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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03297294




Registration number
NCT03297294
Ethics application status
Date submitted
26/09/2017
Date registered
29/09/2017

Titles & IDs
Public title
Safety and Efficacy of EMA401 in Patients With Painful Diabetic Neuropathy (PDN)
Scientific title
A Double-blind, Placebo-controlled, Randomized Trial to Determine the Safety and Efficacy of EMA401 in Reducing 24-hour Average Pain Intensity Score in Patients With Painful Diabetic Neuropathy (EMPADINE)
Secondary ID [1] 0 0
2016-000281-39
Secondary ID [2] 0 0
CEMA401A2202
Universal Trial Number (UTN)
Trial acronym
EMPADINE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Painful Diabetic Neuropathy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EMA401
Treatment: Drugs - Placebo

Experimental: 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.

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


Treatment: Drugs: EMA401
capsules, oral

Treatment: Drugs: Placebo
Placebo to EMA401 capsules, oral
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in Weekly Mean 24-hour Average Pain Score Using the 11 Point Numerical Rating Scale (NRS) From Baseline to Week 12
Timepoint [1] 0 0
Baseline up to Week 12
Secondary outcome [1] 0 0
Change in Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 12
Timepoint [1] 0 0
Baseline up to Week 12
Secondary outcome [2] 0 0
Change in Brief Pain Inventory-Short Form Interference (BPI-SF) Mean Total Score From Baseline to Week 12
Timepoint [2] 0 0
Baseline up to Week 12
Secondary outcome [3] 0 0
Change in Weekly Mean of the 24-hour Worst Pain Score, Using an 11-point NRS, From Baseline to Week 12
Timepoint [3] 0 0
Baseline up to Week 12
Secondary outcome [4] 0 0
Number of Participants Per Patient Global Impression of Change Category at Week 12
Timepoint [4] 0 0
Baseline up to Week 12
Secondary outcome [5] 0 0
Percentage of Patients Achieving at Least 30% Pain Reduction at Week 12 on NRS 11 Point Scale
Timepoint [5] 0 0
Baseline up to Week 12
Secondary outcome [6] 0 0
Percentage of Patients Achieving at Least 50% Pain Reduction at Week 12 on NRS 11 Point Scale
Timepoint [6] 0 0
Baseline up to Week 12
Secondary outcome [7] 0 0
Mean Change in Insomnia Severity Index (ISI) From Baseline to Week 12
Timepoint [7] 0 0
Baseline up to Week 12
Secondary outcome [8] 0 0
Plasma Pharmacokinetics (PK) Concentrations at Week 8 and 12
Timepoint [8] 0 0
Week 8 (Prior dose, 1-3 hours, 4-6 hours), Week 12 (Prior dose, 1-3 hours, 4-6 hours)
Secondary outcome [9] 0 0
Percentage of Patients Who Required Rescue Medication in Double-blind Treatment Period
Timepoint [9] 0 0
Baseline and weekly up to 12 weeks, once during double-blind period
Secondary outcome [10] 0 0
Percentage of Patients Who Required Rescue Medication in Treatment Withdrawal Period
Timepoint [10] 0 0
Week 12 to Week 13 (planned duration subject to varibility in visit scheduling)
Secondary outcome [11] 0 0
Time to First Rescue Medication Intake
Timepoint [11] 0 0
Baseline up to day 92
Secondary outcome [12] 0 0
Treatment Emergent Adverse Events During Urgent Safety Measure (USM) Follow-Up
Timepoint [12] 0 0
Approximately from 3 weeks after end of study up to 16 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/03/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
25/03/2019
Sample size
Target
Accrual to date
Final
142
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Broadmeadow
Recruitment hospital [2] 0 0
Novartis Investigative Site - Orange
Recruitment hospital [3] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [4] 0 0
Novartis Investigative Site - Heidelberg Heights
Recruitment postcode(s) [1] 0 0
2292 - Broadmeadow
Recruitment postcode(s) [2] 0 0
2800 - Orange
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3081 - Heidelberg Heights
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Graz
Country [2] 0 0
Austria
State/province [2] 0 0
Klagenfurt
Country [3] 0 0
Austria
State/province [3] 0 0
Wien
Country [4] 0 0
Belgium
State/province [4] 0 0
Edegem
Country [5] 0 0
Belgium
State/province [5] 0 0
Liege
Country [6] 0 0
Belgium
State/province [6] 0 0
Pellenberg
Country [7] 0 0
Bulgaria
State/province [7] 0 0
Sofia-Grad
Country [8] 0 0
Bulgaria
State/province [8] 0 0
Sofia
Country [9] 0 0
Canada
State/province [9] 0 0
CAN
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Denmark
State/province [12] 0 0
Aarhus
Country [13] 0 0
Denmark
State/province [13] 0 0
Gentofte
Country [14] 0 0
Denmark
State/province [14] 0 0
Odense C
Country [15] 0 0
Finland
State/province [15] 0 0
Tampere
Country [16] 0 0
France
State/province [16] 0 0
Boulogne Billancourt
Country [17] 0 0
Germany
State/province [17] 0 0
Bielefeld
Country [18] 0 0
Germany
State/province [18] 0 0
Duesseldorf
Country [19] 0 0
Germany
State/province [19] 0 0
Essen
Country [20] 0 0
Germany
State/province [20] 0 0
Halle (Saale)
Country [21] 0 0
Germany
State/province [21] 0 0
Kassel
Country [22] 0 0
Germany
State/province [22] 0 0
Kiel
Country [23] 0 0
Germany
State/province [23] 0 0
Leipzig
Country [24] 0 0
Germany
State/province [24] 0 0
Wiesbaden
Country [25] 0 0
Hungary
State/province [25] 0 0
HUN
Country [26] 0 0
Hungary
State/province [26] 0 0
Balatonfured
Country [27] 0 0
Hungary
State/province [27] 0 0
Budapest
Country [28] 0 0
Hungary
State/province [28] 0 0
Kistarcsa
Country [29] 0 0
Hungary
State/province [29] 0 0
Pecs
Country [30] 0 0
Hungary
State/province [30] 0 0
Szeged
Country [31] 0 0
Norway
State/province [31] 0 0
Oslo
Country [32] 0 0
Poland
State/province [32] 0 0
POL
Country [33] 0 0
Poland
State/province [33] 0 0
Bialystok
Country [34] 0 0
Poland
State/province [34] 0 0
Warszawa
Country [35] 0 0
Portugal
State/province [35] 0 0
Caldas da Rainha
Country [36] 0 0
Portugal
State/province [36] 0 0
Lisboa
Country [37] 0 0
Portugal
State/province [37] 0 0
Matosinhos
Country [38] 0 0
Portugal
State/province [38] 0 0
Porto
Country [39] 0 0
Portugal
State/province [39] 0 0
Viana do Castelo
Country [40] 0 0
Portugal
State/province [40] 0 0
Vila Nova de Gaia
Country [41] 0 0
Slovakia
State/province [41] 0 0
Slovak Republic
Country [42] 0 0
Slovakia
State/province [42] 0 0
Bratislava
Country [43] 0 0
Slovakia
State/province [43] 0 0
Presov
Country [44] 0 0
Spain
State/province [44] 0 0
Andalucia
Country [45] 0 0
Spain
State/province [45] 0 0
Madrid
Country [46] 0 0
United Kingdom
State/province [46] 0 0
West Yorkshire
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Bath
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Bournemouth
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Edinburgh
Country [50] 0 0
United Kingdom
State/province [50] 0 0
London
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Middlesborough
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Oldham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03297294