Intervention: Benzamide, N,N-diethyl-4-(5-hydroxyspiro(2H-1-benzopyran-2,4'-piperidin)-4-yl)-
Trial phase: Phase 2
SMILES: CCN(CC)C(=O)c1ccc(C2=CC3(CCNCC3)Oc3cccc(O)c32)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 75
Group description: 2 x 50 mg ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
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