Chronic PainPhase 2NCT01939366
Cebranopadol Efficacy and Safety in Diabetic Patients Suffering From Chronic Pain Caused by Damage to the Nerves
A Phase 2 study testing Cebranopadol 100 µg, Cebranopadol 300 µg and Cebranopadol 600 µg in people with Chronic Pain and Diabetic Neuropathies, run by Tris Pharma, Inc. at 82 sites in 8 countries.
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®). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Pain, Diabetic Neuropathies, Diabetes Mellitus
- What is being tested?
- Cebranopadol 100 µg, Cebranopadol 300 µg and Cebranopadol 600 µg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 699 participants
- Where
- 82 sitesin 8 countries
- Study dates
- 27 Sep 2013to 28 Jan 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
82 sites in 8 countries.
82 sites in 8 countries
Germany31 sites
DE018
Aschaffenburg, 63739
DE003
Bad Oeynhausen, 32545
DE005
Berlin, 10115
DE023
Berlin, 10117
DE031
Berlin, 10787
DE004
Berlin, 12627
DE025
Berlin, 13125
DE013
Bochum, 44787
DE033
Dresden, 01069
DE017
Düsseldorf, 40210
DE012
Düsseldorf, 40212
DE010
Essen, 45136
DE034
Essen, 45277
DE022
Essen, 45355
DE006
Frankfurt, 60596
DE007
Görlitz, 02826
DE021
Hamburg, 20253
DE020
Hanover, 30159
DE016
Karlsruhe, 76199
DE002
Kiel, 24119
DE030
Künzing, 94550
DE008
Leipzig, 04103
DE009
Leipzig, 04109
DE015
Magdeburg, 39104
DE032
Magdeburg, 39112
DE001
Mainz, 55116
DE028
Mayen, 56727
DE027
München, 81477
DE014
Münster, 48145
DE011
Neuss, 41460
DE024
Schwerin, 19055
United States15 sites
US004
Blackfoot, Idaho, 83221
US008
Brooklyn, New York, 11229
US005
Brooklyn, New York, 11235
US006
Elgin, Illinois, 60123
US001
Garden Grove, California, 92843
US011
Hialeah, Florida, 33012
US019
Laguna Hills, California, 92653
US002
Mesa, Arizona, 85215
US012
Miami, Florida, 33135
US014
National City, California, 91950
US021
New York, New York, 10128
US007
Orange, California, 92868
US009
Orlando, Florida, 32806
US003
West Jordan, Utah, 84088
US016
West Long Branch, New Jersey, 07764
Netherlands8 sites
NL007
Amsterdam, 1091 AC
NL004
Apeldoorn, 7334 DZ
NL005
Beek, 6191 JW
NL001
Eindhoven, 5623 EJ
NL002
Rotterdam, 3039 BD
NL006
Venlo, 5912 BL
NL008
Zwijndrecht, 3331 LZ
NL003
Zwolle, 8025 AB
Austria7 sites
AT007
Graz, 8036
AT005
Salzburg, 5020
AT004
Senftenberg, 3541
AT002
Vienna, 1010
AT003
Vienna, 1060
AT001
Vienna, 1090
AT006
Vienna, 1160
France7 sites
FR008
Corbeil-Essonnes, 91100
FR001
Lille, 59037
FR007
Limoges, 87042
FR005
Montauban, 82013
FR002
Nantes, 44200
FR004
Orléans, 45000
FR006
Paris, 75004
Spain6 sites
ES001
Cuenca, 16002
ES011
Madrid, 28031
ES010
Madrid, 28040
ES009
Madrid, 28041
ES003
Toledo, 45600
ES006
Valencia, 46010
Denmark4 sites
DK005
Aalborg, 9100
DK003
Aarhus, 8000
DK002
Copenhagen, 2000
DK001
Odense, 5000
Italy4 sites
IT005
Ancona, 60127
IT004
Milan, 20162
IT001
Rome, 00133
IT002
Turin, 10126
About this study
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.
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
- Being tested
- Cebranopadol 100 µg, Cebranopadol 300 µg, Cebranopadol 600 µg, Pregabalin, Matching Placebo
- Keywords
- Painful Diabetic Peripheral Neuropathy
- Medical subject headings
- Chronic Pain, Diabetic Neuropathies, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cebranopadol 100 µgDrug
Participants randomized to 100 μg cebranopadol will start with 100 μg per day and will remain on 100 µg per day.
Cebranopadol 300 µgDrug
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 µgDrug
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.
PregabalinDrug
Also called Lyrica®
Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
Matching PlaceboDrug
Placebo will be matched to pregabalin and cebranopadol.
| Study group | Role | What they receive |
|---|---|---|
| Cebranopadol 300 µg | Experimental | Not described Receives: Drug: Cebranopadol 300 µg |
| Cebranopadol 600 µg | Experimental | Not described Receives: Drug: Cebranopadol 600 µg |
| Pregabalin | Active comparator | Not described Receives: Drug: Pregabalin |
| Matching Placebo | Placebo comparator | Not described Receives: Drug: Matching Placebo |
| Cebranopadol 100 µg | Experimental | Not described Receives: Drug: Cebranopadol 100 µg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline; to End of Week 6 of the Maintenance Phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2013 (estimated)
- Study start27 Sep 2013
- Primary completionJan 2015
- Study completion28 Jan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 699 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tris Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Director Clinical Trials, Study director, Grünenthal GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01939366
- Sponsor's protocol ID
- KF6005/08
- Other IDs
- 2013-000473-68, U1111-1151-4331
- Status last verified
- Jul 2021
- First submitted
- 6 Sep 2013
- Last updated
- 15 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01939366
- Acronym / sponsor ID
- KF6005/08
- Conditions
- Chronic Pain, Diabetic Neuropathies, Diabetes Mellitus
- Keywords
- Painful Diabetic Peripheral Neuropathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 699 participants (actual)
- Lead sponsor
- Tris Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Sep 2013 (actual)
- Primary completion
- Jan 2015 (actual)
- Study completion
- 28 Jan 2015 (actual)
- First posted
- 11 Sep 2013 (estimated)
- Results
- Posted 26 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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%
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cebranopadol 100 µgParticipants randomized to 100 μg cebranopadol will start with 100 μg per day and will remain on 100 µg per day. | Drug | Cebranopadol 100 µg |
| Cebranopadol 300 µgParticipants 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. | Drug | Cebranopadol 300 µg |
| Cebranopadol 600 µgParticipants 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. | Drug | Cebranopadol 600 µg |
| PregabalinAlso: Lyrica®Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks. | Drug | Pregabalin |
| Matching PlaceboPlacebo will be matched to pregabalin and cebranopadol. | Drug | Matching Placebo |
Primary outcome
Change in Average Pain Intensity.
Time frame: Baseline; to End of Week 6 of the Maintenance Phase
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Director Clinical Trials study director
Grünenthal GmbH
82 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cebranopadol 100 µg, Cebranopadol 300 µg and Cebranopadol 600 µg in people with Chronic Pain and Diabetic Neuropathies, run by Tris Pharma, Inc. at 82 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 82 sites in Germany, United States, Netherlands, Austria, France and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Average Pain Intensity. (time frame: Baseline; to End of Week 6 of the Maintenance Phase). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2021.