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

NCT ID: NCT03297294

Last Updated: 2021-10-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 142 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-14
• Study Completion Date: 2019-03-25

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).

Detailed Description

This was an interventional, randomized, parallel, placebo-controlled, double-blind treatment study consisting of 3 periods i.e. Screening, Treatment, and Treatment withdrawal. Patients were planned to be randomized in a 1:1 ratio to Placebo b.i.d. or EMA401 100 mg b.i.d.. Concomitant use of pregabalin or duloxetine at stable doses was allowed. Based on historical data, it was planned that the study would enroll approximately 50% of patients who were on stable doses of concomitant pregabalin or duloxetine in the study. At the end of treatment period the 100mg b.i.d. arm was re-randomized (1:1) to the same treatment or placebo. Placebo arm stayed on placebo. The planned duration of treatment period was 12 weeks and 1 week of treatment withdrawal at the end of treatment period.

The study was terminated early due to pre-clinical toxicity data that became available after start of trial. Novartis implemented a Urgent Safety Measure (USM) which instructed sites to discontinue study treatment immediately and to have all patients return for additional laboratory assessments (full hematology including coagulation and clinical chemistry panel). Safety data from the USM was presented as a separate outcome measure table and not included in the Adverse Event section

Conditions

Painful Diabetic Neuropathy

Study Design

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

Study Groups

EMA401

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.

Group Type: EXPERIMENTAL

EMA401

Intervention Type: DRUG

capsules, oral

Placebo

Intervention Type: DRUG

Placebo to EMA401 capsules, oral

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo to EMA401 capsules, oral

Interventions

EMA401

capsules, oral

Intervention Type: DRUG

Placebo

Placebo to EMA401 capsules, oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

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

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Broadmeadow, New South Wales, Australia

Novartis Investigative Site

Orange, New South Wales, Australia

Novartis Investigative Site

Adelaide, South Australia, Australia

Novartis Investigative Site

Heidelberg Heights, Victoria, Australia

Novartis Investigative Site

Graz, , Austria

Novartis Investigative Site

Klagenfurt, , Austria

Novartis Investigative Site

Vienna, , Austria

Novartis Investigative Site

Edegem, , Belgium

Novartis Investigative Site

Liège, , Belgium

Novartis Investigative Site

Pellenberg, , Belgium

Novartis Investigative Site

Sofia, Sofia-Grad, Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Ontario, CAN, Canada

Novartis Investigative Site

Thornhill, Ontario, Canada

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Laval, Quebec, Canada

Novartis Investigative Site

Aarhus, , Denmark

Novartis Investigative Site

Gentofte Municipality, , Denmark

Novartis Investigative Site

Odense C, , Denmark

Novartis Investigative Site

Tampere, , Finland

Novartis Investigative Site

Boulogne-Billancourt, , France

Novartis Investigative Site

Bielefeld, , Germany

Novartis Investigative Site

Düsseldorf, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Halle, , Germany

Novartis Investigative Site

Kassel, , Germany

Novartis Investigative Site

Kiel, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Wiesbaden, , Germany

Novartis Investigative Site

Debrecen, HUN, Hungary

Novartis Investigative Site

Esztergom, HUN, Hungary

Novartis Investigative Site

Szeged, HUN, Hungary

Novartis Investigative Site

Balatonfüred, , Hungary

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Kistarcsa, , Hungary

Novartis Investigative Site

Pécs, , Hungary

Novartis Investigative Site

Szeged, , Hungary

Novartis Investigative Site

Oslo, , Norway

Novartis Investigative Site

Krakow, POL, Poland

Novartis Investigative Site

Bialystok, , Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Caldas da Rainha, , Portugal

Novartis Investigative Site

Lisbon, , Portugal

Novartis Investigative Site

Matosinhos Municipality, , Portugal

Novartis Investigative Site

Porto, , Portugal

Novartis Investigative Site

Viana do Castelo, , Portugal

Novartis Investigative Site

Vila Nova de Gaia, , Portugal

Novartis Investigative Site

Lučenec, Slovak Republic, Slovakia

Novartis Investigative Site

Bratislava, , Slovakia

Novartis Investigative Site

Bratislava, , Slovakia

Novartis Investigative Site

Prešov, , Slovakia

Novartis Investigative Site

Prešov, , Slovakia

Novartis Investigative Site

Seville, Andalusia, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Bradford, West Yorkshire, United Kingdom

Novartis Investigative Site

Bath, , United Kingdom

Novartis Investigative Site

Bournemouth, , United Kingdom

Novartis Investigative Site

Edinburgh, , United Kingdom

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

Middlesbrough, , United Kingdom

Novartis Investigative Site

Oldham, , United Kingdom

Countries

Australia; Austria; Belgium; Bulgaria; Canada; Denmark; Finland; France; Germany; Hungary; Norway; Poland; Portugal; Slovakia; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33675631 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=619

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Other Identifiers

2016-000281-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CEMA401A2202

Identifier Type: -

Identifier Source: org_study_id