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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence ABCD | Experimental | 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 | Experimental | 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 ABDC | Experimental | 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 | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RDEA3170 10 mg | Drug |
| ||
| RDEA3170 2.5 mg |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Cmax of RDEA3170 in fasted condition. | 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. |
| Time of Occurrence of Maximum Observed Concentration (Tmax) | Tmax of RDEA3170 following various treatments. | 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. |
| Area Under the Concentration-time Curve From Time Zero to the Quantifiable Last Sampling Timepoint (AUC Last) | AUC last of RDEA3170 in fasted condition. | 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. |
| Area Under the Concentration-time Curve From 0 to Infinity (AUC∞) | AUC∞ of RDEA3170 the fasted condition. | 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. |
| Apparent Terminal Half-life (t1/2) | t1/2 of RDEA3170 following various treatments. | 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: Effect of High Fat Meal on the PK of RDEA3170 Tablets | Cmax of RDEA3170 in high-fat fed state. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Single Dose Pharmacodynamics (PD) Profile of RDEA3170 From Serum and Urine | 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. | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| J. Hall, MD | Ardea Biosciences, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Austin | Texas | 78744 | United States |
Fifteen subjects were randomized to 1 of 4 treatment sequences (ABCD, BACD, ABDC, BADC) in a 1:1:1:1 ratio.
15 subjects were randomized
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence ABCD | 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). |
| FG001 | Sequence BACD | 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). |
| FG002 | Sequence ABDC | 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). |
| FG003 | Sequence BADC | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sequence ABCD | 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. |
| BG001 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Plasma Concentration (Cmax) | Cmax of RDEA3170 in fasted condition. | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | 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. |
|
7 weeks
Overall number of baseline participants used to determine number of participants at risk.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment A | 10 mg dose of RDEA3170, administered as 4 × 2.5 mg tablets, in the fasted state. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jesse Hall, MD | Study Information Center AstraZeneca | +1 877-240-9479 | information.center@astrazeneca.com |
Not provided
| ID | Term |
|---|---|
| D006073 | Gout |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D000070657 | Crystal Arthropathies |
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| ID | Term |
|---|---|
| C000628929 | verinurad |
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| Drug |
|
| AUC Last: Effect of High Fat Meal on the PK of RDEA3170 Tablets |
AUC last of RDEA3170 in high-fat fed state. |
| 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∞: Effect of High Fat Meal on the PK of RDEA3170 Tablets | AUC∞ of RDEA3170 in high-fat fed state. | 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: Effect of Low Fat Meal on the PK of RDEA3170 Tablets | Cmax of RDEA3170 in low-fat fed state. | 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: Effect of Low Fat Meal on the PK of RDEA3170 Tablets | AUC last of RDEA3170 in low-fat fed state. | 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∞: Effect of Low Fat Meal on the PK of RDEA3170 Tablets | AUC∞ of RDEA3170 in low-fat fed state. | 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. |
| Incidence of Treatment-Emergent Adverse Events | 7 weeks. |
| BG002 | 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 |
| BG003 | 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 |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Age, Customized | Number | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | Participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
|
| Primary | Time of Occurrence of Maximum Observed Concentration (Tmax) | Tmax of RDEA3170 following various treatments. | Posted | Median | Full Range | hr | 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. |
|
|
|
| Primary | Area Under the Concentration-time Curve From Time Zero to the Quantifiable Last Sampling Timepoint (AUC Last) | AUC last of RDEA3170 in fasted condition. | Posted | Geometric Mean | 95% Confidence Interval | ng·hr/mL | 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. |
|
|
|
|
| Primary | Area Under the Concentration-time Curve From 0 to Infinity (AUC∞) | AUC∞ of RDEA3170 the fasted condition. | Posted | Geometric Mean | 95% Confidence Interval | ng·hr/mL | 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. |
|
|
|
|
| Primary | Apparent Terminal Half-life (t1/2) | t1/2 of RDEA3170 following various treatments. | Posted | Geometric Mean | 95% Confidence Interval | hr | 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. |
|
|
|
| Primary | Cmax: Effect of High Fat Meal on the PK of RDEA3170 Tablets | Cmax of RDEA3170 in high-fat fed state. | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | 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. |
|
|
|
|
| Primary | AUC Last: Effect of High Fat Meal on the PK of RDEA3170 Tablets | AUC last of RDEA3170 in high-fat fed state. | Posted | Geometric Mean | 95% Confidence Interval | ng·hr/mL | 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. |
|
|
|
|
| Primary | AUC∞: Effect of High Fat Meal on the PK of RDEA3170 Tablets | AUC∞ of RDEA3170 in high-fat fed state. | Posted | Geometric Mean | 95% Confidence Interval | ng·hr/mL | 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. |
|
|
|
|
| Primary | Cmax: Effect of Low Fat Meal on the PK of RDEA3170 Tablets | Cmax of RDEA3170 in low-fat fed state. | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | 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. |
|
|
|
|
| Primary | AUC Last: Effect of Low Fat Meal on the PK of RDEA3170 Tablets | AUC last of RDEA3170 in low-fat fed state. | Posted | Geometric Mean | 95% Confidence Interval | ng·hr/mL | 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. |
|
|
|
|
| Primary | AUC∞: Effect of Low Fat Meal on the PK of RDEA3170 Tablets | AUC∞ of RDEA3170 in low-fat fed state. | Posted | Geometric Mean | 95% Confidence Interval | ng·hr/mL | 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. |
|
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|
|
| Secondary | Single Dose Pharmacodynamics (PD) Profile of RDEA3170 From Serum and Urine | 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. | Posted | Mean | Standard Error | Percent | 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. |
|
|
|
| Secondary | Incidence of Treatment-Emergent Adverse Events | Posted | Number | Number of Participants | 7 weeks. |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | Treatment B | 10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fasted state. | 0 | 15 | 1 | 15 |
| EG002 | Treatment C | 10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (low-fat, high calorie meal). | 0 | 15 | 1 | 15 |
| EG003 | Treatment D | 10 mg dose of RDEA3170, administered as a single 10 mg tablet, in the fed state (high-fat, high calorie meal). | 0 | 15 | 3 | 15 |
| Nausea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
|
| Periarthritis | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
|
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.
| D012216 |
| Rheumatic Diseases |
| D011686 | Purine-Pyrimidine Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| Urine Uric Acid % Change(0-24h) |
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| Renal Clearance of Uric Acid % Change (0-24h) |
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| Fractional Excretion of Uric Acid % Change (0-24h) |
|