RDEA3170 Bioavailability Study

Phase 1

Completed

• Conditions: Gout
• Interventions: Drug: RDEA3170 10 mg; Drug: RDEA3170 2.5 mg

• Registration Number: NCT02336594
• Lead Sponsor: Ardea Biosciences, Inc.

Brief Summary

This is a Phase 1, randomized, open-label, 4-way crossover pharmacokinetic (PK) and pharmacodynamic (PD) study in healthy adult male subjects designed to assess the relative bioavailability of RDEA3170 2.5 mg tablets administered as a 10 mg dose (2.5 mg × 4 tablets) and of a single RDEA3170 10 mg tablet. This study will also assess the effect of a low-fat and high-fat meal on the PK and PD of RDEA3170 10 mg tablets.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-11
• Study First Submitted: 2014-11-06
• Primary Completion: 2015-01
• Study First Submitted QC: 2015-01-09
• Study First Posted: 2015-01-13
• Study Completion: 2015-03
• Results First Submitted: 2017-05-15
• Status Verified: 2017-10
• Results First Submitted QC: 2017-10-09
• Last Update Submitted: 2017-10-09
• Results First Posted: 2017-10-13
• Last Update Posted: 2017-10-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 15

Inclusion Criteria

• Subject is able to understand the study procedures and the risks involved and is willing to provide written informed consent before the first study-related activity
• Subject has a body weight ≥ 50 kg (110 lbs.) and a body mass index ≥ 18 and ≤ 40 kg/m2
• Subject has a Screening serum urate level ≤ 7 mg/dL
• Subject is free of any clinically significant disease or medical condition, per the Investigator's judgment

Exclusion Criteria

• Subject has a history or suspicion of kidney stones
• Subject has undergone major surgery within 3 months prior to Screening
• Subject 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 Day 1
• Subject has inadequate venous access or unsuitable veins for repeated venipuncture
• Subject has a Screening serum creatinine value above the upper limit of normal during Screening or at Day -2 (Admission)
• Subject cannot swallow multiple tablets
• Subject is a heavy caffeine drinker
• Subject is unwilling to comply with the dietary restrictions of the study
• Subject is unable or unwilling to comply with the study requirements or has a situation or condition that, in the opinion of the Investigator, may interfere with participation in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence ABDC	RDEA3170 10 mg	2.5 x 4 mg tablets qd fasted, 10 mg tablet qd fasted, 10 mg tablet qd fed high-fat, 10 mg tablet qd fed low-fat
Sequence ABDC	RDEA3170 2.5 mg	2.5 x 4 mg tablets qd fasted, 10 mg tablet qd fasted, 10 mg tablet qd fed high-fat, 10 mg tablet qd fed low-fat
Sequence BADC	RDEA3170 2.5 mg	10 mg tablet qd fasted, 2.5 mg x 4 tablets qd fasted, 10 mg tablet qd fed high-fat, 10 mg tablet qd fed low-fat
Sequence ABCD	RDEA3170 10 mg	2.5 mg x 4 tablets qd (once daily) fasted, 10 mg tablet qd fasted, 10 mg tablet qd fed low-fat, 10 mg tablet qd fed high-fat.
Sequence ABCD	RDEA3170 2.5 mg	2.5 mg x 4 tablets qd (once daily) fasted, 10 mg tablet qd fasted, 10 mg tablet qd fed low-fat, 10 mg tablet qd fed high-fat.
Sequence BACD	RDEA3170 10 mg	10 mg tablet qd fasted, 2.5 mg x 4 tablets qd fasted, 10 mg tablet qd fed low-fat, 10 mg tablet qd fed high-fat
Sequence BACD	RDEA3170 2.5 mg	10 mg tablet qd fasted, 2.5 mg x 4 tablets qd fasted, 10 mg tablet qd fed low-fat, 10 mg tablet qd fed high-fat
Sequence BADC	RDEA3170 10 mg	10 mg tablet qd fasted, 2.5 mg x 4 tablets qd fasted, 10 mg tablet qd fed high-fat, 10 mg tablet qd fed low-fat

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax)	Days 1 and 5 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose.	Cmax of RDEA3170 in fasted condition.
Time of Occurrence of Maximum Observed Concentration (Tmax)	Days 1 and 5 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose.	Tmax of RDEA3170 following various treatments.
Area Under the Concentration-time Curve From Time Zero to the Quantifiable Last Sampling Timepoint (AUC Last)	Days 1 and 5 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose.	AUC last of RDEA3170 in fasted condition.
Area Under the Concentration-time Curve From 0 to Infinity (AUC∞)	Days 1 and 5 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose.	AUC∞ of RDEA3170 the fasted condition.
Apparent Terminal Half-life (t1/2)	Days 1 and 5 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose.	t1/2 of RDEA3170 following various treatments.
Cmax: Effect of High Fat Meal on the PK of RDEA3170 Tablets	Days 1 to 13 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose.	Cmax of RDEA3170 in high-fat fed state.
AUC Last: Effect of High Fat Meal on the PK of RDEA3170 Tablets	Days 1 to 13 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose.	AUC last of RDEA3170 in high-fat fed state.
AUC Last: Effect of Low Fat Meal on the PK of RDEA3170 Tablets	Days 1 to 9 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose.	AUC last of RDEA3170 in low-fat fed state.
AUC∞: Effect of Low Fat Meal on the PK of RDEA3170 Tablets	Days 1 to 9 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose.	AUC∞ of RDEA3170 in low-fat fed state.
AUC∞: Effect of High Fat Meal on the PK of RDEA3170 Tablets	Days 1 to 13 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose.	AUC∞ of RDEA3170 in high-fat fed state.
Cmax: Effect of Low Fat Meal on the PK of RDEA3170 Tablets	Days 1 to 9 at predose, 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours postdose.	Cmax of RDEA3170 in low-fat fed state.

Secondary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	7 weeks.
Single Dose Pharmacodynamics (PD) Profile of RDEA3170 From Serum and Urine	Day -1: -24, -23, -22, -21, -20, -18, -16, -14, and -12 hours predose. Days 1, 5, 9, and 13: predose (within 30 minutes prior to dosing) and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose.	PD profiles of uric acid from serum and urine. PD parameters were evaluated to assess whether any potential differences in PK for the 2 different tablets resulted in differences in uric acid excretion.