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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Grünenthal GmbH
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Grünenthal GmbH
ClinicalTrials.gov Identifier:
NCT01939366
First received: September 6, 2013
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

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®, indicated for your pain condition). 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.


Condition Intervention Phase
Chronic Pain
Diabetic Neuropathies
Diabetes Mellitus
Drug: Cebranopadol 100 µg
Drug: Cebranopadol 300 µg
Drug: Cebranopadol 600 µg
Drug: Pregabalin
Drug: Matching Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Grünenthal GmbH:

Primary Outcome Measures:
  • Change in average pain intensity. [ Time Frame: Baseline; to end of Week 6 of the Maintenance Phase ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 350
Study Start Date: September 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cebranopadol 300 µg 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.
Experimental: Cebranopadol 600 µg 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.
Active Comparator: Pregabalin Drug: Pregabalin
Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
Other Name: Lyrica®
Placebo Comparator: Matching Placebo Drug: Matching Placebo
Placebo will be matched to pregabalin and cebranopadol.
Experimental: Cebranopadol 100 µg 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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01939366

Contacts
Contact: Grünenthal Clinical Trial Help Desk +49 241 569 3223 Clinical-Trials@grunenthal.com
Contact: René Allard +49 241 569 3001 Clinical-Trials@grunenthal.com

  Show 81 Study Locations
Sponsors and Collaborators
Grünenthal GmbH
Forest Laboratories
Investigators
Study Director: Director Clinical Trials Grünenthal GmbH
  More Information

No publications provided

Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT01939366     History of Changes
Other Study ID Numbers: KF6005/08, 2013-000473-68, U1111-1151-4331
Study First Received: September 6, 2013
Last Updated: August 26, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Denmark: Danish Health and Medicines Authority
Austria: Austrian Medicines and Medical Devices Agency
Italy: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United States: Food and Drug Administration

Keywords provided by Grünenthal GmbH:
Painful Diabetic Peripheral Neuropathy

Additional relevant MeSH terms:
Diabetic Neuropathies
Diabetes Mellitus
Peripheral Nervous System Diseases
Chronic Pain
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Neuromuscular Diseases
Nervous System Diseases
Diabetes Complications
Pain
Neurologic Manifestations
Signs and Symptoms
Pregabalin
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 16, 2014