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| Name | Class |
|---|---|
| Contract Research Organization: USA | UNKNOWN |
| PAREXEL Early Phase Clinical Unit Baltimore | UNKNOWN |
| PAREXEL Early Phase Clinical Unit-Los Angeles | UNKNOWN |
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This is a randomized, placebo controlled, double-blind, 2-way crossover study conducted on asymptomatic hyperuricemic patients. The core study consists of screening period, 2 treatment periods (verinurad + febuxostat + dapagliflozin/placebo) and follow-up visit
This is a randomized, placebo controlled, double-blind, 2-way crossover study to assess the effect of intensive UA lowering therapy with verinurad (RDEA3170), febuxostat, and dapagliflozin on urinary excretion of UA, in asymptomatic hyperuricemic patients. Thirty-six asymptomatic hyperuricemic patients aged 18 to 65 years (inclusive) will be enrolled into this study at 2 study centers. Twenty-four patients have been enrolled and completed the study to date. Due to inadequate urine sampling, 12 additional patients were included to ensure an adequate sample size (at least 20 evaluable patients) to evaluate the effects of intensive UA lowering with verinurad, febuxostat and dapagliflozin on urinary excretion of UA. With 24 completers available during the interim analysis, this will provide for a total sample size of 36 evaluable patients.
Before any study specific assessments are performed, potential patients must provide informed consent. Each patient will undergo the below mentioned visits:
On Day -2 of Treatment period 1, patient will be randomized (1:1) to 1 of 2 treatment sequences (AB or BA). Each randomized patient will receive orally once daily fixed dose of the below mentioned 2 treatments for 7 consecutive days (1 treatment per treatment period).
Treatment Period 1 and Treatment Period 2 will be separated by a washout period of 7 to 21 days.
Patients will return to the Clinical Unit for a Follow-up Visit, 14 to 28 days after Day 1 of Treatment Period 2.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A | Experimental | Randomized patients will receive orally once daily fixed dose of the following drugs: verinurad + febuxostat + dapagliflozin; |
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| Treatment B | Experimental | Randomized patients will receive orally once daily fixed dose of the following drugs: verinurad + febuxostat + dapagliflozin matched placebo |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Verinurad | Drug | Randomized patients will receive orally once daily fixed dose of verinurad in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Peak Urinary Excretion of Uric Acid (UA) on Day 7 | Change from baseline in peak UA excretion during the first 8 hours on Day 7 of treatment to assess the effects of intensive UA lowering therapy with verinurad, febuxostat and dapagliflozin. Urine sample was collected in hourly intervals, and the highest amount of UA excreted in any interval was designated as peak UA excretion for each patient and treatment period. | On Day -1 and Day 7 of each treatment period |
| Change From Baseline in Plasma Concentration (Cmax) on Day 7 | Cmax assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin | On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose) |
| Change From Baseline in Area Under Plasma Concentration Time Curve From Time Zero to the Time of Last Measurable Concentration (AUClast) on Day 7 | AUClast assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin | On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose) |
| Change From Baseline in Area Under Plasma Concentration Time Curve Over a Dosing Interval (24 Hours) (AUCτ) on Day 7 | AUCτ assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin | On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Urinary Excretion of Serum UA (sUA) on Day 7 | Change from baseline in sUA to assess the intensive UA lowering effect of RDEA3170, febuxostat and dapagliflozin by evaluating the sUA levels after 7 days of treatment. | At Day -1 and Day 7 |
| Change From Baseline in Time to Reach Maximum Observed Concentration (Tmax) on Day 7 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Glendale | California | 91206 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33075806 | Derived | Stack AG, Han D, Goldwater R, Johansson S, Dronamraju N, Oscarsson J, Johnsson E, Parkinson J, Erlandsson F. Dapagliflozin Added to Verinurad Plus Febuxostat Further Reduces Serum Uric Acid in Hyperuricemia: The QUARTZ Study. J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2347-e2356. doi: 10.1210/clinem/dgaa748. |
| Label | URL |
|---|---|
| Related Info | View source |
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Patients who provided informed consent underwent screening procedures within the 28 days. Patients returned to the Clinical Unit on Day -2 of Treatment Period 1 and were randomized (1:1) to two treatment sequences ( treatment AB or BA).
The trial was conducted at two study centres: Baltimore and Los Angeles. The date of the first subject visit was 25 Oct 2017 and the date of the last subject last visit was 19 Jul 2018. A total of 36 adults asymptomatic hyperuricemic patients were included into this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Sequence A+B | Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin (Treatment A). Each patient randomized to treatment A in period 1 received Treatment B in period 2 as this is 2-way crossover study |
| FG001 | Treatment Sequence B+A |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period 1 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 16, 2018 | Jun 27, 2019 |
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| Clinical Laboratory: USA |
| UNKNOWN |
| Harbor Hospital Laboratory | UNKNOWN |
| GenX Laboratories Inc. | UNKNOWN |
| Analytical Laboratory (Pharmacokinetic Sample Analysis): USA | UNKNOWN |
| Covance Bioanalytical Services, LLC | UNKNOWN |
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The pharmacokineticist will remain blinded during the study conduct, unless otherwise required based on study findings. The pharmacokineticist will be unblinded to perform the final PK analyses after all patients have completed the study, final bioanalytical results are available and all required study data are considered clean. This may occur before database lock.
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| Febuxostat | Drug | Randomized patients will receive orally once daily fixed dose of febuxostat in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo |
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| Dapagliflozin | Drug | Randomized patients will receive orally once daily fixed dose of dapagliflozin in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo |
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| Dapagliflozin matched placebo | Other | Randomized patients will receive orally once daily fixed dose of dapagliflozin matched placebo in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo |
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tmax assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin |
| On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose) |
| Change From Baseline in Time of Last Measurable Concentration (Tlast) on Day 7 | tlast assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin | On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose) |
| Baltimore |
| Maryland |
| 21225 |
| United States |
| Related Info | View source |
Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + placebo (Treatment B). Each patient randomized to treatment B in period 1 received Treatment A in period 2 as this is 2-way crossover study |
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| NOT COMPLETED |
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| Treatment Period 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Subjects | Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin/placebo. Each patient randomized to treatment A in period 1 received Treatment B in period 2 and each patient randomized to treatment B in period 1 received Treatment A in period 2 |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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 | Change From Baseline in Peak Urinary Excretion of Uric Acid (UA) on Day 7 | Change from baseline in peak UA excretion during the first 8 hours on Day 7 of treatment to assess the effects of intensive UA lowering therapy with verinurad, febuxostat and dapagliflozin. Urine sample was collected in hourly intervals, and the highest amount of UA excreted in any interval was designated as peak UA excretion for each patient and treatment period. | Protocol Analysis Set | Posted | Least Squares Mean | 95% Confidence Interval | milligrams (mg) | On Day -1 and Day 7 of each treatment period |
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| Primary | Change From Baseline in Plasma Concentration (Cmax) on Day 7 | Cmax assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin | Pharmacokinetic Analysis Set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose) |
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| Primary | Change From Baseline in Area Under Plasma Concentration Time Curve From Time Zero to the Time of Last Measurable Concentration (AUClast) on Day 7 | AUClast assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin | Pharmacokinetic Analysis Set | Posted | Geometric Mean | Geometric Coefficient of Variation | h∙ng/mL | On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose) |
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| Secondary | Change From Baseline in Urinary Excretion of Serum UA (sUA) on Day 7 | Change from baseline in sUA to assess the intensive UA lowering effect of RDEA3170, febuxostat and dapagliflozin by evaluating the sUA levels after 7 days of treatment. | Pharmacodynamic Analysis Set | Posted | Least Squares Mean | 95% Confidence Interval | umol/L | At Day -1 and Day 7 |
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| Secondary | Change From Baseline in Time to Reach Maximum Observed Concentration (Tmax) on Day 7 | tmax assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin | Pharmacokinetic Analysis Set | Posted | Median | Full Range | hour | On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose) |
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| Secondary | Change From Baseline in Time of Last Measurable Concentration (Tlast) on Day 7 | tlast assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin | Pharmacokinetic Analysis Set | Posted | Median | Full Range | hour | On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose) |
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| Primary | Change From Baseline in Area Under Plasma Concentration Time Curve Over a Dosing Interval (24 Hours) (AUCτ) on Day 7 | AUCτ assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin | Pharmacokinetic Analysis Set | Posted | Geometric Mean | Geometric Coefficient of Variation | h∙ng/mL | On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose) |
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Adverse events were collected from the start of randomization throughout the treatment period up to and including the Follow-up Visit. Serious adverse events were recorded from the time of informed consent.
From screening (Day -28) to follow-up (Day 23)
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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 Sequence A+B | Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin (Treatment A). Each patient randomized to treatment A in period 1 received Treatment B in period 2 as this is 2-way crossover study | 0 | 35 | 0 | 35 | 7 | 35 |
| EG001 | Treatment Sequence B+A | Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + placebo (Treatment B). Each patient randomized to treatment B in period 1 received Treatment A in period 2 as this is 2-way crossover study | 0 | 36 | 0 | 36 | 5 | 36 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Catheter Site Pain | General disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Influenza Like Illness | General disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Vessel Puncture Site Haematoma | General disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
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| Eyelid Injury | Injury, poisoning and procedural complications | MedDRA 20.1 | Non-systematic Assessment |
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| Skin Abrasion | Injury, poisoning and procedural complications | MedDRA 20.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 20.1 | Non-systematic Assessment |
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| Dry Skin | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
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The initial plan was to recruit 24 patients, but due to difficulties in determining the peak urinary uric acid excretion in 11 patients, it was decided to include 12 additional patients to ensure adequate sample size.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Fredrik Erlandsson | AstraZeneca RD, Gothenburg | 1-877-240-9479 | information.center@astrazeneca.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | May 10, 2018 | Jun 27, 2019 | Prot_001.pdf |
| ID | Term |
|---|---|
| D006073 | Gout |
| D033461 | Hyperuricemia |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D000070657 | Crystal Arthropathies |
| 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 |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000628929 | verinurad |
| D000069465 | Febuxostat |
| C529054 | dapagliflozin |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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