date of signing informed consent is defined as the beginning of the Screening Period. This inclusion criterion will be assessed only at the Screening Visit.
- Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential. A female of non-childbearing potential (defined as a female who is post-menopausal [amenorrhea for at least 12 consecutive months], has had a hysterectomy, bilateral tubal ligation, bilateral oophorectomy or bilateral salpingectomy.
- Satisfactory medical assessment with no clinically significant or relevant abnormal findings as determined by medical/surgical history, physical examination, vital signs, 12-lead electrocardiogram, and clinical laboratory evaluation (hematology, biochemistry, thyroid function, and urinalysis) that are likely to interfere with the participant's participation or ability to complete the study as assessed by the investigator.
- An understanding, ability, and willingness to fully comply with study procedures and restrictions.
- Body mass index (BMI) between 18.5 and 30.0 kilograms per square meter (kg/m^2) inclusive; assessed only at the screening visit.
- Able to swallow (multiple capsules or tablets at 1 time or consecutively at 1 time) all investigational product.
- Healthy as determined by the investigator on the basis of screening evaluations.
Exclusion Criteria:
- Current or recurrent disease or conditions (example: cardiovascular, renal, liver, gastrointestinal, malignancy or other conditions) that could affect the absorption, action, or disposition of either omeprazole or anagrelide or its metabolites, or could affect clinical assessments or clinical laboratory evaluations.
- Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the participant unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the investigational product or study procedures.
- Significant illness, as judged by the investigator, within the 2 weeks of administration of the first dose of investigational product.
- Use of any medication (including prescription, over-the-counter, herbal, multivitamin, oral contraceptives and other hormonal contraceptive treatments, or homeopathic preparations) within the 30 days prior to the first dose of study drug or during the study through Day 9 (occasional use of acetaminophen is allowed).
- Treatment with any known hepatic and/or P450 enzyme-altering agents, including CYP1A2 inducers or inhibitors within 30 days prior to the first dose of investigational product. This includes: Strong inhibitor- ciprofloxacin, enoxacin, fluvoxamine, and zafirlukast; Moderate inhibitor- methoxsalen, mexiletine, and oral contraceptives; Moderate inducer- phenytoin, rifampin, ritonavir, smoking, teriflunomide; Inducer- lansoprazole
A history of any of the following medical conditions:
- History of previous bone marrow suppression.
- History of hypersensitivity to the investigational product.
- History of adverse hematologic reaction, (such as neutropenia, thrombocytopenia, anemia) to any drug.
- History of symptomatic or clinically meaningful orthostatic hypotension or syncope, as assessed by the investigator.
- History of controlled or uncontrolled hypertension or a systolic blood pressure greater than or equal to (>=) 140 millimeters of mercury (mmHg) or diastolic blood pressure >= 90 mmHg at the Screening Visit or Day -1.
- Participant has any history of seizure disorder.
- History or presence of known structural cardiac abnormalities, syncope, cardiac conduction problems (PR interval greater than (>) 220 milliseconds (ms), second or third-degree heart block, bundle branch block [except congenital right bundle branch block], or prolonged QTc interval) or exercise-related cardiac events.
- History of alcohol or other substance abuse within the last year.
A participant's alcohol consumption that fulfils one of the following: (Note: One alcohol unit=1 beer [12 ounce {oz}]=1 wine [5 oz]=1 liquor [1.5 oz])
- Has consumed alcohol within 2 days prior to the first dose of investigational product.
- Male participants who consume more than 3 units of alcohol per day.
- Female participants who consume more than 2 units of alcohol per day.
- Positive screening test results for alcohol, drugs of abuse, or pregnancy (females of childbearing potential only) at the Screening Visit or Day -1.
- A positive human immunodeficiency virus (HIV) antibody screen, hepatitis B surface antigen (HBsAG) or hepatitis C virus antibody (HCV) screen.
- Use of tobacco in any form (smoking or chewing) or other nicotine-containing products in any form (gum, patch) within 30 days prior to the first dose of investigational product and during the in-house stay at the CRC.
- A positive urine cotinine test that is >= 50 Nano grams per milliliter (ng/mL) at either the Screening Visit or on Day -1.
- Routine consumption of more than 2 units of caffeine per day or participants who experience caffeine-withdrawal headaches or have a history of caffeine-withdrawal headaches. (One caffeine unit is contained in the following items: one 6-oz cup of coffee, two 12-oz cans of cola, one 12-oz cup of tea, and three 1-oz chocolate bars. Decaffeinated coffee, tea, or cola are not considered to contain caffeine.)
- Consumption of grapefruit, Seville oranges, and/or products containing these items within 7 days prior to the first dose of investigational product.
- Donation of blood or blood products (egg, plasma, or platelets) within 60 days prior to the first dose of investigational product.
- Known or suspected intolerance or hypersensitivity to the investigational products (anagrelide or omeprazole) or closely related compounds, or any of the stated ingredients.
Within 30 days prior to the first dose of investigational product:
- Have used an investigational product (if elimination half-life is <6 days, otherwise 5 half-lives).
- Have been enrolled in a clinical study (including vaccine studies) that, in the Investigator's opinion, may impact this Shire-sponsored study.
- Prior screen failure, participation, or enrollment in this study.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: SPD422 + Omeprazole
Participants will receive 1 milligram (mg) of SPD422 (Anagrelide hydrochloride) (2*0.5 mg) capsule orally on Day 1 in 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 Days 2 to Day 7, followed by 1 mg of Anagrelide in fasted state in combination with Omeprazole 40 mg on Day 8.
|
Participants will receive 1 mg of SPD422 (2*0.5 mg) capsule orally on Day 1 and 8 in fasted state.
Other Names:
Participants will receive 40 mg of Omeprazole orally once daily on Days 2 - 8.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Observed Plasma Concentration (Cmax) of Anagrelide (SPD422)
Time Frame: 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
|
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.
|
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
|
Maximum Observed Plasma Concentration (Cmax) of 3-Hydroxy (OH)-Anagrelide (Active Metabolite of Anagrelide)
Time Frame: 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
|
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.
|
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
|
Area Under the Concentration Versus Time Curve From Zero to Last Time Point (AUC[0-t]) of Anagrelide (SPD422) in Plasma
Time Frame: 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
|
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.
|
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
|
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
Time Frame: 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
|
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.
|
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
|
Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity]) of Anagrelide (SPD422) in Plasma
Time Frame: 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
|
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.
|
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
|
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
Time Frame: 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
|
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.
|
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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time Frame: From start of study drug administration up to follow-up (up to Day 18)
|
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.
|
From start of study drug administration up to follow-up (up to Day 18)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 26, 2019
Primary Completion (Actual)
April 10, 2019
Study Completion (Actual)
April 10, 2019
Study Registration Dates
First Submitted
March 6, 2019
First Submitted That Met QC Criteria
March 6, 2019
First Posted (Actual)
March 7, 2019
Study Record Updates
Last Update Posted (Actual)
June 15, 2021
Last Update Submitted That Met QC Criteria
May 24, 2021
Last Verified
May 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SPD422-113
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5).
These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/.
For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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