Safety and Efficacy Study of ADL5859 in Participants With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
Condition: Peripheral Neuropathy; Neuropathic Pain
MeSH terms: Peripheral Nervous System Diseases; Neuralgia
Intervention: ADL5859; Duloxetine; Placebo
Intervention MeSH terms: Duloxetine Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 226.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Diabetic Peripheral Neuropathy; Neuropathic Pain

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.
    

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