MPC-004 for the Treatment of an Acute Gout Flare (AGREE)

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00506883
First received: July 23, 2007
Last updated: October 30, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Gout
Drug: High Dose Colchicine (4.8 mg total dose)
Drug: Low Dose Colchicine (1.8mg total dose)
Other: Placebo Control
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Responders [ Time Frame: 24 hours after baseline ] [ Designated as safety issue: No ]
    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.


Enrollment: 185
Study Start Date: April 2007
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
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.
Other Name: Colcrys TM, Colchicine 0.6 mg
Experimental: 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
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
Other Name: Colcrys TM, Colchicine 0.6 mg
Placebo Comparator: Placebo 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.
Other Name: Placebo capsule

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00506883

  Show 83 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Chair: Matthew W Davis, MD, RPh AR Scientific, Inc.
  More Information

No publications provided by Takeda

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Matthew Davis, MD, AR Scientific
ClinicalTrials.gov Identifier: NCT00506883     History of Changes
Other Study ID Numbers: MPC 004-06-3001
Study First Received: July 23, 2007
Results First Received: August 12, 2009
Last Updated: October 30, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Gout
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Colchicine
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 23, 2014