RDEA3170 and Febuxostat Combination Study in Gout Subjects
Sponsor
Ardea Biosciences, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02246673
Collaborator
(none)
64
6
4
16
10.7
0.7
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
64 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2a, Randomized, Open-Label Study to Evaluate the Pharmacodynamic Effects and Safety of RDEA3170 Administered in Combination With Febuxostat Compared to Febuxostat Administered Alone in Adult Subjects With Gout
Study Start Date
:
Oct 1, 2014
Actual Primary Completion Date
:
Jul 1, 2015
Actual Study Completion Date
:
Feb 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: RDEA3170 10 mg 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. |
Drug: RDEA3170 10 mg
Drug: Febuxostat 40 mg
Drug: Febuxostat 80 mg
|
| Experimental: RDEA3170 15 mg 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. |
Drug: RDEA3170 15 mg
Drug: RDEA3170 5 mg
Drug: Febuxostat 40 mg
Drug: Febuxostat 80 mg
|
| Experimental: RDEA3170 5 mg 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. |
Drug: Febuxostat 40 mg
Drug: Febuxostat 80 mg
|
| Experimental: RDEA3170 2.5 mg 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. |
Drug: RDEA3170 2.5
Drug: Febuxostat 40 mg
Drug: Febuxostat 80 mg
|
Outcome Measures
Primary Outcome Measures
- Serum Urate Maximum Percentage (%) Change (Emax, CB) [28 days]
Maximum observed percentage (%) change from baseline in serum urate concentrations.
- Urine Uric Acid % Change (0-24h) (Aeur, CB) [28 days]
Percentage (%) change from baseline in the amount of uric acid recovered in urine.
- Renal Clearance of Uric Acid % Change (0-24h) (CLur, CB) [28 days]
Percentage (%) change from baseline in renal clearance of uric acid.
- Fract. Excretion of Uric Acid % Change (0-24h) (FEUA, CB) [28 days]
Percentage (%) change from baseline in fractional excretion of uric acid.
Secondary Outcome Measures
- Maximum Observed Plasma Concentration (Cmax) [Days 7 to 28]
Cmax of multiple-dose RDEA3170 administered in combination with febuxostat from plasma
- Time of Occurrence of Maximum Observed Concentration (Tmax) [Days 7 to 28]
Tmax of multiple-dose RDEA3170 administered in combination with febuxostat from plasma
- Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) [Days 7 to 28]
AUC 0-24 of multiple-dose RDEA3170 administered in combination with febuxostat from plasma
- Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) [Days 7 to 28]
AUC last of multiple-dose RDEA3170 administered in combination with febuxostat from plasma
- Apparent Terminal Half-life (t1/2) [Days 7 to 28]
t1/2 of multiple-dose RDEA3170 administered in combination with febuxostat from plasma
- Incidence of Treatment-Emergent Adverse Events [10 weeks]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Able to understand the study procedures and the risks involved and is willing to provide written informed consent before the first study-related activity.
-
Meets one or more criteria for the diagnosis of gout as per the American Rheumatism Association Criteria for the Classification of Acute Arthritis of Primary Gout.
-
Body weight ≥ 50 kg (110 lbs) and a body mass index ≥ 18 and ≤ 45 kg/m2.
-
Screening serum urate level ≥ 8 mg/dL.
-
Free of any clinically significant disease or medical condition, per the Investigator's judgment.
Exclusion Criteria:
-
Unable to take colchicine for gout flare prophylaxis.
-
History or suspicion of kidney stones.
-
Any gastrointestinal disorder that affects motility and/or absorption.
-
Unstable angina, New York Heart Association class III or IV heart failure, ischemic heart disease, stroke, or deep venous thrombosis within 12 months prior to Day 1; or subject is currently receiving anticoagulants.
-
Screening laboratory parameters that are outside the normal limits and are considered clinically significant by the Investigator.
-
Estimated creatinine clearance < 60 mL/min calculated by the Cockcroft-Gault formula using ideal body weight during the Screening period.
-
Taking losartan, fenofibrate, guaifenesin, or sodium-glucose linked transporter-2 inhibitors; chronic and stable doses are permitted if doses are stable for at least 14 days prior to study medication dosing.
-
Unable or unwilling to comply with the study requirements or has a situation or condition that, in the opinion of the Investigator, may interfere with participation in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Anaheim | California | United States | 92801 | |
| 2 | Glendale | California | United States | 91206 | |
| 3 | South Miami | Florida | United States | 33143 | |
| 4 | Overland Park | Kansas | United States | 66211 | |
| 5 | Overland Park | Kansas | United States | 66212 | |
| 6 | Dallas | Texas | United States | 75231 |
Sponsors and Collaborators
- Ardea Biosciences, Inc.
Investigators
- Study Director: J. Hall, Ardea Biosciences, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT02246673
Other Study ID Numbers:
- RDEA3170-204
First Posted:
Sep 23, 2014
Last Update Posted:
Jul 27, 2017
Last Verified:
Jun 1, 2017
Study Results
Participant Flow
| Recruitment Details | 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. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 |
|---|---|---|---|---|---|
| Arm/Group Description | (RDEA3170 10 mg + Febuxostat 40 mg; RDEA3170 10 mg + Febuxostat 80 mg) | (RDEA3170 15 mg + Febuxostat 40 mg; RDEA3170 15 mg + Febuxostat 80 mg) | (RDEA3170 5 mg + Febuxostat 40 mg; RDEA3170 5 mg + Febuxostat 80 mg) | (RDEA3170 2.5 mg + Febuxostat 40 mg; RDEA3170 2.5 mg + Febuxostat 80 mg) | (RDEA3170 10 mg + Febuxostat 40 mg; RDEA3170 15 mg + Febuxostat 40 mg; RDEA3170 20 mg + Febuxostat 40 mg) |
| Period Title: Overall Study | |||||
| STARTED | 14 | 12 | 12 | 14 | 12 |
| COMPLETED | 13 | 12 | 12 | 12 | 11 |
| NOT COMPLETED | 1 | 0 | 0 | 2 | 1 |
Baseline Characteristics
| Arm/Group Title | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Total of all reporting groups | |||||
| Overall Participants | 14 | 12 | 12 | 14 | 12 | 64 |
| Age (Years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [Years] |
45
(8.9)
|
50
(8.2)
|
50
(8.5)
|
48
(11.5)
|
49
(10.9)
|
48
(9.6)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
14
100%
|
12
100%
|
12
100%
|
14
100%
|
12
100%
|
64
100%
|
Outcome Measures
| Title | Serum Urate Maximum Percentage (%) Change (Emax, CB) |
|---|---|
| Description | Maximum observed percentage (%) change from baseline in serum urate concentrations. |
| Time Frame | 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Febuxostat 40 mg | Febuxostat 80 mg | RDEA3170 10 mg + Febuxostat 40 mg | RDEA3170 10 mg + Febuxostat 80 mg | RDEA3170 15 mg + Febuxostat 40 mg | RDEA3170 15 mg + Febuxostat 80 mg | RDEA3170 5 mg + Febuxostat 40 mg | RDEA3170 5 mg + Febuxostat 80 mg | RDEA3170 2.5 mg + Febuxostat 40 mg | RDEA3170 2.5 mg + Febuxostat 80 mg | RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Days 7/14/21/28 Overall (Cohorts 1 through 5) | Days 7/28 Overall (Cohorts 1 through 5) | Days 7/14/21/28 Overall (Cohorts 1 and 5) | Days 14/21 Overall (Cohort 1) | Days 7/14/21/28 Overall (Cohorts 2 and 5) | Days 14/21 Overall (Cohort 2) | Days 14/21 Overall (Cohort 3) | Days 14/21 Overall (Cohort 3) | Days 14/21 Overall (Cohort 4) | Days 14/21 Overall (Cohort 4) | Days 14/21 Overall (Cohort 5) |
| Measure Participants | 58 | 47 | 22 | 10 | 23 | 11 | 12 | 12 | 12 | 12 | 11 |
| Mean (Standard Error) [Percentage (%)] |
-43.5
(1.10)
|
-55.6
(1.37)
|
-70.4
(1.35)
|
-79.1
(2.53)
|
-74.9
(1.18)
|
-82.4
(1.76)
|
-59.4
(2.81)
|
-66.7
(2.32)
|
-52.5
(2.51)
|
-62.7
(2.69)
|
-77.3
(1.18)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 10 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | -28.18 | |
| Confidence Interval |
(2-Sided) 95% -33.85 to -22.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 10 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | -25.29 | |
| Confidence Interval |
(2-Sided) 95% -31.23 to -19.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 15 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 2 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | -29.15 | |
| Confidence Interval |
(2-Sided) 95% -33.15 to -25.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 15 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 2 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | -22.25 | |
| Confidence Interval |
(2-Sided) 95% -26.36 to -18.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 5 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 3 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | -17.52 | |
| Confidence Interval |
(2-Sided) 95% -21.54 to -13.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 5 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 3 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | -15.51 | |
| Confidence Interval |
(2-Sided) 95% -19.53 to -11.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 2.5 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 4 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | -9.74 | |
| Confidence Interval |
(2-Sided) 95% -13.97 to -5.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 2.5 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 4 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0221 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | -4.98 | |
| Confidence Interval |
(2-Sided) 95% -9.19 to -0.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 5 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | -35.38 | |
| Confidence Interval |
(2-Sided) 95% -38.89 to -31.87 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 10 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 5 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | -27.08 | |
| Confidence Interval |
(2-Sided) 95% -30.60 to -23.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 15 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 5 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | -31.26 | |
| Confidence Interval |
(2-Sided) 95% -34.77 to -27.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Urine Uric Acid % Change (0-24h) (Aeur, CB) |
|---|---|
| Description | Percentage (%) change from baseline in the amount of uric acid recovered in urine. |
| Time Frame | 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Febuxostat 40 mg | Febuxostat 80 mg | RDEA3170 10 mg + Febuxostat 40 mg | RDEA3170 10 mg + Febuxostat 80 mg | RDEA3170 15 mg + Febuxostat 40 mg | RDEA3170 15 mg + Febuxostat 80 mg | RDEA3170 5 mg + Febuxostat 40 mg | RDEA3170 5 mg + Febuxostat 80 mg | RDEA3170 2.5 mg + Febuxostat 40 mg | RDEA3170 2.5 mg + Febuxostat 80 mg | RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Days 7/14/21/28 Overall (Cohorts 1 through 5) | Days 14/21 Overall (Cohorts 1 through 5) | Days 7/14/21/28 Overall (Cohorts 1 and 5) | Days 14/21 Overall (Cohort 1) | Days 7/14/21/28 Overall (Cohorts 2 and 5) | Days 14/21 Overall (Cohort 2) | Days 14/21 Overall (Cohort 3) | Days 14/21 Overall (Cohort 3) | Days 14/21 Overall (Cohort 4) | Days 14/21 Overall (Cohort 4) | Days 14/21 Overall (Cohort 5) |
| Measure Participants | 56 | 45 | 24 | 13 | 22 | 10 | 10 | 10 | 11 | 11 | 10 |
| Mean (Standard Error) [Percentage (%)] |
-48.6
(1.71)
|
-60.3
(1.58)
|
-23.7
(5.56)
|
-36.6
(6.75)
|
-22.9
(4.15)
|
-44.4
(5.57)
|
-26.2
(8.28)
|
-39.2
(5.95)
|
-40.2
(4.07)
|
-61.1
(2.16)
|
-14.2
(10.9)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 10 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 24.27 | |
| Confidence Interval |
(2-Sided) 95% 12.57 to 35.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 10 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0013 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 20.08 | |
| Confidence Interval |
(2-Sided) 95% 8.38 to 31.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 15 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 2 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 23.70 | |
| Confidence Interval |
(2-Sided) 95% 14.23 to 33.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 15 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 2 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0008 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 18.37 | |
| Confidence Interval |
(2-Sided) 95% 8.30 to 28.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 5 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 3 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0101 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 18.82 | |
| Confidence Interval |
(2-Sided) 95% 4.86 to 32.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 5 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 3 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0055 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 20.52 | |
| Confidence Interval |
(2-Sided) 95% 6.56 to 34.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 2.5 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 4 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0065 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 10.36 | |
| Confidence Interval |
(2-Sided) 95% 3.13 to 17.59 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 2.5 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 4 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6140 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 1.79 | |
| Confidence Interval |
(2-Sided) 95% -5.37 to 8.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 5 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 30.83 | |
| Confidence Interval |
(2-Sided) 95% 15.62 to 46.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 10 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 5 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0019 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 24.38 | |
| Confidence Interval |
(2-Sided) 95% 9.63 to 39.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 15 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 5 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0009 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 26.35 | |
| Confidence Interval |
(2-Sided) 95% 11.59 to 41.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Renal Clearance of Uric Acid % Change (0-24h) (CLur, CB) |
|---|---|
| Description | Percentage (%) change from baseline in renal clearance of uric acid. |
| Time Frame | 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Febuxostat 40 mg | Febuxostat 80 mg | RDEA3170 10 mg + Febuxostat 40 mg | RDEA3170 10 mg + Febuxostat 80 mg | RDEA3170 15 mg + Febuxostat 40 mg | RDEA3170 15 mg + Febuxostat 80 mg | RDEA3170 5 mg + Febuxostat 40 mg | RDEA3170 5 mg + Febuxostat 80 mg | RDEA3170 2.5 mg + Febuxostat 40 mg | RDEA3170 2.5 mg + Febuxostat 80 mg | RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Days 7/14/21/28 Overall (Cohorts 1 through 5) | Days 14/21 Overall (Cohorts 1 through 5) | Days 7/14/21/28 Overall (Cohorts 1 and 5) | Days 14/21 Overall (Cohort 1) | Days 7/14/21/28 Overall (Cohorts 2 and 5) | Days 14/21 Overall (Cohort 2) | Days 14/21 Overall (Cohort 3) | Days 14/21 Overall (Cohort 3) | Days 14/21 Overall (Cohort 4) | Days 14/21 Overall (Cohort 4) | Days 14/21 Overall (Cohort 5) |
| Measure Participants | 50 | 37 | 21 | 10 | 20 | 10 | 10 | 10 | 10 | 10 | 9 |
| Mean (Standard Error) [Percentage (%)] |
-15.2
(2.53)
|
-18.8
(2.52)
|
125
(17.4)
|
153
(30.5)
|
157
(15.9)
|
172
(30.0)
|
58.7
(15.7)
|
68.4
(24.7)
|
20.9
(10.1)
|
0.011
(7.36)
|
223
(47.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 10 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 139.11 | |
| Confidence Interval |
(2-Sided) 95% 93.92 to 184.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 10 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 174.47 | |
| Confidence Interval |
(2-Sided) 95% 125.52 to 233.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 15 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 2 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 168.03 | |
| Confidence Interval |
(2-Sided) 95% 123.13 to 212.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 15 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 2 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 188.75 | |
| Confidence Interval |
(2-Sided) 95% 138.04 to 239.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 5 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 3 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 70.43 | |
| Confidence Interval |
(2-Sided) 95% 33.74 to 107.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 5 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 3 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 91.50 | |
| Confidence Interval |
(2-Sided) 95% 54.81 to 128.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 2.5 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 4 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 40.11 | |
| Confidence Interval |
(2-Sided) 95% 25.17 to 55.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 2.5 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 4 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0350 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 15.96 | |
| Confidence Interval |
(2-Sided) 95% 1.20 to 30.71 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 5 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 236.08 | |
| Confidence Interval |
(2-Sided) 95% 178.29 to 293.86 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 10 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 5 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 146.20 | |
| Confidence Interval |
(2-Sided) 95% 90.40 to 202.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 15 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 5 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 176.57 | |
| Confidence Interval |
(2-Sided) 95% 120.77 to 232.38 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Fract. Excretion of Uric Acid % Change (0-24h) (FEUA, CB) |
|---|---|
| Description | Percentage (%) change from baseline in fractional excretion of uric acid. |
| Time Frame | 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Febuxostat 40 mg | Febuxostat 80 mg | RDEA3170 10 mg + Febuxostat 40 mg | RDEA3170 10 mg + Febuxostat 80 mg | RDEA3170 15 mg + Febuxostat 40 mg | RDEA3170 15 mg + Febuxostat 80 mg | RDEA3170 5 mg + Febuxostat 40 mg | RDEA3170 5 mg + Febuxostat 80 mg | RDEA3170 2.5 mg + Febuxostat 40 mg | RDEA3170 2.5 mg + Febuxostat 80 mg | RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Days 7/14/21/28 Overall (Cohorts 1 through 5) | Days 14/21 Overall (Cohorts 1 through 5) | Days 7/14/21/28 Overall (Cohorts 1 and 5) | Days 14/21 Overall (Cohort 1) | Days 7/14/21/28 Overall (Cohorts 2 and 5) | Days 14/21 Overall (Cohort 2) | Days 14/21 Overall (Cohort 3) | Days 14/21 Overall (Cohort 3) | Days 14/21 Overall (Cohort 4) | Days 14/21 Overall (Cohort 4) | Days 14/21 Overall (Cohort 5) |
| Measure Participants | 47 | 33 | 21 | 8 | 19 | 10 | 7 | 7 | 10 | 10 | 9 |
| Mean (Standard Error) [Percentage (%)] |
-20.6
(1.82)
|
-20.8
(2.62)
|
100
(13.4)
|
155
(32.4)
|
133
(12.2)
|
152
(26.2)
|
46.6
(9.36)
|
54.8
(20.5)
|
15.2
(9.30)
|
4.73
(6.15)
|
162
(23.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 10 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 135.82 | |
| Confidence Interval |
(2-Sided) 95% 93.33 to 178.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 10 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 178.58 | |
| Confidence Interval |
(2-Sided) 95% 129.25 to 227.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 15 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 2 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 163.98 | |
| Confidence Interval |
(2-Sided) 95% 120.80 to 207.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 15 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 2 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 169.93 | |
| Confidence Interval |
(2-Sided) 95% 122.82 to 217.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 5 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 3 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 59.60 | |
| Confidence Interval |
(2-Sided) 95% 28.85 to 90.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 5 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 3 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 73.54 | |
| Confidence Interval |
(2-Sided) 95% 42.79 to 104.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 2.5 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 4 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 33.70 | |
| Confidence Interval |
(2-Sided) 95% 21.21 to 46.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 80 mg, RDEA3170 2.5 mg + Febuxostat 80 mg |
|---|---|---|
| Comments | Cohort 4 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 27.08 | |
| Confidence Interval |
(2-Sided) 95% 14.58 to 39.58 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 5 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 188.83 | |
| Confidence Interval |
(2-Sided) 95% 152.55 to 225.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 10 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 5 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 116.83 | |
| Confidence Interval |
(2-Sided) 95% 81.76 to 151.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Febuxostat 40 mg, RDEA3170 15 mg + Febuxostat 40 mg |
|---|---|---|
| Comments | Cohort 5 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The model included treatment and period as fixed effects and subject(s) as a random effect. | |
| Method of Estimation | Estimation Parameter | Geometric Least Squares mean Ratio |
| Estimated Value | 151.66 | |
| Confidence Interval |
(2-Sided) 95% 116.59 to 186.73 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maximum Observed Plasma Concentration (Cmax) |
|---|---|
| Description | Cmax of multiple-dose RDEA3170 administered in combination with febuxostat from plasma |
| Time Frame | Days 7 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RDEA3170 10 mg + Febuxostat 40 mg | RDEA3170 10 mg + Febuxostat 80 mg | RDEA3170 15 mg + Febuxostat 40 mg | RDEA3170 15 mg + Febuxostat 80 mg | RDEA3170 5 mg + Febuxostat 40 mg | RDEA3170 5 mg + Febuxostat 80 mg | RDEA3170 2.5 mg + Febuxostat 40 mg | RDEA3170 2.5 mg + Febuxostat 80 mg | RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Overall (Cohorts 1 and 5) | Overall (Cohort 1) | Overall (Cohorts 2 and 5) | Overall (Cohort 2) | Overall (Cohort 3) | Overall (Cohort 3) | Overall (Cohort 4) | Overall (Cohort 4) | Overall (Cohort 5) |
| Measure Participants | 24 | 13 | 23 | 11 | 12 | 12 | 12 | 12 | 11 |
| Geometric Mean (95% Confidence Interval) [ng/mL] |
15.5
|
16.1
|
21.2
|
20.4
|
7.20
|
7.54
|
3.45
|
3.37
|
26.1
|
| Title | Time of Occurrence of Maximum Observed Concentration (Tmax) |
|---|---|
| Description | Tmax of multiple-dose RDEA3170 administered in combination with febuxostat from plasma |
| Time Frame | Days 7 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RDEA3170 10 mg + Febuxostat 40 mg | RDEA3170 10 mg + Febuxostat 80 mg | RDEA3170 15 mg + Febuxostat 40 mg | RDEA3170 15 mg + Febuxostat 80 mg | RDEA3170 5 mg + Febuxostat 40 mg | RDEA3170 5 mg + Febuxostat 80 mg | RDEA3170 2.5 mg + Febuxostat 40 mg | RDEA3170 2.5 mg + Febuxostat 80 mg | RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Overall (Cohorts 1 and 5) | Days 14/21 Overall (Cohort 1) | Overall (Cohorts 2 and 5) | Days 14/21 Overall (Cohort 2) | Overall (Cohort 3) | Days 14/21 Overall (Cohort 3) | Overall (Cohort 4) | Days 14/21 Overall (Cohort 4) | Days 14/21 Overall (Cohort 5) |
| Measure Participants | 24 | 13 | 23 | 11 | 12 | 12 | 12 | 12 | 11 |
| Median (Full Range) [hr] |
3.00
|
3.00
|
3.00
|
4.00
|
3.50
|
4.00
|
3.50
|
2.50
|
3.00
|
| Title | Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) |
|---|---|
| Description | AUC 0-24 of multiple-dose RDEA3170 administered in combination with febuxostat from plasma |
| Time Frame | Days 7 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RDEA3170 10 mg + Febuxostat 40 mg | RDEA3170 10 mg + Febuxostat 80 mg | RDEA3170 15 mg + Febuxostat 40 mg | RDEA3170 15 mg + Febuxostat 80 mg | RDEA3170 5 mg + Febuxostat 40 mg | RDEA3170 5 mg + Febuxostat 80 mg | RDEA3170 2.5 mg + Febuxostat 40 mg | RDEA3170 2.5 mg + Febuxostat 80 mg | RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Overall (Cohorts 1 and 5) | Overall (Cohort 1) | Overall (Cohorts 2 and 5) | Overall (Cohort 2) | Overall (Cohort 3) | Overall (Cohort 3) | Overall (Cohort 4) | Overall (Cohort 4) | Overall (Cohort 5) |
| Measure Participants | 24 | 13 | 23 | 11 | 12 | 12 | 12 | 12 | 11 |
| Geometric Mean (95% Confidence Interval) [ng·hr/mL] |
123
|
138
|
186
|
225
|
62.2
|
57.6
|
28.0
|
27.4
|
216
|
| Title | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) |
|---|---|
| Description | AUC last of multiple-dose RDEA3170 administered in combination with febuxostat from plasma |
| Time Frame | Days 7 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RDEA3170 10 mg + Febuxostat 40 mg | RDEA3170 10 mg + Febuxostat 80 mg | RDEA3170 15 mg + Febuxostat 40 mg | RDEA3170 15 mg + Febuxostat 80 mg | RDEA3170 5 mg + Febuxostat 40 mg | RDEA3170 5 mg + Febuxostat 80 mg | RDEA3170 2.5 mg + Febuxostat 40 mg | RDEA3170 2.5 mg + Febuxostat 80 mg | RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Overall (Cohorts 1 and 5) | Overall (Cohort 1) | Overall (Cohorts 2 and 5) | Overall (Cohort 2) | Overall (Cohort 3) | Overall (Cohort 3) | Overall (Cohort 4) | Overall (Cohort 4) | Overall (Cohort 5) |
| Measure Participants | 24 | 13 | 23 | 11 | 12 | 12 | 12 | 12 | 11 |
| Geometric Mean (95% Confidence Interval) [ng·hr/mL] |
123
|
138
|
186
|
225
|
62.2
|
62.6
|
28.0
|
26.8
|
216
|
| Title | Apparent Terminal Half-life (t1/2) |
|---|---|
| Description | t1/2 of multiple-dose RDEA3170 administered in combination with febuxostat from plasma |
| Time Frame | Days 7 to 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RDEA3170 10 mg + Febuxostat 40 mg | RDEA3170 10 mg + Febuxostat 80 mg | RDEA3170 15 mg + Febuxostat 40 mg | RDEA3170 15 mg + Febuxostat 80 mg | RDEA3170 5 mg + Febuxostat 40 mg | RDEA3170 5 mg + Febuxostat 80 mg | RDEA3170 2.5 mg + Febuxostat 40 mg | RDEA3170 2.5 mg + Febuxostat 80 mg | RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Overall (Cohorts 1 and 5) | Overall (Cohort 1) | Overall (Cohorts 2 and 5) | Overall (Cohort 2) | Overall (Cohort 3) | Overall (Cohort 3) | Overall (Cohort 4) | Overall (Cohort 4) | Overall (Cohort 5) |
| Measure Participants | 24 | 12 | 23 | 11 | 12 | 11 | 12 | 12 | 11 |
| Geometric Mean (95% Confidence Interval) [hr] |
8.26
|
9.64
|
10.6
|
10.8
|
13.2
|
11.3
|
13.0
|
12.5
|
11.6
|
| Title | Incidence of Treatment-Emergent Adverse Events |
|---|---|
| Description | |
| Time Frame | 10 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Febuxostat 40 mg | Febuxostat 80 mg | RDEA3170 10 mg + Febuxostat 40 mg | RDEA3170 10 mg + Febuxostat 80 mg | RDEA3170 15 mg + Febuxostat 40 mg | RDEA3170 15 mg + Febuxostat 80 mg | RDEA3170 5 mg + Febuxostat 40 mg | RDEA3170 5 mg + Febuxostat 80 mg | RDEA3170 2.5 mg + Febuxostat 40 mg | RDEA3170 2.5 mg + Febuxostat 80 mg | RDEA3170 20 mg + Febuxostat 40 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Overall (Cohorts 1 through 5) | Overall (Cohorts 1 through 5) | Overall (Cohorts 1 and 5) | Overall (Cohort 1) | Overall (Cohorts 2 and 5) | Overall (Cohort 2) | Overall (Cohort 3) | Overall (Cohort 3) | Overall (Cohort 4) | Overall (Cohort 4) | Overall (Cohort 5) |
| Measure Participants | 61 | 51 | 25 | 13 | 23 | 12 | 12 | 12 | 12 | 13 | 11 |
| Number [Number of participants] |
3
21.4%
|
8
66.7%
|
4
33.3%
|
6
42.9%
|
1
8.3%
|
0
0%
|
0
NaN
|
1
NaN
|
1
NaN
|
0
NaN
|
2
NaN
|
Adverse Events
| Time Frame | 10 weeks | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Febuxostat 40 mg | Febuxostat 80 mg | Overall RDEA3170 + Febuxostat Combination | |||
| Arm/Group Description | ||||||
All Cause Mortality |
||||||
| Febuxostat 40 mg | Febuxostat 80 mg | Overall RDEA3170 + Febuxostat Combination | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Febuxostat 40 mg | Febuxostat 80 mg | Overall RDEA3170 + Febuxostat Combination | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/61 (0%) | 0/51 (0%) | 0/62 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Febuxostat 40 mg | Febuxostat 80 mg | Overall RDEA3170 + Febuxostat Combination | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/61 (4.9%) | 8/51 (15.7%) | 13/62 (21%) | |||
| Ear and labyrinth disorders | ||||||
| Tympanic Membrane Hyperaemia | 0/61 (0%) | 0 | 1/51 (2%) | 1 | 0/62 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Dyspepsia | 1/61 (1.6%) | 1 | 0/51 (0%) | 0 | 2/62 (3.2%) | 2 |
| Aphthous Stomatitis | 0/61 (0%) | 0 | 0/51 (0%) | 0 | 1/62 (1.6%) | 2 |
| Constipation | 1/61 (1.6%) | 1 | 0/51 (0%) | 0 | 0/62 (0%) | 0 |
| Diarrhoea | 0/61 (0%) | 0 | 0/51 (0%) | 0 | 1/62 (1.6%) | 1 |
| General disorders | ||||||
| Fatigue | 0/61 (0%) | 0 | 0/51 (0%) | 0 | 1/62 (1.6%) | 1 |
| Hepatobiliary disorders | ||||||
| Hepatitis | 0/61 (0%) | 0 | 1/51 (2%) | 1 | 0/62 (0%) | 0 |
| Hepatitis Acute | 0/61 (0%) | 0 | 1/51 (2%) | 1 | 0/62 (0%) | 0 |
| Infections and infestations | ||||||
| Herpes Simplex | 0/61 (0%) | 0 | 0/51 (0%) | 0 | 1/62 (1.6%) | 1 |
| Pharyngitis | 0/61 (0%) | 0 | 0/51 (0%) | 0 | 1/62 (1.6%) | 1 |
| Upper Respiratory Tract Infection | 0/61 (0%) | 0 | 0/51 (0%) | 0 | 1/62 (1.6%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Excoriation | 0/61 (0%) | 0 | 1/51 (2%) | 1 | 0/62 (0%) | 0 |
| Investigations | ||||||
| Hepatic Enzyme Increased | 1/61 (1.6%) | 1 | 0/51 (0%) | 0 | 0/62 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Decreased Appetite | 0/61 (0%) | 0 | 1/51 (2%) | 1 | 0/62 (0%) | 0 |
| Hypertriglyceridaemia | 0/61 (0%) | 0 | 1/51 (2%) | 1 | 0/62 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Pain In Extremity | 0/61 (0%) | 0 | 0/51 (0%) | 0 | 3/62 (4.8%) | 3 |
| Musculoskeletal Pain | 0/61 (0%) | 0 | 0/51 (0%) | 0 | 2/62 (3.2%) | 2 |
| Nervous system disorders | ||||||
| Headache | 0/61 (0%) | 0 | 1/51 (2%) | 1 | 1/62 (1.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 0/61 (0%) | 0 | 0/51 (0%) | 0 | 1/62 (1.6%) | 1 |
| Oropharyngeal Pain | 0/61 (0%) | 0 | 0/51 (0%) | 0 | 1/62 (1.6%) | 1 |
| Productive Cough | 0/61 (0%) | 0 | 0/51 (0%) | 0 | 1/62 (1.6%) | 1 |
| Throat Irritation | 0/61 (0%) | 0 | 0/51 (0%) | 0 | 1/62 (1.6%) | 1 |
| Vascular disorders | ||||||
| Hypertension | 0/61 (0%) | 0 | 1/51 (2%) | 1 | 0/62 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Jesse Hall, MD |
|---|---|
| Organization | Study Information Center AstraZeneca |
| Phone | +1 877-240-9479 |
| information.center@astrazeneca.com |
Responsible Party:
Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT02246673
Other Study ID Numbers:
- RDEA3170-204
First Posted:
Sep 23, 2014
Last Update Posted:
Jul 27, 2017
Last Verified:
Jun 1, 2017