Clinical trial NCT04641273: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
Keywords: Diabetic Neuropathic Pain
Neuropathic Pain
Diabetic Polyneuropathy
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-11-23
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 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
timeFrame: Part A: from baseline to end of intervention (in total up to 9 weeks)
measure: 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
timeFrame: Part B: from baseline to end of intervention (in total up to 13 weeks)
Secondary outcomes:
measure: Change in Neuropathic Pain Symptom Inventory (NPSI) score from baseline to the end of intervention
timeFrame: 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).
measure: Patient Global Impression of Change (PGI-C) at the end of intervention
timeFrame: 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)
measure: 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)
timeFrame: 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)
measure: Number of participants with treatment emergent adverse events (TEAE)
timeFrame: Start of intervention to 14 days after stop of treatment
Other outcomes:
Locations:
city: Chocen
country: Czechia
facility: NEUROHK s.r.o
city: Praha 10
country: Czechia
facility: Clintrial s.r.o.
city: Praha 1
country: Czechia
facility: Diabet2, s.r.o.
city: Praha 4
country: Czechia
facility: Diabetologicka a endokrinologicka ambulance, Milan Kvapil
city: Pribram
country: Czechia
facility: Diabetologicka a endokrinologicka ambulance, Milan Kvapil,
city: Rychnov nad Kneznou
country: Czechia
facility: Vestra Clinics s.r.o.
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
city: Herlev
country: Denmark
facility: Steno Diabetes Center Copenhagen
city: Holbæk
country: Denmark
facility: Holbæk Sygehus
city: Kolding
country: Denmark
facility: Kolding Sygehus
city: Klaukkala
country: Finland
facility: Diagnos Klaukkalan Lääkäriasema
city: Kuopio
country: Finland
facility: Health Step Finland Oy
city: Tampere
country: Finland
facility: Tampereen yliopistollinen sairaala, keskussairaala
city: Turku
country: Finland
facility: Turun yliopistollinen keskussairaala
city: Boulogne billancourt
country: France
facility: Hopital Ambroise Pare
city: Dijon
country: France
facility: Hôpital François Mitterrand - Dijon
city: NIMES cedex 9
country: France
facility: Hopital Carémeau - Nîmes
city: Paris
country: France
facility: Hôpital Lariboisière - Paris
city: Heidelberg
country: Germany
facility: St. Josefskrankenhaus
state: Baden-Württemberg
city: Hannover
country: Germany
facility: Siteworks GmbH
state: Niedersachsen
city: Essen
country: Germany
facility: InnoDiab Forschung GmbH
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Medamed Studienambulanz GmbH
state: Sachsen
city: Markkleeberg
country: Germany
facility: Praxis Hr. Dr. med. Jens Taggeselle
state: Sachsen
city: Jena
country: Germany
facility: Friedrich-Schiller-Uni. Jena
state: Thüringen
city: Berlin
country: Germany
facility: emovis GmbH
city: Wiesbaden
country: Germany
facility: DKD Helios Klinik Wiesbaden
city: Pecs
country: Hungary
facility: Coromed Smo Kft
city: Hamar
country: Norway
facility: AKTIMED Helse AS
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Ullevål
city: Oslo
country: Norway
facility: Oslo universitetssykehus HF, Aker
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych PI-House
city: Katowice
country: Poland
facility: Vita Longa Sp. z o.o.
city: Krakow
country: Poland
facility: LANDA - Specjalist. Gabinety Lekarskie
city: Krakow
country: Poland
facility: Diamond Clinic Specjalistyczne Poradnie Lekarskie
city: Warszawa
country: Poland
facility: Instytut Diabetologii w Warszawie
city: Wroclaw
country: Poland
facility: Futuremeds sp. z o. o.
city: Bratislava
country: Slovakia
facility: MEDISPEKTRUM s.r.o.
city: Dubnica nad Vahom
country: Slovakia
facility: KONZILIUM s.r.o.
city: Krompachy
country: Slovakia
facility: NEURES, s.r.o.
city: Liptovsky Mikulas
country: Slovakia
facility: Liptovska nemocnica s poliklinikou MUDr. Ivana Stodolu
city: Roznava
country: Slovakia
facility: Tatratrial s. r. o.
city: Stockholm
country: Sweden
facility: Medect Clinical Trials AB
Study officials:
References:
citation: Fletcher MC. Selectivity of the P2X3 receptor antagonist Eliapixant, and its potential use in the treatment of endometriosis. Purinergic Signal. 2022 Mar;18(1):1-3. doi: 10.1007/s11302-021-09831-5. Epub 2022 Jan 3. No abstract available.