RDEA3170 and Allopurinol Combination Study in Gout Subjects

• Sponsor: Ardea Biosciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02279641
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Actual Duration (Months): 10.3
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This is a Phase 1b, randomized, open-label, drug-drug interaction study in adult male subjects with gout. It is designed to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of RDEA3170 or allopurinol alone and in combination in the fed state.

Condition or Disease	Intervention/Treatment	Phase
Gout	Drug: RDEA3170 10 mg; Drug: allopurinol 300 mg	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Phase 1b, Randomized, Open-label Study to Evaluate the Potential Pharmacokinetic and Pharmacodynamic Interactions Between RDEA3170 and Allopurinol in Adult Male Subjects With Gout
• Actual Study Start Date: Nov 1, 2014
• Actual Primary Completion Date: Apr 6, 2015
• Actual Study Completion Date: Sep 11, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequence A RDEA3170 qd (once daily), RDEA3170 + allopurinol qd, allopurinol qd	Drug: RDEA3170 10 mg; Drug: allopurinol 300 mg
Experimental: Sequence B allopurinol qd, RDEA3170 + allopurinol qd, RDEA3170 qd	Drug: RDEA3170 10 mg; Drug: allopurinol 300 mg

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) [22 days]

   Cmax of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170

2. Time of Occurrence of Maximum Observed Concentration (Tmax) [22 days]

   Tmax of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination

3. Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) [22 days]

   AUC 0-24 of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170

4. Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) [22 days]

   AUC last of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170

5. Apparent Terminal Half-life (t1/2) [22 days]

   t1/2 of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination

6. Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24) [22 days]

   Ae0-24 of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170

7. Renal Clearance of the Drug From Time Zero up to 24 Hours Postdose (CRL0-24) [22 days]

   CLR0-24 of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination

8. Pharmacodynamics (PD) Profile of Uric Acid From Serum and Urine [22 days]

9. Maximum Observed Plasma Concentration (Cmax) [22 days]

   Cmax of RDEA3170 Alone and In Combination with Allopurinol

10. Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24) [22 days]

    AUC 0-24 of RDEA3170 Alone and In Combination with Allopurinol

11. Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last) [22 days]

    AUC last of RDEA3170 Alone and In Combination with Allopurinol

12. Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24) [22 days]

    Ae0-24 of RDEA3170 Alone and In Combination with Allopurinol

Secondary Outcome Measures

1. Incidence of Treatment-Emergent Adverse Events [22 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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 and ≤ 10 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 an estimated creatinine clearance < 60 mL/min calculated by the Cockcroft-Gault formula using ideal body weight at Screening prior to Day -2.

• Subject is on unstable doses of chronic medications. Subjects taking medications for chronic medical conditions must be on stable doses during the course of the study, including the Screening period. Dose adjustments are allowed if deemed medically necessary by the investigator and following discussion with the medical monitor

• Chronic and stable doses of losartan, fenofibrate, guaifenesin, and sodium-glucose linked transporter-2 inhibitors are permitted if the dose is 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Overland Park	Kansas	United States	66212

Sponsors and Collaborators

• Ardea Biosciences, Inc.

Investigators

• Study Director: J. Hall, MD, Ardea Biosciences, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ardea Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT02279641
• Other Study ID Numbers: RDEA3170-107
• First Posted: Oct 31, 2014
• Last Update Posted: Dec 20, 2017
• Last Verified: Dec 1, 2017

• Additional relevant MeSH terms: Gout; Allopurinol; Verinurad

Study Results

Participant Flow

Recruitment Details	12 subjects were randomized
Pre-assignment Detail	Twelve subjects were randomized to 1 of 2 treatment sequences (Sequence A or B) in a 1:1 ratio.

Arm/Group Title	RDEA3170 or Allopurinol Alone and in Combination (Sequence A)	RDEA3170 or Allopurinol Alone and in Combination (Sequence B)
Arm/Group Description	Days 1 to 7: 10 mg once daily (qd) RDEA3170; Days 8 to 14: 10 mg qd RDEA3170 + 300 mg qd allopurinol; Days 15 to 21: 300 mg qd allopurinol	Days 1 to 7: 300 mg qd allopurinol; Days 8 to 14: 10 mg qd RDEA3170 + 300 mg qd allopurinol; Days 15 to 21: 10 mg qd RDEA3170
Period Title: Overall Study
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sequence A	Sequence B	Total
Arm/Group Description	Days 1 to 7: 10 mg once daily (qd) RDEA3170; Days 8 to 14: 10 mg qd RDEA3170 + 300 mg qd allopurinol; Days 15 to 21: 300 mg qd allopurinol	Days 1 to 7: 300 mg qd allopurinol; Days 8 to 14: 10 mg qd RDEA3170 + 300 mg qd allopurinol; Days 15 to 21: 10 mg qd RDEA3170	Total of all reporting groups
Overall Participants	6	6	12
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	53 (10.1)	49 (10.4)	51 (10.0)
Age, Customized (Number) [Number]
<65	6 100%	6 100%	12 100%
>=65	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	6 100%	6 100%	12 100%
Region of Enrollment (Number) [Number]
United States	6 100%	6 100%	12 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Description	Cmax of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allopurinol: Allopurinol Alone	Allopurinol: RDEA3170 + Allopurinol	Oxypurinol: Allopurinol Alone	Oxypurinol: RDEA3170 + Allopurinol
Arm/Group Description	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd
Measure Participants	12	12	12	12
Geometric Mean (95% Confidence Interval) [μg/mL]	1.13	1.51	12.8	8.68

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allopurinol: Allopurinol Alone, Allopurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	133
	Confidence Interval	(2-Sided) 90%; 111 to 159
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxypurinol: Allopurinol Alone, Oxypurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	67.9
	Confidence Interval	(2-Sided) 90%; 65.2 to 70.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Time of Occurrence of Maximum Observed Concentration (Tmax)
Description	Tmax of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allopurinol: Allopurinol Alone	Allopurinol: RDEA3170 + Allopurinol	Oxypurinol: Allopurinol Alone	Oxypurinol: RDEA3170 + Allopurinol	RDEA3170: RDEA3170 Alone	RDEA3170: RDEA3170 + Allopurinol
Arm/Group Description	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	RDEA3170 10 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd
Measure Participants	12	12	12	12	12	12
Median (Full Range) [hr]	1.50	1.25	4.00	3.50	3.00	3.00

3. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24)
Description	AUC 0-24 of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allopurinol: Allopurinol Alone	Allopurinol: RDEA3170 + Allopurinol	Oxypurinol: Allopurinol Alone	Oxypurinol: RDEA3170 + Allopurinol	RDEA3170: RDEA3170 + Allopurinol
Arm/Group Description	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd
Measure Participants	12	12	12	12	12
Geometric Mean (95% Confidence Interval) [μg·hr/mL]	3.69	3.68	255	157	115

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allopurinol: Allopurinol Alone, Allopurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	102
	Confidence Interval	(2-Sided) 90%; 93.3 to 111
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxypurinol: Allopurinol Alone, Oxypurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	61.8
	Confidence Interval	(2-Sided) 90%; 58.1 to 65.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	RDEA3170: RDEA3170 Alone
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	95.9
	Confidence Interval	(2-Sided) 90%; 88.4 to 104
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)
Description	AUC last of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allopurinol: Allopurinol Alone	Allopurinol: RDEA3170 + Allopurinol	Oxypurinol: Allopurinol Alone	Oxypurinol: RDEA3170 + Allopurinol
Arm/Group Description	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd
Measure Participants	12	12	12	12
Geometric Mean (95% Confidence Interval) [μg·hr/mL]	3.50	3.61	255	157

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allopurinol: Allopurinol Alone, Allopurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	103
	Confidence Interval	(2-Sided) 90%; 94.9 to 112
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxypurinol: Allopurinol Alone, Oxypurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	61.8
	Confidence Interval	(2-Sided) 90%; 58.1 to 65.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Apparent Terminal Half-life (t1/2)
Description	t1/2 of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allopurinol: Allopurinol Alone	Allopurinol: RDEA3170 + Allopurinol	Oxypurinol: Allopurinol Alone	Oxypurinol: RDEA3170 + Allopurinol	RDEA3170: RDEA3170 Alone	RDEA3170: RDEA3170 + Allopurinol
Arm/Group Description	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	RDEA3170 10 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd
Measure Participants	12	12	12	12	12	12
Geometric Mean (95% Confidence Interval) [hr]	1.06	0.992	43.2	29.1	11.5	12.5

6. Primary Outcome

Title	Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24)
Description	Ae0-24 of Allopurinol/Oxypurinol Alone and In Combination with RDEA3170
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allopurinol: Allopurinol Alone	Allopurinol: RDEA3170 + Allopurinol	Oxypurinol: Allopurinol Alone	Oxypurinol: RDEA3170 + Allopurinol
Arm/Group Description	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd
Measure Participants	12	12	12	12
Geometric Mean (95% Confidence Interval) [mg]	25.4	22.7	231	275

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allopurinol: Allopurinol Alone, Allopurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	89.5
	Confidence Interval	(2-Sided) 90%; 81.8 to 98.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxypurinol: Allopurinol Alone, Oxypurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	119
	Confidence Interval	(2-Sided) 90%; 114 to 125
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Primary Outcome

Title	Renal Clearance of the Drug From Time Zero up to 24 Hours Postdose (CRL0-24)
Description	CLR0-24 of Allopurinol/Oxypurinol and RDEA3170 Alone and In Combination
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allopurinol: Allopurinol Alone	Allopurinol: RDEA3170 + Allopurinol	Oxypurinol: Allopurinol Alone	Oxypurinol: RDEA3170 + Allopurinol	RDEA3170: RDEA3170 Alone	RDEA3170: RDEA3170 + Allopurinol
Arm/Group Description	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	Allopurinol 300 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	RDEA3170 10 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd
Measure Participants	12	12	12	12	12	12
Geometric Mean (95% Confidence Interval) [mL/min]	120	103	15.1	29.2	9.28	9.75

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allopurinol: Allopurinol Alone, Allopurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	87.5
	Confidence Interval	(2-Sided) 90%; 79.3 to 96.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxypurinol: Allopurinol Alone, Oxypurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	193
	Confidence Interval	(2-Sided) 90%; 177 to 210
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	RDEA3170: RDEA3170 Alone, RDEA3170: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	105
	Confidence Interval	(2-Sided) 90%; 94.4 to 117
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Primary Outcome

Title	Pharmacodynamics (PD) Profile of Uric Acid From Serum and Urine
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RDEA3170: RDEA3170 Alone	Oxypurinol: RDEA3170 + Allopurinol	Allopurinol: Allopurinol Alone
Arm/Group Description	RDEA3170 10 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	Allopurinol 300 mg qd
Measure Participants	12	12	12
Serum Urate Maximum % Change	-50.5 (2.43)	-65.2 (1.57)	-43.0 (1.57)
Urine Uric Acid % Change (0-24h)	9.88 (7.61)	-21.6 (5.58)	-47.4 (2.67)
Renal Clearance of Uric Acid % Change (0-24h)	122 (46.8)	125 (42.2)	-8.50 (6.04)
Fract. Excretion of Uric Acid % Change (0-24h)	77.4 (18.0)	78.4 (21.9)	-12.0 (5.46)

9. Secondary Outcome

Title	Incidence of Treatment-Emergent Adverse Events
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RDEA3170: RDEA3170 Alone	Oxypurinol: RDEA3170 + Allopurinol	Allopurinol: Allopurinol Alone
Arm/Group Description	RDEA3170 10 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd	Allopurinol 300 mg qd
Measure Participants	12	12	12
Number [Number of participants]	2 (2.43) 33.3%	1 (1.57) 16.7%	3 (1.57) 25%

10. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Description	Cmax of RDEA3170 Alone and In Combination with Allopurinol
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RDEA3170: RDEA3170 Alone	RDEA3170: RDEA3170 + Allopurinol
Arm/Group Description	RDEA3170 10 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd
Measure Participants	12	12
Geometric Mean (95% Confidence Interval) [ng/mL]	14.6	14.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allopurinol: Allopurinol Alone, Allopurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	98.7
	Confidence Interval	(2-Sided) 95%; 87.7 to 111
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero up to 24 Hours Postdose (AUC 0-24)
Description	AUC 0-24 of RDEA3170 Alone and In Combination with Allopurinol
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RDEA3170: RDEA3170 Alone	RDEA3170: RDEA3170 + Allopurinol
Arm/Group Description	RDEA3170 10 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd
Measure Participants	12	12
Geometric Mean (95% Confidence Interval) [μg*hr/mL]	120	115

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allopurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	95.9
	Confidence Interval	(2-Sided) 95%; 88.4 to 104
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Sampling Timepoint (AUC Last)
Description	AUC last of RDEA3170 Alone and In Combination with Allopurinol
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RDEA3170: RDEA3170 Alone	RDEA3170: RDEA3170 + Allopurinol
Arm/Group Description	RDEA3170 10 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd
Measure Participants	12	12
Geometric Mean (95% Confidence Interval) [ng·hr/mL]	120	115

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allopurinol: Allopurinol Alone, Allopurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	95.9
	Confidence Interval	(2-Sided) 95%; 88.4 to 104
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Primary Outcome

Title	Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24)
Description	Ae0-24 of RDEA3170 Alone and In Combination with Allopurinol
Time Frame	22 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RDEA3170: RDEA3170 Alone	RDEA3170: RDEA3170 + Allopurinol
Arm/Group Description	RDEA3170 10 mg qd	RDEA3170 10 mg qd + Allopurinol 300 mg qd
Measure Participants	12	12
Geometric Mean (95% Confidence Interval) [ug]	66.8	67.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Allopurinol: Allopurinol Alone, Allopurinol: RDEA3170 + Allopurinol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Informal BE assessment using the conventional BE limits of 80% to 125%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio (%)
	Estimated Value	101
	Confidence Interval	(2-Sided) 95%; 86.7 to 117
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	22 days
Adverse Event Reporting Description	Overall number of baseline participants used to determine number of participants at risk.
Arm/Group Title	RDEA3170 10 mg qd		RDEA3170 10 mg qd + Allopurinol 300 mg qd		Allopurinol 300 mg qd
Arm/Group Description	RDEA3170 10 mg qd		RDEA3170 10 mg qd + Allopurinol 300 mg qd		Allopurinol 300 mg qd
All Cause Mortality
	RDEA3170 10 mg qd		RDEA3170 10 mg qd + Allopurinol 300 mg qd		Allopurinol 300 mg qd
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	RDEA3170 10 mg qd		RDEA3170 10 mg qd + Allopurinol 300 mg qd		Allopurinol 300 mg qd
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	RDEA3170 10 mg qd		RDEA3170 10 mg qd + Allopurinol 300 mg qd		Allopurinol 300 mg qd
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)		1/12 (8.3%)		3/12 (25%)
Gastrointestinal disorders
Diarrhoea	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0
Toothache	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Vomiting	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0
Infections and infestations
Gastroenteritis	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Nasopharyngitis	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0
Nervous system disorders
Dizziness	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0
Headache	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
Petechiae	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Rash	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

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Principal Investigators are NOT employed by the organization sponsoring the study.

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