Phase 2a RDEA3170 and Allopurinol Combination Study in Gout Subjects

A Phase 2a, Randomized, Open-Label Study to Evaluate the Pharmacodynamic Effects and Safety of RDEA3170 Administered in Combination With Allopurinol Compared With Allopurinol Administered Alone in Adult Subjects With Gout

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02498652

Enrollment

Registered

2015-07-15

Start date

2015-07-28

Completion date

2016-06-02

Last updated

2018-01-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gout

Brief summary

This is a Phase 2a, randomized, open-label, multicenter study to assess the pharmacodynamic (PD) effects of RDEA3170 administered in combination with allopurinol compared with allopurinol administered alone in adult subjects with gout.

Interventions

DRUGRDEA3170 2.5 mg

Cohort 1: RDEA3170 2.5 mg, 7.5 mg (2.5 mg × 3 tablets), and 15 mg (2.5 mg × 6 tablets). Cohort 2: RDEA3170 5 mg (2.5 mg × 2 tablets), 10 mg (2.5 mg × 4 tablets), and 20 mg (2.5 mg × 8 tablets).

DRUGallopurinol 300 mg

allopurinol 300 mg, allopurinol 600 mg (300 mg x 2 tablets)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Subject is able to understand the study procedures and the risks involved and is willing to provide written informed consent before the first study-related activity. * Subject 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. * Subject has a body weight ≥ 50 kg (110 lbs.) and a body mass index ≥ 18 and ≤ 45 kg/m2. * Subject has a Screening serum urate level ≥ 8 mg/dL. * Subject is free of any clinically significant disease or medical condition, per the Investigator's judgment.

Exclusion criteria

* Subject is unable to take colchicine for gout flare prophylaxis. * Subject has a history or suspicion of kidney stones. * Subject has any gastrointestinal disorder that affects motility and/or absorption. * Subject had 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. * Subject has Screening laboratory parameters that are outside the normal limits and are considered clinically significant by the Investigator. * Subject has an estimated creatinine clearance \< 60 mL/min calculated by the Cockcroft-Gault formula using ideal body weight during the Screening period. * Subject is 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. * Subject is 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.

Design outcomes

Primary

Measure	Time frame	Description
Cohort 2 - Renal Hypoxanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeHXO, CB (%))	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2)
Cohort 1 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol.	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1)
Cohort 1 - Renal Xanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeXO, CB (%))	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1)
Cohort 1 - Renal Hypoxanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeHXO, CB (%))	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1)
Cohort 2 - Maximum Percentage (%) Change in Serum Urate of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (Emax, CB (%))	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2)
Cohort 2 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol.	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2)
Cohort 2 - Renal Xanthine Excretion at 0-24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (AeXO, CB (%))	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 2)
Cohort 1 - Maximum Percentage (%) Change in Serum Urate of Multiple-dose RDEA3170 Administered in Combination With Allopurinol (Emax, CB (%))	Screening, Days -1 , 1, 7, 14, 21, 28, and 35 (Pre-dose and Post-dose)	Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1)

Secondary

Measure	Time frame	Description
Time of Occurrence of Maximum Observed Concentration (Tmax)	Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)	Tmax of Allopurinol alone or in combination with RDEA3170
Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24)	Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)	AUC 0-24 of Allopurinol alone or in combination with RDEA3170
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)	Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)	AUC last of Allopurinol alone or in combination with RDEA3170
Apparent Terminal Half-life (t1/2)	Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)	t1/2 of Allopurinol alone or in combination with RDEA3170
Number of Participants With Treatment-Emergent Adverse Events	11 weeks	—
Maximum Observed Concentration (Cmax)	Day 7, 14, 21, 28 and 35 (predose through 24 hours postdose)	Cmax of Allopurinol alone or in combination with RDEA3170

Countries

United States

Participant flow

Recruitment details

41 subjects were randomized.

Pre-assignment details

Forty-one subjects were randomized and received at least 1 dose of randomized study medication; 20 subjects in Cohort 1 and 21 subjects in Cohort 2. Subjects were randomized into 1 of 8 sequences across the 2 cohorts (20 subjects each) in a 1:1 ratio.A total of 40 subjects completed the study.

Participants by arm

Arm	Count
Cohort 1 Allopurinol 300 mg once daily (qd), 600 mg qd, RDEA3170 2.5 mg qd, 15 mg qd and 7.5 mg qd	20
Cohort 2 Allopurinol 300 mg qd, 600 mg (300 mg bid), RDEA3170 5 mg qd, 20 mg qd and 10 mg qd	21
Total	41

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Protocol Violation	0	1

Baseline characteristics

Characteristic	Cohort 1	Cohort 2	Total
Age, Continuous	50 Years STANDARD_DEVIATION 12.7	48 Years STANDARD_DEVIATION 10.9	49 Years STANDARD_DEVIATION 11.7
Region of Enrollment United States	20 Participants	21 Participants	41 Participants
Sex/Gender, Customized Female	19 Participants	21 Participants	40 Participants
Sex/Gender, Customized Male	1 Participants	0 Participants	1 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 20	0 / 21
other Total, other adverse events	6 / 20	6 / 21
serious Total, serious adverse events	1 / 20	0 / 21

Outcome results

Primary

Cohort 1 - Concentration of Serum Urate at 24hr of Multiple-dose RDEA3170 Administered in Combination With Allopurinol.

Pharmacodynamics (PD) profile of multiple-dose RDEA3170 administered in combination with allopurinol (Cohort 1)