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

NCT ID: NCT01939366

Last Updated: 2021-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 699 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-27
• Study Completion Date: 2015-01-28

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.

Conditions

Chronic Pain; Diabetic Neuropathies; Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cebranopadol 300 µg

Group Type: EXPERIMENTAL

Cebranopadol 300 µg

Intervention Type: DRUG

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.

Cebranopadol 600 µg

Group Type: EXPERIMENTAL

Cebranopadol 600 µg

Intervention Type: DRUG

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.

Pregabalin

Group Type: ACTIVE_COMPARATOR

Pregabalin

Intervention Type: DRUG

Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.

Matching Placebo

Group Type: PLACEBO_COMPARATOR

Matching Placebo

Intervention Type: DRUG

Placebo will be matched to pregabalin and cebranopadol.

Cebranopadol 100 µg

Group Type: EXPERIMENTAL

Cebranopadol 100 µg

Intervention Type: DRUG

Participants randomized to 100 μg cebranopadol will start with 100 μg per day and will remain on 100 µg per day.

Interventions

Cebranopadol 100 µg

Participants randomized to 100 μg cebranopadol will start with 100 μg per day and will remain on 100 µg per day.

Intervention Type: DRUG

Cebranopadol 300 µg

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.

Intervention Type: DRUG

Cebranopadol 600 µg

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.

Intervention Type: DRUG

Pregabalin

Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.

Intervention Type: DRUG

Matching Placebo

Placebo will be matched to pregabalin and cebranopadol.

Intervention Type: DRUG

Other Intervention Names

Lyrica®

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tris Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Director Clinical Trials

Role: STUDY_DIRECTOR

Grünenthal GmbH

Locations

US002

Mesa, Arizona, United States

US001

Garden Grove, California, United States

US019

Laguna Hills, California, United States

US014

National City, California, United States

US007

Orange, California, United States

US011

Hialeah, Florida, United States

US012

Miami, Florida, United States

US009

Orlando, Florida, United States

US004

Blackfoot, Idaho, United States

US006

Elgin, Illinois, United States

US016

West Long Branch, New Jersey, United States

US008

Brooklyn, New York, United States

US005

Brooklyn, New York, United States

US021

New York, New York, United States

US003

West Jordan, Utah, United States

AT007

Graz, , Austria

AT005

Salzburg, , Austria

AT004

Senftenberg, , Austria

AT002

Vienna, , Austria

AT003

Vienna, , Austria

AT001

Vienna, , Austria

AT006

Vienna, , Austria

DK005

Aalborg, , Denmark

DK003

Aarhus, , Denmark

DK002

Copenhagen, , Denmark

DK001

Odense, , Denmark

FR008

Corbeil-Essonnes, , France

FR001

Lille, , France

FR007

Limoges, , France

FR005

Montauban, , France

FR002

Nantes, , France

FR004

Orléans, , France

FR006

Paris, , France

DE018

Aschaffenburg, , Germany

DE003

Bad Oeynhausen, , Germany

DE005

Berlin, , Germany

DE023

Berlin, , Germany

DE031

Berlin, , Germany

DE004

Berlin, , Germany

DE025

Berlin, , Germany

DE013

Bochum, , Germany

DE033

Dresden, , Germany

DE017

Düsseldorf, , Germany

DE012

Düsseldorf, , Germany

DE010

Essen, , Germany

DE034

Essen, , Germany

DE022

Essen, , Germany

DE006

Frankfurt, , Germany

DE007

Görlitz, , Germany

DE021

Hamburg, , Germany

DE020

Hanover, , Germany

DE016

Karlsruhe, , Germany

DE002

Kiel, , Germany

DE030

Künzing, , Germany

DE008

Leipzig, , Germany

DE009

Leipzig, , Germany

DE015

Magdeburg, , Germany

DE032

Magdeburg, , Germany

DE001

Mainz, , Germany

DE028

Mayen, , Germany

DE027

München, , Germany

DE014

Münster, , Germany

DE011

Neuss, , Germany

DE024

Schwerin, , Germany

IT005

Ancona, , Italy

IT004

Milan, , Italy

IT001

Rome, , Italy

IT002

Turin, , Italy

NL007

Amsterdam, , Netherlands

NL004

Apeldoorn, , Netherlands

NL005

Beek, , Netherlands

NL001

Eindhoven, , Netherlands

NL002

Rotterdam, , Netherlands

NL006

Venlo, , Netherlands

NL008

Zwijndrecht, , Netherlands

NL003

Zwolle, , Netherlands

ES001

Cuenca, , Spain

ES011

Madrid, , Spain

ES010

Madrid, , Spain

ES009

Madrid, , Spain

ES003

Toledo, , Spain

ES006

Valencia, , Spain

Countries

United States; Austria; Denmark; France; Germany; Italy; Netherlands; Spain

Other Identifiers

2013-000473-68

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1151-4331

Identifier Type: OTHER

Identifier Source: secondary_id

KF6005/08

Identifier Type: -

Identifier Source: org_study_id