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

Neuropathic Pain Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00603265
• Other study ID #: 33CL231
• Status: Completed
• Phase: Phase 2
• First received: January 17, 2008
• Last updated: June 4, 2015
• Start date: November 2007
• Est. completion date: August 2008

Study information

• Verified date: June 2015
• Source: Cubist Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 226
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Neuralgia
• Neuropathic Pain
• Peripheral Nervous System Diseases
• Peripheral Neuropathy

Intervention

Drug:
• ADL5859

• Duloxetine

• Placebo

Locations

Country	Name	City	State
United States	Advanced Regional Center for Clinical Research (Ankle & Foot Care)	Altoona	Pennsylvania
United States	Clnical Study Center of Asheville	Asheville	North Carolina
United States	Beacon Clinical Research	Brockton	Massachusetts
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Healthcare Research	Florissant	Missouri
United States	Nerve & Muscle Center of Texas	Houston	Texas
United States	FPA Clinical Research	Kissimmee	Florida
United States	Innovative Research of West Florida, Inc.	Largo	Florida
United States	Advanced Biomedical Research of America	Las Vegas	Nevada
United States	The Pain Treatment Center of the Bluegrass	Lexington	Kentucky
United States	Panhandle Family Care Associates & Emerald Coast Research Grp, Inc.	Marianna	Florida
United States	Clinical Research Consultants, Research Department	Medford	Oregon
United States	Radiant Research-Akron	Mogadore	Ohio
United States	Renstar Medical Research	Ocala	Florida
United States	Creighton Diabetes Center, Creighton Univ. Sch. of Medicine	Omaha	Nebraska
United States	Radiant Research-St.Petersburg	Pinellas Park	Florida
United States	Integrated Research Group	Riverside	California
United States	Diabetes & Glandular Disease Research Associates	San Antonio	Texas
United States	Invisions Consultants LLC	San Antonio	Texas
United States	S.A.M. Clinical Research Center	San Antonio	Texas
United States	Doctor's Research Network	South Miami	Florida
United States	Neurology & Neuroscience Center of Ohio	Toledo	Ohio
United States	Torrance Clinical Research	Torrance	California
United States	Tidewater Integrated Medical Research	Virginia Beach	Virginia
United States	Laszlo J. Mate, MD	West Palm Beach	Florida
United States	Metabolic Research Institute, Inc.	West Palm Beach	Florida
United States	Aquilo Research	Yukon	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Cubist Pharmaceuticals LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Percentage of Responders	A responder was defined as a participant who showed a reduction in average pain (as measured by NPRS) of at least 30% from baseline to Week 4. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The percentage of participants who qualified as responders is presented per treatment arm.	Baseline, Week 4	No
Secondary	Patient Global Impression of Change (PGIC)	PGIC is a participant-rated instrument that measures the change in the participant's overall status for the previous 2 weeks based on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The number of participants in each category is presented.	Week 4	No
Secondary	Change in Sleep Interference Scale (SIS) From Baseline	Sleep Interference was assessed on an 11-point Numeric Rating Scale where a score of 0 indicated "pain did not interfere with sleep" and a score of 10 indicated "pain completely interfered with sleep". Here, "n" signifies "Number of participants" for Baseline and Month 3 telephone interview whereas "n" signifies "number of observations" for Month 1, 2, and 3 because a participant could have had multiple visits during Month 1, 2, and 3 as this was a non-interventional study with no scheduled study visits, except Baseline visit and the Month 3 telephone interview. LS means were calculated using ANCOVA with treatment group as a main factor and baseline SIS score as a covariate. Change from baseline = SIS score at baseline - SIS score at Week 4.	Baseline, Week 4	No
Secondary	Change From Baseline in the Evening Assessment of the 24-hour Overall Mean Pain Intensity Score	At each of the evening pain assessments, participants assessed their overall pain intensity over the preceding 24 hours using NPRS. 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 at Baseline and Week 4. Change from baseline = NPRS at baseline - NPRS at Week 4.	Baseline, Week 4	No
Secondary	Change From Baseline in NPRS at Rest in the Clinic	The mean of the daily average scores were calculated from the NPRS pain assessments obtained 1 time per week over a 4-week period. NPRS assessments were taken while the participant was at rest. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. LS means were calculated using ANCOVA with treatment group as a main factor and baseline NPRS score as a covariate. Change from baseline = NPRS at baseline - NPRS at Weeks 1, 2, 3, and 4.	Baseline, Week 1, Week 2, Week 3, Week 4	No
Secondary	Change From Baseline in NPRS After Walking 50 Feet in the Clinic	The mean of the daily average scores were calculated from the NPRS pain assessments obtained 1 time per week over a 4-week period. NPRS assessments were taken after the participant walked 50 feet in the clinic. The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. LS means were calculated using ANCOVA with treatment group as a main factor and baseline NPRS score as a covariate. Change from baseline = NPRS at baseline - NPRS at Weeks 1, 2, 3, and 4.	Baseline, Week 1, Week 2, Week 3, Week 4	No