MPC-004 for the Treatment of an Acute Gout Flare

Gout Clinical Trial

— AGREE  

Official title:

A Multicenter, Randomized, Double Blind, Placebo Controlled, Parallel Group, 1 Week, Dose Comparison Study to Evaluate the Efficacy, Safety, and Tolerability of MPC-004 in Patients With an Acute Gout Flare

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00506883
• Other study ID #: MPC 004-06-3001
• Status: Completed
• Phase: Phase 3
• First received: July 23, 2007
• Last updated: October 30, 2012
• Start date: April 2007
• Est. completion date: October 2007

Study information

• Verified date: October 2012
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is a multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-comparison to determine the efficacy and safety of a standard-dose of colchicine (4.8 mg) versus low-dose colchicine (1.8 mg) or placebo for acute gout flares.

Description:

This study is a multi-center, randomized, double-blind, placebo-controlled, parallel group trial to compare the efficacy and safety of standard-dose colchicine (STD)(total dose = 4.8 mg) versus low-dose colchicine (total dose 1.8 mg) or placebo for the treatment of acute gout flares. Eight hundred and thirteen patients with a confirmed diagnosis of gout were screened. 238 of the screened patients failed screening; 235(98.7%) failed because they did not meet inclusion/exclusion criteria. The 575 eligible patients were randomly assigned (1:1:1) to one of three treatment groups . At the randomization visit the investigator dispensed a blister card containing eight identical looking capsules (in a combination of active drug and placebo capsules) in a double blind fashion for use during their next gout flare. Patients were instructed to self-initiate treatment with the study medication within 12 hours of a gout flare onset. Gout flares were determined by calling a Gout Flare Call Center established for this purpose. At Investigator discretion, rescue medication could also be provided, but patients were encouraged not to use rescue medication within the first 24 hours after starting treatment with study drug. Of the 575 study participants, 185 had a qualifying gout flare and 390 did not. Patients used a diary to record study drug administration, pain score, the presence or absence of gastrointestinal adverse events (nausea, vomiting, diarrhea, and abdominal pain) and the timing of any rescue medication use prior to beginning treatment and 1, 2, 3, 4, 5, 6, 7, 8, 16, 24, 32, 40, 48, 56, 64, and 72 hours after the start of dosing.

The pain score was based on a scale of 1 - 10 where 1 was no pain and 10 was the worst pain imaginable. Efficacy was defined as a 50% reduction in pain score in the target joint at 24 hours in patients who did not use rescue medicine. The primary efficacy analysis was to be based on an Intent-to-Treat (ITT) population, defined as all patients who were randomized, contacted the Call Center, and were instructed to begin taking study drug. An otherwise qualified patient was excluded from the ITT population only if the patient returned a study drug blister pack completely unused.

Secondary outcome measures compared the efficacy of STD dose colchicine to a low dose regimen and placebo using the same criteria for efficacy as for the primary outcome measure.

Additional secondary outcome measures were time to 50% and 90% reduction in pain in the target joint analyzed by treatment group using Kaplan-Meier methods, and the change in mean pain intensity from 0 to 72 hours plotted by time point for each treatment group.

All safety analyses were carried out using the safety population defined as all patients who received at least one dose of study medication regardless of authorization by the Call Center To determine the safety of colchicine when administered via two different dose regimens all patients who had a gout flare were seen by the investigator as soon as possible after onset and evaluated until the flare and any adverse events resolved. All adverse effects, whether recorded by the patient in the diary or obtained by systematic evaluation by the investigator were recorded and reported in tabular form. Treatment-emergent adverse events (TEAE) were summarized by MedDRA System Organ Class and preferred terms and tabulated according treatment arm, overall incidence, severity and relationship to study medication. Multiple events within a patient were counted once and at greatest severity and closest relationship to study medication.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 185
• Est. completion date: October 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients of either gender and of any race =18 years of age.

2. If female, patients must be postmenopausal as evidenced by lack of menses for =12 consecutive months.

3. Patients must present with a confirmed diagnosis of gout.

4. Patients must have experienced =2 acute gouty arthritic attacks in the 12 months prior to randomization.

5. Patients on urate lowering therapy must be on a stable dose and schedule with no changes in therapy for 4 weeks prior to randomization and expected to remain on a stable regimen during study participation.

6. Patients must be willing to adhere to the study schedule and the protocol requirements.

7. Patients must be willing and able to give written informed consent. A HIPAA and/or state privacy consent must also be signed.

Exclusion Criteria:

1. Patients with acute polyarticular gout (>4 joints).

2. Patients who have experienced >2 acute gouty arthritic attacks per month, or >12 attacks overall, in the 6 months prior to randomization.

3. Patients with arthritis due to any cause other than gout that may confound any study assessments per Investigator discretion.

4. Patients with a history of myocardial infarction, unstable angina, cerebrovascular events, or coronary artery bypass grafting within the previous 6 months prior to screening.

5. Patients with active myeloid leukemia, obstructive gastrointestinal cancer, or metastatic cancer.

6. Patients with chronic renal dysfunction (creatinine clearance <60 mL/min as estimated with the Cockcroft Gault formula).

7. Patients with chronic hepatic dysfunction.

8. Patients with a history of alcohol or substance abuse within the 12 months prior to randomization.

9. Patients who have any concomitant illness or other finding that, in the opinion of the Investigator, would confound the study data or place the patient at unacceptable risk if the patient were to participate in the study, or that would require frequent adjustments in concomitant medications during the course of the study.

10. Patients using systemic corticosteroid, cyclosporine, adalimumab, etanercept, infliximab, anakinra, abatacept, mycophenolate, azathioprine, anticoagulants (warfarin, heparin, low molecular weight heparin [LMWH], antithrombin agents, thrombin inhibitors, or selective Factor Xa inhibitors [note, use of aspirin =325 mg/day is allowed]), or chronic use of non steroidal anti inflammatory drugs (NSAIDs), acetaminophen, tramadol, and other analgesics such as opiates at screening

11. Use of any investigational drug within 30 days prior to randomization.

12. Patients currently participating in another research study or anticipated to enroll in such during participation in this study.

13. Patients for whom informed consent cannot be obtained.

14. Patients who have previously been randomized into this study and begun ingestion of study drug.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gout

Intervention

Drug:
• High Dose Colchicine (4.8 mg total dose)
At randomization, patients were given an identical looking blister pack containing (8) over encapsulated colchicine 0.6 mg tablets identical in appearance to placebo capsules. Patients were instructed to take 2 capsules initially (1.2 mg) followed by an additional capsule (0.6 mg) every hour for a total of six additional doses (total colchicine dose 4.8 mg) beginning within 12 hours of onset of a qualifying gout flare as confirmed by calling the gout flare call center.
• Low Dose Colchicine (1.8mg total dose)
At randomization, patients were given an identical looking blister pack containing (3) over encapsulated colchicine 0.6 mg tablets identical in appearance to placebo capsules and five placebo capsules. Patients were instructed to take 2 capsules initially (0.6 mg x 2) followed by an additional capsule every hour for a total of six additional doses (one active (0.6 mg) and 5 placebo capsules), a total colchicine dose = 1.8 mg) beginning within 12 hours of onset of a qualifying gout flare as confirmed by calling the gout flare call center

Other:
• Placebo Control
At randomization, patients were given an identical looking blister pack containing (8) placebo capsules identical in appearance to the study drug. Patients were instructed to take 2 capsules initially followed by an additional capsule every hour for a total of six additional doses beginning within 12 hours of onset of a qualifying gout flare as confirmed by calling the gout flare call center.

Locations

Country	Name	City	State
United States	Gulf Coast Research	Baton Rouge	Louisiana
United States	Arthritis Consultants of the Carolinas	Belmont	North Carolina
United States	Innovative Clinical Trials	Birmingham	Alabama
United States	Southwest Medical Associates	Brewster	New York
United States	Global Research Partners & Consultants, Inc.	Calhoun	Georgia
United States	Physicians Clinic of Iowa	Cedar Rapids	Iowa
United States	Arthritis & Osteoporosis Consultants of the Carolinas	Charlotte	North Carolina
United States	Florida Medical Center	Clearwater	Florida
United States	Tomac, Inc.	Columbiana	Alabama
United States	Nature Coast Clinical Research	Crystal River	Florida
United States	The Center for Arthritis & Osteoporosis	Elizabethtown	Kentucky
United States	Medical Center Healthcare Research	Florissant	Missouri
United States	Arthritis and Osteoporosis Center of Maryland	Frederick	Maryland
United States	Southeastern Integrated Medical	Gainesville	Florida
United States	George E. Platt, MD	Green Cove Springs	Florida
United States	Arthritis Associates	Hattiesburg	Mississippi
United States	Rheumatology Associates of North Alabama	Huntsville	Alabama
United States	Irvine Center for Clinical Research	Irvine	California
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	NEA Clinic	Jonesboro	Arkansas
United States	Health Awareness, Inc.	Jupiter	Florida
United States	Medical Research Trust	Lake Worth	Florida
United States	Justus Fiechtner, MD, MPH	Lansing	Michigan
United States	North Georgia Rheumatology Group, PC	Lawrenceville	Georgia
United States	Lake County Research Associates	Libertyville	Illinois
United States	Arkansas Primary Care Clinic	Little Rock	Arkansas
United States	David H. Neustadt PSCq	Louisville	Kentucky
United States	Arthritis & Osteoporisis Associates	Manalapan	New Jersey
United States	Rheumatology and Arthritis Associates	Medford	New Jersey
United States	Idaho Arthritis & Osteoporosis Center	Meridian	Idaho
United States	Concorde medical Group	New York	New York
United States	Hillcrest Medical Center	Orange City	Florida
United States	Farmer MD, PA	Ormond Beach	Florida
United States	Coastal Medical Research, Inc.	Port Orange	Florida
United States	Rancho Cucamonga Clinical Trials	Rancho Cucamonga	California
United States	Arthritis Center of Reno	Reno	Nevada
United States	Medex Healthcare	Saint Louis	Missouri
United States	Future Care Studies	Springfield	Massachusetts
United States	Southwest Florida Clinical Research Center	Tampa	Florida
United States	Arthritis & Osteoporosis Center of South Georgia	Tifton	Georgia
United States	Genova Clinical Research	Tucson	Arizona
United States	Geodessey Research, LLC	Vero Beach	Florida
United States	The Center for Rheumatology & Bone Research	Wheaton	Maryland
United States	Bond Clinic	Winter Haven	Florida
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Responders	Responders were defined as patients who achieved a = 50% reduction in target joint pain score from baseline at 24 hours without using rescue drug, using an 11 point scale from 0 to 10, with 10 being the worst pain imaginable after beginning therapy.	24 hours after baseline	No