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

NCT03866434 | Completed Phase 1 Results FDA Drug

• 1 other identifier: SPD422-113
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (6)

• Maximum Observed Plasma Concentration (Cmax) of Anagrelide (SPD422)

  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)

  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

  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

  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

  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

  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 Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

  From start of study drug administration up to follow-up (up to Day 18)

Study Arms (1)

SPD422 + Omeprazole

EXPERIMENTAL

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; Drug: Omeprazole

Interventions

SPD422 DRUG

Participants will receive 1 mg of SPD422 (2\*0.5 mg) capsule orally on Day 1 and 8 in fasted state.

Also known as: Anagrelide hydrochloride

SPD422 + Omeprazole

Omeprazole DRUG

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

SPD422 + Omeprazole

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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 \[1.5 oz\])

Sponsors & Collaborators

• Shire: lead

Study Sites (1)

New Orleans Center for Clinical Research

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Interventions

anagrelide; Omeprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single sequence crossover drug-drug interaction study

Study Record Dates

• First Submitted: March 6, 2019
• First Posted: March 7, 2019
• Study Start: February 26, 2019
• Primary Completion: April 10, 2019
• Study Completion: April 10, 2019
• Last Updated: June 15, 2021
• Results First Posted: April 24, 2020

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

US (1)