Trial Outcomes & Findings for A Study to Assess the Effect of Intensive Uric Acid (UA) Lowering Therapy With RDEA3170, Febuxostat, Dapagliflozin on Urinary Excretion of UA (NCT NCT03316131)
NCT ID: NCT03316131
Last Updated: 2019-08-28
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
36 participants
Primary outcome timeframe
On Day -1 and Day 7 of each treatment period
Results posted on
2019-08-28
Participant Flow
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.
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).
Participant milestones
| Measure |
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
|
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
|
|---|---|---|
|
Treatment Period 1
STARTED
|
18
|
18
|
|
Treatment Period 1
COMPLETED
|
18
|
18
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 2
STARTED
|
18
|
18
|
|
Treatment Period 2
COMPLETED
|
17
|
18
|
|
Treatment Period 2
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
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
|
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
|
|---|---|---|
|
Treatment Period 2
Protocol deviation
|
1
|
0
|
Baseline Characteristics
A Study to Assess the Effect of Intensive Uric Acid (UA) Lowering Therapy With RDEA3170, Febuxostat, Dapagliflozin on Urinary Excretion of UA
Baseline characteristics by cohort
| Measure |
All Subjects
n=36 Participants
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
|
|---|---|
|
Age, Continuous
|
42.3 years
STANDARD_DEVIATION 12.01 • n=99 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
17 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: On Day -1 and Day 7 of each treatment periodPopulation: Protocol Analysis Set
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.
Outcome measures
| Measure |
Treatment Sequence A+B
n=36 Participants
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
|
Treatment Sequence B+A
n=36 Participants
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
|
|---|---|---|
|
Change From Baseline in Peak Urinary Excretion of Uric Acid (UA) on Day 7
|
-12.87 milligrams (mg)
Interval -21.03 to -4.7
|
-13.15 milligrams (mg)
Interval -21.31 to -4.98
|
PRIMARY outcome
Timeframe: 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)Population: Pharmacokinetic Analysis Set
Cmax assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
Outcome measures
| Measure |
Treatment Sequence A+B
n=36 Participants
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
|
Treatment Sequence B+A
n=36 Participants
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
|
|---|---|---|
|
Change From Baseline in Plasma Concentration (Cmax) on Day 7
Verinurad
|
17.52 ng/mL
Geometric Coefficient of Variation 45.87
|
15.26 ng/mL
Geometric Coefficient of Variation 52.48
|
|
Change From Baseline in Plasma Concentration (Cmax) on Day 7
M1
|
25.28 ng/mL
Geometric Coefficient of Variation 41.55
|
25.61 ng/mL
Geometric Coefficient of Variation 57.24
|
|
Change From Baseline in Plasma Concentration (Cmax) on Day 7
M8
|
18.45 ng/mL
Geometric Coefficient of Variation 35.45
|
18.42 ng/mL
Geometric Coefficient of Variation 44.36
|
PRIMARY outcome
Timeframe: 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)Population: Pharmacokinetic Analysis Set
AUClast assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
Outcome measures
| Measure |
Treatment Sequence A+B
n=36 Participants
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
|
Treatment Sequence B+A
n=36 Participants
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
|
|---|---|---|
|
Change From Baseline in Area Under Plasma Concentration Time Curve From Time Zero to the Time of Last Measurable Concentration (AUClast) on Day 7
Verinurad
|
149.1 h∙ng/mL
Geometric Coefficient of Variation 37.79
|
141.0 h∙ng/mL
Geometric Coefficient of Variation 44.90
|
|
Change From Baseline in Area Under Plasma Concentration Time Curve From Time Zero to the Time of Last Measurable Concentration (AUClast) on Day 7
M1
|
212.7 h∙ng/mL
Geometric Coefficient of Variation 42.74
|
221.3 h∙ng/mL
Geometric Coefficient of Variation 49.13
|
|
Change From Baseline in Area Under Plasma Concentration Time Curve From Time Zero to the Time of Last Measurable Concentration (AUClast) on Day 7
M8
|
174.2 h∙ng/mL
Geometric Coefficient of Variation 34.57
|
176.5 h∙ng/mL
Geometric Coefficient of Variation 36.85
|
PRIMARY outcome
Timeframe: 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)Population: Pharmacokinetic Analysis Set
AUCτ assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
Outcome measures
| Measure |
Treatment Sequence A+B
n=36 Participants
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
|
Treatment Sequence B+A
n=36 Participants
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
|
|---|---|---|
|
Change From Baseline in Area Under Plasma Concentration Time Curve Over a Dosing Interval (24 Hours) (AUCτ) on Day 7
Verinurad
|
149.0 h∙ng/mL
Geometric Coefficient of Variation 37.84
|
140.9 h∙ng/mL
Geometric Coefficient of Variation 44.90
|
|
Change From Baseline in Area Under Plasma Concentration Time Curve Over a Dosing Interval (24 Hours) (AUCτ) on Day 7
M1
|
212.6 h∙ng/mL
Geometric Coefficient of Variation 42.78
|
221.1 h∙ng/mL
Geometric Coefficient of Variation 49.13
|
|
Change From Baseline in Area Under Plasma Concentration Time Curve Over a Dosing Interval (24 Hours) (AUCτ) on Day 7
M8
|
174.1 h∙ng/mL
Geometric Coefficient of Variation 34.59
|
176.3 h∙ng/mL
Geometric Coefficient of Variation 36.81
|
SECONDARY outcome
Timeframe: At Day -1 and Day 7Population: Pharmacodynamic Analysis Set
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.
Outcome measures
| Measure |
Treatment Sequence A+B
n=36 Participants
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
|
Treatment Sequence B+A
n=36 Participants
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
|
|---|---|---|
|
Change From Baseline in Urinary Excretion of Serum UA (sUA) on Day 7
|
-327.161 umol/L
Interval -352.559 to -301.762
|
-264.851 umol/L
Interval -290.06 to -239.643
|
SECONDARY outcome
Timeframe: 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)Population: Pharmacokinetic Analysis Set
tmax assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
Outcome measures
| Measure |
Treatment Sequence A+B
n=36 Participants
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
|
Treatment Sequence B+A
n=36 Participants
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
|
|---|---|---|
|
Change From Baseline in Time to Reach Maximum Observed Concentration (Tmax) on Day 7
Verinurad
|
4.00 hour
Interval 2.0 to 8.0
|
4.00 hour
Interval 3.0 to 8.08
|
|
Change From Baseline in Time to Reach Maximum Observed Concentration (Tmax) on Day 7
M1
|
4.00 hour
Interval 2.0 to 8.0
|
4.00 hour
Interval 3.0 to 4.03
|
|
Change From Baseline in Time to Reach Maximum Observed Concentration (Tmax) on Day 7
M8
|
4.00 hour
Interval 3.0 to 8.02
|
4.00 hour
Interval 3.0 to 8.08
|
SECONDARY outcome
Timeframe: 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)Population: Pharmacokinetic Analysis Set
tlast assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
Outcome measures
| Measure |
Treatment Sequence A+B
n=36 Participants
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
|
Treatment Sequence B+A
n=36 Participants
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
|
|---|---|---|
|
Change From Baseline in Time of Last Measurable Concentration (Tlast) on Day 7
Verinurad
|
24.00 hour
Interval 23.85 to 24.47
|
24.00 hour
Interval 23.22 to 24.4
|
|
Change From Baseline in Time of Last Measurable Concentration (Tlast) on Day 7
M1
|
24.00 hour
Interval 23.85 to 24.47
|
24.00 hour
Interval 23.22 to 24.4
|
|
Change From Baseline in Time of Last Measurable Concentration (Tlast) on Day 7
M8
|
24.00 hour
Interval 23.85 to 24.47
|
24.00 hour
Interval 23.22 to 24.4
|
Adverse Events
Treatment Sequence A+B
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Treatment Sequence B+A
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment Sequence A+B
n=35 participants at risk
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
|
Treatment Sequence B+A
n=36 participants at risk
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
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
2.9%
1/35 • 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)
|
2.8%
1/36 • 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)
|
|
Gastrointestinal disorders
Flatulence
|
2.9%
1/35 • 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)
|
2.8%
1/36 • 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)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/35 • 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)
|
2.8%
1/36 • 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)
|
|
General disorders
Catheter Site Pain
|
0.00%
0/35 • 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)
|
2.8%
1/36 • 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)
|
|
General disorders
Influenza Like Illness
|
2.9%
1/35 • 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)
|
0.00%
0/36 • 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)
|
|
General disorders
Vessel Puncture Site Haematoma
|
2.9%
1/35 • 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)
|
2.8%
1/36 • 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)
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/35 • 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)
|
2.8%
1/36 • 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)
|
|
Injury, poisoning and procedural complications
Eyelid Injury
|
2.9%
1/35 • 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)
|
0.00%
0/36 • 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)
|
|
Injury, poisoning and procedural complications
Skin Abrasion
|
0.00%
0/35 • 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)
|
2.8%
1/36 • 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)
|
|
Nervous system disorders
Headache
|
2.9%
1/35 • 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)
|
2.8%
1/36 • 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)
|
|
Psychiatric disorders
Insomnia
|
2.9%
1/35 • 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)
|
0.00%
0/36 • 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)
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
0.00%
0/35 • 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)
|
2.8%
1/36 • 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)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place