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Study to Evaluate the Effect of Omeprazole on the Pharmacokinetics of SPD422 (Anagrelide Hydrochloride) in Healthy Adult Participants

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ClinicalTrials.gov Identifier: NCT03866434
Recruitment Status : Not yet recruiting
First Posted : March 7, 2019
Last Update Posted : March 7, 2019
Sponsor:
Information provided by (Responsible Party):
Shire

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: SPD422 Drug: Omeprazole Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Single sequence crossover drug-drug interaction study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : March 15, 2019
Estimated Primary Completion Date : April 15, 2019
Estimated Study Completion Date : April 15, 2019

Resource links provided by the National Library of Medicine


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.
Drug: SPD422
Participants will receive 1 mg of SPD422 (2*0.5 mg) capsule orally on Day 1 and 8 in fasted state.
Other Name: Anagrelide hydrochloride

Drug: Omeprazole
Participants will receive 40 mg of Omeprazole orally once daily on Days 2 - 8.




Primary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) of Anagrelide (SPD422) on Day 1 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 ]
    Cmax of Anagrelide (SPD422) on Day 1 will be reported.

  2. Maximum Plasma Concentration (Cmax) of Anagrelide (SPD422) on Day 8 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 and 24 hours on Day 8 ]
    Cmax of Anagrelide (SPD422) administered in combination with Omeprazole on Day 8 will be reported.

  3. Maximum Concentration (Cmax) of 3-OH-anagrelide (Active Metabolite of Anagrelide) in Plasma on Day 1 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 ]
    Cmax of 3-OH-Anagrelide (Active Metabolite of Anagrelide) on Day 1 will be reported.

  4. Maximum Concentration (Cmax) of 3-OH-anagrelide (Active Metabolite of Anagrelide) in Plasma on Day 8 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 and 24 hours on Day 8 ]
    Cmax of 3-OH-Anagrelide (Active Metabolite of Anagrelide) administered in combination with Omeprazole on Day 8 will be reported.

  5. Area Under the Concentration Versus Time Curve From Zero to Last Time Point (AUC0-t) of Anagrelide in Plasma on Day 1 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 ]
    AUC0-t of Anagrelide (SPD422) on Day 1 will be reported.

  6. Area Under the Concentration Versus Time Curve From Zero to Last Time Point (AUC0-t) of Anagrelide in Plasma on Day 8 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 and 24 hours on Day 8 ]
    AUC0-t of Anagrelide (SPD422) administered in combination with Omeprazole on Day 8 will be reported.

  7. Area Under the Concentration Versus Time Curve From Zero to Last Time Point (AUC0-t) of 3-OH-anagrelide (Active Metabolite of Anagrelide) in Plasma on Day 1 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 ]
    AUC0-t of 3-OH-Anagrelide (Active Metabolite of Anagrelide) on Day 1 will be reported.

  8. Area Under the Concentration Versus Time Curve From Zero to Last Time Point (AUC0-t) of 3-OH-anagrelide (Active Metabolite of Anagrelide) in Plasma on Day 8 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 and 24 hours on Day 8 ]
    AUC0-t of 3-OH-Anagrelide (Active Metabolite of Anagrelide) administered in combination with Omeprazole on Day 8 will be reported.

  9. Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC0-infinity) of Anagrelide in Plasma on Day 1 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 ]
    AUC0-infinity of Anagrelide (SPD422) on Day 1 will be reported.

  10. Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC0-infinity) of Anagrelide in Plasma on Day 8 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 and 24 hours on Day 8 ]
    AUC0-infinity of Anagrelide (SPD422) administered in combination with Omeprazole on Day 8 will be reported.

  11. Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC0-infinity) of 3-OH-anagrelide (Active Metabolite of Anagrelide) in Plasma on Day 1 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 hours on Day 1 ]
    AUC0-infinity of 3-OH-Anagrelide (Active Metabolite of Anagrelide) on Day 1 will be reported.

  12. Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC0-infinity) of 3-OH-anagrelide (Active Metabolite of Anagrelide) in Plasma on Day 8 [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12 and 24 hours on Day 8 ]
    AUC0-infinity of 3-OH-Anagrelide (Active Metabolite of Anagrelide) administered in combination with Omeprazole on Day 8 will be reported.


Secondary Outcome Measures :
  1. Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [ Time Frame: From start of treatment up to follow-up (up to Day 18) ]
    An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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:

    1. History of previous bone marrow suppression.
    2. History of hypersensitivity to the investigational product.
    3. History of adverse hematologic reaction, (such as neutropenia, thrombocytopenia, anemia) to any drug.
    4. History of symptomatic or clinically meaningful orthostatic hypotension or syncope, as assessed by the investigator.
    5. 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.
    6. Participant has any history of seizure disorder.
    7. 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.
    8. 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])

    1. Has consumed alcohol within 2 days prior to the first dose of investigational product.
    2. Male participants who consume more than 3 units of alcohol per day.
    3. 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:

    1. Have used an investigational product (if elimination half-life is <6 days, otherwise 5 half-lives).
    2. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03866434


Contacts
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Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com

Locations
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United States, Tennessee
New Orleans Center for Clinical Research Not yet recruiting
Knoxville, Tennessee, United States, 37920
Contact: Site contact    865-305-9100    BSmith@noccr.com   
Principal Investigator: William Smith, MD         
Sponsors and Collaborators
Shire
Investigators
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Study Director: Study Director Shire

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Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT03866434     History of Changes
Other Study ID Numbers: SPD422-113
First Posted: March 7, 2019    Key Record Dates
Last Update Posted: March 7, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. 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.
URL: https://www.shiretrials.com/en/our-commitment-to-transparency/data-sharing-with-researchers

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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

Additional relevant MeSH terms:
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Omeprazole
Anagrelide
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Fibrinolytic Agents
Fibrin Modulating Agents
Platelet Aggregation Inhibitors