Safety and Efficacy of EMA401 in Patients With Painful Diabetic Neuropathy (PDN)
Condition: Painful Diabetic Neuropathy
MeSH terms: Peripheral Nervous System Diseases; Diabetic Neuropathies; Pain
Intervention: EMA401; Placebo
Intervention description: capsules, oral; Placebo to EMA401 capsules, oral
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 142.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Painful diabetic neuropathy; Neuropathic pain; Angiotensin II type 2 receptor antagonist; adult; EMA401; diabetic neuropathy

Summary:

      The purpose of this study is to evaluate safety and efficacy of EMA401 compared to placebo in
      patients with painful diabetic neuropathy (PDN).
    

Eligibility criteria:

        Inclusion Criteria:

          -  At the time of Screening, must have had documented diagnosis of Type I OR Type II
             diabetes mellitus (DM) with painful distal symmetrical sensorimotor neuropathy (ICD-10
             code G63.2) of more than 6 months duration with any one or more of the following:

               -  Neuropathic symptoms (e.g. numbness, non-painful paresthesias or tingling,
                  non-painful sensory distortions or misinterpretations, etc.)

               -  Decreased distal sensation (e.g. decreased vibration, pinprick sensation, light
                  touch, etc.)

          -  Been assessed as suffering from moderate to severe neuropathic pain across the
             Screening epoch (NRS ≥ 4).

          -  A score of ≥4 on the Douleur Neuropathique en 4 Questions (DN4) questionnaire at
             Screening.

        Exclusion Criteria:

          -  Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they were using highly effective methods of contraception
             during dosing and for 3 days after stopping of study medication. Highly effective
             contraception methods included:

               -  Total abstinence (when this was is in line with the preferred and usual lifestyle
                  of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal,
                  post-ovulation methods) and withdrawal were not acceptable methods of
                  contraception.

               -  Female sterilization (have had surgical bilateral oophorectomy with or without
                  hysterectomy), total hysterectomy or tubal ligation at least six weeks before
                  taking investigational drug. In case of oophorectomy alone, only when the
                  reproductive status of the woman had been confirmed by follow up hormone level
                  assessment.

               -  Male sterilization (at least 6 months prior to screening). For female subjects on
                  the study, the vasectomized male partner should have been the sole partner for
                  that subject.

               -  Placement of an intrauterine device (IUD) or intrauterine system (IUS).

          -  History or current diagnosis of electrocardiogram (ECG) abnormalities indicating
             significant risk of safety for patients participating in the study.

          -  Major depressive episode within 6 months prior to Screening and/or a history of
             diagnosed recurrent major depressive disorder according to Diagnostic and Statistical
             Manual of Mental Disorders, 5th Edition (DSM-V) diagnostic criteria.

          -  Had evidence of significant renal insufficiency or pre-existing liver condition.

          -  Had platelets ≤ 100 x 10^9/L, or neutrophil count < 1.2 x 10^9/L (or equivalent),
             hemoglobin ≤ 100 g/L for women or hemoglobin ≤ 110 g/L for men.

          -  Participants whose glycemic control had been unstable within 3 months immediately
             prior to screening (e.g., ketoacidosis requiring hospitalization, any recent episode
             of hypoglycemia requiring assistance through medical intervention, uncontrolled
             hyperglycemia)

          -  Patients who had any differential diagnosis of PDN including but not limited to other
             neuropathies (e.g. Vitamin B12 deficiency, Chronic Inflammatory Demyelinating
             Polyneuropathy), polyradiculopathies, central disorders (e.g. demyelinating disease),
             or rheumatological disease (e.g., foot arthritis, plantar fasciitis).

          -  Patient was unwilling or unable to complete daily eDiary.