Clinical trial NCT01939366: Cebranopadol Efficacy and Safety in Diabetic Patients Suffering From Chronic Pain Caused by Damage to the Nerves
Official title: Efficacy, Safety and Tolerability of Multiple Doses of Oral Cebranopadol in Subjects With Moderate to Severe Chronic Pain Due to Diabetic Peripheral Neuropathy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Pain
Diabetic Neuropathies
Diabetes Mellitus
Keywords: Painful Diabetic Peripheral Neuropathy
Lead sponsor: Tris Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2013-09-11
Enrollment: 699
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change in Average Pain Intensity.
timeFrame: Baseline; to End of Week 6 of the Maintenance Phase
Secondary outcomes:
Other outcomes:
Locations:
city: Mesa
country: United States
facility: US002
state: Arizona
city: Garden Grove
country: United States
facility: US001
state: California
city: Laguna Hills
country: United States
facility: US019
state: California
city: National City
country: United States
facility: US014
state: California
city: Orange
country: United States
facility: US007
state: California
city: Hialeah
country: United States
facility: US011
state: Florida
city: Miami
country: United States
facility: US012
state: Florida
city: Orlando
country: United States
facility: US009
state: Florida
city: Blackfoot
country: United States
facility: US004
state: Idaho
city: Elgin
country: United States
facility: US006
state: Illinois
city: West Long Branch
country: United States
facility: US016
state: New Jersey
city: Brooklyn
country: United States
facility: US008
state: New York
city: Brooklyn
country: United States
facility: US005
state: New York
city: New York
country: United States
facility: US021
state: New York
city: West Jordan
country: United States
facility: US003
state: Utah
city: Graz
country: Austria
facility: AT007
city: Salzburg
country: Austria
facility: AT005
city: Senftenberg
country: Austria
facility: AT004
city: Vienna
country: Austria
facility: AT002
city: Vienna
country: Austria
facility: AT003
city: Vienna
country: Austria
facility: AT001
city: Vienna
country: Austria
facility: AT006
city: Aalborg
country: Denmark
facility: DK005
city: Aarhus
country: Denmark
facility: DK003
city: Copenhagen
country: Denmark
facility: DK002
city: Odense
country: Denmark
facility: DK001
city: Corbeil Essonnes
country: France
facility: FR008
city: Lille
country: France
facility: FR001
city: Limoges cedex
country: France
facility: FR007
city: Montauban cedex
country: France
facility: FR005
city: Nantes
country: France
facility: FR002
city: Orléans
country: France
facility: FR004
city: Paris
country: France
facility: FR006
city: Aschaffenburg
country: Germany
facility: DE018
city: Bad Oeynhausen
country: Germany
facility: DE003
city: Berlin
country: Germany
facility: DE005
city: Berlin
country: Germany
facility: DE023
city: Berlin
country: Germany
facility: DE031
city: Berlin
country: Germany
facility: DE004
city: Berlin
country: Germany
facility: DE025
city: Bochum
country: Germany
facility: DE013
city: Dresden
country: Germany
facility: DE033
city: Düsseldorf
country: Germany
facility: DE017
city: Düsseldorf
country: Germany
facility: DE012
city: Essen
country: Germany
facility: DE010
city: Essen
country: Germany
facility: DE034
city: Essen
country: Germany
facility: DE022
city: Frankfurt
country: Germany
facility: DE006
city: Görlitz
country: Germany
facility: DE007
city: Hamburg
country: Germany
facility: DE021
city: Hannover
country: Germany
facility: DE020
city: Karlsruhe
country: Germany
facility: DE016
city: Kiel
country: Germany
facility: DE002
city: Künzing
country: Germany
facility: DE030
city: Leipzig
country: Germany
facility: DE008
city: Leipzig
country: Germany
facility: DE009
city: Magdeburg
country: Germany
facility: DE015
city: Magdeburg
country: Germany
facility: DE032
city: Mainz
country: Germany
facility: DE001
city: Mayen
country: Germany
facility: DE028
city: München
country: Germany
facility: DE027
city: Münster
country: Germany
facility: DE014
city: Neuss
country: Germany
facility: DE011
city: Schwerin
country: Germany
facility: DE024
city: Ancona
country: Italy
facility: IT005
city: Milano
country: Italy
facility: IT004
city: Rome
country: Italy
facility: IT001
city: Turin
country: Italy
facility: IT002
city: Amsterdam
country: Netherlands
facility: NL007
city: Apeldoorn
country: Netherlands
facility: NL004
city: Beek
country: Netherlands
facility: NL005
city: Eindhoven
country: Netherlands
facility: NL001
city: Rotterdam
country: Netherlands
facility: NL002
city: Venlo
country: Netherlands
facility: NL006
city: Zwijndrecht
country: Netherlands
facility: NL008
city: Zwolle
country: Netherlands
facility: NL003
city: Cuenca
country: Spain
facility: ES001
city: Madrid
country: Spain
facility: ES011
city: Madrid
country: Spain
facility: ES010
city: Madrid
country: Spain
facility: ES009
city: Toledo
country: Spain
facility: ES003
city: Valencia
country: Spain
facility: ES006
Study officials:
affiliation: Grünenthal GmbH
name: Director Clinical Trials
role: STUDY_DIRECTOR
References: