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

NCT02492776 | Completed Phase 1

• 2 other identifiers: 7264-020AF219-020
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Volunteers

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

Gefapixant + Omeprazole

EXPERIMENTAL

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; Drug: Gefapixant

Interventions

Omeprazole DRUG

20 mg oral capsules administered once daily for 8 days

Also known as: Prilosec

Gefapixant + Omeprazole

Gefapixant DRUG

Gefapixant oral tablet (25 mg administered as a divided 50 mg tablet) administered twice daily for 5 days

Also known as: AF-219, MK-7264

Gefapixant + Omeprazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead
• Celerion: collaborator

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

Related Publications (1)

• 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.

  PMID: 35510785 RESULT

MeSH Terms

Interventions

Omeprazole; Gefapixant

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Dennis Swearingen, MD

  Celerion

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2015
• First Posted: July 9, 2015
• Study Start: July 7, 2015
• Primary Completion: August 4, 2015
• Study Completion: August 11, 2015
• Last Updated: July 22, 2022

Record last verified: 2022-07

Locations

US (1)