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

• Change from baseline in the mean NPRS proportion of subjects with 30% reduction in average pain score. [ Time Frame: Weekly ] [ Designated as safety issue: No ]
• Patient Global Impression of Change (PGIC) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
• Change in Sleep Interference Scale (SIS) from baseline [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
• Change from baseline in the evening assessment of the 24-hour overall mean pain intensity score [ Time Frame: Weekly ] [ Designated as safety issue: No ]
• Change from baseline in NPRS at rest in the clinic [ Time Frame: Weekly ] [ Designated as safety issue: No ]
• Change from baseline in NPRS after walking 50 feet in the clinic [ Time Frame: Weekly ] [ Designated as safety issue: No ]

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. The study drug, ADL5859, has not been previously tested in diabetic patients; it is anticipated to provide pain relief in DPN because it demonstrated effectiveness in animal studies.

• Peripheral Neuropathy
• Neuropathic Pain

• Drug: ADL5859
  2 x 50 mg capsules twice daily for 28 days
• Drug: duloxetine
  2 x 30 mg capsules once daily for 28 days
  Other Name: Cymbalta
• Drug: Placebo
  Two capsules filled with lactose as a non-active comparator

• Experimental: ADL5859
  Intervention: Drug: ADL5859
• Active Comparator: Duloxetine
  Intervention: Drug: duloxetine
• Sham Comparator: Placebo
  lactose capsules
  Intervention: Drug: Placebo

Inclusion Criteria:

• Male and female subjects between 18 and 75 years of age, inclusive
• Body weight of at least 45 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 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 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 MNSI
• Average weekly pain score of greater than or equal to 4 on the NPRS for symmetrical neuropathic pain in the feet and legs
• For male subjects, be surgically sterile or agree to use an appropriate method of contraception
• For female subjects of childbearing potential, be surgically sterile or using an intrauterine device, or injectable, transdermal, or combination oral contraceptive deemed highly effective by the 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 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 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); SSRIs; SNRIs; tricyclic antidepressants; opioids; NSAIDS; anticonvulsants; aspirin (with the exception of low-dose aspirin as cardiovascular prophylaxis); or 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