Clinical trial NCT02492776: A Multiple-Dose Pharmacokinetics Study of Two Gefapixant (AF-219/MK-7264) Formulations
Official title: A Study in Healthy Subjects to Assess the Multiple-Dose Pharmacokinetics of Two AF-219 Formulations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Volunteers
Lead sponsor: Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
Collaborators: name: Celerion
First posted: 2015-07-09
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Plasma concentration profiles of two different oral formulations of gefapixant
timeFrame: 12 hours
measure: Plasma concentration profile of gefapixant following administration of omeprazole
timeFrame: 5.5 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Celerion
name: Dennis Swearingen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gupta P, Hussain A, Ford AP, Smith S, Nussbaum JC, Stoch A, Iwamoto M. Clinical Formulation Bridging of Gefapixant, a P2X3-Receptor Antagonist, for the Treatment of Chronic Cough. Clin Pharmacol Drug Dev. 2022 Sep;11(9):1054-1067. doi: 10.1002/cpdd.1105. Epub 2022 May 5.