Lesinurad Interaction Study With Ranitidine

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: lesinurad 400 mg; Drug: ranitidine 150 mg; Drug: lesinurad 400 mg + ranitidine 150 mg

• Registration Number: NCT01908257
• Lead Sponsor: Ardea Biosciences, Inc.

Brief Summary

This is a drug-drug interaction study in healthy volunteers to evaluate the potential pharmacokinetic (PK) effects of ranitidine on lesinurad.

Detailed Description

This study will evaluate the potential effect of ranitidine on the pharmacokinetics of lesinurad. An earlier study demonstrated an effect on lesinurad PK in the presence of both calcium-containing and magnesium- and aluminum-containing antacids. The current study will assess whether raising gastric pH, without the presence of these cations, affects lesinurad PK and PD under the fasted state. If an impact is seen, then the optional second cohort will be conducted under the fed state.

Study Timeline

• Study Start: 2013-07
• Study First Submitted: 2013-07-23
• Study First Submitted QC: 2013-07-23
• Study First Posted: 2013-07-25
• Primary Completion: 2013-09
• Study Completion: 2013-11
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-08
• Last Update Posted: 2014-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 16

Inclusion Criteria

• body weight ≥ 50 kg (110 lbs) and body mass index ≥ 18 and ≤ 30 kg/m2.
• Screening sUA value ≤ 7.0 mg/dL.
• free of any clinically significant disease that requires a physician's care and/or would interfere with study evaluations or procedures.
• Subject has no clinically relevant abnormalties in vital signs, ECG, physical examination or safety laboratory values per the Investigator's judgment.

Exclusion Criteria

• history or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic renal,urological, or psychiatric disorders.
• history or suspicion of kidney stones.
• undergone major surgery within 3 months prior to Day 1.
• donated blood or experienced significant blood loss (> 450 mL) within 12 weeks prior to Day 1 or gave a plasma donation within 4 weeks prior to the Screening visit.
• inadequate venous access or unsuitable veins for repeated venipuncture.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence 1 fasted	lesinurad 400 mg	Day 1: Lesinurad 400 mg once daily (qd) Day 5: Ranitidine 150 mg twice daily (bid) Day 6: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad. Day 7: Ranitidine 150 mg (bid)
Sequence 1 fasted	ranitidine 150 mg	Day 1: Lesinurad 400 mg once daily (qd) Day 5: Ranitidine 150 mg twice daily (bid) Day 6: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad. Day 7: Ranitidine 150 mg (bid)
Sequence 1 fasted	lesinurad 400 mg + ranitidine 150 mg	Day 1: Lesinurad 400 mg once daily (qd) Day 5: Ranitidine 150 mg twice daily (bid) Day 6: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad. Day 7: Ranitidine 150 mg (bid)
Sequence 2 fasted	lesinurad 400 mg	Day 1: Ranitidine 150 mg (bid) Day 2: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad Day 3: Ranitidine 150 mg (bid) Day 7: Lesinurad 400 mg (qd)
Sequence 2 fasted	ranitidine 150 mg	Day 1: Ranitidine 150 mg (bid) Day 2: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad Day 3: Ranitidine 150 mg (bid) Day 7: Lesinurad 400 mg (qd)
Sequence 2 fasted	lesinurad 400 mg + ranitidine 150 mg	Day 1: Ranitidine 150 mg (bid) Day 2: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad Day 3: Ranitidine 150 mg (bid) Day 7: Lesinurad 400 mg (qd)

Primary Outcome Measures

Name	Time	Method
PK profile of lesinurad from plasma and urine	Days 1 and 6 (Sequence 1) or Days 2 and 7 (Sequence 2)	Profile in terms of Cmax, Tmax, AUC, CL/F, t1/2; Cmax: maximum concentration; Tmax: time to reach max plasma concentration; AUC: area under the concentration-time curve; CL/F: total body clearance corrected for bioavailability; t1/2: apparent terminal half-life

Secondary Outcome Measures

Name	Time	Method
Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters	6 weeks
PD profile of lesinurad from serum	Days 1 and 6 (Sequence 1) or Days 2 and 7 (Sequence 2)	Profile in terms of serum urate concentration