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

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

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.

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.

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