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

NCT04641273 | Terminated Phase 2

• 2 other identifiers: 208872020-002066-14
• Study Type: interventional
• Target: 154
• Locations: 10 countries
• Sites: 42

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

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (4)

• Change in Neuropathic Pain Symptom Inventory (NPSI) score from baseline to the end of intervention

  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

  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)

  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)

  Start of intervention to 14 days after stop of treatment

Study Arms (7)

Part A: BAY1817080 150 mg BID

EXPERIMENTAL

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

Drug: BAY1817080

Part A: Placebo BID

PLACEBO COMPARATOR

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

Drug: Placebo for BAY1817080

Part B: BAY1817080 25 mg BID

EXPERIMENTAL

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.

Drug: BAY1817080; Drug: Placebo for Pregabalin

Part B: BAY1817080 75 mg BID

EXPERIMENTAL

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.

Drug: BAY1817080; Drug: Placebo for Pregabalin

Part B: BAY1817080 150 mg BID

EXPERIMENTAL

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.

Drug: BAY1817080; Drug: Placebo for Pregabalin

Part B: Placebo BID

PLACEBO COMPARATOR

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.

Drug: Placebo for BAY1817080; Drug: Placebo for Pregabalin

Part B: Pregabalin

ACTIVE COMPARATOR

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.

Drug: Placebo for BAY1817080; Drug: Pregabalin

Interventions

BAY1817080 DRUG

Tablet, intake orally.

Part A: BAY1817080 150 mg BID; Part B: BAY1817080 150 mg BID; Part B: BAY1817080 25 mg BID; Part B: BAY1817080 75 mg BID

Placebo for BAY1817080 DRUG

Tablet, intake orally.

Part A: Placebo BID; Part B: Placebo BID; Part B: Pregabalin

Placebo for Pregabalin DRUG

Capsule, intake orally.

Part B: BAY1817080 150 mg BID; Part B: BAY1817080 25 mg BID; Part B: BAY1817080 75 mg BID; Part B: Placebo BID

Pregabalin DRUG

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

Part B: Pregabalin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (42)

NEUROHK s.r.o

Choceň, 565 01, Czechia

Location

Clintrial s.r.o.

Prague, 101 00, Czechia

Location

Diabet2, s.r.o.

Prague, 110 00, Czechia

Location

Diabetologicka a endokrinologicka ambulance, Milan Kvapil

Prague, 149 00, Czechia

Location

Diabetologicka a endokrinologicka ambulance, Milan Kvapil,

Příbram, 261 01, Czechia

Location

Vestra Clinics s.r.o.

Rychnov nad Kněžnou, 516 01, Czechia

Location

Aalborg Universitetshospital

Aalborg, 9000, Denmark

Location

Steno Diabetes Center Copenhagen

Herlev, 2730, Denmark

Location

Holbæk Sygehus

Holbæk, 4300, Denmark

Location

Kolding Sygehus

Kolding, 6000, Denmark

Location

Diagnos Klaukkalan Lääkäriasema

Klaukkala, 01800, Finland

Location

Health Step Finland Oy

Kuopio, 70100, Finland

Location

Tampereen yliopistollinen sairaala, keskussairaala

Tampere, 33520, Finland

Location

Turun yliopistollinen keskussairaala

Turku, 20520, Finland

Location

Hopital Ambroise Pare

Boulogne-Billancourt, 92104, France

Location

Hôpital François Mitterrand - Dijon

Dijon, 21000, France

Location

Hopital Carémeau - Nîmes

Nîmes, 30029, France

Location

Hôpital Lariboisière - Paris

Paris, 75475, France

Location

St. Josefskrankenhaus

Heidelberg, Baden-Wurttemberg, 69115, Germany

Location

Siteworks GmbH

Hanover, Lower Saxony, 30449, Germany

Location

InnoDiab Forschung GmbH

Essen, North Rhine-Westphalia, 45136, Germany

Location

Medamed Studienambulanz GmbH

Leipzig, Saxony, 04315, Germany

Location

Praxis Hr. Dr. med. Jens Taggeselle

Markkleeberg, Saxony, 04416, Germany

Location

Friedrich-Schiller-Uni. Jena

Jena, Thuringia, 07747, Germany

Location

emovis GmbH

Berlin, 10629, Germany

Location

DKD Helios Klinik Wiesbaden

Wiesbaden, 65191, Germany

Location

Coromed Smo Kft

Pécs, 7623, Hungary

Location

AKTIMED Helse AS

Hamar, 2317, Norway

Location

Oslo Universitetssykehus HF, Ullevål

Oslo, 0450, Norway

Location

Oslo universitetssykehus HF, Aker

Oslo, 0586, Norway

Location

Centrum Badan Klinicznych PI-House

Gdansk, 80-546, Poland

Location

Vita Longa Sp. z o.o.

Katowice, 40-748, Poland

Location

LANDA - Specjalist. Gabinety Lekarskie

Krakow, 31-156, Poland

Location

Diamond Clinic Specjalistyczne Poradnie Lekarskie

Krakow, 31-559, Poland

Location

Instytut Diabetologii w Warszawie

Warsaw, 02-117, Poland

Location

Futuremeds sp. z o. o.

Wroclaw, 50-088, Poland

Location

MEDISPEKTRUM s.r.o.

Bratislava, 851 04, Slovakia

Location

KONZILIUM s.r.o.

Dubnica nad Váhom, 018 41, Slovakia

Location

NEURES, s.r.o.

Krompachy, 053 42, Slovakia

Location

Liptovska nemocnica s poliklinikou MUDr. Ivana Stodolu

Liptovský Mikuláš, 03123, Slovakia

Location

Tatratrial s. r. o.

Rožňava, 04801, Slovakia

Location

Medect Clinical Trials AB

Stockholm, 11526, Sweden

Location

Related Publications (2)

• 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.

  PMID: 37851336 DERIVED

• 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.

  PMID: 34978027 DERIVED

Related Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

MeSH Terms

Conditions

Neuralgia; Diabetic Neuropathies

Interventions

Pregabalin

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2020
• First Posted: November 23, 2020
• Study Start: January 22, 2021
• Primary Completion: September 23, 2021
• Study Completion: October 18, 2021
• Last Updated: December 12, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8); FI (4); FR (4); HU (1); NO (3); PL (6); SL (5); SE (1); DK (4); CZ (6)