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This is a Phase 1, single-dose, open-label, pharmacokinetic (PK) and pharmacodynamic (PD) study of RDEA3170 in adult male subjects with mild, moderate, and severe renal impairment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Mild renal impairment | Experimental | RDEA3170 15 mg once daily fasted |
|
| Cohort 2: Moderate renal impairment | Experimental | RDEA3170 15 mg once daily fasted |
|
| Cohort 3: Severe renal impairment | Experimental | RDEA3170 15 mg once daily fasted |
|
| Cohort 4: Control subjects with normal renal function | Experimental | RDEA3170 15 mg once daily fasted |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RDEA3170 | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Cmax following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
| Time of Occurrence of Maximum Observed Concentration (Tmax) | Tmax following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
| Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) | AUC∞ following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
| Apparent Terminal Half-life (t1/2) | t1/2 following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
| Non-renal Clearance From Time 0 to 72 Hours Postdose (CLNR 0-72) |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | 5 weeks | |
| Pharmacodynamics (PD) Profiles of Uric Acid From Serum and Urine | Screening, Day -1 ( -24, -21, -18, -and -12 hours predose), and Day 1 (within 30 minutes prior to dosing and at 3, 6, 12, 24, 30, 36, 48, 54, 60, and 72 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 |
|---|---|---|---|---|---|---|
| Lakewood | Colorado | 80228 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29949102 | Derived | Smith WB, Hall J, Berg JK, Kazimir M, Yamamoto A, Walker S, Lee CA, Shen Z, Wilson DM, Zhou D, Gillen M, Marbury TC. Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Verinurad, a Selective Uric Acid Reabsorption Inhibitor. Clin Drug Investig. 2018 Aug;38(8):703-713. doi: 10.1007/s40261-018-0652-2. |
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Thirty-one subjects were randomized to 1 of 4 cohorts. Cohort 1: mild renal impairment; Cohort 2: moderate renal impairment; Cohort 3: severe renal impairment and Cohort 4: normal renal function. All 31 subjects received a single dose of 15 mg RDEA3170 (6 x 2.5 mg) in the fasted state.
31 subjects were randomized
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: Mild Renal Impairment + RDEA3170 15 mg | Mild Renal Impairment (eCrCl of 60 to < 90 mL/min) + RDEA3170 15 mg once daily (qd) fasted |
| FG001 | Cohort 2: Moderate Renal Impairment + RDEA3170 15 mg | Moderate Renal Impairment (eCrCl of 30 to < 60 mL/min) + RDEA3170 15 mg qd fasted |
| FG002 | Cohort 3: Severe Renal Impairment + RDEA3170 15 mg | Severe Renal Impairment (eCrCl of 15 to < 30 mL/min) + RDEA3170 15 mg qd fasted |
| FG003 | Cohort 4: Normal Renal Function + RDEA3170 15 mg | Control subjects With Normal Renal Function (eCrCl of ≥ 90 mL/min) + RDEA3170 15 mg qd fasted |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: Mild Renal Impairment + RDEA3170 15 mg | Mild Renal Impairment (eCrCl of 60 to < 90 mL/min) + RDEA3170 15 mg once daily (qd) fasted |
| BG001 | Cohort 2: Moderate Renal Impairment + RDEA3170 15 mg |
| 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 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Incidence of Treatment-Emergent Adverse Events | Posted | Number | Number of participants | 5 weeks |
|
5 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 | Cohort 1: Mild Renal Impairment + RDEA3170 15 mg | Mild Renal Impairment (eCrCl of 60 to < 90 mL/min) + RDEA3170 15 mg once daily (qd) fasted |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.1 | 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 |
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CLNR 0-72 following a single administration of RDEA3170 to subjects with various degrees of renal function |
| Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
| Total Body Clearance Corrected for Bioavailability (CL/F) | CL/F following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
| Renal Clearance Time 0 to 72 Hours Postdose (CLR 0-72) | CLR 0-72 following a single administration of RDEA3170 to subjects with various degrees of renal function | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
| Orlando |
| Florida |
| 32809 |
| United States |
| Minneapolis | Minnesota | 55404 | United States |
| Knoxville | Tennessee | 37920 | United States |
Moderate Renal Impairment (eCrCl of 30 to < 60 mL/min) + RDEA3170 15 mg qd fasted
| BG002 | Cohort 3: Severe Renal Impairment + RDEA3170 15 mg | Severe Renal Impairment (eCrCl of 15 to < 30 mL/min) + RDEA3170 15 mg qd fasted |
| BG003 | Cohort 4: Normal Renal Function + RDEA3170 15 mg | Control subjects With Normal Renal Function (eCrCl of ≥ 90 mL/min) + RDEA3170 15 mg qd fasted |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | Participants |
|
| OG003 | Cohort 4: Normal Renal Function + RDEA3170 15 mg | Control subjects With Normal Renal Function (eCrCl of ≥ 90 mL/min) + RDEA3170 15 mg qd fasted |
|
|
| Secondary | Pharmacodynamics (PD) Profiles of Uric Acid From Serum and Urine | Posted | Mean | Standard Error | Maximum Percentage (%) Change | Screening, Day -1 ( -24, -21, -18, -and -12 hours predose), and Day 1 (within 30 minutes prior to dosing and at 3, 6, 12, 24, 30, 36, 48, 54, 60, and 72 hours postdose) |
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) | Cmax following a single administration of RDEA3170 to subjects with various degrees of renal function | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
|
|
|
|
| Primary | Time of Occurrence of Maximum Observed Concentration (Tmax) | Tmax following a single administration of RDEA3170 to subjects with various degrees of renal function | Posted | Median | Full Range | hr | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
|
|
|
| Primary | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last following a single administration of RDEA3170 to subjects with various degrees of renal function | Posted | Geometric Mean | 95% Confidence Interval | ng.hr/mL | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
|
|
|
|
| Primary | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) | AUC∞ following a single administration of RDEA3170 to subjects with various degrees of renal function | Posted | Geometric Mean | 95% Confidence Interval | ng.hr/mL | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
|
|
|
|
| Primary | Apparent Terminal Half-life (t1/2) | t1/2 following a single administration of RDEA3170 to subjects with various degrees of renal function | Posted | Geometric Mean | 95% Confidence Interval | hr | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
|
|
|
| Primary | Non-renal Clearance From Time 0 to 72 Hours Postdose (CLNR 0-72) | CLNR 0-72 following a single administration of RDEA3170 to subjects with various degrees of renal function | Posted | Geometric Mean | 95% Confidence Interval | L/hr | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
|
|
|
|
| Primary | Total Body Clearance Corrected for Bioavailability (CL/F) | CL/F following a single administration of RDEA3170 to subjects with various degrees of renal function | Posted | Geometric Mean | 95% Confidence Interval | L/hr | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
|
|
|
|
| Primary | Renal Clearance Time 0 to 72 Hours Postdose (CLR 0-72) | CLR 0-72 following a single administration of RDEA3170 to subjects with various degrees of renal function | Posted | Geometric Mean | 95% Confidence Interval | mL/min | Day 1: within 30 minutes prior to dosing and at 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 48, 54, 60, and 72 hours postdose |
|
|
|
|
| 0 |
| 8 |
| 3 |
| 8 |
| EG001 | Cohort 2: Moderate Renal Impairment + RDEA3170 15 mg | Moderate Renal Impairment (eCrCl of 30 to < 60 mL/min) + RDEA3170 15 mg qd fasted | 0 | 8 | 1 | 8 |
| EG002 | Cohort 3: Severe Renal Impairment + RDEA3170 15 mg | Severe Renal Impairment (eCrCl of 15 to < 30 mL/min) + RDEA3170 15 mg qd fasted | 0 | 7 | 2 | 7 |
| EG003 | Cohort 4: Normal Renal Function + RDEA3170 15 mg | Control subjects With Normal Renal Function (eCrCl of ≥ 90 mL/min) + RDEA3170 15 mg qd fasted | 0 | 8 | 1 | 8 |
| Constipation | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Vessel puncture site haemorrhage | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pseudofolliculitis barbae | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA 15.1 | 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) |
|
| Renal Clearance of Uric Acid % Change (0-24h) |
|
| Fract. Excretion of Uric Acid % Change (0-24h) |
|
| Urine Uric Acid % Change (24-48h) |
|
| Urine Uric Acid % Change (48-72h) |
|
| Renal Clearance of Uric Acid % Change (24-48h) |
|
| Renal Clearance of Uric Acid % Change (48-72h) |
|
| Fract. Excretion of Uric Acid % Change (24-48h) |
|
| Fract. Excretion of Uric Acid % Change (48-72h) |
|
| Fixed Effects Model |
Treatment as a fixed effect was used to analyze the natural log-transformed PK parameters and GLSMRs are back-transformed to the original scale. |
| Geometric Least Squares Mean Ratio (%) |
| 173 |
| 2-Sided |
| 90 |
| 131 |
| 230 |
| Non-Inferiority or Equivalence |
Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Fixed Effects Model | Treatment as a fixed effect was used to analyze the natural log-transformed PK parameters and GLSMRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 228 | 2-Sided | 90 | 155 | 336 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Fixed Effects Model |
Treatment as a fixed effect was used to analyze the natural log-transformed PK parameters and GLSMRs are back-transformed to the original scale. |
| Geometric Least Squares Mean Ratio (%) |
| 222 |
| 2-Sided |
| 90 |
| 171 |
| 287 |
| Non-Inferiority or Equivalence |
Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Fixed Effects Model | Treatment as a fixed effect was used to analyze the natural log-transformed PK parameters and GLSMRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 211 | 2-Sided | 90 | 139 | 319 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Fixed Effects Model |
Treatment as a fixed effect was used to analyze the natural log-transformed PK parameters and GLSMRs are back-transformed to the original scale. |
| Geometric Least Squares Mean Ratio (%) |
| 248 |
| 2-Sided |
| 90 |
| 168 |
| 366 |
| Non-Inferiority or Equivalence |
Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Fixed Effects Model | Treatment as a fixed effect was used to analyze the natural log-transformed PK parameters and GLSMRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 230 | 2-Sided | 90 | 146 | 363 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Fixed Effects Model |
Treatment as a fixed effect was used to analyze the natural log-transformed PK parameters and GLSMRs are back-transformed to the original scale. |
| Geometric Least Squares Mean Ratio (%) |
| 45.1 |
| 2-Sided |
| 90 |
| 34.9 |
| 58.3 |
| Non-Inferiority or Equivalence |
Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Fixed Effects Model | Treatment as a fixed effect was used to analyze the natural log-transformed PK parameters and GLSMRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 47.8 | 2-Sided | 90 | 31.5 | 72.5 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Fixed Effects Model |
Treatment as a fixed effect was used to analyze the natural log-transformed PK parameters and GLSMRs are back-transformed to the original scale. |
| Geometric Least Squares Mean Ratio (%) |
| 40.3 |
| 2-Sided |
| 90 |
| 27.3 |
| 59.5 |
| Non-Inferiority or Equivalence |
Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Fixed Effects Model | Treatment as a fixed effect was used to analyze the natural log-transformed PK parameters and GLSMRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 43.5 | 2-Sided | 90 | 27.5 | 68.7 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Fixed Effects Model |
Treatment as a fixed effect was used to analyze the natural log-transformed PK parameters and GLSMRs are back-transformed to the original scale. |
| Geometric Least Squares Mean Ratio (%) |
| 58.3 |
| 2-Sided |
| 90 |
| 30.2 |
| 113 |
| Non-Inferiority or Equivalence |
Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Fixed Effects Model | Treatment as a fixed effect was used to analyze the natural log-transformed PK parameters and GLSMRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 21.2 | 2-Sided | 90 | 13.6 | 32.8 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |