RDEA3170 Tablet and Capsule Bioavailability Study

• Sponsor: Ardea Biosciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02448368
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arms: 8
• Actual Duration (Months): 9
• Patients Per Site Per Month: 3.9

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the relative bioavailability of RDEA3170 capsules compared with RDEA3170 tablets.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: RDEA3170,10 mg; Drug: RDEA3170, 2.5 mg; Drug: RDEA3170, 5 mg; Drug: RDEA3170, 10 mg; Drug: RDEA3170, 2.5 mg	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Phase 1, Randomized, Open-Label, Study in Healthy Adult Male Subjects to Assess the Relative Bioavailability and Food Effect of Various Formulations of RDEA3170
• Actual Study Start Date: May 1, 2015
• Actual Primary Completion Date: Jun 26, 2015
• Actual Study Completion Date: Jan 29, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment A RDEA3170, 5 mg (FN24), administered in the fasted state.	Drug: RDEA3170, 5 mg; Approximately 20 subjects will be randomized to 1 of 10 treatment sequences with single doses occurring on Days 1, 5, 9, 13, and 17.; Other Names: Cohort 1
Experimental: Treatment B RDEA3170, 5 mg (FN24), administered in the fed state (high-fat, high-calorie meal).	Drug: RDEA3170, 5 mg; Approximately 20 subjects will be randomized to 1 of 10 treatment sequences with single doses occurring on Days 1, 5, 9, 13, and 17.; Other Names: Cohort 1
Experimental: Treatment C RDEA3170, 10 mg (FN25), administered in the fasted state.	Drug: RDEA3170,10 mg; Approximately 20 subjects will be randomized to 1 of 10 treatment sequences with single doses occurring on Days 1, 5, 9, 13, and 17.; Other Names: Cohort 1
Experimental: Treatment D RDEA3170, 10 mg (FN25), administered in the fed state (high-fat, high-calorie meal).	Drug: RDEA3170,10 mg; Approximately 20 subjects will be randomized to 1 of 10 treatment sequences with single doses occurring on Days 1, 5, 9, 13, and 17.; Other Names: Cohort 1
Experimental: Treatment E RDEA3170, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.	Drug: RDEA3170, 2.5 mg; Approximately 20 subjects will be randomized to 1 of 10 treatment sequences with single doses occurring on Days 1, 5, 9, 13, and 17.; Other Names: Cohort 1
Experimental: Treatment I RDEA3170, 10 mg (FN26), administered in the fasted state.	Drug: RDEA3170, 10 mg; Fifteen subjects were randomized to 1 of 3 treatment sequences with single doses occurring on Days 1, 5, and 9.; Other Names: Cohort 3
Experimental: Treatment J RDEA3170, 10 mg (FN26), administered in the fed state (high-fat, high-calorie meal).	Drug: RDEA3170, 10 mg; Fifteen subjects were randomized to 1 of 3 treatment sequences with single doses occurring on Days 1, 5, and 9.; Other Names: Cohort 3
Experimental: Treatment K RDEA3170, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.	Drug: RDEA3170, 2.5 mg; Fifteen subjects were randomized to 1 of 3 treatment sequences with single doses occurring on Days 1, 5, and 9.; Other Names: Cohort 3

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) [Day 1, 5, 9, 13, 17]

   Cmax is the maximum observed concentration of a drug after administration

2. Time of Occurrence of Maximum Observed Concentration (Tmax) [Day 1, 5, 9, 13, 17]

   Tmax is the time of occurrence of cmax

3. Area Under the Concentration-time Curve From Time Zero to the Quantifiable Last Sampling Timepoint (AUC Last) [Day 1, 5, 9, 13, 17]

   AUC last is the area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint

4. Area Under the Concentration-time Curve From 0 to Infinity (AUC∞) [Day 1, 5, 9, 13, 17]

   AUC 0-∞ is a meausre of total concentration from time zero to infinity

5. Apparent Terminal Half-life (t1/2) [Day 1, 5, 9, 13, 17]

   t1/2 is a measure of apparent terminal half-life

6. Maximum Observed Plasma Concentration (Cmax): Effect of High Fat Meal on the PK of RDEA3170 Capsules [Day 1, 5, 9, 13, 17]

   Cmax is the maximum observed concentration of a drug after administration

7. AUC Last: Effect of High Fat Meal on the PK of RDEA3170 Capsules [Day 1, 5, 9, 13, 17]

   AUC last is the area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint

8. AUC∞: Effect of High Fat Meal on the PK of RDEA3170 Capsules [Day 1, 5, 9, 13, 17]

   AUC 0-∞ is a meausre of total concentration from time zero to infinity

Secondary Outcome Measures

1. Pharmacodynamics (PD) Profile of RDEA3170 [Day -1, 1, 5, 9, 13, 17]

   Serum samples were collected at the following timepoints in relation to RDEA3170 dosing: Day 1 (Cohort 1 and Cohort 3): -24, -23, -22, -21, -20, -18, -16, -14, and -12 hours prior to dosing. Days 1, 5, and 9 (Cohort 1 and Cohort 3), and Days 13 and 17 (Cohort 1 only): predose (within 30 minutes prior to dosing) and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose. Urine samples (total catch) were collected at the following timepoints in relation to RDEA3170 dosing: Day 1 (Cohort 1 and Cohort 3): -24 to -21, -21 to -18, -18 to -12, and -12 to 0 hours predose. Days 1, 5, and 9 (Cohort 1 and Cohort 3), and Days 13 and 17 (Cohort 1 only): 0 to 3, 3 to 6, 6 to 12, and 12 to 24 hours postdose.

2. Incidence of Treatment-Emergent Adverse Events [8 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 of 4 to 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 within 12 weeks prior to Day 1 or gave a plasma donation within 4 weeks prior to Day 1.

• Subject has clinically unacceptable physical examination, per the Investigator's judgment.

• Subject has clinically relevant abnormalities in blood pressure, heart rate, or body temperature, per the Investigator's judgment.

• Subject has Screening clinical safety laboratory parameters (serum chemistry [other than serum creatinine and serum urate], hematology, coagulation or urinalysis) that are outside the normal limits and are considered clinically significant by the Investigator.

• Subject has a serum creatinine value above the upper limit of normal at the Screening visit.

• Subject has clinically relevant abnormalities in 12-lead electrocardiogram, per the Investigator's judgment.

• Subject has a history of cardiac abnormalities

• Subject cannot swallow multiple tablets or capsules.

• Subject has received any strong or moderate enzyme-inducing drug or product within 2 months prior to Day 1.

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: NCT02448368
• Other Study ID Numbers: RDEA3170-111
• First Posted: May 19, 2015
• Last Update Posted: Aug 20, 2018
• Last Verified: Nov 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Verinurad

Study Results

Participant Flow

Recruitment Details	35 participants were randomized
Pre-assignment Detail	Twenty subjects were randomized to 1 of 10 treatment sequences in Cohort 1 with single doses. Fifteen subjects were randomized to 1 of 3 treatment sequences (IJK, JKI, and KIJ) in optional Cohort 3, with single doses occurring on Days 1, 5, and 9. The optional Cohort 2 to evaluate RDEA3170 capsules, 5 mg FN23 was not conducted per Sponsor decision.

Arm/Group Title	Cohort 1: Sequence ABECD (Days 1, 5, 9, 13, and 17)	Cohort 1: Sequence AEBDC (Days 1, 5, 9, 13, and 17)	Cohort 1: Sequence EADBC (Days 1, 5, 9, 13, and 17)	Cohort 1: Sequence EDACB (Days 1, 5, 9, 13, and 17)	Cohort 1: Sequence DECAB (Days 1, 5, 9, 13, and 17)	Cohort 1: Sequence BACED (Days 1, 5, 9, 13, and 17)	Cohort 1: Sequence BCADE (Days 1, 5, 9, 13, and 17)	Cohort 1: Sequence CBDAE (Days 1, 5, 9, 13, and 17)	Cohort 1: Sequence CDBEA (Days 1, 5, 9, 13, and 17)	Cohort 1: Sequence DCEBA (Days 1, 5, 9, 13, and 17)	Cohort 3: Sequence IJK (Days 1, 5, and 9)	Cohort 3: Sequence JKI (Days 1, 5, and 9)	Cohort 3: Sequence KIJ (Days 1, 5, and 9)
Arm/Group Description	5 mg FN24 capsules, fasted; 5 mg FN24 capsules, fed; 10 mg FN17 tablets, fasted; 10 mg FN25 capsules, fasted; 10 mg FN25 capsules, fed	5 mg FN24 capsules, fasted; 10 mg FN17 tablets, fasted; 5 mg FN24 capsules, fed; 10 mg FN25 capsules, fed; 10 mg FN25 capsules, fasted	10 mg FN17 tablets, fasted; 5 mg FN24 capsules, fasted; 10 mg FN25 capsules, fed; 5 mg FN24 capsules, fed; 10 mg FN25 capsules, fasted	10 mg FN17 tablets, fasted; 10 mg FN25 capsules, fed; 5 mg FN24 capsules, fasted; 10 mg FN25 capsules, fasted; 5 mg FN24 capsules, fed	10 mg FN25 capsules, fed; 10 mg FN17 tablets, fasted; 10 mg FN25 capsules, fasted; 5 mg FN24 capsules, fasted; 5 mg FN24 capsules, fed	5 mg FN24 capsules, fed; 5 mg FN24 capsules, fasted; 10 mg FN25 capsules, fasted; 10 mg FN17 tablets, fasted; 10 mg FN25 capsules, fed	5 mg FN24 capsules, fed; 10 mg FN25 capsules, fasted; 5 mg FN24 capsules, fasted; 10 mg FN25 capsules, fed; 10 mg FN17 tablets, fasted	10 mg FN25 capsules, fasted; 5 mg FN24 capsules, fed; 10 mg FN25 capsules, fed; 5 mg FN24 capsules, fasted; 10 mg FN17 tablets, fasted	10 mg FN25 capsules, fasted; 10 mg FN25 capsules, fed; 5 mg FN24 capsules, fed; 10 mg FN17 tablets, fasted; 5 mg FN24 capsules, fasted	10 mg FN25 capsules, fed; 10 mg FN25 capsules, fasted; 10 mg FN17 tablets, fasted; 5 mg FN24 capsules, fed; 5 mg FN24 capsules, fasted	10 mg FN26 capsules, fasted; 10 mg FN26 capsules, fed; 10 mg FN17 tablets, fasted	10 mg FN26 capsules, fed; 10 mg FN17 tablets, fasted; 10 mg FN26 capsules, fasted	10 mg FN17 tablets, fasted; 10 mg FN26 capsules, fasted; 10 mg FN26 capsules, fed
Period Title: Overall Study
STARTED	2	2	2	2	2	2	2	2	2	2	5	5	5
COMPLETED	2	2	2	2	2	2	2	2	2	2	5	5	5
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 3 (Optional)	Total
Arm/Group Description	Treatment A: RDEA3170 capsules, 5 mg (FN24), administered in the fasted state. Treatment B: RDEA3170 capsules, 5 mg FN24, administered in the fed state (high-fat, high-calorie meal). Treatment C: RDEA3170 capsules, 10 mg (FN25), administered in the fasted state. Treatment D: RDEA3170 capsules, 10 mg FN25, administered in the fed state (high-fat, high-calorie meal). Treatment E: RDEA3170 tablets, 2.5 mg FN17, administered as 10 mg (4 × 2.5 mg), in the fasted state.	Treatment I: RDEA3170 capsules, 10 mg (FN26), administered in the fasted state. Treatment J: RDEA3170 capsules, 10 mg FN26, administered in the fed state (high-fat, high-calorie meal). Treatment K: RDEA3170 tablets, 2.5 mg FN17, administered as 10 mg (4 × 2.5 mg), in the fasted state	Total of all reporting groups
Overall Participants	20	15	35
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	35 (8.9)	41 (12.0)	38 (10.45)
Sex/Gender, Customized (Number) [Number]
Male	20 100%	15 100%	35 100%
Female	0 0%	0 0%	0 0%
Region of Enrollment (Number) [Number]
United States	20 100%	15 100%	35 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Description	Cmax is the maximum observed concentration of a drug after administration
Time Frame	Day 1, 5, 9, 13, 17

Outcome Measure Data

Analysis Population Description

A subject in Treatment A was excluded from pharmacokinetic (PK) analysis on Day 13 following oral administration of 5 mg (FN24) capsules under the fasted condition due to a suspected dosing error. There was no evaluable PK available on Day 13 for this subject.

Arm/Group Title	Treatment A	Treatment C	Treatment E	Treatment I	Treatment K
Arm/Group Description	Verinurad capsules, 5 mg (FN24), administered in the fasted state.	Verinurad capsules, 10 mg (FN25), administered in the fasted state.	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fasted state.	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state
Measure Participants	19	20	20	15	15
Geometric Mean (95% Confidence Interval) [ng/mL]	14.9	23.4	12.9	14.0	13.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment E
	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	232
	Confidence Interval	(2-Sided) 90%; 202 to 266
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment C, Treatment E
	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	181
	Confidence Interval	(2-Sided) 90%; 164 to 200
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment I, Treatment K
	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	106
	Confidence Interval	(2-Sided) 90%; 91.5 to 124
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Time of Occurrence of Maximum Observed Concentration (Tmax)
Description	Tmax is the time of occurrence of cmax
Time Frame	Day 1, 5, 9, 13, 17

Outcome Measure Data

Analysis Population Description

A subject in Treatment A was excluded from pharmacokinetic (PK) analysis on Day 13 following oral administration of 5 mg (FN24) capsules under the fasted condition due to a suspected dosing error. There was no evaluable PK available on Day 13 for this subject.

Arm/Group Title	Treatment A	Treatment B	Treatment C	Treatment D	Treatment E	Treatment I	Treatment J	Treatment K
Arm/Group Description	Verinurad capsules, 5 mg (FN24), administered in the fasted state.	RDEA3170 capsules, 5 mg (FN24), administered in the fed state (highfat, high-calorie meal).	Verinurad capsules, 10 mg (FN25), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN25), administered in the fed state (high-fat, high-calorie meal)	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fed state (high-fat, high-calorie meal).	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.
Measure Participants	19	20	20	20	20	15	15	15
Median (Full Range) [hr]	3.00 (2.05)	4.00 (1.69)	3.50 (1.74)	4.00 (1.05)	2.00 (1.54)	2.00 (2.71)	6.00 (2.45)	3.00 (2.66)

3. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to the Quantifiable Last Sampling Timepoint (AUC Last)
Description	AUC last is the area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint
Time Frame	Day 1, 5, 9, 13, 17

Outcome Measure Data

Analysis Population Description

A subject in Treatment A was excluded from pharmacokinetic (PK) analysis on Day 13 following oral administration of 5 mg (FN24) capsules under the fasted condition due to a suspected dosing error. There was no evaluable PK available on Day 13 for this subject.

Arm/Group Title	Treatment A	Treatment C	Treatment E	Treatment I	Treatment K
Arm/Group Description	Verinurad capsules, 5 mg (FN24), administered in the fasted state.	Verinurad capsules, 10 mg (FN25), administered in the fasted state.	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fasted state.	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state
Measure Participants	19	20	20	15	15
Geometric Mean (95% Confidence Interval) [ng·hr/mL]	91.2	185	109	149	115

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment E
	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	170
	Confidence Interval	(2-Sided) 90%; 147 to 195
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment C, Treatment E
	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	170
	Confidence Interval	(2-Sided) 90%; 146 to 199
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment I, Treatment K
	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	129
	Confidence Interval	(2-Sided) 90%; 114 to 146
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Area Under the Concentration-time Curve From 0 to Infinity (AUC∞)
Description	AUC 0-∞ is a meausre of total concentration from time zero to infinity
Time Frame	Day 1, 5, 9, 13, 17

Outcome Measure Data

Analysis Population Description

A subject in Treatment A was excluded from pharmacokinetic (PK) analysis on Day 13 following oral administration of 5 mg (FN24) capsules under the fasted condition due to a suspected dosing error. There was no evaluable PK available on Day 13 for this subject.

Arm/Group Title	Treatment A	Treatment C	Treatment E	Treatment I	Treatment K
Arm/Group Description	Verinurad capsules, 5 mg (FN24), administered in the fasted state.	Verinurad capsules, 10 mg (FN25), administered in the fasted state.	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fasted state.	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state
Measure Participants	19	20	20	20	20
Geometric Mean (95% Confidence Interval) [ng·hr/mL]	95.7	192	121	161	123

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment E
	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	161
	Confidence Interval	(2-Sided) 90%; 139 to 187
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment C, Treatment E
	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	159
	Confidence Interval	(2-Sided) 90%; 135 to 188
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment I, Treatment K
	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	131
	Confidence Interval	(2-Sided) 90%; 116 to 147
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Apparent Terminal Half-life (t1/2)
Description	t1/2 is a measure of apparent terminal half-life
Time Frame	Day 1, 5, 9, 13, 17

Outcome Measure Data

Analysis Population Description

A subject in Treatment A was excluded from pharmacokinetic (PK) analysis on Day 13 following oral administration of 5 mg (FN24) capsules under the fasted condition due to a suspected dosing error. There was no evaluable PK available on Day 13 for this subject.

Arm/Group Title	Treatment A	Treatment B	Treatment C	Treatment D	Treatment E	Treatment I	Treatment J	Treatment K
Arm/Group Description	Verinurad capsules, 5 mg (FN24), administered in the fasted state.	RDEA3170 capsules, 5 mg (FN24), administered in the fed state (highfat, high-calorie meal).	Verinurad capsules, 10 mg (FN25), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN25), administered in the fed state (high-fat, high-calorie meal)	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fed state (high-fat, high-calorie meal).	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.
Measure Participants	19	20	20	20	20	15	15	15
Geometric Mean (95% Confidence Interval) [hr]	13.6 (2.05)	14.9 (1.69)	14.0 (1.74)	12.9 (1.05)	17.3 (1.54)	14.4 (2.71)	15.8 (2.45)	13.2 (2.66)

6. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax): Effect of High Fat Meal on the PK of RDEA3170 Capsules
Description	Cmax is the maximum observed concentration of a drug after administration
Time Frame	Day 1, 5, 9, 13, 17

Outcome Measure Data

Analysis Population Description

A subject in Treatment A was excluded from pharmacokinetic (PK) analysis on Day 13 following oral administration of 5 mg (FN24) capsules under the fasted condition due to a suspected dosing error. There was no evaluable PK available on Day 13 for this subject.

Arm/Group Title	Treatment A	Treatment B	Treatment C	Treatment D	Treatment I	Treatment J
Arm/Group Description	Verinurad capsules, 5 mg (FN24), administered in the fasted state.	RDEA3170 capsules, 5 mg (FN24), administered in the fed state (highfat, high-calorie meal).	Verinurad capsules, 10 mg (FN25), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN25), administered in the fed state (high-fat, high-calorie meal)	RDEA3170 capsules, 10 mg (FN26), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fed state (high-fat, high-calorie meal).
Measure Participants	19	20	20	20	15	15
Geometric Mean (95% Confidence Interval) [ng/mL]	14.9	15.0	23.4	23.3	14.0	16.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment C
	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	99.4
	Confidence Interval	(2-Sided) 90%; 88.3 to 112
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment E, Treatment I
	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	99.9
	Confidence Interval	(2-Sided) 90%; 85.5 to 117
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment K, Treatment I
	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	116
	Confidence Interval	(2-Sided) 90%; 94.8 to 143
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Primary Outcome

Title	AUC Last: Effect of High Fat Meal on the PK of RDEA3170 Capsules
Description	AUC last is the area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint
Time Frame	Day 1, 5, 9, 13, 17

Outcome Measure Data

Analysis Population Description

A subject in Treatment A was excluded from pharmacokinetic (PK) analysis on Day 13 following oral administration of 5 mg (FN24) capsules under the fasted condition due to a suspected dosing error. There was no evaluable PK available on Day 13 for this subject.

Arm/Group Title	Treatment A	Treatment B	Treatment C	Treatment D	Treatment I	Treatment J
Arm/Group Description	Verinurad capsules, 5 mg (FN24), administered in the fasted state.	RDEA3170 capsules, 5 mg (FN24), administered in the fed state (highfat, high-calorie meal).	Verinurad capsules, 10 mg (FN25), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN25), administered in the fed state (high-fat, high-calorie meal)	RDEA3170 capsules, 10 mg (FN26), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fed state (high-fat, high-calorie meal).
Measure Participants	19	20	20	20	15	15
Geometric Mean (95% Confidence Interval) [ng·hr/mL]	91.2	99.2	185	192	149	172

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment C
	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	107
	Confidence Interval	(2-Sided) 90%; 98.3 to 116
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment E, Treatment I
	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	104
	Confidence Interval	(2-Sided) 90%; 95.0 to 113
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment K, Treatment I
	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	115
	Confidence Interval	(2-Sided) 90%; 95.3 to 140
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Primary Outcome

Title	AUC∞: Effect of High Fat Meal on the PK of RDEA3170 Capsules
Description	AUC 0-∞ is a meausre of total concentration from time zero to infinity
Time Frame	Day 1, 5, 9, 13, 17

Outcome Measure Data

Analysis Population Description

A subject in Treatment A was excluded from pharmacokinetic (PK) analysis on Day 13 following oral administration of 5 mg (FN24) capsules under the fasted condition due to a suspected dosing error. There was no evaluable PK available on Day 13 for this subject.

Arm/Group Title	Treatment A	Treatment B	Treatment C	Treatment D	Treatment I	Treatment J
Arm/Group Description	Verinurad capsules, 5 mg (FN24), administered in the fasted state.	RDEA3170 capsules, 5 mg (FN24), administered in the fed state (highfat, high-calorie meal).	Verinurad capsules, 10 mg (FN25), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN25), administered in the fed state (high-fat, high-calorie meal)	RDEA3170 capsules, 10 mg (FN26), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fed state (high-fat, high-calorie meal).
Measure Participants	19	20	20	20	15	15
Geometric Mean (95% Confidence Interval) [ng·hr/mL]	95.7	104	192	199	161	182

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment C
	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	107
	Confidence Interval	(2-Sided) 90%; 98.1 to 116
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment E, Treatment I
	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	103
	Confidence Interval	(2-Sided) 90%; 94.6 to 113
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment K, Treatment I
	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	113
	Confidence Interval	(2-Sided) 90%; 93.3 to 137
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Pharmacodynamics (PD) Profile of RDEA3170
Description	Serum samples were collected at the following timepoints in relation to RDEA3170 dosing: Day 1 (Cohort 1 and Cohort 3): -24, -23, -22, -21, -20, -18, -16, -14, and -12 hours prior to dosing. Days 1, 5, and 9 (Cohort 1 and Cohort 3), and Days 13 and 17 (Cohort 1 only): predose (within 30 minutes prior to dosing) and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose. Urine samples (total catch) were collected at the following timepoints in relation to RDEA3170 dosing: Day 1 (Cohort 1 and Cohort 3): -24 to -21, -21 to -18, -18 to -12, and -12 to 0 hours predose. Days 1, 5, and 9 (Cohort 1 and Cohort 3), and Days 13 and 17 (Cohort 1 only): 0 to 3, 3 to 6, 6 to 12, and 12 to 24 hours postdose.
Time Frame	Day -1, 1, 5, 9, 13, 17

Outcome Measure Data

Analysis Population Description

A subject in Treatment A was excluded from pharmacokinetic (PK) analysis on Day 13 (but not from pharmacodynamics analysis) following oral administration of 5 mg (FN24) capsules under the fasted condition due to a suspected dosing error. There was no evaluable PK available on Day 13 for this subject.

Arm/Group Title	Treatment A	Treatment B	Treatment C	Treatment D	Treatment E	Treatment I	Treatment J	Treatment K
Arm/Group Description	Verinurad capsules, 5 mg (FN24), administered in the fasted state.	RDEA3170 capsules, 5 mg (FN24), administered in the fed state (highfat, high-calorie meal).	Verinurad capsules, 10 mg (FN25), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN25), administered in the fed state (high-fat, high-calorie meal)	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fed state (high-fat, high-calorie meal).	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.
Measure Participants	20	20	20	20	20	15	15	15
Serum Urate Maximum % Change	-29.1 (2.05)	-40.6 (1.69)	-42.5 (1.74)	-52.3 (1.05)	-30.3 (1.54)	-35.2 (2.71)	-46.2 (2.45)	-29.3 (2.66)
Urine Uric Acid % Change (0-24h)	79.2 (21.6)	92.3 (19.0)	109 (27.8)	88.8 (13.6)	76.8 (14.4)	49.5 (8.22)	53.7 (8.56)	53.9 (10.0)
Renal Clearance of Uric Acid % Change (0-24h)	137 (33.1)	175 (27.2)	226 (48.4)	216 (23.7)	142 (27.1)	117 (17.4)	153 (17.2)	107 (17.7)
Fractional Excretion of uric acid % Change (0-24h)	119 (13.1)	157 (12.9)	214 (14.5)	214 (14.3)	145 (15.1)	137 (18.4)	168 (15.5)	120 (14.2)

10. Secondary Outcome

Title	Incidence of Treatment-Emergent Adverse Events
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received any dose of investigational product.

Arm/Group Title	Treatment A	Treatment B	Treatment C	Treatment D	Treatment E	Treatment I	Treatment J	Treatmnet K
Arm/Group Description	Verinurad capsules, 5 mg (FN24), administered in the fasted state.	RDEA3170 capsules, 5 mg (FN24), administered in the fed state (highfat, high-calorie meal).	Verinurad capsules, 10 mg (FN25), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN25), administered in the fed state (high-fat, high-calorie meal)	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fasted state.	RDEA3170 capsules, 10 mg (FN26), administered in the fed state (high-fat, high-calorie meal).	RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state
Measure Participants	20	20	20	20	20	15	15	15
Number [Number of participants]	1 5%	1 6.7%	0 0%	0 NaN	0 NaN	2 NaN	2 NaN	0 NaN

Adverse Events

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		Treatment E		Treatment I		Treatment J		Treatment K
Arm/Group Description	Verinurad capsules, 5 mg (FN24), administered in the fasted state.		Verinurad capsules, 5 mg (FN24), administered in the fed state (highfat, high-calorie meal).		Verinurad capsules, 10 mg (FN25), administered in the fasted state.		RDEA3170 capsules, 10 mg (FN25), administered in the fed state (high-fat, high-calorie meal)		RDEA3170 tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.		Verinurad capsules, 10 mg (FN26), administered in the fasted state.		Verinurad capsules, 10 mg (FN26), administered in the fed state (high-fat, high-calorie meal).		Verinurad tablets, 2.5 mg (FN17), administered as 10 mg (4 × 2.5 mg), in the fasted state.
All Cause Mortality
	Treatment A		Treatment B		Treatment C		Treatment D		Treatment E		Treatment I		Treatment J		Treatment K
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment A		Treatment B		Treatment C		Treatment D		Treatment E		Treatment I		Treatment J		Treatment K
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Treatment A		Treatment B		Treatment C		Treatment D		Treatment E		Treatment I		Treatment J		Treatment K
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		1/20 (5%)		0/20 (0%)		0/20 (0%)		0/20 (0%)		2/15 (13.3%)		2/15 (13.3%)		0/15 (0%)
Gastrointestinal disorders
Diarrhoea	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	2/15 (13.3%)	2	1/15 (6.7%)	1	0/15 (0%)	0
Infections and infestations
Viral Infection	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Nervous system disorders
Headache	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/15 (0%)	0	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.