MPC-004 for the Treatment of an Acute Gout Flare

NCT ID: NCT00506883

Last Updated: 2012-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 185 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2007-10-31

Brief 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.

Detailed 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.

Conditions

Gout

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

High Dose Colchicine

After confirmation of a gout flare, patients were to begin standard dosing of colchicine 4.8mg (two capsules (1.8mg) initially followed by additional one capsule doses (0.6mg) every hour for an additional 6 doses).

Group Type: EXPERIMENTAL

High Dose Colchicine (4.8 mg total dose)

Intervention Type: DRUG

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

Within 12 hours of a confirmed gout flare, patients were to begin the low dose colchicine regimen consisting of a total dose of 1.8 mg - two colchicine capsules initially (1.2 mg)followed an hour later by a single additional capsule of active drug(0.6 mg)then by 5 additional hourly doses of an identical looking placebo capsules

Group Type: EXPERIMENTAL

Low Dose Colchicine (1.8mg total dose)

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo Control

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Intervention Type: OTHER

Other Intervention Names

Colcrys TM, Colchicine 0.6 mg; Colcrys TM, Colchicine 0.6 mg; Placebo capsule

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

AR Scientific

Principal Investigators

Matthew W Davis, MD, RPh

Role: STUDY_CHAIR

AR Scientific, Inc.

Locations

Innovative Clinical Trials

Birmingham, Alabama, United States

Birmingham, Alabama, United States

Tomac, Inc.

Columbiana, Alabama, United States

Rheumatology Associates of North Alabama

Huntsville, Alabama, United States

Genova Clinical Research

Tucson, Arizona, United States

Tucson, Arizona, United States

NEA Clinic

Jonesboro, Arkansas, United States

Arkansas Primary Care Clinic

Little Rock, Arkansas, United States

Irvine Center for Clinical Research

Irvine, California, United States

La Jolla, California, United States

Paramount, California, United States

Rancho Cucamonga Clinical Trials

Rancho Cucamonga, California, United States

San Diego, California, United States

West Covina, California, United States

Florida Medical Center

Clearwater, Florida, United States

Nature Coast Clinical Research

Crystal River, Florida, United States

Southeastern Integrated Medical

Gainesville, Florida, United States

George E. Platt, MD

Green Cove Springs, Florida, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Health Awareness, Inc.

Jupiter, Florida, United States

Lake Mary, Florida, United States

Medical Research Trust

Lake Worth, Florida, 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

Southwest Florida Clinical Research Center

Tampa, Florida, United States

Geodessey Research, LLC

Vero Beach, Florida, United States

Bond Clinic

Winter Haven, Florida, United States

Global Research Partners & Consultants, Inc.

Calhoun, Georgia, United States

Decatur, Georgia, United States

North Georgia Rheumatology Group, PC

Lawrenceville, Georgia, United States

Arthritis & Osteoporosis Center of South Georgia

Tifton, Georgia, United States

Boise, Idaho, United States

Idaho Arthritis & Osteoporosis Center

Meridian, Idaho, United States

Lake County Research Associates

Libertyville, Illinois, United States

Moline, Illinois, United States

Physicians Clinic of Iowa

Cedar Rapids, Iowa, United States

The Center for Arthritis & Osteoporosis

Elizabethtown, Kentucky, United States

David H. Neustadt PSCq

Louisville, Kentucky, United States

Gulf Coast Research

Baton Rouge, Louisiana, United States

Arthritis and Osteoporosis Center of Maryland

Frederick, Maryland, United States

Rockville, Maryland, United States

The Center for Rheumatology & Bone Research

Wheaton, Maryland, United States

Future Care Studies

Springfield, Massachusetts, United States

Clinical Pharmacology Study Group

Worcester, Massachusetts, United States

Justus Fiechtner, MD, MPH

Lansing, Michigan, United States

Arthritis Associates

Hattiesburg, Mississippi, United States

Medical Center Healthcare Research

Florissant, Missouri, United States

Medex Healthcare

St Louis, Missouri, United States

Las Vegas, Nevada, United States

Arthritis Center of Reno

Reno, Nevada, United States

Arthritis & Osteoporisis Associates

Manalapan, New Jersey, United States

Rheumatology and Arthritis Associates

Medford, New Jersey, United States

Voorhees Township, New Jersey, United States

Albany, New York, United States

Southwest Medical Associates

Brewster, New York, United States

Concorde medical Group

New York, New York, United States

Rochester, New York, United States

Syracuse, New York, United States

Williamsville, New York, United States

Arthritis Consultants of the Carolinas

Belmont, North Carolina, United States

Arthritis & Osteoporosis Consultants of the Carolinas

Charlotte, North Carolina, United States

Dayton, Ohio, United States

Mayfield Village, Ohio, United States

Middleburg Heights, Ohio, United States

Duncansville, Pennsylvania, United States

Harleysville, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Orangeburg, South Carolina, United States

Milan, Tennessee, United States

New Tazewell, Tennessee, United States

Arlington, Texas, United States

Austin, Texas, United States

Carrollton, Texas, United States

Fort Worth, Texas, United States

Houston, Texas, United States

Irving, Texas, United States

San Antonio, Texas, United States

Sugarland, Texas, United States

Ettrick, Virginia, United States

Portsmouth, Virginia, United States

Reston, Virginia, United States

Suffolk, Virginia, United States

Countries

United States

References

Terkeltaub RA, Furst DE, Bennett K, Kook KA, Crockett RS, Davis MW. High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010 Apr;62(4):1060-8. doi: 10.1002/art.27327.

Reference Type: DERIVED

PMID: 20131255 (View on PubMed)

Other Identifiers

MPC 004-06-3001

Identifier Type: -

Identifier Source: org_study_id