Relative Bioavailability of an Extemporaneous Oral Suspension of Aprepitant in Healthy Adult Volunteers

Antiemetic therapies have improved in recent years, but chemotherapy-induced nausea and vomiting (CINV) are still common and are among the most distressing side effects of chemotherapy. Aprepitant is commercially available in Canada as capsules. An oral liquid aprepitant formulation would be ideal for oral administration to patients unable to swallow capsules.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Nausea and Vomiting
• Intervention / Treatment: Drug: Aprepitant Capsule 125 MG; Drug: Aprepitant oral suspension 20 mg/mL

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male or female subjects as determined by responsible physician (see 4.3) (i.e. have no clinically significant diseases captured in the medical history, on physical examination and/or laboratory tests)
• 18 to 55 years of age
• BMI within 18.5 to 30 kg/m2
• Non-smoker
• Systolic blood pressure between 90-140 mmHg, diastolic blood pressure between 60-90 mmHg, and heart rate between 60-100 bpm, inclusive.
• Female subjects of childbearing potential should be either sexually inactive (abstinent) or be using one of acceptable methods of birth control for 15 days prior to the first dose of the study, throughout the study and for at least 30 days after the last aprepitant dose.
• Able to swallow whole aprepitant capsules
• Willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer.

Exclusion Criteria:

• Clinically significant illness or surgery within 8 weeks prior to dosing.
• Positive for hepatitis B, hepatitis C, or HIV at screening as per medical history.
• History of allergic reactions to the study drug and/or its excipients.
• Subjects concurrently treated with drugs that are metabolized through CYP3A4, including but not limited to pimozide, terfenadine, astemizole, or cisapride, ketoconazole, itraconazole, clarithromycin, diltiazem, warfarin, rifampin, carbamazepine, and phenytoin etc.
• History of drug or alcohol abuse within the last 6 months.
• Severe mental disorders.
• Blood donation of 50 mL to 499 mL of whole blood within 30 days, or more than 499 mL of whole blood within 56 days prior to drug administration.
• Pregnant or breastfeeding.
• Use of recreational drugs, prescription medications (other than hormonal contraceptive agents),non-prescription medications (over-the-counter) or natural health products within 7 days or 5 half-lives (whichever is longer) prior to the administration of the first dose of study medication.
• Consumed grapefruit or grapefruit products within 7 days of each study period
• Any reason which, in the opinion of the investigator, would prevent the subject from participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Aprepitant Capsule Study Period #1	Drug: Aprepitant Capsule 125 MG; Patients will be randomized to either the aprepitant capsule or oral suspension for the first study period, and will receive the alternate formulation during the second study period
Other: Aprepitant Oral Suspension Study Period#1	Drug: Aprepitant oral suspension 20 mg/mL; Patients will be randomized to either the aprepitant capsule or oral suspension for the first study period, and will receive the alternate formulation during the second study period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bioavailability of the oral suspension relative to the capsule	6 weeks

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children

Publications and helpful links

General Publications

• Patel P, Nathan PC, Walker SE, Zupanec S, Volpe J, Dupuis LL. Relative bioavailability of an extemporaneously prepared aprepitant oral suspension in healthy adults. J Oncol Pharm Pract. 2019 Dec;25(8):1907-1915. doi: 10.1177/1078155219828806. Epub 2019 Feb 5.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2017
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): January 5, 2018

Study Registration Dates

• First Submitted: August 8, 2017
• First Submitted That Met QC Criteria: August 8, 2017
• First Posted (Actual): August 10, 2017

Study Record Updates

• Last Update Posted (Actual): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 1, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Neurokinin-1 Receptor Antagonists; Aprepitant; Fosaprepitant
• Other Study ID Numbers: 1000056100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No