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This is a Phase 1b, randomized, open-label, drug-drug interaction study in adult male subjects with gout. It is designed to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of RDEA3170 or allopurinol alone and in combination in the fed state.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence A | Experimental | RDEA3170 qd (once daily), RDEA3170 + allopurinol qd, allopurinol qd |
|
| Sequence B | Experimental | allopurinol qd, RDEA3170 + allopurinol qd, RDEA3170 qd |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RDEA3170 10 mg | Drug |
| ||
| allopurinol 300 mg |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Cmax of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170 | 22 days |
| Time of Occurrence of Maximum Observed Concentration (Tmax) | Tmax of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination | 22 days |
| Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) | AUC 0-24 of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170 | 22 days |
| Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170 | 22 days |
| Apparent Terminal Half-life (t1/2) | t1/2 of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination | 22 days |
| Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24) | Ae0-24 of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170 | 22 days |
| Renal Clearance of the Drug From Time Zero up to 24 Hours Postdose (CRL0-24) | CLR0-24 of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination | 22 days |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | 22 days |
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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 |
|---|---|---|---|---|---|---|
| Overland Park | Kansas | 66212 | United States |
Twelve subjects were randomized to 1 of 2 treatment sequences (Sequence A or B) in a 1:1 ratio.
12 subjects were randomized
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| ID | Title | Description |
|---|---|---|
| FG000 | RDEA3170 or Allopurinol Alone and in Combination (Sequence A) | Days 1 to 7: 10 mg once daily (qd) RDEA3170; Days 8 to 14: 10 mg qd RDEA3170 + 300 mg qd allopurinol; Days 15 to 21: 300 mg qd allopurinol |
| FG001 | RDEA3170 or Allopurinol Alone and in Combination (Sequence B) | Days 1 to 7: 300 mg qd allopurinol; Days 8 to 14: 10 mg qd RDEA3170 + 300 mg qd allopurinol; Days 15 to 21: 10 mg qd RDEA3170 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sequence A | Days 1 to 7: 10 mg once daily (qd) RDEA3170; Days 8 to 14: 10 mg qd RDEA3170 + 300 mg qd allopurinol; Days 15 to 21: 300 mg qd allopurinol |
| BG001 | Sequence B | Days 1 to 7: 300 mg qd allopurinol; Days 8 to 14: 10 mg qd RDEA3170 + 300 mg qd allopurinol; Days 15 to 21: 10 mg qd RDEA3170 |
| 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 Allopurinol/Oxypurinol Alone and In Combination with RDEA3170 | Posted | Geometric Mean | 95% Confidence Interval | μg/mL | 22 days |
|
22 days
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 | RDEA3170 10 mg qd | RDEA3170 10 mg qd |
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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 |
| D000493 | Allopurinol |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Drug |
|
| Pharmacodynamics (PD) Profile of Uric Acid From Serum and Urine |
| 22 days |
| Maximum Observed Plasma Concentration (Cmax) | Cmax of RDEA3170 Alone and In Combination with Allopurinol | 22 days |
| Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) | AUC 0-24 of RDEA3170 Alone and In Combination with Allopurinol | 22 days |
| Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last of RDEA3170 Alone and In Combination with Allopurinol | 22 days |
| Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24) | Ae0-24 of RDEA3170 Alone and In Combination with Allopurinol | 22 days |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Age, Customized | Number | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | Participants |
|
| OG003 | Oxypurinol: RDEA3170 + Allopurinol | RDEA3170 10 mg qd + Allopurinol 300 mg qd |
|
|
|
| Primary | Time of Occurrence of Maximum Observed Concentration (Tmax) | Tmax of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination | Posted | Median | Full Range | hr | 22 days |
|
|
|
| Primary | Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) | AUC 0-24 of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170 | Posted | Geometric Mean | 95% Confidence Interval | μg·hr/mL | 22 days |
|
|
|
|
| Primary | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170 | Posted | Geometric Mean | 95% Confidence Interval | μg·hr/mL | 22 days |
|
|
|
|
| Primary | Apparent Terminal Half-life (t1/2) | t1/2 of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination | Posted | Geometric Mean | 95% Confidence Interval | hr | 22 days |
|
|
|
| Primary | Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24) | Ae0-24 of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170 | Posted | Geometric Mean | 95% Confidence Interval | mg | 22 days |
|
|
|
|
| Primary | Renal Clearance of the Drug From Time Zero up to 24 Hours Postdose (CRL0-24) | CLR0-24 of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination | Posted | Geometric Mean | 95% Confidence Interval | mL/min | 22 days |
|
|
|
|
| Primary | Pharmacodynamics (PD) Profile of Uric Acid From Serum and Urine | Posted | Mean | Standard Error | Percentage (%) | 22 days |
|
|
|
| Secondary | Incidence of Treatment-Emergent Adverse Events | Posted | Number | Number of participants | 22 days |
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) | Cmax of RDEA3170 Alone and In Combination with Allopurinol | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | 22 days |
|
|
|
|
| Primary | Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) | AUC 0-24 of RDEA3170 Alone and In Combination with Allopurinol | Posted | Geometric Mean | 95% Confidence Interval | μg*hr/mL | 22 days |
|
|
|
|
| Primary | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) | AUC last of RDEA3170 Alone and In Combination with Allopurinol | Posted | Geometric Mean | 95% Confidence Interval | ng·hr/mL | 22 days |
|
|
|
|
| Primary | Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24) | Ae0-24 of RDEA3170 Alone and In Combination with Allopurinol | Posted | Geometric Mean | 95% Confidence Interval | ug | 22 days |
|
|
|
|
| 0 |
| 12 |
| 2 |
| 12 |
| EG001 | RDEA3170 10 mg qd + Allopurinol 300 mg qd | RDEA3170 10 mg qd + Allopurinol 300 mg qd | 0 | 12 | 1 | 12 |
| EG002 | Allopurinol 300 mg qd | Allopurinol 300 mg qd | 0 | 12 | 3 | 12 |
| Toothache | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue 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 |
| 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 (%) |
| 61.8 |
| 2-Sided |
| 90 |
| 58.1 |
| 65.7 |
| 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 (%) | 95.9 | 2-Sided | 90 | 88.4 | 104 | 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 (%) |
| 61.8 |
| 2-Sided |
| 90 |
| 58.1 |
| 65.7 |
| 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 (%) |
| 119 |
| 2-Sided |
| 90 |
| 114 |
| 125 |
| 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 (%) |
| 193 |
| 2-Sided |
| 90 |
| 177 |
| 210 |
| 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 (%) | 105 | 2-Sided | 90 | 94.4 | 117 | Non-Inferiority or Equivalence | Informal BE assessment using the conventional BE limits of 80% to 125%. |
| Urine Uric Acid % Change (0-24h) |
|
| Renal Clearance of Uric Acid % Change (0-24h) |
|
| Fract. Excretion of Uric Acid % Change (0-24h) |
|