stop_circleTerminated/Withdrawn

Neuropathic pain associated with diabetic peripheral neuropathy

A 2-part trial to learn more about how BAY1817080 works, how safe it is, and what the right dose is for participants with diabetic neuropathic pain

Trial purpose

People suffering from diabetes often have high blood sugar levels. Over time this can affect many organs including the nerves in hands and feet and can cause a nerve pain called diabetic neuropathic pain (DNP). There are treatments for DNP but in many patients they do not reach a good pain reduction and have unwanted side effects.
In this trial, the researchers will look at how BAY1817080 works and how safe it is. They will compare it to a placebo or another treatment for DNP called pregabalin. A placebo looks like a treatment but does not have any medicine in it. The researchers will use a placebo to learn if the participants’ results are due to BAY1817080 or if the results could be due to chance. The researchers will also learn more about the right dose of BAY1817080 for these participants.
The trial will include participants who have DNP and either type 1 or type 2 diabetes. It will include about 440 men and women who are at least 18 years old.
This trial will have 2 parts. In Part 1, the participants will take either BAY1817080 or the placebo. These treatments will be taken as a tablet by mouth twice a day for 8 weeks. In Part 2, participants will take BAY 1817080, pregabalin, or a matching placebo of either treatment. BAY1817080 and a placebo will be taken as a tablet by mouth twice a day for 12 weeks. Pregabalin and a placebo will be taken as a capsule by mouth twice a day for 12 weeks.
The participants in Part 1 will visit their trial site 6 times. The participants in Part 2 will visit their trial site 7 times. At these visits, the doctors will ask the participants if they have any health problems, take blood samples, and do a physical exam. They will also ask the participants to complete questionnaires about their pain and other symptoms.

Key Participants Requirements

Sex

All

Age

18 Years
  • - Adults ≥ 18 years of age at the time of signing the informed consent.
    - At the time of screening, have documented diagnosis of type 1 OR type 2 diabetes mellitus (DM) with painful distal symmetrical sensorimotor neuropathy of more than 6 months duration according to modified Toronto Clinical Neuropathy Score.
    - Weekly mean 24-hour average pain NRS ≥ 4 with adequate variability (not the same score on all daily pain ratings) and compliance (non-missing pain score on at least 6 out of 7 consecutive days) in daily pain recording during the 7 day NRS baseline period.
    - Neuropathic pain according to the DN4 questionnaire (Douleur Neuropathique 4 Questions).
    - Women of childbearing potential must agree to use acceptable effective or highly effective birth control methods.
  • - Any differential diagnosis of peripheral diabetic neuropathy (PDN) including but not limited to other neuropathies (e.g. vitamin B12 deficiency, Chronic Inflammatory Demyelinating Polyneuropathy), polyradiculopathies, central disorders (e.g. demyelinating disease), or rheumatological disease (e.g. foot arthritis, plantar fasciitis).
    - Any other diseases or conditions that according to the investigator can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study intervention (e.g. chronic bowel disease, Crohn's disease and ulcerative colitis).
    - Any serious or unstable diseases or conditions including psychiatric disorders that might interfere with the conduct of the study or the interpretation of the results.
    - Major surgery or radiological procedures (e.g. PTA (Percutaneous transluminal angioplasty) and stenting of peripheral vascular lesions in lower extremities) within 3 months before screening visit or scheduled during the study period, which might interfere pain response evaluation.
    - Symptomatic peripheral arterial disease in lower or upper extremities, including diabetic ulcers.
    - Previous use of strong opioids (e.g. oxymorphone, oxycodone) for neuropathic pain anytime, or topical use of capsaicin within 3 months prior to the screening visit.
    - History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for study participants.
    - Moderate-to-severe hepatic impairment defined as Child-Pugh Class B or C.
    - Have platelets ≤ 100 x 109/L, or neutrophil count < 1.2 x 109/L (or equivalent), hemoglobin ≤ 100 g/L for women or hemoglobin ≤ 110 g/L for men at screening.
    - Glycemic control unstable (hemoglobin HbA1c ≥11%) within 3 months prior to screening (e.g. ketoacidosis requiring hospitalization, any recent episode of hypoglycemia requiring assistance through medical intervention, uncontrolled hyperglycemia).
    - ALT >2xULN, or AST >2xULN, or total bilirubin greater than ULN, or alkaline phosphatase (AP) >2xULN, or INR greater than ULN (unless related to anticoagulation treatment) at screening.
    - Positive hepatitis B virus surface antigen (HBsAg) or positive hepatitis C virus antibodies (anti-HCV) and detection of mRNA (HCV-mRNA tested only if hepatitis C virus antibodies detected).
    - Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2 calculated by Modification of Diet in Renal Disease (MDRD) formula (local formulas will be used where applicable.
    - Uncontrolled hypertension despite optimal treatment with antihypertensive(s), indicated by a sitting systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg.

Trial summary

Enrollment Goal
154
Trial Dates
January 2021 - October 2021
Phase
Phase 2
Could I Receive a placebo
Yes
Products
Eliapixant (BAY1817080)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Aalborg UniversitetshospitalAalborg, 9000, Denmark
Completed
Steno Diabetes Center CopenhagenHerlev, 2730, Denmark
Completed
Holbæk SygehusHolbæk, 4300, Denmark
Withdrawn
Aarhus Universitetshospital, SkejbyAarhus N, 8200, Denmark
Withdrawn
ÖbackaklinikenHärnösand, 871 31, Sweden
Withdrawn
Center For Diabetes, Academic Specialist CenterStockholm, 113 65, Sweden
Withdrawn
Universitetssjukhuset LinköpingLinköping, 58185, Sweden
Withdrawn
ClinSmartUppsala, 752 37, Sweden
Terminated
Medect Clinical Trials ABStockholm, 11526, Sweden
Withdrawn
Universitätsklinikum AKH WienWien, 1090, Austria
Withdrawn
Zentrum f. klinische Studien Dr. Hanusch GmbHWien, 1060, Austria
Withdrawn
Klinik HietzingWien, 1130, Austria
Withdrawn
Medizinische Universität InnsbruckInnsbruck, 6020, Austria
Withdrawn
Landeskrankenhaus FeldkirchFeldkirch, 6807, Austria
Terminated
St. JosefskrankenhausHeidelberg, 69115, Germany
Withdrawn
Diabetespraxis Dr. BraunBerlin, 13187, Germany
Terminated
InnoDiab Forschung GmbHEssen, 45136, Germany
Withdrawn
Private Diabetologik Praxis Dr. Täschner / Dr. BonigutLeipzig, 04249, Germany
Terminated
Praxis Hr. Dr. med. Jens TaggeselleMarkkleeberg, 04416, Germany
Terminated
Siteworks GmbHHannover, 30449, Germany
Terminated
DKD Helios Klinik WiesbadenWiesbaden, 65191, Germany
Terminated
Friedrich-Schiller-Uni. JenaJena, 07747, Germany
Completed
Instytut Diabetologii w WarszawieWarszawa, 02-117, Poland
Completed
Diamond Clinic Specjalistyczne Poradnie LekarskieKrakow, 31-559, Poland
Completed
LANDA - Specjalist. Gabinety LekarskieKrakow, 31-156, Poland
Completed
Centrum Badan Klinicznych PI-HouseGdansk, 80-546, Poland
Withdrawn
Twoja Przychodnia-Centrum Medyczne Nowa SolNowa Sol, 67-100, Poland
Completed
Futuremeds sp. z o. o.Wroclaw, 50-088, Poland
Completed
Vita Longa Sp. z o.o.Katowice, 40-748, Poland
Withdrawn
PTC-Primary care Trial CenterGöteborg, 413 45, Sweden
Completed
Kolding SygehusKolding, 6000, Denmark
Withdrawn
Sykehuset Innlandet HF HamarHamar, 2326, Norway
Terminated
Oslo universitetssykehus HF, AkerOslo, 0586, Norway
Terminated
AKTIMED Helse ASHamar, 2317, Norway
Terminated
Oslo Universitetssykehus HF, UllevålOslo, 0450, Norway
Terminated
Diabetologicka a endokrinologicka ambulance, Milan KvapilPraha 4, 149 00, Czechia
Terminated
Clintrial s.r.o.Praha 10, 101 00, Czechia
Terminated
Diabet2, s.r.o.Praha 1, 110 00, Czechia
Terminated
Vestra Clinics s.r.o.Rychnov nad Kneznou, 516 01, Czechia
Terminated
Diabetologicka a endokrinologicka ambulance, Milan Kvapil,Pribram, 261 01, Czechia
Terminated
NEUROHK s.r.oChocen, 565 01, Czechia
Withdrawn
ClinDiab Kft.Budapest, 1089, Hungary
Completed
COROMED SMO KFTPecs, 7623, Hungary
Withdrawn
Belinus Bt.Debrecen, 4025, Hungary
Withdrawn
SZTE ÁOK Szent Györgyi Albert Klinikai KozpontSzeged, 6720, Hungary
Withdrawn
Kanizsai Dorottya HospitalNagykanizsa, 8800, Hungary
Terminated
MEDISPEKTRUM s.r.o.Bratislava, 851 04, Slovakia
Withdrawn
Fakultna nemocnica AGEL Skalica, a.s.Skalica, 909 82, Slovakia
Terminated
KONZILIUM s.r.o.Dubnica nad Vahom, 018 41, Slovakia
Terminated
Liptovska nemocnica s poliklinikou MUDr. Ivana StodoluLiptovsky Mikulas, 03123, Slovakia
Terminated
Tatratrial s. r. o.Roznava, 04801, Slovakia
Terminated
NEURES, s.r.o.Krompachy, 053 42, Slovakia
Terminated
Hopital Ambroise PareBoulogne billancourt, 92104, France
Withdrawn
Cochin - ParisPARIS, 75674, France
Terminated
Hopital Carémeau - NîmesNIMES cedex 9, 30029, France
Terminated
Hôpital François Mitterrand - DijonDIJON, 21000, France
Terminated
Hôpital Lariboisière - ParisPARIS, 75475, France
Terminated
emovis GmbHBerlin, 10629, Germany
Terminated
Medamed Studienambulanz GmbHLeipzig, 04315, Germany
Terminated
Tampereen yliopistollinen sairaala, keskussairaalaTampere, 33520, Finland
Terminated
Turun yliopistollinen keskussairaalaTurku, 20520, Finland
Terminated
Health Step Finland OyKuopio, 70100, Finland
Terminated
Diagnos Klaukkalan LääkäriasemaKlaukkala, 01800, Finland
Withdrawn
PRAGLANDIAPraha 5, 150 00, Czechia
Withdrawn
VFN, Fakultni poliklinikaPraha 2, 128 08, Czechia
Withdrawn
Nemocnice Pardubickeho kraje, a.s., Pardubicka nemocnicePardubice, 530 03, Czechia
Withdrawn
DPCKh Orszagos Hematologiai es Infektologiai IntezetBudapest, 1097, Hungary
Withdrawn
Obudai Egeszsegugyi CentrumBudapest, 1036, Hungary
Withdrawn
Trial Pharma Kft.Gyula, 5700, Hungary
Withdrawn
Trial Pharma Kft.Bekescsaba, 5600, Hungary
Withdrawn
Trial Pharma Kft.Oroshaza, 5900, Hungary
Withdrawn
DIABEDA s.r.o.Bratislava, 83106, Slovakia
Withdrawn
MEDI-DIA s.r.o.Sabinov, 08301, Slovakia
Withdrawn
Fakultna nemocnica NitraNitra, 949 01, Slovakia
Withdrawn
Osaka General Medical CenterOsaka, 558-8558, Japan
Withdrawn
Meitetsu HospitalNagoya, 451-8511, Japan
Withdrawn
Dokkyo Medical University HospitalShimotsuga-gun, 321-0293, Japan
Withdrawn
Japan Red Cross Society Azumino HospitalAzumino, 399-8292, Japan
Withdrawn
Jiyugaoka YAMADA ClinicObihiro, 080-0848, Japan
Withdrawn
Seino Internal Medicine ClinicKoriyama, 963-8851, Japan
Withdrawn
Saiki Central HospitalSaiki, 876-0851, Japan
Withdrawn
Kyosokai AMC NISHI-UMEDA ClinicOsaka, 530-0001, Japan
Withdrawn
Nakakinen ClinicNaka, 311-0113, Japan
Withdrawn
Fukuoka Wajiro HospitalFukuoka, 811-0213, Japan
Withdrawn
Kagoshima University HospitalKagoshima, 890-8520, Japan
Withdrawn
Otsu City HospitalOtsu, 520-0804, Japan
Withdrawn
Nakayama ClinicNagoya, 456-0058, Japan
Withdrawn
Asahikawa City HospitalAsahikawa, 070-8610, Japan
Withdrawn
Nagano Municipal HospitalNagano, 381-8551, Japan
Withdrawn
Yokohama City Minato Red Cross HospitalYokohama, 231-8682, Japan
Withdrawn
Kunisaki Makoto ClinicFukuoka, 819-0168, Japan
Withdrawn
JCHO Shimonoseki Medical CenterShimonoseki, 750-0061, Japan
Withdrawn
Hôpital Gabriel Montpied - Clermont FerrandCLERMONT FERRAND, 63000, France
Withdrawn
Avdelningen för kliniska prövningar AKPÖrebro, 703 62, Sweden

Primary Outcome

  • Change in weekly mean 24-hour average pain intensity score using the 11-point Numeric Rating Scale (NRS) from baseline to the end of intervention
    NRS is an one-item assessment of average neuropathic pain intensity which is presented as an 11-point Likert scale with 0 as “no pain” and 10 as “worst imaginable pain”.
    date_rangeTime Frame:
    Part A: from baseline to end of intervention (in total up to 9 weeks)
  • Change in weekly mean 24-hour average pain intensity score using the 11-point Numeric Rating Scale (NRS) from baseline to the end of intervention
    NRS is an one-item assessment of average neuropathic pain intensity which is presented as an 11-point Likert scale with 0 as “no pain” and 10 as “worst imaginable pain”.
    date_rangeTime Frame:
    Part B: from baseline to end of intervention (in total up to 13 weeks)

Secondary Outcome

  • Change in Neuropathic Pain Symptom Inventory (NPSI) score from baseline to the end of intervention
    The Neuropathic Pain Symptom Inventory (NPSI) is a PRO developed to evaluate different symptoms of neuropathic pain.
    date_rangeTime Frame:
    Part A: at visit 2, visit 4 (day 15 +/- 2), visit 5 (day 29 +/-2) and visit 7 EOI (day 57 +/-2). Part B: at visit 2, visit 4 (day 15 +/- 2), visit 5 (day 29 +/-2), visit 7 (day 57 +/-2) and visit 8 EOI (day 85 +/-2).
  • Patient Global Impression of Change (PGI-C) at the end of intervention
    The PGI-C is an one-item, self-reported instrument used to assess patients’ impression of disease severity and change, with a 7-point scale response-option. Scores range from 1 (“very much better”) to 7 (“very much worse”).
    date_rangeTime Frame:
    Part A: at visit 5 (day 29 +/-2) and at end of intervention (day 57 +/- 2). Part B: at visit 5 (day 29 +/-2), at visit 7 (day 57 +/- 2) and at end of intervention (day 85 +/-2)
  • The proportion of participants achieving a ≥30% and a ≥50% reduction in weekly mean 24-hour average pain intensity score (i.e. responder rates using NRS)
    date_rangeTime Frame:
    Part A: from baseline to end of intervention (in total up to 9 weeks). Part B: from baseline to end of intervention (in total up to 13 weeks)
  • Number of participants with treatment emergent adverse events (TEAE)
    date_rangeTime Frame:
    Start of intervention to 14 days after stop of treatment

Trial design

A randomized, placebo-controlled, double-blind, parallel-group, multicenter combined Phase 2a/2b study to assess the efficacy and safety of BAY 1817080 in patients with diabetic neuropathic pain
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
N/A
Assignment
Parallel Assignment
Trial Arms
7