Lesinurad Interaction Study With Ranitidine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT01908257
First received: July 23, 2013
Last updated: January 8, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Healthy
Drug: lesinurad 400 mg
Drug: ranitidine 150 mg
Drug: lesinurad 400 mg + ranitidine 150 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Ardea Biosciences, Inc.:

Primary Outcome Measures:
  • PK profile of lesinurad from plasma and urine [ Time Frame: Days 1 and 6 (Sequence 1) or Days 2 and 7 (Sequence 2) ] [ Designated as safety issue: No ]

    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:
  • Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • PD profile of lesinurad from serum [ Time Frame: Days 1 and 6 (Sequence 1) or Days 2 and 7 (Sequence 2) ] [ Designated as safety issue: No ]
    Profile in terms of serum urate concentration


Enrollment: 16
Study Start Date: July 2013
Study Completion Date: November 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01908257

Locations
United States, California
Cypress, California, United States, 90630
Sponsors and Collaborators
Ardea Biosciences, Inc.
Investigators
Study Director: S. Bradley, MD Ardea Biosciences, Inc.
  More Information

No publications provided

Responsible Party: Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT01908257     History of Changes
Other Study ID Numbers: RDEA594-127
Study First Received: July 23, 2013
Last Updated: January 8, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Ranitidine
Ranitidine bismuth citrate
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 31, 2014