Effect of AKB-6548 on the Pharmacokinetics of Celecoxib

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Celecoxib; Drug: AKB-6548

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Celecoxib	Drug: Celecoxib; Other Names: CELEBREX®
Experimental: AKB-6548 and Celecoxib; AKB-6548; celecoxib	Drug: Celecoxib; Other Names: CELEBREX®; Drug: AKB-6548

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Akebia Therapeutics

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: July 13, 2015
• First Submitted That Met QC Criteria: July 17, 2015
• First Posted (Estimate): July 20, 2015

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: November 10, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: AKB-6548-CI-0019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED