Cebranopadol Efficacy and Safety in Diabetic Patients Suffering From Chronic Pain Caused by Damage to the Nerves

Tris Pharma

Status and phase: Completed; Phase 2

Conditions: Diabetes Mellitus; Chronic Pain; Diabetic Neuropathies

Treatments: Drug: Cebranopadol 300 µg; Drug: Cebranopadol 600 µg; Drug: Pregabalin; Drug: Cebranopadol 100 µg; Drug: Matching Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01939366

2013-000473-68 (EudraCT Number)

U1111-1151-4331 (Other Identifier)

KF6005/08

Details and patient eligibility

About

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.

Enrollment: 699 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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699 participants in 5 patient groups, including a placebo group

Cebranopadol 300 µg

Experimental group

Treatment:

Drug: Cebranopadol 300 µg

Cebranopadol 600 µg

Experimental group

Treatment:

Drug: Cebranopadol 600 µg

Pregabalin

Active Comparator group

Treatment:

Drug: Pregabalin

Matching Placebo

Placebo Comparator group

Treatment:

Drug: Matching Placebo

Cebranopadol 100 µg

Experimental group

Treatment:

Drug: Cebranopadol 100 µg