Safety and Efficacy of EMA401 in Patients With Painful Diabetic Neuropathy (PDN)

NCT03297294 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: CEMA401A22022016-000281-39
• Study Type: interventional
• Target: 142
• Locations: 15 countries
• Sites: 60

Brief Summary

The purpose of this study is to evaluate safety and efficacy of EMA401 compared to placebo in patients with painful diabetic neuropathy (PDN).

Conditions

Painful Diabetic Neuropathy

Keywords

Painful diabetic neuropathy; Neuropathic pain; Angiotensin II type 2 receptor antagonist; adult; EMA401; diabetic neuropathy

Outcome Measures

Primary Outcomes (1)

• Change in Weekly Mean 24-hour Average Pain Score Using the 11 Point Numerical Rating Scale (NRS) From Baseline to Week 12

  The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. The following parameters were evaluated using the 11-point NRS: 24-hour Average Pain Score and 24-hour Worst Pain Score Patients evaluated their "average pain" and "worst pain" during the past 24 hours in the evening prior to sleep by touching the appropriate corresponding number between zero and ten on a eDiary device.

  Baseline up to Week 12

Secondary Outcomes (12)

• Change in Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 12

  Baseline up to Week 12

• Change in Brief Pain Inventory-Short Form Interference (BPI-SF) Mean Total Score From Baseline to Week 12

  Baseline up to Week 12

• Change in Weekly Mean of the 24-hour Worst Pain Score, Using an 11-point NRS, From Baseline to Week 12

  Baseline up to Week 12

• Number of Participants Per Patient Global Impression of Change Category at Week 12

  Baseline up to Week 12

• Percentage of Patients Achieving at Least 30% Pain Reduction at Week 12 on NRS 11 Point Scale

  Baseline up to Week 12

Study Arms (2)

EMA401

EXPERIMENTAL

During the treatment epoch, patients will receive EMA401 for 12 weeks. During the treatment withdrawal epoch, patients will receive EMA401 or matching placebo for 1 week.

Drug: EMA401; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo to EMA401 during both the treatment and treatment withdrawal epochs for a total of 13 weeks.

Drug: Placebo

Interventions

EMA401 DRUG

capsules, oral

EMA401

Placebo DRUG

Placebo to EMA401 capsules, oral

EMA401; Placebo

Eligibility Criteria

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

You may qualify if:

• At the time of Screening, must have had documented diagnosis of Type I OR Type II diabetes mellitus (DM) with painful distal symmetrical sensorimotor neuropathy (ICD-10 code G63.2) of more than 6 months duration with any one or more of the following:
• Neuropathic symptoms (e.g. numbness, non-painful paresthesias or tingling, non-painful sensory distortions or misinterpretations, etc.)
• Decreased distal sensation (e.g. decreased vibration, pinprick sensation, light touch, etc.)
• Been assessed as suffering from moderate to severe neuropathic pain across the Screening epoch (NRS ≥ 4).
• A score of ≥4 on the Douleur Neuropathique en 4 Questions (DN4) questionnaire at Screening.

You may not qualify if:

• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using highly effective methods of contraception during dosing and for 3 days after stopping of study medication. Highly effective contraception methods included:
• Total abstinence (when this was is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal were not acceptable methods of contraception.
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman had been confirmed by follow up hormone level assessment.
• Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should have been the sole partner for that subject.
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).
• History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the study.
• Major depressive episode within 6 months prior to Screening and/or a history of diagnosed recurrent major depressive disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) diagnostic criteria.
• Had evidence of significant renal insufficiency or pre-existing liver condition.
• Had platelets ≤ 100 x 10\^9/L, or neutrophil count \< 1.2 x 10\^9/L (or equivalent), hemoglobin ≤ 100 g/L for women or hemoglobin ≤ 110 g/L for men.
• Participants whose glycemic control had been unstable within 3 months immediately prior to screening (e.g., ketoacidosis requiring hospitalization, any recent episode of hypoglycemia requiring assistance through medical intervention, uncontrolled hyperglycemia)
• Patients who had any differential diagnosis of 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).
• Patient was unwilling or unable to complete daily eDiary.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (64)

Novartis Investigative Site

Broadmeadow, New South Wales, 2292, Australia

Location

Novartis Investigative Site

Orange, New South Wales, 2800, Australia

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Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

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Novartis Investigative Site

Heidelberg Heights, Victoria, 3081, Australia

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Novartis Investigative Site

Graz, A-8036, Austria

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Novartis Investigative Site

Klagenfurt, 9020, Austria

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Novartis Investigative Site

Vienna, A-1090, Austria

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Novartis Investigative Site

Edegem, 2650, Belgium

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Novartis Investigative Site

Liège, 4000, Belgium

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Novartis Investigative Site

Pellenberg, 3212, Belgium

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Novartis Investigative Site

Sofia, Sofia-Grad, 1336, Bulgaria

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Novartis Investigative Site

Sofia, 1000, Bulgaria

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Novartis Investigative Site

Sofia, 1407, Bulgaria

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Novartis Investigative Site

Sofia, 1431, Bulgaria

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Novartis Investigative Site

Ontario, CAN, L4J 1W3, Canada

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Novartis Investigative Site

Thornhill, Ontario, L4J 8L7, Canada

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Novartis Investigative Site

Toronto, Ontario, M4G 3E8, Canada

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Novartis Investigative Site

Laval, Quebec, H7T 2P5, Canada

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Novartis Investigative Site

Aarhus, 8000, Denmark

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Novartis Investigative Site

Gentofte Municipality, DK 2820, Denmark

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Novartis Investigative Site

Odense C, DK 5000, Denmark

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Novartis Investigative Site

Tampere, FIN-33520, Finland

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Novartis Investigative Site

Boulogne-Billancourt, 92104, France

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Novartis Investigative Site

Bielefeld, D 33647, Germany

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Novartis Investigative Site

Düsseldorf, 40225, Germany

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Novartis Investigative Site

Essen, 45147, Germany

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Novartis Investigative Site

Halle, 06120, Germany

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Novartis Investigative Site

Kassel, Germany

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Novartis Investigative Site

Kiel, 24119, Germany

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Novartis Investigative Site

Leipzig, 04109, Germany

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Novartis Investigative Site

Wiesbaden, 65191, Germany

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Novartis Investigative Site

Debrecen, HUN, 4032, Hungary

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Novartis Investigative Site

Esztergom, HUN, 2500, Hungary

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Novartis Investigative Site

Szeged, HUN, 6720, Hungary

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Novartis Investigative Site

Balatonfüred, 8230, Hungary

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Novartis Investigative Site

Budapest, 1085, Hungary

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Novartis Investigative Site

Budapest, 1089, Hungary

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Novartis Investigative Site

Kistarcsa, 2143, Hungary

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Novartis Investigative Site

Pécs, 7632, Hungary

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Novartis Investigative Site

Szeged, 6725, Hungary

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Novartis Investigative Site

Oslo, 0450, Norway

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Novartis Investigative Site

Krakow, POL, 31 505, Poland

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Novartis Investigative Site

Bialystok, 15-351, Poland

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Novartis Investigative Site

Warsaw, 00 144, Poland

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Novartis Investigative Site

Caldas da Rainha, 2500 176, Portugal

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Novartis Investigative Site

Lisbon, 1250 203, Portugal

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Novartis Investigative Site

Matosinhos Municipality, 4454 509, Portugal

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Novartis Investigative Site

Porto, 4200 319, Portugal

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Novartis Investigative Site

Viana do Castelo, 4901858, Portugal

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Novartis Investigative Site

Vila Nova de Gaia, 4434 502, Portugal

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Novartis Investigative Site

Lučenec, Slovak Republic, 98401, Slovakia

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Novartis Investigative Site

Bratislava, 83305, Slovakia

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Novartis Investigative Site

Bratislava, 85101, Slovakia

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Novartis Investigative Site

Prešov, 080 01, Slovakia

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Novartis Investigative Site

Prešov, 08001, Slovakia

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Novartis Investigative Site

Seville, Andalusia, 41014, Spain

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Novartis Investigative Site

Madrid, 28222, Spain

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Novartis Investigative Site

Bradford, West Yorkshire, BD9 6RJ, United Kingdom

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Novartis Investigative Site

Bath, BA1 3NG, United Kingdom

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Novartis Investigative Site

Bournemouth, BH7 7DW, United Kingdom

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Novartis Investigative Site

Edinburgh, EH4 2XU, United Kingdom

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Novartis Investigative Site

London, SE1 7EH, United Kingdom

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Novartis Investigative Site

Middlesbrough, TS4 3BW, United Kingdom

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Novartis Investigative Site

Oldham, OL1 2JH, United Kingdom

Location

Related Publications (1)

• Rice ASC, Dworkin RH, Finnerup NB, Attal N, Anand P, Freeman R, Piaia A, Callegari F, Doerr C, Mondal S, Narayanan N, Ecochard L, Flossbach Y, Pandhi S. Efficacy and safety of EMA401 in peripheral neuropathic pain: results of 2 randomised, double-blind, phase 2 studies in patients with postherpetic neuralgia and painful diabetic neuropathy. Pain. 2021 Oct 1;162(10):2578-2589. doi: 10.1097/j.pain.0000000000002252.

  PMID: 33675631 DERIVED

Related Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Conditions

Diabetic Neuropathies; Neuralgia

Interventions

EMA400

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 26, 2017
• First Posted: September 29, 2017
• Study Start: March 14, 2018
• Primary Completion: March 25, 2019
• Study Completion: March 25, 2019
• Last Updated: October 8, 2021
• Results First Posted: June 4, 2020

Record last verified: 2021-10

Locations

AU (3); NO (1); BU (4); GB (7); FR (1); BE (3); HU (9); ES (2); PT (6); CA (4); DK (3); DE (8); PL (3); SL (5); FI (1)