Safety and Efficacy Study of ADL5859 in Participants With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy

NCT00603265 | Completed Phase 2 Results

• 1 other identifier: 33CL231
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 27

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.

Conditions

Peripheral Neuropathy; Neuropathic Pain

Keywords

Diabetic Peripheral Neuropathy; Neuropathic Pain

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Mean Numeric Pain Rating Scale (NPRS) Score

  The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The mean of the daily average scores were calculated from the NPRS pain assessments obtained up to 3 times per day over a 7-day period. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment group as a main factor and baseline NPRS score as a covariate. Change from Baseline = NPRS at baseline - NPRS at Week 4; a positive number in the LS mean indicates a reduction in pain intensity from baseline.

  Baseline, Week 4

Secondary Outcomes (6)

• Percentage of Responders

  Baseline, Week 4

• Patient Global Impression of Change (PGIC)

  Week 4

• Change in Sleep Interference Scale (SIS) From Baseline

  Baseline, Week 4

• Change From Baseline in the Evening Assessment of the 24-hour Overall Mean Pain Intensity Score

  Baseline, Week 4

• Change From Baseline in NPRS at Rest in the Clinic

  Baseline, Week 1, Week 2, Week 3, Week 4

Study Arms (3)

ADL5859

EXPERIMENTAL

2 x 50 milligrams (mg) ADL5859 capsules administered orally once in the morning and once in the evening for 28 days

Drug: ADL5859

Duloxetine

ACTIVE COMPARATOR

2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days

Drug: Duloxetine; Drug: Placebo

Placebo

PLACEBO COMPARATOR

2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days

Drug: Placebo

Interventions

ADL5859 DRUG

ADL5859

Duloxetine DRUG

Also known as: Cymbalta

Duloxetine

Placebo DRUG

Duloxetine; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (27)

Integrated Research Group

Riverside, California, 92506, United States

Location

Torrance Clinical Research

Torrance, California, 90505, United States

Location

FPA Clinical Research

Kissimmee, Florida, 34741, United States

Location

Innovative Research of West Florida, Inc.

Largo, Florida, 33770, United States

Location

Panhandle Family Care Associates & Emerald Coast Research Grp, Inc.

Marianna, Florida, 32446, United States

Location

Renstar Medical Research

Ocala, Florida, 34471, United States

Location

Radiant Research-St.Petersburg

Pinellas Park, Florida, 33781, United States

Location

Doctor's Research Network

South Miami, Florida, 33143, United States

Location

Metabolic Research Institute, Inc.

West Palm Beach, Florida, 33401, United States

Location

Laszlo J. Mate, MD

West Palm Beach, Florida, 33407, United States

Location

The Pain Treatment Center of the Bluegrass

Lexington, Kentucky, 40503, United States

Location

Beacon Clinical Research

Brockton, Massachusetts, 02301, United States

Location

Healthcare Research

Florissant, Missouri, 63031, United States

Location

Creighton Diabetes Center, Creighton Univ. Sch. of Medicine

Omaha, Nebraska, 68131, United States

Location

Advanced Biomedical Research of America

Las Vegas, Nevada, 89123, United States

Location

Clnical Study Center of Asheville

Asheville, North Carolina, 28801, United States

Location

Radiant Research-Akron

Mogadore, Ohio, 44260, United States

Location

Neurology & Neuroscience Center of Ohio

Toledo, Ohio, 43623, United States

Location

Aquilo Research

Yukon, Oklahoma, 73099, United States

Location

Clinical Research Consultants, Research Department

Medford, Oregon, 97504, United States

Location

Advanced Regional Center for Clinical Research (Ankle & Foot Care)

Altoona, Pennsylvania, 16602, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Nerve & Muscle Center of Texas

Houston, Texas, 77030, United States

Location

Invisions Consultants LLC

San Antonio, Texas, 78217, United States

Location

Diabetes & Glandular Disease Research Associates

San Antonio, Texas, 78229, United States

Location

S.A.M. Clinical Research Center

San Antonio, Texas, 78229, United States

Location

Tidewater Integrated Medical Research

Virginia Beach, Virginia, 23451, United States

Location

MeSH Terms

Conditions

Peripheral Nervous System Diseases; Neuralgia

Interventions

N,N-diethyl-4-(5-hydroxyspiro(chromene-2,4'-piperidine)-4-yl)benzamide; Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Vice President, Clinical Research
• Organization: Cubist Pharmaceuticals

(781) 860-8660

Study Officials

• Bruce Berger, MD

  Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2008
• First Posted: January 29, 2008
• Study Start: November 1, 2007
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: July 1, 2015
• Results First Posted: July 1, 2015

Record last verified: 2015-06

Locations

US (27)