Cebranopadol Efficacy and Safety in Diabetic Patients Suffering From Chronic Pain Caused by Damage to the Nerves
Condition: Chronic Pain; Diabetic Neuropathies; Diabetes Mellitus
MeSH terms: Diabetic Neuropathies; Chronic Pain
Intervention: Cebranopadol 100 µg; Cebranopadol 300 µg; Cebranopadol 600 µg; Pregabalin; Matching Placebo
Intervention description: Participants randomized to 100 μg cebranopadol will start with 100 μg per day and will remain on 100 µg per day.; Participants randomized to 300 μg cebranopadol will start with 100 μg per day and increase to 300 µg per day on day 4 and will remain on 300 µg per day.; Participants randomized to 600 μg cebranopadol will start with 200 μg per day and increase to 400 µg per day on day 4 and to 600 µg on day 7, thereafter they will remain on 600 µg per day.; Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.; Placebo will be matched to pregabalin and cebranopadol.
Intervention MeSH terms: Pregabalin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 699.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Painful Diabetic Peripheral Neuropathy

Summary:

      The purpose of this trial is to evaluate if cebranopadol is safe and can decrease pain in
      patients when compared to placebo (a tablet that does not contain active product) and when
      compared to a marketed product containing pregabalin (Lyrica®). Furthermore, this trial will
      be undertaken to find out if the patient's general health and well-being improves under trial
      treatment.

      The concentrations of cebranopadol in the blood will be investigated to get a better
      understanding of how it is absorbed from the gut, distributed and broken down in the body,
      and eliminated from the body.
    

Eligibility criteria:

        Inclusion Criteria:

          -  written signed informed consent

          -  type 1 or type 2 diabetes mellitus

          -  clinical diagnosis of painful Diabetic Polyneuropathic Neuropathy (DPN) with symptoms
             and signs for at least 3 months

          -  must require medication (e.g., non-opioids or opioids up to an equivalent dose of 160
             mg oral morphine/day) for the treatment of pain due to DPN for at least 1 month prior
             to Visit 1 and must be dissatisfied with the current treatment (in terms of efficacy
             and/or tolerability). Medication for the treatment of pain due to DPN should be
             required on at least 4 of 7 consecutive days.

          -  blood glucose to be controlled by a diet, oral anti-hyperglycemic medication, and/or
             insulin for at least 3 months prior. Glycosylated hemoglobin (HbA1C) should not be
             greater than 11%

          -  baseline pain intensity score greater or equal to 5 on the 11-point Numerical Rating
             Scale (NRS) without intake of any analgesic at allocation. For each of the last 3 days
             prior to allocation of treatment, a 24 hour NRS score greater or equal to 4 is
             required

          -  women of childbearing potential must have a negative urine pregnancy test at
             enrollment

          -  using medically acceptable and highly effective methods of birth control (and willing
             to use them during the trial).

        Exclusion Criteria:

          -  presence of other pain that could confound the painful Diabetic Polyneuropathy (DPN)
             assessments, e.g. pain due to nerve entrapment (tarsal tunnel syndrome, osteoarthritis
             of the knee etc), peripheral vascular disease, radiculopathy, plantar fasciitis,
             tendonitis, mononeuritis multiplex, postherpetic neuralgia, complex regional pain
             syndrome, or fibromyalgia.

          -  neuropathy due to etiologies other than diabetes, e.g. autoimmune disorders,
             inflammatory neuropathies (e.g. chronic inflammatory demyelinating polyneuropathy),
             thyroid disease or endocrine disorders (other than diabetes), heavy metal or toxic
             neuropathy, nutritional deficiency, metabolic disorders, vasculitis, infections,
             injury, or paraneoplastic syndromes.

          -  severe or extensive diabetic ulcers or amputations due to diabetes

          -  Charcot's joints due to diabetes.

          -  any clinically significant disease or laboratory findings, e.g., significant unstable
             cardiac, vascular, pulmonary, gastrointestinal, endocrine, metabolic, neurological, or
             psychiatric disorders.

          -  inability to comply with the protocol and with the intake of trial medication that, in
             the investigator's opinion, might indicate that the participant is unsuitable for the
             trial.

          -  conditions that require treatment with medication that is not allowed to be taken
             during the trial

          -  previous or current alcohol or drug abuse or opioid dependency.

          -  severe functional hepatic impairment corresponding to Child-Pugh classification C.

          -  history of acute hepatitis

          -  impaired renal function, a creatinine clearance less than 60 mL/min at the enrollment
             (Cockcroft-Gault calculated).

          -  history of any major gastrointestinal procedures (e.g., gastric bypass) or
             gastrointestinal conditions (e.g. acute diarrhea, blind loop syndrome, gastric dumping
             syndrome, Whipple's disease) that might affect the absorption or metabolism of
             cebranopadol or pregabalin.

          -  risk factors for or history of torsade de pointes and/or marked prolongation of the QT
             interval (e.g. heart failure, hypokalemia, or bradycardia).

          -  history of seizure disorder and/or epilepsy or any condition associated with a
             significant risk for seizure disorder or epilepsy at the discretion of the
             investigator.