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This is a Phase 2a, randomized, open-label, multicenter study to assess the pharmacodynamic (PD) effects and safety of RDEA3170 administered in combination with febuxostat compared to febuxostat administered alone in adult subjects with gout.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RDEA3170 10 mg | Experimental | Once daily (qd) with febuxostat 40mg (qd) for 7 days, and with febuxostat 80 mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days. |
|
| RDEA3170 15 mg | Experimental | Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days. |
|
| RDEA3170 5 mg | Experimental | Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days. |
|
| RDEA3170 2.5 mg | Experimental | Once daily with febuxostat 40mg (qd) for 7 days and with febuxostat 80mg (qd) for 7 days; febuxostat 40 mg (qd) only for 7 days, and febuxostat 80 mg (qd) only for 7 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RDEA3170 15 mg | Drug |
| ||
| RDEA3170 10 mg |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Urate Maximum Percentage (%) Change (Emax, CB) | Maximum observed percentage (%) change from baseline in serum urate concentrations. | 28 days |
| Urine Uric Acid % Change (0-24h) (Aeur, CB) | Percentage (%) change from baseline in the amount of uric acid recovered in urine. | 28 days |
| Renal Clearance of Uric Acid % Change (0-24h) (CLur, CB) | Percentage (%) change from baseline in renal clearance of uric acid. | 28 days |
| Fract. Excretion of Uric Acid % Change (0-24h) (FEUA, CB) | Percentage (%) change from baseline in fractional excretion of uric acid. | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Cmax of multiple-dose RDEA3170 administered in combination with febuxostat from plasma | Days 7 to 28 |
| Time of Occurrence of Maximum Observed Concentration (Tmax) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| J. Hall | Ardea Biosciences, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Anaheim | California | 92801 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32951150 | Derived | Rekic D, Johansson S, Leander J. Higher Febuxostat Exposure Observed in Asian Compared with Caucasian Subjects Independent of Bodyweight. Clin Pharmacokinet. 2021 Mar;60(3):319-328. doi: 10.1007/s40262-020-00943-6. Epub 2020 Sep 19. | |
| 29657831 | Derived | Fleischmann R, Winkle P, Hall J, Valdez S, Liu S, Yan X, Hicks L, Lee C, Miner JN, Gillen M, Hernandez-Illas M. Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with febuxostat in adults with gout: a phase IIa, open-label study. RMD Open. 2018 Apr 9;4(1):e000647. doi: 10.1136/rmdopen-2018-000647. eCollection 2018. |
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Cohorts 1 through 4 were conducted sequentially and Cohort 5 was conducted following review of the available PD/PK results of Cohort 2. Subjects in Cohorts 1 through 4 were randomized to 1 of 2 treatment sequences (ABCD or DCBA) in a 1:1 ration and subjects in Cohort 5 were randomized to 1 of 2 treatment sequences (EHGF or GFHE) in a 1:1 ratio.
Sixty-four subjects were randomized and received at least 1 dose of randomized study medication. Five cohorts of approximately 12 adult subjects with gout per cohort were randomized into the study. Overall, a total of 60 subjects completed the study in accordance with the protocol.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | (RDEA3170 10 mg + Febuxostat 40 mg; RDEA3170 10 mg + Febuxostat 80 mg) |
| FG001 | Cohort 2 | (RDEA3170 15 mg + Febuxostat 40 mg; RDEA3170 15 mg + Febuxostat 80 mg) |
| FG002 | Cohort 3 | (RDEA3170 5 mg + Febuxostat 40 mg; RDEA3170 5 mg + Febuxostat 80 mg) |
| FG003 | Cohort 4 | (RDEA3170 2.5 mg + Febuxostat 40 mg; RDEA3170 2.5 mg + Febuxostat 80 mg) |
| FG004 | Cohort 5 | (RDEA3170 10 mg + Febuxostat 40 mg; RDEA3170 15 mg + Febuxostat 40 mg; RDEA3170 20 mg + Febuxostat 40 mg) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | |
| BG001 | Cohort 2 | |
| BG002 | Cohort 3 |
| 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 | Serum Urate Maximum Percentage (%) Change (Emax, CB) | Maximum observed percentage (%) change from baseline in serum urate concentrations. | Posted | Mean | Standard Error | Percentage (%) | 28 days |
|
10 weeks
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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 | Febuxostat 40 mg |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspepsia | Gastrointestinal disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jesse Hall, MD | Study Information Center AstraZeneca | +1 877-240-9479 | information.center@astrazeneca.com |
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| 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 |
| D000069465 | Febuxostat |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
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|
| RDEA3170 2.5 | Drug |
|
| RDEA3170 5 mg | Drug |
|
| Febuxostat 40 mg | Drug |
|
| Febuxostat 80 mg | Drug |
|
Tmax of multiple-dose RDEA3170 administered in combination with febuxostat from plasma
| Days 7 to 28 |
| Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) | AUC 0-24 of multiple-dose RDEA3170 administered in combination with febuxostat from plasma | Days 7 to 28 |
| Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last of multiple-dose RDEA3170 administered in combination with febuxostat from plasma | Days 7 to 28 |
| Apparent Terminal Half-life (t1/2) | t1/2 of multiple-dose RDEA3170 administered in combination with febuxostat from plasma | Days 7 to 28 |
| Incidence of Treatment-Emergent Adverse Events | 10 weeks |
| Glendale |
| California |
| 91206 |
| United States |
| South Miami | Florida | 33143 | United States |
| Overland Park | Kansas | 66211 | United States |
| Overland Park | Kansas | 66212 | United States |
| Dallas | Texas | 75231 | United States |
| Withdrawal by Subject |
|
| Lost to Follow-up |
|
| Protocol Violation |
|
| BG003 | Cohort 4 |
| BG004 | Cohort 5 |
| BG005 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG003 | RDEA3170 10 mg + Febuxostat 80 mg | Days 14/21 Overall (Cohort 1) |
| OG004 | RDEA3170 15 mg + Febuxostat 40 mg | Days 7/14/21/28 Overall (Cohorts 2 and 5) |
| OG005 | RDEA3170 15 mg + Febuxostat 80 mg | Days 14/21 Overall (Cohort 2) |
| OG006 | RDEA3170 5 mg + Febuxostat 40 mg | Days 14/21 Overall (Cohort 3) |
| OG007 | RDEA3170 5 mg + Febuxostat 80 mg | Days 14/21 Overall (Cohort 3) |
| OG008 | RDEA3170 2.5 mg + Febuxostat 40 mg | Days 14/21 Overall (Cohort 4) |
| OG009 | RDEA3170 2.5 mg + Febuxostat 80 mg | Days 14/21 Overall (Cohort 4) |
| OG010 | RDEA3170 20 mg + Febuxostat 40 mg | Days 14/21 Overall (Cohort 5) |
|
|
|
| Primary | Urine Uric Acid % Change (0-24h) (Aeur, CB) | Percentage (%) change from baseline in the amount of uric acid recovered in urine. | Posted | Mean | Standard Error | Percentage (%) | 28 days |
|
|
|
|
| Primary | Renal Clearance of Uric Acid % Change (0-24h) (CLur, CB) | Percentage (%) change from baseline in renal clearance of uric acid. | Posted | Mean | Standard Error | Percentage (%) | 28 days |
|
|
|
|
| Primary | Fract. Excretion of Uric Acid % Change (0-24h) (FEUA, CB) | Percentage (%) change from baseline in fractional excretion of uric acid. | Posted | Mean | Standard Error | Percentage (%) | 28 days |
|
|
|
|
| Secondary | Maximum Observed Plasma Concentration (Cmax) | Cmax of multiple-dose RDEA3170 administered in combination with febuxostat from plasma | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | Days 7 to 28 |
|
|
|
| Secondary | Time of Occurrence of Maximum Observed Concentration (Tmax) | Tmax of multiple-dose RDEA3170 administered in combination with febuxostat from plasma | Posted | Median | Full Range | hr | Days 7 to 28 |
|
|
|
| Secondary | Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) | AUC 0-24 of multiple-dose RDEA3170 administered in combination with febuxostat from plasma | Posted | Geometric Mean | 95% Confidence Interval | ng·hr/mL | Days 7 to 28 |
|
|
|
| Secondary | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last of multiple-dose RDEA3170 administered in combination with febuxostat from plasma | Posted | Geometric Mean | 95% Confidence Interval | ng·hr/mL | Days 7 to 28 |
|
|
|
| Secondary | Apparent Terminal Half-life (t1/2) | t1/2 of multiple-dose RDEA3170 administered in combination with febuxostat from plasma | Posted | Geometric Mean | 95% Confidence Interval | hr | Days 7 to 28 |
|
|
|
| Secondary | Incidence of Treatment-Emergent Adverse Events | Posted | Number | Number of participants | 10 weeks |
|
|
|
| 0 |
| 61 |
| 3 |
| 61 |
| EG001 | Febuxostat 80 mg | 0 | 51 | 8 | 51 |
| EG002 | Overall RDEA3170 + Febuxostat Combination | 0 | 62 | 13 | 62 |
| Aphthous Stomatitis | Gastrointestinal disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Productive Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Throat Irritation | Respiratory, thoracic and mediastinal disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Herpes Simplex | Infections and infestations | MedDRA Version 17.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA Version 17.0 | Systematic Assessment |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 17.0 | Systematic Assessment |
|
| Hepatitis | Hepatobiliary disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Hepatitis Acute | Hepatobiliary disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Tympanic Membrane Hyperaemia | Ear and labyrinth disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA Version 17.0 | Systematic Assessment |
|
| Hepatic Enzyme Increased | Investigations | MedDRA Version 17.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA Version 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 |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Cohort 1
| Mixed Models Analysis |
The model included treatment and period as fixed effects and subject(s) as a random effect. |
| 0.0013 |
| Geometric Least Squares mean Ratio |
| 20.08 |
| 2-Sided |
| 95 |
| 8.38 |
| 31.79 |
| Superiority or Other |
| Cohort 2 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 23.70 | 2-Sided | 95 | 14.23 | 33.17 | Superiority or Other |
| Cohort 2 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | 0.0008 | Geometric Least Squares mean Ratio | 18.37 | 2-Sided | 95 | 8.30 | 28.44 | Superiority or Other |
| Cohort 3 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | 0.0101 | Geometric Least Squares mean Ratio | 18.82 | 2-Sided | 95 | 4.86 | 32.79 | Superiority or Other |
| Cohort 3 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | 0.0055 | Geometric Least Squares mean Ratio | 20.52 | 2-Sided | 95 | 6.56 | 34.48 | Superiority or Other |
| Cohort 4 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | 0.0065 | Geometric Least Squares mean Ratio | 10.36 | 2-Sided | 95 | 3.13 | 17.59 | Superiority or Other |
| Cohort 4 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect | 0.6140 | Geometric Least Squares mean Ratio | 1.79 | 2-Sided | 95 | -5.37 | 8.94 | Superiority or Other |
| Cohort 5 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | 0.0002 | Geometric Least Squares mean Ratio | 30.83 | 2-Sided | 95 | 15.62 | 46.04 | Superiority or Other |
| Cohort 5 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | 0.0019 | Geometric Least Squares mean Ratio | 24.38 | 2-Sided | 95 | 9.63 | 39.14 | Superiority or Other |
| Cohort 5 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | 0.0009 | Geometric Least Squares mean Ratio | 26.35 | 2-Sided | 95 | 11.59 | 41.11 | Superiority or Other |
Cohort 1
| Mixed Models Analysis |
The model included treatment and period as fixed effects and subject(s) as a random effect. |
| <0.0001 |
| Geometric Least Squares mean Ratio |
| 174.47 |
| 2-Sided |
| 95 |
| 125.52 |
| 233.42 |
| Superiority or Other |
| Cohort 2 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 168.03 | 2-Sided | 95 | 123.13 | 212.93 | Superiority or Other |
| Cohort 2 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 188.75 | 2-Sided | 95 | 138.04 | 239.46 | Superiority or Other |
| Cohort 3 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | 0.0005 | Geometric Least Squares mean Ratio | 70.43 | 2-Sided | 95 | 33.74 | 107.12 | Superiority or Other |
| Cohort 3 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 91.50 | 2-Sided | 95 | 54.81 | 128.19 | Superiority or Other |
| Cohort 4 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 40.11 | 2-Sided | 95 | 25.17 | 55.05 | Superiority or Other |
| Cohort 4 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | 0.0350 | Geometric Least Squares mean Ratio | 15.96 | 2-Sided | 95 | 1.20 | 30.71 | Superiority or Other |
| Cohort 5 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 236.08 | 2-Sided | 95 | 178.29 | 293.86 | Superiority or Other |
| Cohort 5 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 146.20 | 2-Sided | 95 | 90.40 | 202.01 | Superiority or Other |
| Cohort 5 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 176.57 | 2-Sided | 95 | 120.77 | 232.38 | Superiority or Other |
Cohort 1
| Mixed Models Analysis |
The model included treatment and period as fixed effects and subject(s) as a random effect. |
| <0.0001 |
| Geometric Least Squares mean Ratio |
| 178.58 |
| 2-Sided |
| 95 |
| 129.25 |
| 227.90 |
| Superiority or Other |
| Cohort 2 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 163.98 | 2-Sided | 95 | 120.80 | 207.16 | Superiority or Other |
| Cohort 2 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 169.93 | 2-Sided | 95 | 122.82 | 217.03 | Superiority or Other |
| Cohort 3 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | 0.0007 | Geometric Least Squares mean Ratio | 59.60 | 2-Sided | 95 | 28.85 | 90.34 | Superiority or Other |
| Cohort 3 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 73.54 | 2-Sided | 95 | 42.79 | 104.28 | Superiority or Other |
| Cohort 4 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 33.70 | 2-Sided | 95 | 21.21 | 46.20 | Superiority or Other |
| Cohort 4 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | 0.0001 | Geometric Least Squares mean Ratio | 27.08 | 2-Sided | 95 | 14.58 | 39.58 | Superiority or Other |
| Cohort 5 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 188.83 | 2-Sided | 95 | 152.55 | 225.10 | Superiority or Other |
| Cohort 5 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 116.83 | 2-Sided | 95 | 81.76 | 151.90 | Superiority or Other |
| Cohort 5 | Mixed Models Analysis | The model included treatment and period as fixed effects and subject(s) as a random effect. | <0.0001 | Geometric Least Squares mean Ratio | 151.66 | 2-Sided | 95 | 116.59 | 186.73 | Superiority or Other |