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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03866434
• Other study ID #: SPD422-113
• Status: Completed
• Phase: Phase 1
• Start date: February 26, 2019
• Est. completion date: April 10, 2019

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 10, 2019
• Est. primary completion date: April 10, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• SPD422
Participants will receive 1 mg of SPD422 (2*0.5 mg) capsule orally on Day 1 and 8 in fasted state.
• Omeprazole
Participants will receive 40 mg of Omeprazole orally once daily on Days 2 - 8.

Locations

Country	Name	City	State
United States	New Orleans Center for Clinical Research	Knoxville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	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)