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

NCT01939366 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: KF6005/082013-000473-68U1111-1151-4331
• Study Type: interventional
• Target: 699
• Locations: 8 countries
• Sites: 82

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

Keywords

Painful Diabetic Peripheral Neuropathy

Outcome Measures

Primary Outcomes (1)

• Change in Average Pain Intensity.

  Participants will be asked to record their pain intensity in the evening. Participants are asked to rate how much pain they had on average in the past 24 hours. The participant scores their pain intensity on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". Baseline average pain scores are calculated from the averages of all scores recorded during the 3 days prior to randomization. The average pain at week 6 will be the average pain scores calculated from all pain scores measured during week 6.

  Baseline; to End of Week 6 of the Maintenance Phase

Study Arms (5)

Cebranopadol 300 µg

EXPERIMENTAL

Drug: Cebranopadol 300 µg

Cebranopadol 600 µg

EXPERIMENTAL

Drug: Cebranopadol 600 µg

Pregabalin

ACTIVE COMPARATOR

Drug: Pregabalin

Matching Placebo

PLACEBO COMPARATOR

Drug: Matching Placebo

Cebranopadol 100 µg

EXPERIMENTAL

Drug: Cebranopadol 100 µg

Interventions

Cebranopadol 100 µg DRUG

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

Cebranopadol 100 µg

Cebranopadol 300 µg 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 300 µg

Cebranopadol 600 µg 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.

Cebranopadol 600 µg

Pregabalin DRUG

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

Also known as: Lyrica®

Pregabalin

Matching Placebo DRUG

Placebo will be matched to pregabalin and cebranopadol.

Matching Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tris Pharma, Inc.: lead

Study Sites (82)

US002

Mesa, Arizona, 85215, United States

Location

US001

Garden Grove, California, 92843, United States

Location

US019

Laguna Hills, California, 92653, United States

Location

US014

National City, California, 91950, United States

Location

US007

Orange, California, 92868, United States

Location

US011

Hialeah, Florida, 33012, United States

Location

US012

Miami, Florida, 33135, United States

Location

US009

Orlando, Florida, 32806, United States

Location

US004

Blackfoot, Idaho, 83221, United States

Location

US006

Elgin, Illinois, 60123, United States

Location

US016

West Long Branch, New Jersey, 07764, United States

Location

US008

Brooklyn, New York, 11229, United States

Location

US005

Brooklyn, New York, 11235, United States

Location

US021

New York, New York, 10128, United States

Location

US003

West Jordan, Utah, 84088, United States

Location

AT007

Graz, 8036, Austria

Location

AT005

Salzburg, 5020, Austria

Location

AT004

Senftenberg, 3541, Austria

Location

AT002

Vienna, 1010, Austria

Location

AT003

Vienna, 1060, Austria

Location

AT001

Vienna, 1090, Austria

Location

AT006

Vienna, 1160, Austria

Location

DK005

Aalborg, 9100, Denmark

Location

DK003

Aarhus, 8000, Denmark

Location

DK002

Copenhagen, 2000, Denmark

Location

DK001

Odense, 5000, Denmark

Location

FR008

Corbeil-Essonnes, 91100, France

Location

FR001

Lille, 59037, France

Location

FR007

Limoges, 87042, France

Location

FR005

Montauban, 82013, France

Location

FR002

Nantes, 44200, France

Location

FR004

Orléans, 45000, France

Location

FR006

Paris, 75004, France

Location

DE018

Aschaffenburg, 63739, Germany

Location

DE003

Bad Oeynhausen, 32545, Germany

Location

DE005

Berlin, 10115, Germany

Location

DE023

Berlin, 10117, Germany

Location

DE031

Berlin, 10787, Germany

Location

DE004

Berlin, 12627, Germany

Location

DE025

Berlin, 13125, Germany

Location

DE013

Bochum, 44787, Germany

Location

DE033

Dresden, 01069, Germany

Location

DE017

Düsseldorf, 40210, Germany

Location

DE012

Düsseldorf, 40212, Germany

Location

DE010

Essen, 45136, Germany

Location

DE034

Essen, 45277, Germany

Location

DE022

Essen, 45355, Germany

Location

DE006

Frankfurt, 60596, Germany

Location

DE007

Görlitz, 02826, Germany

Location

DE021

Hamburg, 20253, Germany

Location

DE020

Hanover, 30159, Germany

Location

DE016

Karlsruhe, 76199, Germany

Location

DE002

Kiel, 24119, Germany

Location

DE030

Künzing, 94550, Germany

Location

DE008

Leipzig, 04103, Germany

Location

DE009

Leipzig, 04109, Germany

Location

DE015

Magdeburg, 39104, Germany

Location

DE032

Magdeburg, 39112, Germany

Location

DE001

Mainz, 55116, Germany

Location

DE028

Mayen, 56727, Germany

Location

DE027

München, 81477, Germany

Location

DE014

Münster, 48145, Germany

Location

DE011

Neuss, 41460, Germany

Location

DE024

Schwerin, 19055, Germany

Location

IT005

Ancona, 60127, Italy

Location

IT004

Milan, 20162, Italy

Location

IT001

Rome, 00133, Italy

Location

IT002

Turin, 10126, Italy

Location

NL007

Amsterdam, 1091 AC, Netherlands

Location

NL004

Apeldoorn, 7334 DZ, Netherlands

Location

NL005

Beek, 6191 JW, Netherlands

Location

NL001

Eindhoven, 5623 EJ, Netherlands

Location

NL002

Rotterdam, 3039 BD, Netherlands

Location

NL006

Venlo, 5912 BL, Netherlands

Location

NL008

Zwijndrecht, 3331 LZ, Netherlands

Location

NL003

Zwolle, 8025 AB, Netherlands

Location

ES001

Cuenca, 16002, Spain

Location

ES011

Madrid, 28031, Spain

Location

ES010

Madrid, 28040, Spain

Location

ES009

Madrid, 28041, Spain

Location

ES003

Toledo, 45600, Spain

Location

ES006

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Chronic Pain; Diabetic Neuropathies; Diabetes Mellitus

Interventions

6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenylspiro(cyclohexane-1,1'(3'H)-pyrano(3,4-b)indol)-4-amine; Pregabalin

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study Director
• Organization: Grünenthal GmbH

Clinical-Trials@grunenthal.com

+49 241 569 3223

Study Officials

• Director Clinical Trials

  Grünenthal GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2013
• First Posted: September 11, 2013
• Study Start: September 27, 2013
• Primary Completion: January 1, 2015
• Study Completion: January 28, 2015
• Last Updated: July 15, 2021
• Results First Posted: December 26, 2019

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (15); IT (4); DE (31); NL (8); DK (4); FR (7); ES (6); AU (7)