Clinical trial NCT00506883: MPC-004 for the Treatment of an Acute Gout Flare
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gout
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2007-07-25
Enrollment: 185
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Responders
timeFrame: 24 hours after baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Innovative Clinical Trials
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Columbiana
country: United States
facility: Tomac, Inc.
state: Alabama
city: Huntsville
country: United States
facility: Rheumatology Associates of North Alabama
state: Alabama
city: Tucson
country: United States
facility: Genova Clinical Research
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Jonesboro
country: United States
facility: NEA Clinic
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Primary Care Clinic
state: Arkansas
city: Irvine
country: United States
facility: Irvine Center for Clinical Research
state: California
city: La Jolla
country: United States
state: California
city: Paramount
country: United States
state: California
city: Rancho Cucamonga
country: United States
facility: Rancho Cucamonga Clinical Trials
state: California
city: San Diego
country: United States
state: California
city: West Covina
country: United States
state: California
city: Clearwater
country: United States
facility: Florida Medical Center
state: Florida
city: Crystal River
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Gainesville
country: United States
facility: Southeastern Integrated Medical
state: Florida
city: Green Cove Springs
country: United States
facility: George E. Platt, MD
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Jupiter
country: United States
facility: Health Awareness, Inc.
state: Florida
city: Lake Mary
country: United States
state: Florida
city: Lake Worth
country: United States
facility: Medical Research Trust
state: Florida
city: Orange City
country: United States
facility: Hillcrest Medical Center
state: Florida
city: Ormond Beach
country: United States
facility: Farmer MD, PA
state: Florida
city: Port Orange
country: United States
facility: Coastal Medical Research, Inc.
state: Florida
city: Tampa
country: United States
facility: Southwest Florida Clinical Research Center
state: Florida
city: Vero Beach
country: United States
facility: Geodessey Research, LLC
state: Florida
city: Winter Haven
country: United States
facility: Bond Clinic
state: Florida
city: Calhoun
country: United States
facility: Global Research Partners & Consultants, Inc.
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Lawrenceville
country: United States
facility: North Georgia Rheumatology Group, PC
state: Georgia
city: Tifton
country: United States
facility: Arthritis & Osteoporosis Center of South Georgia
state: Georgia
city: Boise
country: United States
state: Idaho
city: Meridian
country: United States
facility: Idaho Arthritis & Osteoporosis Center
state: Idaho
city: Libertyville
country: United States
facility: Lake County Research Associates
state: Illinois
city: Moline
country: United States
state: Illinois
city: Cedar Rapids
country: United States
facility: Physicians Clinic of Iowa
state: Iowa
city: Elizabethtown
country: United States
facility: The Center for Arthritis & Osteoporosis
state: Kentucky
city: Louisville
country: United States
facility: David H. Neustadt PSCq
state: Kentucky
city: Baton Rouge
country: United States
facility: Gulf Coast Research
state: Louisiana
city: Frederick
country: United States
facility: Arthritis and Osteoporosis Center of Maryland
state: Maryland
city: Rockville
country: United States
state: Maryland
city: Wheaton
country: United States
facility: The Center for Rheumatology & Bone Research
state: Maryland
city: Springfield
country: United States
facility: Future Care Studies
state: Massachusetts
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Lansing
country: United States
facility: Justus Fiechtner, MD, MPH
state: Michigan
city: Hattiesburg
country: United States
facility: Arthritis Associates
state: Mississippi
city: Florissant
country: United States
facility: Medical Center Healthcare Research
state: Missouri
city: Saint Louis
country: United States
facility: Medex Healthcare
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Reno
country: United States
facility: Arthritis Center of Reno
state: Nevada
city: Manalapan
country: United States
facility: Arthritis & Osteoporisis Associates
state: New Jersey
city: Medford
country: United States
facility: Rheumatology and Arthritis Associates
state: New Jersey
city: Voorhees
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: Brewster
country: United States
facility: Southwest Medical Associates
state: New York
city: New York
country: United States
facility: Concorde medical Group
state: New York
city: Rochester
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Williamsville
country: United States
state: New York
city: Belmont
country: United States
facility: Arthritis Consultants of the Carolinas
state: North Carolina
city: Charlotte
country: United States
facility: Arthritis & Osteoporosis Consultants of the Carolinas
state: North Carolina
city: Dayton
country: United States
state: Ohio
city: Mayfield Village
country: United States
state: Ohio
city: Middleburg Heights
country: United States
state: Ohio
city: Duncansville
country: United States
state: Pennsylvania
city: Harleysville
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Orangeburg
country: United States
state: South Carolina
city: Milan
country: United States
state: Tennessee
city: New Tazewell
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Carrollton
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Irving
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Sugarland
country: United States
state: Texas
city: Ettrick
country: United States
state: Virginia
city: Portsmouth
country: United States
state: Virginia
city: Reston
country: United States
state: Virginia
city: Suffolk
country: United States
state: Virginia
Study officials:
affiliation: AR Scientific, Inc.
name: Matthew W Davis, MD, RPh
role: STUDY_CHAIR
References:
citation: 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.