A Study of AC-201 Controlled-Release Tablet (CR Tablet) in Patients With Gout

• Sponsor: TWi Biotechnology, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02287818
• Collaborator: (none)
• Enrollment: 127
• Location: 1
• Arms: 2
• Duration (Months): 22.9
• Patients Per Site Per Month: 5.6

Study Details

Study Description

Brief Summary

The study is designed to test the urate-lowering effect, safety, and tolerability of AC-201CR in an initial dosing period, followed by the addition of a ULT to test the efficacy and safety of the combination and prophylaxis of gout flares during ULT.

Condition or Disease	Intervention/Treatment	Phase
Gout	Drug: Placebo; Drug: AC-201; Drug: Febuxostat	Phase 2

Detailed Description

AC-201CR is a control released formulation of AC-201 that in previous clinical studies showed potential dual effects in both reducing serum uric acid (sUA) and gout flares. The mechanism of action of AC-201 includes the inhibition of the production and activity of caspase-1 and interleukin-1β (IL-1β), and selective inhibition of re-absorption transporters in the kidney. The goal of gout treatment is to reduce serum uric acid (sUA) concentrations below the urate solubility limit while avoiding acute gout flares. However, the initiation of urate-lowering therapy (ULT) increases the occurrence of acute gouty arthritis flares. IL-1β plays a key role in mediating this inflammatory response.

Study Design

• Study Type: Interventional
• Actual Enrollment: 127 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF AC-201 IN SUBJECTS WITH GOUT
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Oct 27, 2016
• Actual Study Completion Date: Oct 27, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo plus Febuxostat	Drug: Placebo; Placebo twice daily from Day 1 to Week 12; Other Names: PBO ; Drug: Febuxostat; Febuxostat 40 mg once daily from Week 4 to Week 16; titration to 80 mg once daily at Week 8 as needed to achieve serum uric acid concentration <6 mg/dL; Other Names: ULT
Experimental: AC-201 AC-201 CR tablet plus Febuxostat	Drug: AC-201; AC-201 CR tablet 100 mg twice daily from Day 1 to Week 12; Other Names: AC-201 CR tablet ; Drug: Febuxostat; Febuxostat 40 mg once daily from Week 4 to Week 16; titration to 80 mg once daily at Week 8 as needed to achieve serum uric acid concentration <6 mg/dL; Other Names: ULT

Outcome Measures

Primary Outcome Measures

1. Proportion of Subjects Achieving Serum Uric Acid Concentration <6.0 mg/dL [8 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female age 20 to 65 years, inclusive.

2. Meets ≥6 of the 12 American College of Rheumatology preliminary criteria (1977) for the classification of acute arthritis of primary gout (Appendix 2), OR have proven tophus or documented monosodium urate (MSU) crystals in the joint fluid.

3. Serum uric acid ≥7.5 mg/dL and ≤10 mg/dL at screening with ≥1 gouty arthritis flare within one year prior to screening, OR serum uric acid ≥9 mg/dL and ≤10 mg/dL at screening with or without prior gout flares.

Exclusion Criteria:

1. Use of allopurinol, febuxostat, benzbromarone, probenecid, or sulfinpyrazone within 2 weeks prior to screening.

2. Occurrence of a gouty arthritis flare within 1 week prior to screening or during the screening period through baseline.

3. Use of colchicine within 1 week prior to screening.

4. Use of Glucocorticoids, NSAIDs or COX-2 inhibitors within 1 week prior to screening.

5. Allergy, contraindication, or intolerance to febuxostat.

6. Severe renal impairment.

7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration >2 times the upper limit of laboratory normal range (>2x ULN) at screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Taipei Veteran General Hospital (TVGH)	Taipei		Taiwan	112

Sponsors and Collaborators

• TWi Biotechnology, Inc.

Investigators

• Principal Investigator: Chang-Youh Tsai, Taipei Veteran General Hospital (TVGH)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: TWi Biotechnology, Inc.
• ClinicalTrials.gov Identifier: NCT02287818
• Other Study ID Numbers: AC-201-GOU-002
• First Posted: Nov 11, 2014
• Last Update Posted: Jun 28, 2022
• Last Verified: Jun 1, 2022

• Additional relevant MeSH terms: Gout; Febuxostat

Study Results

Participant Flow

Arm/Group Title	Placebo	AC-201
Arm/Group Description	Placebo plus Febuxostat Placebo: Placebo twice daily from Day 1 to Week 12 Febuxostat: Febuxostat 40 mg once daily from Week 4 to Week 16; titration to 80 mg once daily at Week 8 as needed to achieve serum uric acid concentration <6 mg/dL	AC-201 CR tablet plus Febuxostat AC-201: AC-201 CR tablet 100 mg twice daily from Day 1 to Week 12 Febuxostat: Febuxostat 40 mg once daily from Week 4 to Week 16; titration to 80 mg once daily at Week 8 as needed to achieve serum uric acid concentration <6 mg/dL
Period Title: Overall Study
STARTED	60	67
COMPLETED	53	54
NOT COMPLETED	7	13

Baseline Characteristics

Arm/Group Title	Placebo	AC-201	Total
Arm/Group Description	Placebo plus Febuxostat Placebo: Placebo twice daily from Day 1 to Week 12 Febuxostat: Febuxostat 40 mg once daily from Week 4 to Week 16; titration to 80 mg once daily at Week 8 as needed to achieve serum uric acid concentration <6 mg/dL	AC-201 CR tablet plus Febuxostat AC-201: AC-201 CR tablet 100 mg twice daily from Day 1 to Week 12 Febuxostat: Febuxostat 40 mg once daily from Week 4 to Week 16; titration to 80 mg once daily at Week 8 as needed to achieve serum uric acid concentration <6 mg/dL	Total of all reporting groups
Overall Participants	60	67	127
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.5 (13.1)	47.3 (11.7)	47.4 (12.3)
Sex: Female, Male (Count of Participants)
Female	1 1.7%	5 7.5%	6 4.7%
Male	59 98.3%	62 92.5%	121 95.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	60 100%	67 100%	127 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Taiwan	60 100%	67 100%	127 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects Achieving Serum Uric Acid Concentration <6.0 mg/dL
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	AC-201
Arm/Group Description	Placebo plus Febuxostat Placebo: Placebo twice daily from Day 1 to Week 12 Febuxostat: Febuxostat 40 mg once daily from Week 4 to Week 16; titration to 80 mg once daily at Week 8 as needed to achieve serum uric acid concentration <6 mg/dL	AC-201 CR tablet plus Febuxostat AC-201: AC-201 CR tablet 100 mg twice daily from Day 1 to Week 12 Febuxostat: Febuxostat 40 mg once daily from Week 4 to Week 16; titration to 80 mg once daily at Week 8 as needed to achieve serum uric acid concentration <6 mg/dL
Measure Participants	60	67
Count of Participants [Participants]	33 55%	43 64.2%

Adverse Events

Arm/Group Title	Placebo		AC-201
Arm/Group Description	Placebo plus Febuxostat Placebo: Placebo twice daily from Day 1 to Week 12 Febuxostat: Febuxostat 40 mg once daily from Week 4 to Week 16; titration to 80 mg once daily at Week 8 as needed to achieve serum uric acid concentration <6 mg/dL		AC-201 CR tablet plus Febuxostat AC-201: AC-201 CR tablet 100 mg twice daily from Day 1 to Week 12 Febuxostat: Febuxostat 40 mg once daily from Week 4 to Week 16; titration to 80 mg once daily at Week 8 as needed to achieve serum uric acid concentration <6 mg/dL
All Cause Mortality
	Placebo		AC-201
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/67 (0%)
Serious Adverse Events
	Placebo		AC-201
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/67 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		AC-201
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/60 (48.3%)		43/67 (64.2%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders	1/60 (1.7%)		0/67 (0%)
Cardiac disorders
Cardiac disorders	1/60 (1.7%)		0/67 (0%)
Gastrointestinal disorders
Gastrointestinal disorders	7/60 (11.7%)		25/67 (37.3%)
General disorders
General disorders and administration site	1/60 (1.7%)		1/67 (1.5%)
Hepatobiliary disorders
Hepatobiliary disorders	1/60 (1.7%)		2/67 (3%)
Immune system disorders
Immune system disorders	0/60 (0%)		1/67 (1.5%)
Infections and infestations
Infections and infestations	5/60 (8.3%)		6/67 (9%)
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications	1/60 (1.7%)		0/67 (0%)
Investigations
Investigations	6/60 (10%)		6/67 (9%)
Metabolism and nutrition disorders
Metabolism and nutrition disorders	0/60 (0%)		1/67 (1.5%)
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	6/60 (10%)		6/67 (9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified	1/60 (1.7%)		1/67 (1.5%)
Nervous system disorders
Nervous system disorders	1/60 (1.7%)		4/67 (6%)
Renal and urinary disorders
Renal and urinary disorders	1/60 (1.7%)		0/67 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	2/60 (3.3%)		0/67 (0%)
Skin and subcutaneous tissue disorders
Skin And subcutaneous tissue disorders	2/60 (3.3%)		1/67 (1.5%)
Vascular disorders
Vascular disorders	1/60 (1.7%)		0/67 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.