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This is a Phase 2a, randomized, open-label, multicenter study to assess the pharmacodynamic (PD) effects of RDEA3170 administered in combination with allopurinol compared with allopurinol administered alone in adult subjects with gout.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RDEA3170 2.5 mg, 7.5 mg and 15 mg | Experimental | RDEA3170 2.5 mg, 7.5 mg and 15 mg once daily (qd) in combination with allopurinol 300 mg (qd and twice daily (bid)) |
|
| RDEA3170 5 mg, 10 mg and 20 mg | Experimental | RDEA3170 5 mg, 10 mg 20 mg qd in combination with allopurinol 300 mg (qd and bid) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RDEA3170 2.5 mg | Drug | Cohort 1: RDEA3170 2.5 mg, 7.5 mg (2.5 mg × 3 tablets), and 15 mg (2.5 mg × 6 tablets). Cohort 2: RDEA3170 5 mg (2.5 mg × 2 tablets), 10 mg (2.5 mg × 4 tablets), and 20 mg (2.5 mg × 8 tablets). |
| Measure | Description | Time Frame |
|---|---|---|
| Cohort 1 - Maximum Percentage (%) Change in Serum Urate of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (Emax, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
| Cohort 1 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol. | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
| Cohort 1 - Renal Xanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeXO, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
| Cohort 1 - Renal Hypoxanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeHXO, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
| Cohort 2 - Maximum Percentage (%) Change in Serum Urate of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (Emax, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Concentration (Cmax) | Cmax of Allopurinol alone or in combination with RDEA3170 | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) |
| Time of Occurrence of Maximum Observed Concentration (Tmax) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jesse Hall, MD | Ardea Biosciences, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Anaheim | California | 92801 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29531784 | Derived | Fleischmann R, Winkle P, Miner JN, Yan X, Hicks L, Valdez S, Hall J, Liu S, Shen Z, Gillen M, Hernandez-Illas M. Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with allopurinol in adults with gout: a phase IIa, open-label study. RMD Open. 2018 Feb 8;4(1):e000584. doi: 10.1136/rmdopen-2017-000584. eCollection 2018. |
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Forty-one subjects were randomized and received at least 1 dose of randomized study medication; 20 subjects in Cohort 1 and 21 subjects in Cohort 2. Subjects were randomized into 1 of 8 sequences across the 2 cohorts (20 subjects each) in a 1:1 ratio.A total of 40 subjects completed the study.
41 subjects were randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | Allopurinol 300 mg once daily (qd), 600 mg qd, RDEA3170 2.5 mg qd, 15 mg qd and 7.5 mg qd |
| FG001 | Cohort 2 | Allopurinol 300 mg qd, 600 mg (300 mg bid), RDEA3170 5 mg qd, 20 mg qd and 10 mg qd |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | Allopurinol 300 mg once daily (qd), 600 mg qd, RDEA3170 2.5 mg qd, 15 mg qd and 7.5 mg qd |
| BG001 | Cohort 2 | Allopurinol 300 mg qd, 600 mg (300 mg bid), RDEA3170 5 mg qd, 20 mg qd and 10 mg qd |
| 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 | Cohort 1 - Maximum Percentage (%) Change in Serum Urate of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (Emax, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1) | Posted | Mean | Standard Error | Maximum Percentage (%) Change | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
|
11 Weeks.
Total # Affected by any Other Adverse Event includes subjects who may appear more than once; Other Adverse Events were reported for 6 subjects in Cohort 1 and 6 subjects in Cohort 2.
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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 | RDEA3170 2.5 mg, 7.5 mg and 15 mg qd in combination with allopurinol 300 mg (qd and bid) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA Version 17.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 17.0 | Systematic Assessment |
Reliable urine uric acid values were not obtained due to sample processing errors, and this has resulted in the inability to assess the PD effects of RDEA3170 and/or allopurinol in urine.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jesse Hall, MD | Study Information Center AstraZeneca | (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 |
| D000493 | Allopurinol |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| allopurinol 300 mg | Drug | allopurinol 300 mg, allopurinol 600 mg (300 mg x 2 tablets) |
|
| Cohort 2 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol. |
Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2) |
| Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
| Cohort 2 - Renal Xanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeXO, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
| Cohort 2 - Renal Hypoxanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeHXO, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2) | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
Tmax of Allopurinol alone or in combination with RDEA3170
| Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) |
| Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) | AUC 0-24 of Allopurinol alone or in combination with RDEA3170 | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) |
| Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last of Allopurinol alone or in combination with RDEA3170 | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) |
| Apparent Terminal Half-life (t1/2) | t1/2 of Allopurinol alone or in combination with RDEA3170 | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) |
| Number of Participants With Treatment-Emergent Adverse Events | 11 weeks |
| DeLand |
| Florida |
| 32720 |
| United States |
| South Miami | Florida | 33143 | United States |
| Dallas | Texas | 75231 | United States |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex/Gender, Customized | Number | Participants |
|
| Region of Enrollment | Number | Participants |
|
Allopurinol 600 mg (300 mg bid) |
| OG003 | Treatment R1 | Allopurinol 300 mg qd + RDEA3170 2.5 mg qd |
| OG004 | Treatment R3 | Allopurinol 300 mg qd + RDEA3170 7.5 mg qd |
| OG005 | Treatment R5 | Allopurinol 300 mg qd + RDEA3170 15 mg qd |
|
|
| Primary | Cohort 1 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol. | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1) | Posted | Mean | Standard Error | mg/dL | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
|
|
|
| Primary | Cohort 1 - Renal Xanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeXO, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1) | Posted | Mean | Standard Error | Percentage (%) Change | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
|
|
|
| Primary | Cohort 1 - Renal Hypoxanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeHXO, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1) | Posted | Mean | Standard Error | Percentage (%) Change | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
|
|
|
| Primary | Cohort 2 - Maximum Percentage (%) Change in Serum Urate of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (Emax, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2) | Posted | Mean | Standard Error | Maximum Percentage (%) Change | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
|
|
|
| Secondary | Maximum Observed Concentration (Cmax) | Cmax of Allopurinol alone or in combination with RDEA3170 | Posted | Geometric Mean | 95% Confidence Interval | µg/mL | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) |
|
|
|
|
| Secondary | Time of Occurrence of Maximum Observed Concentration (Tmax) | Tmax of Allopurinol alone or in combination with RDEA3170 | Posted | Geometric Mean | 95% Confidence Interval | hr | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) |
|
|
|
| Secondary | Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) | AUC 0-24 of Allopurinol alone or in combination with RDEA3170 | Posted | Geometric Mean | 95% Confidence Interval | µg·hr/mL | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) |
|
|
|
| Secondary | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last of Allopurinol alone or in combination with RDEA3170 | Posted | Geometric Mean | 95% Confidence Interval | µg·hr/mL | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) |
|
|
|
|
| Secondary | Apparent Terminal Half-life (t1/2) | t1/2 of Allopurinol alone or in combination with RDEA3170 | Posted | Geometric Mean | 95% Confidence Interval | hr | Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose) |
|
|
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events | Posted | Number | Number of participants | 11 weeks |
|
|
|
| Primary | Cohort 2 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol. | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2) | Posted | Mean | Standard Error | mg/dL | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
|
|
|
| Primary | Cohort 2 - Renal Xanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeXO, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2) | Posted | Mean | Standard Error | Percentage (%) Change | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
|
|
|
| Primary | Cohort 2 - Renal Hypoxanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeHXO, CB (%)) | Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2) | Posted | Mean | Standard Error | Percentage (%) Change | Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose) |
|
|
|
| 0 |
| 20 |
| 1 |
| 20 |
| 6 |
| 20 |
| EG001 | Cohort 2 | RDEA3170 5 mg, 10 mg 20 mg qd in combination with allopurinol 300 mg (qd and bid) | 0 | 21 | 0 | 21 | 6 | 21 |
| Headache | Nervous system disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA Version 17.0 | Systematic Assessment |
|
| Neck Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Arthropod Bite | Injury, poisoning and procedural complications | MedDRA Version 17.0 | Systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA Version 17.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Seasonal Allergy | Immune system disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Renal Failure Acute | Renal and urinary disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Erectile Dysfunction | Reproductive system and breast disorders | MedDRA Version 17.0 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue 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 |
| Mixed Models Analysis |
Fixed effect for treatment and random effects for subjects. |
| Geometric Least Squares Mean Ratio (%) |
| 92.6 |
| 2-Sided |
| 90 |
| 78.1 |
| 110 |
| Non-Inferiority or Equivalence |
Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Mixed Models Analysis | Fixed effect for treatment and random effects for subjects. GLMSRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 102 | 2-Sided | 90 | 85.7 | 120 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Mixed Models Analysis | Fixed effect for treatment and random effects for subjects. GLMSRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 88.9 | 2-Sided | 90 | 78.4 | 101 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Mixed Models Analysis | Fixed effect for treatment and random effects for subjects. GLMSRs are back-transformed to the original scale | Geometric Least Squares Mean Ratio (%) | 100 | 2-Sided | 90 | 87.7 | 114 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Mixed Models Analysis | Fixed effect for treatment and random effects for subjects. GLMSRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 101 | 2-Sided | 90 | 85.5 | 119 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Mixed Models Analysis |
Fixed effect for treatment and random effects for subjects. GLMSRs are back-transformed to the original scale. |
| Geometric Least Squares Mean Ratio (%) |
| 98.0 |
| 2-Sided |
| 90 |
| 90.4 |
| 106 |
| Non-Inferiority or Equivalence |
Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Mixed Models Analysis | Fixed effect for treatment and random effects for subjects. GLMSRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 104 | 2-Sided | 90 | 94.5 | 114 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Mixed Models Analysis | Fixed effect for treatment and random effects for subjects. GLMSRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 92.0 | 2-Sided | 90 | 86.7 | 97.7 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Mixed Models Analysis | Fixed effect for treatment and random effects for subjects. GLMSRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 98.9 | 2-Sided | 90 | 91.0 | 107 | Non-Inferiority | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Mixed Models Analysis | Fixed effect for treatment and random effects for subjects. GLMSRs are back-transformed to the original scale. | Geometric Least Squares Mean Ratio (%) | 97.5 | 2-Sided | 90 | 92.8 | 102 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125% |