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

NCT ID: NCT04641273

Last Updated: 2022-12-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-22
• Study Completion Date: 2021-10-18

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.

Conditions

Neuropathic Pain Associated With Diabetic Peripheral Neuropathy

Keywords

Diabetic Neuropathic Pain; Neuropathic Pain; Diabetic Polyneuropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part B: BAY1817080 150 mg BID

In Part B, New participants will be screened for this part of the study and will be randomized to this arm with BAY1817080 150 mg BID and placebo for pregabalin.

Group Type: EXPERIMENTAL

BAY1817080

Intervention Type: DRUG

Tablet, intake orally.

Placebo for Pregabalin

Intervention Type: DRUG

Capsule, intake orally.

Part B: Placebo BID

In Part B, New participants will be screened for this part of the study and will be randomized to this arm with placebo for BAY1817080 and placebo for pregabalin.

Group Type: PLACEBO_COMPARATOR

Placebo for BAY1817080

Intervention Type: DRUG

Tablet, intake orally.

Placebo for Pregabalin

Intervention Type: DRUG

Capsule, intake orally.

Part B: Pregabalin

In Part B, New participants will be screened for this part of the study and will be randomized to this arm with placebo for BAY1817080 and pregabalin.

Group Type: ACTIVE_COMPARATOR

Placebo for BAY1817080

Intervention Type: DRUG

Tablet, intake orally.

Pregabalin

Intervention Type: DRUG

Capsule, intake orally. Starting dose 75 mg BID first week, increase to 150 mg BID in second week.

Part A: BAY1817080 150 mg BID

In Part A, Participants will be randomized to this arm with BAY1817080 150 mg BID.

Group Type: EXPERIMENTAL

BAY1817080

Intervention Type: DRUG

Tablet, intake orally.

Part A: Placebo BID

In Part A, Participants will be randomized to this arm with placebo for BAY1817080.

Group Type: PLACEBO_COMPARATOR

Placebo for BAY1817080

Intervention Type: DRUG

Tablet, intake orally.

Part B: BAY1817080 25 mg BID

In Part B, New participants will be screened for this part of the study and will be randomized to this arm with BAY1817080 25 mg BID and placebo for pregabalin.

Group Type: EXPERIMENTAL

BAY1817080

Intervention Type: DRUG

Tablet, intake orally.

Placebo for Pregabalin

Intervention Type: DRUG

Capsule, intake orally.

Part B: BAY1817080 75 mg BID

In Part B, New participants will be screened for this part of the study and will be randomized to this arm with BAY1817080 75 mg BID and placebo for pregabalin.

Group Type: EXPERIMENTAL

BAY1817080

Intervention Type: DRUG

Tablet, intake orally.

Placebo for Pregabalin

Intervention Type: DRUG

Capsule, intake orally.

Interventions

BAY1817080

Tablet, intake orally.

Intervention Type: DRUG

Placebo for BAY1817080

Tablet, intake orally.

Intervention Type: DRUG

Placebo for Pregabalin

Capsule, intake orally.

Intervention Type: DRUG

Pregabalin

Capsule, intake orally. Starting dose 75 mg BID first week, increase to 150 mg BID in second week.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

NEUROHK s.r.o

Choceň, , Czechia

Clintrial s.r.o.

Prague, , Czechia

Diabet2, s.r.o.

Prague, , Czechia

Diabetologicka a endokrinologicka ambulance, Milan Kvapil

Prague, , Czechia

Diabetologicka a endokrinologicka ambulance, Milan Kvapil,

Příbram, , Czechia

Vestra Clinics s.r.o.

Rychnov nad Kněžnou, , Czechia

Aalborg Universitetshospital

Aalborg, , Denmark

Steno Diabetes Center Copenhagen

Herlev, , Denmark

Holbæk Sygehus

Holbæk, , Denmark

Kolding Sygehus

Kolding, , Denmark

Diagnos Klaukkalan Lääkäriasema

Klaukkala, , Finland

Health Step Finland Oy

Kuopio, , Finland

Tampereen yliopistollinen sairaala, keskussairaala

Tampere, , Finland

Turun yliopistollinen keskussairaala

Turku, , Finland

Hopital Ambroise Pare

Boulogne-Billancourt, , France

Hôpital François Mitterrand - Dijon

Dijon, , France

Hopital Carémeau - Nîmes

Nîmes, , France

Hôpital Lariboisière - Paris

Paris, , France

St. Josefskrankenhaus

Heidelberg, Baden-Wurttemberg, Germany

Siteworks GmbH

Hanover, Lower Saxony, Germany

InnoDiab Forschung GmbH

Essen, North Rhine-Westphalia, Germany

Medamed Studienambulanz GmbH

Leipzig, Saxony, Germany

Praxis Hr. Dr. med. Jens Taggeselle

Markkleeberg, Saxony, Germany

Friedrich-Schiller-Uni. Jena

Jena, Thuringia, Germany

emovis GmbH

Berlin, , Germany

DKD Helios Klinik Wiesbaden

Wiesbaden, , Germany

Coromed Smo Kft

Pécs, , Hungary

AKTIMED Helse AS

Hamar, , Norway

Oslo Universitetssykehus HF, Ullevål

Oslo, , Norway

Oslo universitetssykehus HF, Aker

Oslo, , Norway

Centrum Badan Klinicznych PI-House

Gdansk, , Poland

Vita Longa Sp. z o.o.

Katowice, , Poland

LANDA - Specjalist. Gabinety Lekarskie

Krakow, , Poland

Diamond Clinic Specjalistyczne Poradnie Lekarskie

Krakow, , Poland

Instytut Diabetologii w Warszawie

Warsaw, , Poland

Futuremeds sp. z o. o.

Wroclaw, , Poland

MEDISPEKTRUM s.r.o.

Bratislava, , Slovakia

KONZILIUM s.r.o.

Dubnica nad Váhom, , Slovakia

NEURES, s.r.o.

Krompachy, , Slovakia

Liptovska nemocnica s poliklinikou MUDr. Ivana Stodolu

Liptovský Mikuláš, , Slovakia

Tatratrial s. r. o.

Rožňava, , Slovakia

Medect Clinical Trials AB

Stockholm, , Sweden

Countries

Austria; Japan; Czechia; Denmark; Finland; France; Germany; Hungary; Norway; Poland; Slovakia; Sweden

References

Bouhassira D, Tesfaye S, Sarkar A, Soisalon-Soininen S, Stemper B, Baron R. Efficacy and safety of eliapixant in diabetic neuropathic pain and prediction of placebo responders with an exploratory novel algorithm: results from the randomized controlled phase 2a PUCCINI study. Pain. 2024 Apr 1;165(4):785-795. doi: 10.1097/j.pain.0000000000003085. Epub 2023 Oct 18.

Reference Type: DERIVED

PMID: 37851336 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34978027 (View on PubMed)

Related Links

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Other Identifiers

2020-002066-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20887

Identifier Type: -

Identifier Source: org_study_id