Lesinurad Interaction Study With Ranitidine

A Phase 1, Open-Label, Drug-Drug Interaction Study to Evaluate the Potential Effects of Ranitidine on the Pharmacokinetics of Lesinurad in Healthy Adult Male Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: lesinurad 400 mg; Drug: ranitidine 150 mg; Drug: lesinurad 400 mg + ranitidine 150 mg

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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630

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:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sequence 1 fasted; 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)	Drug: lesinurad 400 mg; Drug: ranitidine 150 mg; Drug: lesinurad 400 mg + ranitidine 150 mg
EXPERIMENTAL: Sequence 2 fasted; 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)	Drug: lesinurad 400 mg; Drug: ranitidine 150 mg; Drug: lesinurad 400 mg + ranitidine 150 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK profile of lesinurad from plasma and urine	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	Days 1 and 6 (Sequence 1) or Days 2 and 7 (Sequence 2)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.
• Investigators: Study Director: S. Bradley, MD, Ardea Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: July 23, 2013
• First Submitted That Met QC Criteria: July 23, 2013
• First Posted (ESTIMATE): July 25, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): January 9, 2014
• Last Update Submitted That Met QC Criteria: January 8, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Gastrointestinal Agents; Anti-Ulcer Agents; Histamine Antagonists; Histamine Agents; Gout Suppressants; Histamine H2 Antagonists; Renal Agents; Uricosuric Agents; Ranitidine; Ranitidine bismuth citrate; Lesinurad
• Other Study ID Numbers: RDEA594-127