A Multiple-Dose Pharmacokinetics Study of Three Gefapixant (AF-219/MK-7264) Formulations

A Study in Healthy Subjects to Assess the Multiple- Dose Pharmacokinetics of Three AF-219 Formulations

The purpose of this study is to compare the multiple dose pharmacokinetics (PK) of three gefapixant (AF-219) formulations; to assess the effect of Omeprazole on the multiple dose PK of three gefapixant formulations; and, to assess the safety and tolerability of gefapixant.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Omeprazole; Drug: Omeprazole; Drug: Gefapixant; Drug: Gefapixant

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Be informed of the nature of the study and have provided written informed voluntary consent
• Be able to speak, read, and understand English;
• Be healthy males or females, of any race, between 18 and 55 years of age, inclusive;
• Have a body mass index (BMI) >18.5 and <32.0 kg/m2 and weigh 50 - 100 kg;
• Be in good general health with no clinically relevant abnormalities based on the medical history, physical examination, clinical laboratory evaluations (hematology, clinical chemistry, and urinalysis), and 12-lead electrocardiogram;
• Be only non-smokers or intermittent (social) smokers for at least 5 years, and able to refrain from smoking (or using nicotine) while in confinement;
• If a female of child-bearing potential or not post-menopausal, agree to use 2 forms of acceptable birth control;
• Be able to communicate effectively with the Investigator and other study center personnel and agree to comply with the study procedures and restrictions

Exclusion Criteria:

• Have previously received gefapixant;
• Any disease or condition that might affect drug absorption, metabolism, or excretion or clinically significant cardiovascular, hematological, renal, hepatic, pulmonary, endocrine, gastrointestinal, immunological, dermatological, neurological, or psychiatric disease;
• Clinically significant illness or clinically significant surgery within 4 weeks before the administration of study medication;
• Any past sinus surgery, upper respiratory tract infection within 2 weeks before dosing, or history of hay-fever during the time of the year that dosing will be taking place;
• History of GERD, heartburn, or nausea more than once a month, or any similar symptoms requiring the regular use of antacids, or any use of H2-histamine blockers or proton pump inhibitors within 12 months of Screening;
• QTcB >450 msec in males or >470 msec in females;
• Known or suspected hypersensitivity or allergic reaction to any of the components of gefapixant or omeprazole capsules;
• If female, is pregnant or breast feeding, or has a positive pregnancy test pre-dose;
• Blood loss or blood donation of >550 mL within 90 days or plasma donation >500 mL within 14 days before administration of the first dose of study drug;
• Chronic use of any systemic medications (other than allowable oral and implanted contraceptives and with the exception of vitamins taken at standard supplement doses); use of a drug therapy (including herbal preparations, e.g., St. John's wort) known to induce or inhibit hepatic drug metabolism within 30 days before the first dose of study medication; or use of any medications [prescription or over-the-counter (OTC)], including antacids, high-dose multivitamins, nutritional supplements, and herbal preparations, within 14 days before the first dose of study drug, unless deemed acceptable by the Investigator and Sponsor;
• Past or current history or evidence of drug or alcohol abuse, regular use of more than 2 units of alcohol per day (1 unit of alcohol = 150 mL of wine, 360 mL of beer, or 45 mL of alcohol 40%), use of any recreational soft drugs (e.g., marijuana) within 3 months of screening, use of any hard drugs (such as cocaine, phencyclidine (PCP), and crack) within 1 year of screening, and/or a positive screen for substances of abuse or alcohol at screening or pre-dose;
• Ingestion of grapefruit or grapefruit juice within 48 hours before dose administration;
• Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C antibody, or human immunodeficiency virus (HIV) antibody;
• Receipt of an investigational product or device, or participation in a drug research study within a period of 30 days (or 5 half lives of the drug, whichever is longer) before the first dose of study medication;
• Receipt of an investigational immunomodulator or monoclonal antibody within 180 days (or 5 half lives, whichever is longer) before the first dose of study medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Gefapixant + Omeprazole; Gefapixant oral tablets (15mg and 30 mg) administered twice daily for 15 days + Omeprazole oral capsules (20 mg or 40 mg) administered once or twice daily for 10 days

Drug: Omeprazole; 20 mg oral capsules administered once daily for 10 days; Other Names: Prilosec; Drug: Omeprazole; 40 mg oral capsules administered twice daily for 10 days; Other Names: Prilosec; Drug: Gefapixant; Gefapixant oral tablets (15 mg administered as two 7.5 mg tablets) administered twice daily for 15 days; Other Names: AF-219; MK-7264; Drug: Gefapixant; Gefapixant oral tablets (30 mg administered as four 7.5 mg tablets) administered twice daily for 15 days; Other Names: AF-219; MK-7264

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) profiles of three different oral formulations of gefapixant	Plasma gefapixant concentration versus time profiles will be plotted for each subject; similar summary plots will be constructed for each treatment period. Plasma gefapixant PK parameters will be calculated using noncompartmental methods and summarized using descriptive statistics by each treatment.	12 hours
Maximum plasma concentration (Cmax) profile of gefapixant following administration of Omeprazole	Analysis of variance (ANOVA) will be performed on log normal-transformed Cmax and AUC0-t values to determine the extent of a drug interaction, if any, of Omeprazole on the plasma gefapixant PK parameters	12 hours

Collaborators and Investigators

• Sponsor: Afferent Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2016
• Primary Completion (Actual): June 15, 2016
• Study Completion (Actual): June 21, 2016

Study Registration Dates

• First Submitted: May 27, 2016
• First Submitted That Met QC Criteria: June 1, 2016
• First Posted (Estimate): June 6, 2016

Study Record Updates

• Last Update Posted (Actual): April 18, 2017
• Last Update Submitted That Met QC Criteria: April 17, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Volunteers
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: 7264-023; AF219-023 (Other Identifier: Afferent Pharmaceuticals)

Plan for Individual participant data (IPD)

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