Clinical trial NCT00603265: Safety and Efficacy Study of ADL5859 in Participants With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
Official title: A Phase 2a, Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group, Multicenter Study to Assess the Safety and Efficacy of ADL5859 100 mg BID in Subjects With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peripheral Neuropathy
Neuropathic Pain
Keywords: Diabetic Peripheral Neuropathy
Neuropathic Pain
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2008-01-29
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effectiveness of ADL5859 in relieving the pain associated with diabetic peripheral neuropathy (DPN) compared with placebo and duloxetine (a marketed drug approved for the treatment of painful DPN). The pain symptoms of DPN are thought to be due to damage to nerves caused by the diabetes.

Detailed description: Participants were permitted to take acetaminophen 650 to 975 mg every 4 to 6 hours (up to a total of 4 grams in 24 hours) as needed for pain relief.

Eligibility criteria: Inclusion Criteria:

* Male and female participants between 18 and 75 years of age, inclusive
* Body weight of at least 45 kilograms (kg)
* Diabetes mellitus (type I or II) that is documented to be under stable glycemic control over a period of at least 3 months, as indicated by a glycosylated hemoglobin (HbgAIC) of less than or equal to 12% and a stable dose of insulin or oral diabetic medication for 90 days prior to starting study medication
* No change in diabetic medications is planned for the duration of the study
* Evidence of symmetrical, bilateral pain in the lower extremities due to diabetic peripheral neuropathy (DPN)
* Presence of daily pain due to DPN for at least 3 months
* Score greater than or equal to 3 on the physical examination portion of the Michigan Neuropathy Screening Instrument (MNSI)
* Average weekly pain score of greater than or equal to 4 on the numeric pain rating scale (NPRS) for symmetrical neuropathic pain in the feet and legs
* For male participants, be surgically sterile or agree to use an appropriate method of contraception
* For female participants of childbearing potential, be surgically sterile or using an intrauterine device, or injectable, transdermal, or combination oral contraceptive deemed highly effective by the Food and Drug Administration (FDA)
* Be willing and able to comply with the protocol requirements
* Be able to understand and willing to provide written informed consent in English

Exclusion Criteria:

* Presence of pain conditions that cannot be distinguished from DPN
* Presence of significant renal disease, as indicated by a serum creatinine greater than or equal to 2.0 milligrams per deciliter (mg/dL), or presence of significant hepatic disease
* Have a history of a seizure disorder
* Presence of serious or unstable cardiovascular disease, respiratory disease, hematologic illness, or a psychiatric condition
* History of evidence of symptomatic orthostatic hypotension
* History of a major depressive disorder, generalized anxiety disorder, eating disorder, or substance abuse (including alcohol) within the past year
* History or evidence of mania, bipolar disorder, or psychosis
* History of allergy to acetaminophen or duloxetine
* Score of greater than or equal to 18 on the Beck Depression Inventory II (BDI-II) or score of greater than zero on Item 9 of the BDI-II
* Use of any of the following concomitant medications: fluvoxamine; quinolone antimicrobials (ciprofloxacin and enoxacin); selective serotonin reuptake inhibitors (SSRIs); serotonin norepinephrine reuptake inhibitors (SNRIs); tricyclic antidepressants; opioids; nonsteroidal anti-inflammatory drugs (NSAIDS); anticonvulsants; aspirin (with the exception of low-dose aspirin as cardiovascular prophylaxis); or cytochrome P4503A (CYP3A) and P-glycoprotein transporter inhibitors
* Pregnant, lactating, or plans to become pregnant during the study
* Presence of foot or toe amputation
* Participation in another study with an investigational compound within the previous 30 days prior to study medication administration, or concurrent participation in another clinical study

Primary outcomes:
measure: Change From Baseline in Mean Numeric Pain Rating Scale (NPRS) Score
timeFrame: Baseline, Week 4
Secondary outcomes:
measure: Percentage of Responders
timeFrame: Baseline, Week 4
measure: Patient Global Impression of Change (PGIC)
timeFrame: Week 4
measure: Change in Sleep Interference Scale (SIS) From Baseline
timeFrame: Baseline, Week 4
measure: Change From Baseline in the Evening Assessment of the 24-hour Overall Mean Pain Intensity Score
timeFrame: Baseline, Week 4
measure: Change From Baseline in NPRS at Rest in the Clinic
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4
measure: Change From Baseline in NPRS After Walking 50 Feet in the Clinic
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4
Other outcomes:
Locations:
city: Riverside
country: United States
facility: Integrated Research Group
state: California
city: Torrance
country: United States
facility: Torrance Clinical Research
state: California
city: Kissimmee
country: United States
facility: FPA Clinical Research
state: Florida
city: Largo
country: United States
facility: Innovative Research of West Florida, Inc.
state: Florida
city: Marianna
country: United States
facility: Panhandle Family Care Associates & Emerald Coast Research Grp, Inc.
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Pinellas Park
country: United States
facility: Radiant Research-St.Petersburg
state: Florida
city: South Miami
country: United States
facility: Doctor's Research Network
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute, Inc.
state: Florida
city: West Palm Beach
country: United States
facility: Laszlo J. Mate, MD
state: Florida
city: Lexington
country: United States
facility: The Pain Treatment Center of the Bluegrass
state: Kentucky
city: Brockton
country: United States
facility: Beacon Clinical Research
state: Massachusetts
city: Florissant
country: United States
facility: Healthcare Research
state: Missouri
city: Omaha
country: United States
facility: Creighton Diabetes Center, Creighton Univ. Sch. of Medicine
state: Nebraska
city: Las Vegas
country: United States
facility: Advanced Biomedical Research of America
state: Nevada
city: Asheville
country: United States
facility: Clnical Study Center of Asheville
state: North Carolina
city: Mogadore
country: United States
facility: Radiant Research-Akron
state: Ohio
city: Toledo
country: United States
facility: Neurology & Neuroscience Center of Ohio
state: Ohio
city: Yukon
country: United States
facility: Aquilo Research
state: Oklahoma
city: Medford
country: United States
facility: Clinical Research Consultants, Research Department
state: Oregon
city: Altoona
country: United States
facility: Advanced Regional Center for Clinical Research (Ankle & Foot Care)
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Houston
country: United States
facility: Nerve & Muscle Center of Texas
state: Texas
city: San Antonio
country: United States
facility: Invisions Consultants LLC
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Research Associates
state: Texas
city: San Antonio
country: United States
facility: S.A.M. Clinical Research Center
state: Texas
city: Virginia Beach
country: United States
facility: Tidewater Integrated Medical Research
state: Virginia
Study officials:
affiliation: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
name: Bruce Berger, MD
role: STUDY_DIRECTOR
References: