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

Neuropathic Pain Associated With Diabetic Peripheral Neuropathy Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04641273
• Other study ID #: 20887
• Secondary ID: 2020-002066-14
• Status: Terminated
• Phase: Phase 2
• Start date: January 22, 2021
• Est. completion date: October 18, 2021

Study information

• Verified date: December 2022
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 154
• Est. completion date: October 18, 2021
• Est. primary completion date: September 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
• Peripheral Nervous System Diseases

Intervention

Drug:
• BAY1817080
Tablet, intake orally.
• Placebo for BAY1817080
Tablet, intake orally.
• Placebo for Pregabalin
Capsule, intake orally.
• Pregabalin
Capsule, intake orally. Starting dose 75 mg BID first week, increase to 150 mg BID in second week.

Locations

Country	Name	City	State
Czechia	NEUROHK s.r.o	Chocen
Czechia	Diabet2, s.r.o.	Praha 1
Czechia	Clintrial s.r.o.	Praha 10
Czechia	Diabetologicka a endokrinologicka ambulance, Milan Kvapil	Praha 4
Czechia	Diabetologicka a endokrinologicka ambulance, Milan Kvapil,	Pribram
Czechia	Vestra Clinics s.r.o.	Rychnov nad Kneznou
Denmark	Aalborg Universitetshospital	Aalborg
Denmark	Steno Diabetes Center Copenhagen	Herlev
Denmark	Holbæk Sygehus	Holbæk
Denmark	Kolding Sygehus	Kolding
Finland	Diagnos Klaukkalan Lääkäriasema	Klaukkala
Finland	Health Step Finland Oy	Kuopio
Finland	Tampereen yliopistollinen sairaala, keskussairaala	Tampere
Finland	Turun yliopistollinen keskussairaala	Turku
France	Hopital Ambroise Pare	Boulogne billancourt
France	Hôpital François Mitterrand - Dijon	Dijon
France	Hopital Carémeau - Nîmes	NIMES cedex 9
France	Hôpital Lariboisière - Paris	Paris
Germany	emovis GmbH	Berlin
Germany	InnoDiab Forschung GmbH	Essen	Nordrhein-Westfalen
Germany	Siteworks GmbH	Hannover	Niedersachsen
Germany	St. Josefskrankenhaus	Heidelberg	Baden-Württemberg
Germany	Friedrich-Schiller-Uni. Jena	Jena	Thüringen
Germany	Medamed Studienambulanz GmbH	Leipzig	Sachsen
Germany	Praxis Hr. Dr. med. Jens Taggeselle	Markkleeberg	Sachsen
Germany	DKD Helios Klinik Wiesbaden	Wiesbaden
Hungary	Coromed Smo Kft	Pecs
Norway	AKTIMED Helse AS	Hamar
Norway	Oslo universitetssykehus HF, Aker	Oslo
Norway	Oslo Universitetssykehus HF, Ullevål	Oslo
Poland	Centrum Badan Klinicznych PI-House	Gdansk
Poland	Vita Longa Sp. z o.o.	Katowice
Poland	Diamond Clinic Specjalistyczne Poradnie Lekarskie	Krakow
Poland	LANDA - Specjalist. Gabinety Lekarskie	Krakow
Poland	Instytut Diabetologii w Warszawie	Warszawa
Poland	Futuremeds sp. z o. o.	Wroclaw
Slovakia	MEDISPEKTRUM s.r.o.	Bratislava
Slovakia	KONZILIUM s.r.o.	Dubnica nad Vahom
Slovakia	NEURES, s.r.o.	Krompachy
Slovakia	Liptovska nemocnica s poliklinikou MUDr. Ivana Stodolu	Liptovsky Mikulas
Slovakia	Tatratrial s. r. o.	Roznava
Sweden	Medect Clinical Trials AB	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

Czechia,  Denmark,  Finland,  France,  Germany,  Hungary,  Norway,  Poland,  Slovakia,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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".	Part A: from baseline to end of intervention (in total up to 9 weeks)
Primary	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".	Part B: from baseline to end of intervention (in total up to 13 weeks)
Secondary	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.	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).
Secondary	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").	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)
Secondary	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)		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)
Secondary	Number of participants with treatment emergent adverse events (TEAE)		Start of intervention to 14 days after stop of treatment

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