RDEA3170 Bioavailability Study

• Sponsor: Ardea Biosciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02336594
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 4
• Duration (Months): 3.9
• Patients Per Site Per Month: 3.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gout	Drug: RDEA3170 10 mg; Drug: RDEA3170 2.5 mg	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Phase 1, Randomized, Open-Label, Crossover Study in Healthy Adult Male Subjects to Assess the Relative Bioavailability of Two RDEA3170 Tablets
• Study Start Date: Nov 1, 2014
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequence ABCD 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.	Drug: RDEA3170 10 mg; Drug: RDEA3170 2.5 mg
Experimental: Sequence BACD 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	Drug: RDEA3170 10 mg; Drug: RDEA3170 2.5 mg
Experimental: Sequence ABDC 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	Drug: RDEA3170 10 mg; Drug: RDEA3170 2.5 mg
Experimental: Sequence BADC 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	Drug: RDEA3170 10 mg; Drug: RDEA3170 2.5 mg

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

Secondary Outcome Measures

1. 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.

2. Incidence of Treatment-Emergent Adverse Events [7 weeks.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Austin	Texas	United States	78744

Sponsors and Collaborators

• Ardea Biosciences, Inc.

Investigators

• Study Director: J. Hall, MD, Ardea Biosciences, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ardea Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT02336594
• Other Study ID Numbers: RDEA3170-110
• First Posted: Jan 13, 2015
• Last Update Posted: Oct 13, 2017
• Last Verified: Oct 1, 2017

• Additional relevant MeSH terms: Verinurad

Study Results

Participant Flow

Recruitment Details	15 subjects were randomized
Pre-assignment Detail	Fifteen subjects were randomized to 1 of 4 treatment sequences (ABCD, BACD, ABDC, BADC) in a 1:1:1:1 ratio.

Arm/Group Title	Sequence ABCD	Sequence BACD	Sequence ABDC	Sequence BADC
Arm/Group Description	Day 1 (Treatment A): 10 mg dose of RDEA3170, administered as 4 × 2.5 mg ER tablets, in the fasted state; Day 5 (Treatment B): 10 mg dose of RDEA3170, administered as a single 10 mg ER tablet, in the fasted state; Day 9 (Treatment C): 10 mg dose of RDEA3170, administered as a single 10 mg ER tablet, in the fed state (low-fat, high-calorie meal); Day 13 (Treatment D): 10 mg dose of RDEA3170, administered as a single 10 mg ER tablet, in the fed state (high-fat, high-calorie meal).	Day 1 (Treatment B): 10 mg dose of RDEA3170, administered as a single 10 mg ER tablet, in the fasted state; Day 5 (Treatment A): 10 mg dose of RDEA3170, administered as 4 × 2.5 mg ER tablets, in the fasted state; Day 9 (Treatment C): 10 mg dose of RDEA3170, administered as a single 10 mg ER tablet, in the fed state (low-fat, high-calorie meal); Day 13 (Treatment D): 10 mg dose of RDEA3170, administered as a single 10 mg ER tablet, in the fed state (high-fat, high-calorie meal).	Day 1 (Treatment A): 10 mg dose of RDEA3170, administered as 4 × 2.5 mg ER tablets, in the fasted state; Day 5 (Treatment B): 10 mg dose of RDEA3170, administered as a single 10 mg ER tablet, in the fasted state; Day 9 (Treatment D): 10 mg dose of RDEA3170, administered as a single 10 mg ER tablet, in the fed state (high-fat, high-calorie meal); Day 13 (Treatment C): 10 mg dose of RDEA3170, administered as a single 10 mg ER tablet, in the fed state (low-fat, high-calorie meal).	Day 1 (Treatment B): 10 mg dose of RDEA3170, administered as a single 10 mg ER tablet, in the fasted state; Day 5 (Treatment A): 10 mg dose of RDEA3170, administered as 4 × 2.5 mg ER tablets, in the fasted state; Day 9 (Treatment D): 10 mg dose of RDEA3170, administered as a single 10 mg ER tablet, in the fed state (high-fat, high-calorie meal); Day 13 (Treatment C): 10 mg dose of RDEA3170, administered as a single 10 mg ER tablet, in the fed state (low-fat, high-calorie meal).
Period Title: Overall Study
STARTED	3	4	4	4
COMPLETED	3	4	4	4
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Sequence ABCD	Sequence BACD	Sequence ABDC	Sequence BADC	Total
Arm/Group Description	2.5 mg x 4 tablets qd fasted, 10 mg tablet qd fasted, 10 mg tablet qd fed low-fat, 10 mg tablet qd fed high-fat.	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	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	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	Total of all reporting groups
Overall Participants	3	4	4	4	15
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51 (9.8)	39 (9.7)	40 (12.3)	42 (16.0)	42 (11.9)
Age, Customized (Number) [Number]
<65	3 100%	4 100%	4 100%	4 100%	15 100%
>=65	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	3 100%	4 100%	4 100%	4 100%	15 100%
Region of Enrollment (Number) [Number]
United States	3 100%	4 100%	4 100%	4 100%	15 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Description	Cmax of RDEA3170 in fasted condition.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	10 mg dose of RDEA3170, administered as 4 × 2.5 mg tablets, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.
Measure Participants	15	15
Geometric Mean (95% Confidence Interval) [ng/mL]	14.1	14.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The sample size is not based on formal power calculations, as this study is designed only to provide an initial assessment of the Pharmacokinetics (PK), Pharmacodynamics (PD), and safety profile of RDEA3170.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	107
	Confidence Interval	(2-Sided) 90%; 95.2 to 120
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Time of Occurrence of Maximum Observed Concentration (Tmax)
Description	Tmax of RDEA3170 following various treatments.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment A	Treatment B	Treatment C	Treatment D
Arm/Group Description	10 mg dose of RDEA3170, administered as 4 × 2.5 mg tablets, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (low-fat, high calorie meal).	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (high-fat, high calorie meal).
Measure Participants	15	15	15	15
Median (Full Range) [hr]	2.00	2.00	2.00	4.00

3. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to the Quantifiable Last Sampling Timepoint (AUC Last)
Description	AUC last of RDEA3170 in fasted condition.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	10 mg dose of RDEA3170, administered as 4 × 2.5 mg tablets, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.
Measure Participants	15	15
Geometric Mean (95% Confidence Interval) [ng·hr/mL]	119	114

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The sample size is not based on formal power calculations, as this study is designed only to provide an initial assessment of the PK, PD, and safety profile of RDEA3170.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares mean Ratio (%)
	Estimated Value	97.3
	Confidence Interval	(2-Sided) 90%; 85.6 to 111
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Area Under the Concentration-time Curve From 0 to Infinity (AUC∞)
Description	AUC∞ of RDEA3170 the fasted condition.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	10 mg dose of RDEA3170, administered as 4 × 2.5 mg tablets, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.
Measure Participants	15	15
Geometric Mean (95% Confidence Interval) [ng·hr/mL]	131	130

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The sample size is not based on formal power calculations, as this study is designed only to provide an initial assessment of the PK, PD, and safety profile of RDEA3170.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares mean Ratio (%)
	Estimated Value	100
	Confidence Interval	(2-Sided) 90%; 87.3 to 115
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Apparent Terminal Half-life (t1/2)
Description	t1/2 of RDEA3170 following various treatments.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment A	Treatment B	Treatment C	Treatment D
Arm/Group Description	10 mg dose of RDEA3170, administered as 4 × 2.5 mg tablets, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (low-fat, high calorie meal).	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (high-fat, high calorie meal).
Measure Participants	15	15	15	15
Geometric Mean (95% Confidence Interval) [hr]	16.5	15.5	15.4	16.6

6. Primary Outcome

Title	Cmax: Effect of High Fat Meal on the PK of RDEA3170 Tablets
Description	Cmax of RDEA3170 in high-fat fed state.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment B	Treatment D
Arm/Group Description	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (high-fat, high calorie meal).
Measure Participants	15	15
Geometric Mean (95% Confidence Interval) [ng/mL]	14.9	27.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The sample size is not based on formal power calculations, as this study is designed only to provide an initial assessment of the PK, PD, and safety profile of RDEA3170.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares mean Ratio (%)
	Estimated Value	182
	Confidence Interval	(2-Sided) 90%; 144 to 230
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Primary Outcome

Title	AUC Last: Effect of High Fat Meal on the PK of RDEA3170 Tablets
Description	AUC last of RDEA3170 in high-fat fed state.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment B	Treatment D
Arm/Group Description	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (high-fat, high calorie meal).
Measure Participants	15	15
Geometric Mean (95% Confidence Interval) [ng·hr/mL]	114	160

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The sample size is not based on formal power calculations, as this study is designed only to provide an initial assessment of the PK, PD, and safety profile of RDEA3170.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares mean Ratio (%)
	Estimated Value	140
	Confidence Interval	(2-Sided) 90%; 121 to 163
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Primary Outcome

Title	AUC∞: Effect of High Fat Meal on the PK of RDEA3170 Tablets
Description	AUC∞ of RDEA3170 in high-fat fed state.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment B	Treatment D
Arm/Group Description	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (high-fat, high calorie meal).
Measure Participants	15	15
Geometric Mean (95% Confidence Interval) [ng·hr/mL]	130	173

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The sample size is not based on formal power calculations, as this study is designed only to provide an initial assessment of the PK, PD, and safety profile of RDEA3170.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares mean Ratio (%)
	Estimated Value	134
	Confidence Interval	(2-Sided) 90%; 114 to 156
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Primary Outcome

Title	Cmax: Effect of Low Fat Meal on the PK of RDEA3170 Tablets
Description	Cmax of RDEA3170 in low-fat fed state.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment B	Treatment C
Arm/Group Description	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (low-fat, high calorie meal).
Measure Participants	15	15
Geometric Mean (95% Confidence Interval) [ng/mL]	14.9	11.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The sample size is not based on formal power calculations, as this study is designed only to provide an initial assessment of the PK, PD, and safety profile of RDEA3170.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares mean Ratio (%)
	Estimated Value	79.1
	Confidence Interval	(2-Sided) 90%; 66.4 to 94.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Primary Outcome

Title	AUC Last: Effect of Low Fat Meal on the PK of RDEA3170 Tablets
Description	AUC last of RDEA3170 in low-fat fed state.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment B	Treatment C
Arm/Group Description	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (low-fat, high calorie meal).
Measure Participants	15	15
Geometric Mean (95% Confidence Interval) [ng·hr/mL]	114	97.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The sample size is not based on formal power calculations, as this study is designed only to provide an initial assessment of the PK, PD, and safety profile of RDEA3170.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares mean Ratio (%)
	Estimated Value	85.5
	Confidence Interval	(2-Sided) 90%; 73.9 to 98.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Primary Outcome

Title	AUC∞: Effect of Low Fat Meal on the PK of RDEA3170 Tablets
Description	AUC∞ of RDEA3170 in low-fat fed state.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment B	Treatment C
Arm/Group Description	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (low-fat, high calorie meal).
Measure Participants	15	15
Geometric Mean (95% Confidence Interval) [ng·hr/mL]	130	108

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The sample size is not based on formal power calculations, as this study is designed only to provide an initial assessment of the PK, PD, and safety profile of RDEA3170.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares mean Ratio (%)
	Estimated Value	83.4
	Confidence Interval	(2-Sided) 90%; 73.5 to 94.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Single Dose Pharmacodynamics (PD) Profile of RDEA3170 From Serum and Urine
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment A	Treatment B	Treatment C	Treatment D
Arm/Group Description	10 mg dose of RDEA3170, administered as 4 × 2.5 mg tablets, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (low-fat, high calorie meal).	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (high-fat, high calorie meal).
Measure Participants	15	15	15	15
Serum Urate Maximum % Change	-34.4 (2.08)	-34.4 (2.27)	-37.3 (1.89)	-49.0 (1.96)
Urine Uric Acid % Change(0-24h)	96.6 (12.5)	78.5 (8.38)	53.4 (8.85)	65.9 (9.70)
Renal Clearance of Uric Acid % Change (0-24h)	170 (19.5)	147 (15.6)	128 (18.9)	179 (21.5)
Fractional Excretion of Uric Acid % Change (0-24h)	159 (15.1)	151 (22.0)	149 (22.7)	199 (23.2)

13. Secondary Outcome

Title	Incidence of Treatment-Emergent Adverse Events
Time Frame	7 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment A	Treatment B	Treatment C	Treatment D
Arm/Group Description	10 mg dose of RDEA3170, administered as 4 × 2.5 mg tablets, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (low-fat, high calorie meal).	10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (high-fat, high calorie meal).
Measure Participants	15	15	15	15
Number [Number of Participants]	0 0%	1 25%	1 25%	3 75%

Adverse Events

Time Frame	7 weeks
Adverse Event Reporting Description	Overall number of baseline participants used to determine number of participants at risk.
Arm/Group Title	Treatment A		Treatment B		Treatment C		Treatment D
Arm/Group Description	10 mg dose of RDEA3170, administered as 4 × 2.5 mg tablets, in the fasted state.		10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state.		10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (low-fat, high calorie meal).		10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (high-fat, high calorie meal).
All Cause Mortality
	Treatment A		Treatment B		Treatment C		Treatment D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment A		Treatment B		Treatment C		Treatment D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Treatment A		Treatment B		Treatment C		Treatment D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		1/15 (6.7%)		1/15 (6.7%)		3/15 (20%)
Gastrointestinal disorders
Nausea	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
Infections and infestations
Nasopharyngitis	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	2/15 (13.3%)	2
Musculoskeletal and connective tissue disorders
Periarthritis	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Nervous system disorders
Headache	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI shall submit a copy of the Publication to Sponsor for review at least 45 days prior to its proposed submission. Sponsor reserves the right to delay any such publication for an additional period of 60 days. Upon Sponsor's request, PI agrees to delete from the proposed publication any Confidential Information. PI agrees not to release any publication without the prior written permission of Sponsor.