RDEA3170 Tablet and Capsule Bioavailability Study

• RDEA3170,10 mg (Drug), also known as Cohort 1: Approximately 20 subjects will be randomized to 1 of 10 treatment sequences with single doses occurring on Days 1, 5, 9, 13, and 17.
• RDEA3170, 2.5 mg (Drug), also known as Cohort 1: Approximately 20 subjects will be randomized to 1 of 10 treatment sequences with single doses occurring on Days 1, 5, 9, 13, and 17.
• RDEA3170, 5 mg (Drug), also known as Cohort 1: Approximately 20 subjects will be randomized to 1 of 10 treatment sequences with single doses occurring on Days 1, 5, 9, 13, and 17.
• RDEA3170, 10 mg (Drug), also known as Cohort 3: Fifteen subjects were randomized to 1 of 3 treatment sequences with single doses occurring on Days 1, 5, and 9.
• RDEA3170, 2.5 mg (Drug), also known as Cohort 3: Fifteen subjects were randomized to 1 of 3 treatment sequences with single doses occurring on Days 1, 5, and 9.

Primary outcomes

• Maximum Observed Plasma Concentration (Cmax) [Day 1, 5, 9, 13, 17]: Cmax is the maximum observed concentration of a drug after administration
• Time of Occurrence of Maximum Observed Concentration (Tmax) [Day 1, 5, 9, 13, 17]: Tmax is the time of occurrence of cmax
• 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
• 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
• Apparent Terminal Half-life (t1/2) [Day 1, 5, 9, 13, 17]: t1/2 is a measure of apparent terminal half-life
• 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
• 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
• 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 outcomes

• 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.
• Incidence of Treatment-Emergent Adverse Events [8 weeks]

Sex: Male, ages: 18 Years to 65 Years, accepts healthy volunteers

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.

Participant flow

Outcome results

• Maximum Observed Plasma Concentration (Cmax) (Primary), Geometric mean, ng/mL: Treatment A 14.9 (12.5 to 17.8); Treatment C 23.4 (19.3 to 28.2); Treatment E 12.9 (11.2 to 14.9); Treatment I 14.0 (12.1 to 16.3); Treatment K 13.2 (11.2 to 15.5)
• Time of Occurrence of Maximum Observed Concentration (Tmax) (Primary), Median, hr: Treatment A 3.00 (1.00 to 4.00); Treatment B 4.00 (3.00 to 10.0); Treatment C 3.50 (1.00 to 6.00); Treatment D 4.00 (3.00 to 8.00); Treatment E 2.00 (1.00 to 4.00); Treatment I 2.00 (1.00 to 6.00); Treatment J 6.00 (3.00 to 12.0); Treatment K 3.00 (1.00 to 6.00)
• Area Under the Concentration-time Curve From Time Zero to the Quantifiable Last Sampling Timepoint (AUC Last) (Primary), Geometric mean, ng·hr/mL: Treatment A 91.2 (80.6 to 103); Treatment C 185 (163 to 211); Treatment E 109 (89.9 to 132); Treatment I 149 (130 to 171); Treatment K 115 (96.9 to 137)
• Area Under the Concentration-time Curve From 0 to Infinity (AUC∞) (Primary), Geometric mean, ng·hr/mL: Treatment A 95.7 (84.5 to 108); Treatment C 192 (169 to 219); Treatment E 121 (97.0 to 150); Treatment I 161 (140 to 184); Treatment K 123 (103 to 146)
• Apparent Terminal Half-life (t1/2) (Primary), Geometric mean, hr: Treatment A 13.6 (11.2 to 16.5); Treatment B 14.9 (12.6 to 17.6); Treatment C 14.0 (11.5 to 17.0); Treatment D 12.9 (10.6 to 15.6); Treatment E 17.3 (13.4 to 22.3); Treatment I 14.4 (9.70 to 21.5); Treatment J 15.8 (11.6 to 21.5); Treatment K 13.2 (9.44 to 18.6)
• Maximum Observed Plasma Concentration (Cmax): Effect of High Fat Meal on the PK of RDEA3170 Capsules (Primary), Geometric mean, ng/mL: Treatment A 14.9 (12.5 to 17.8); Treatment B 15.0 (12.6 to 18.0); Treatment C 23.4 (19.3 to 28.2); Treatment D 23.3 (19.2 to 28.3); Treatment I 14.0 (12.1 to 16.3); Treatment J 16.3 (12.9 to 20.7)
• AUC Last: Effect of High Fat Meal on the PK of RDEA3170 Capsules (Primary), Geometric mean, ng·hr/mL: Treatment A 91.2 (80.6 to 103); Treatment B 99.2 (86.4 to 114); Treatment C 185 (163 to 211); Treatment D 192 (171 to 216); Treatment I 149 (130 to 171); Treatment J 172 (136 to 218)
• AUC∞: Effect of High Fat Meal on the PK of RDEA3170 Capsules (Primary), Geometric mean, ng·hr/mL: Treatment A 95.7 (84.5 to 108); Treatment B 104 (90.5 to 119); Treatment C 192 (169 to 219); Treatment D 199 (177 to 224); Treatment I 161 (140 to 184); Treatment J 182 (142 to 233)
• Pharmacodynamics (PD) Profile of RDEA3170 (Secondary), Mean, Percent (%) Change: Treatment A -29.1 +/- 2.05; Treatment B -40.6 +/- 1.69; Treatment C -42.5 +/- 1.74; Treatment D -52.3 +/- 1.05; Treatment E -30.3 +/- 1.54; Treatment I -35.2 +/- 2.71; Treatment J -46.2 +/- 2.45; Treatment K -29.3 +/- 2.66
• Incidence of Treatment-Emergent Adverse Events (Secondary), Number, Number of participants: Treatment A 1; Treatment B 1; Treatment C 0; Treatment D 0; Treatment E 0; Treatment I 2; Treatment J 2; Treatmnet K 0

Adverse events

Other adverse events by term

• J Hall, MD, Study director, Ardea Biosciences, Inc.