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

Diabetes Mellitus Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01939366
• Other study ID #: KF6005/08
• Secondary ID: 2013-000473-68U1
• Status: Completed
• Phase: Phase 2
• Start date: September 27, 2013
• Est. completion date: January 28, 2015

Study information

• Verified date: July 2021
• Source: Tris Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 699
• Est. completion date: January 28, 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Pain
• Diabetes Mellitus
• Diabetic Neuropathies

Intervention

Drug:
• Cebranopadol 100 µg
Participants randomized to 100 µg cebranopadol will start with 100 µg per day and will remain on 100 µg per day.
• 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.
• 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.
• Pregabalin
Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
• Matching Placebo
Placebo will be matched to pregabalin and cebranopadol.

Locations

Country	Name	City	State
Austria	AT007	Graz
Austria	AT005	Salzburg
Austria	AT004	Senftenberg
Austria	AT001	Vienna
Austria	AT002	Vienna
Austria	AT003	Vienna
Austria	AT006	Vienna
Denmark	DK005	Aalborg
Denmark	DK003	Aarhus
Denmark	DK002	Copenhagen
Denmark	DK001	Odense
France	FR008	Corbeil Essonnes
France	FR001	Lille
France	FR007	Limoges cedex
France	FR005	Montauban cedex
France	FR002	Nantes
France	FR004	Orléans
France	FR006	Paris
Germany	DE018	Aschaffenburg
Germany	DE003	Bad Oeynhausen
Germany	DE004	Berlin
Germany	DE005	Berlin
Germany	DE023	Berlin
Germany	DE025	Berlin
Germany	DE031	Berlin
Germany	DE013	Bochum
Germany	DE033	Dresden
Germany	DE012	Düsseldorf
Germany	DE017	Düsseldorf
Germany	DE010	Essen
Germany	DE022	Essen
Germany	DE034	Essen
Germany	DE006	Frankfurt
Germany	DE007	Görlitz
Germany	DE021	Hamburg
Germany	DE020	Hannover
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
Italy	IT005	Ancona
Italy	IT004	Milano
Italy	IT001	Rome
Italy	IT002	Turin
Netherlands	NL007	Amsterdam
Netherlands	NL004	Apeldoorn
Netherlands	NL005	Beek
Netherlands	NL001	Eindhoven
Netherlands	NL002	Rotterdam
Netherlands	NL006	Venlo
Netherlands	NL008	Zwijndrecht
Netherlands	NL003	Zwolle
Spain	ES001	Cuenca
Spain	ES009	Madrid
Spain	ES010	Madrid
Spain	ES011	Madrid
Spain	ES003	Toledo
Spain	ES006	Valencia
United States	US004	Blackfoot	Idaho
United States	US005	Brooklyn	New York
United States	US008	Brooklyn	New York
United States	US006	Elgin	Illinois
United States	US001	Garden Grove	California
United States	US011	Hialeah	Florida
United States	US019	Laguna Hills	California
United States	US002	Mesa	Arizona
United States	US012	Miami	Florida
United States	US014	National City	California
United States	US021	New York	New York
United States	US007	Orange	California
United States	US009	Orlando	Florida
United States	US003	West Jordan	Utah
United States	US016	West Long Branch	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Tris Pharma, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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