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

Study Overview
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Brief Summary
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The purpose of this study is to compare the multiple dose pharmacokinetics (PK) of two gefapixant (AF-219) formulations; to assess the effect of omeprazole on the multiple dose PK of two gefapixant formulations; and, to assess the safety and tolerability of gefapixant.

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Omeprazole
* Drug: Gefapixant
* Drug: Gefapixant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be informed of the nature of the study and have provided written informed voluntary consent; Able to speak, read, and understand English; Healthy males or females, of any race, between 18 and 55 years of age, inclusive; Body mass index (BMI) >18.5 and <32.0 kg/m2 and weigh 50 - 100 kg; In good general health; 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 (i.e., have not undergone a hysterectomy or bilateral oophorectomy) or not post-menopausal (defined as no menses for at least 12 months), agree to use 2 forms of acceptable birth control; or if a male, they and/or their partner of child-bearing potential agree to use 2 forms of acceptable birth control; when in line with the preferred life style of the subject, true and complete abstinence (not periodic abstinence) is acceptable; Exclusion Criteria: 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; Have a positive screening test for Helicobacter pylori; 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; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gefapixant + Omeprazole<br>Gefapixant oral tablets (25mg, 50 mg) administered twice daily for 13 days + Omeprazole oral capsules (20 mg) administered once daily for 8 days | Drug: Omeprazole<br>* 20 mg oral capsules administered once daily for 8 days<br>* Other names: Prilosec;Drug: Gefapixant<br>* Gefapixant oral tablet (25 mg administered as a divided 50 mg tablet) administered twice daily for 5 days<br>* Other names: MK-7264;Drug: Gefapixant<br>* Gefapixant oral tablet (50 mg tablet) administered twice daily for 8 days<br>* Other names: MK-7264;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration profiles of two 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 | 
| Plasma concentration 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. | 5.5 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Volunteers