Effect of AKB-6548 on the Pharmacokinetics of Celecoxib

Study Overview
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Brief Summary
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To assess the single dose pharmacokinetics (PK) of celecoxib in healthy subjects when administered alone and following multiple daily doses of AKB-6548.

Detailed Description
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To assess the single dose plasma pharmacokinetics (PK), safety, and tolerability of celecoxib in healthy subjects with CYP2C9 extensive metabolizer (EM) genotype when administered alone and following multiple daily doses of AKB-6548.

Official Title
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An Open-label Study in Healthy Subjects to Assess the Effect of Once-daily Multiple Dosing of AKB-6548 on the Pharmacokinetics of the CYP2C9 Substrate Celecoxib

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Celecoxib
* Drug: AKB-6548


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects between 18 and 55 years of age, inclusive, and with a body mass index between 18 and 30 kg/sq.meters, inclusive. Subjects with the following genotype based upon pharmacogenetic testing results: CYP2C9 EM: *1*1. Exclusion Criteria: Current or past history of cardiovascular, cerebrovascular, pulmonary, renal or liver disease. Positive serology results for HBsAg, HCV, and HIV at Screening. Significant renal impairment as evidenced by an estimated glomerular filtration rate (eGFR) of <65 mL/minute/1.73 sq.meters. Known hypersensitivity to celecoxib or sulfonamides. History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Known active cancer or history of chemotherapy use within the previous 24 months. Current or past history of gastric or duodenal ulcers or other diseases of the GI tract (including gastric bypass surgeries) that could interfere with absorption of study drug. Current or past history of gastrointestinal bleeding. Any history of alcohol or drug abuse within the previous year prior to Screening. Subjects with a known history of smoking and/or have used nicotine or nicotine containing products within the past 6 months.

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

Sexes Eligible for Study
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Male

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: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Celecoxib<br>Celecoxib | Drug: Celecoxib<br> <br> * Other names: CELEBREX®;|
| Experimental: AKB-6548 and Celecoxib<br>AKB-6548; celecoxib | Drug: Celecoxib<br> <br> * Other names: CELEBREX®;Drug: AKB-6548<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters (Cmax) | maximum observed plasma concentration (Cmax) for celecoxib | pre-dose to 48 hours post-dose | 
| PK parameters (time to reach Cmax ) | time to reach Cmax for celecoxib | pre-dose to 48 hours post-dose | 
| PK parameters (t½) | terminal elimination half-life (t½) for celecoxib | from pre-dose to 48 hours post-dose | 
| PK parameters (AUC0-t) | concentration (AUC0-t) for celecoxib | pre-dose to 48 hours post-dose | 
| PK parameters (area under the plasma concentration-time curve from 0 to last quantifiable) | area under the plasma concentration-time curve from 0 to last quantifiable | pre-dose to 48 hours post-dose | 
| PK parameters (AUC0-inf) | AUC from time 0 to infinity (AUC0-inf) for celecoxib | from pre-dose to 48 hours post-dose | 
| PK parameters (CL/F) | apparent oral clearance (CL/F) for celecoxib | pre-dose to 48 hours post-dose | 
| PK parameters (Vz/F) | apparent volume of distribution during the terminal phase (Vz/F) for celecoxib | pre-dose to 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability will be measured by vital signs | The safety and tolerability of the single doses of celecoxib alone and in combination with AKB-6548 will be monitored for vital signs, clinical laboratory assays | up to ten days | 
| Safety and Tolerability will be monitoring of adverse events (AEs) | The safety and tolerability of the single doses of celecoxib alone and in combination with AKB-6548 will be monitored for adverse events (AEs) | up to ten days | 
| Safety and Tolerability will be measured by clinical assays | The safety and tolerability of the single doses of celecoxib alone and in combination with AKB-6548 will be monitored for clinical laboratory assays | up to ten days |