Painful Diabetic NeuropathyPhase 2EMPADINENCT03297294
Safety and Efficacy of EMA401 in Patients With Painful Diabetic Neuropathy (PDN)
A Phase 2 study testing EMA401 in people with Painful Diabetic Neuropathy, run by Novartis Pharmaceuticals at 64 sites in 16 countries.
Trial summary
The purpose of this study is to evaluate safety and efficacy of EMA401 compared to placebo in patients with painful diabetic neuropathy (PDN). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Painful Diabetic Neuropathy
- What is being tested?
- EMA401
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 142 participants
- Where
- 64 sitesin 16 countries
- Study dates
- 14 Mar 2018to 25 Mar 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
64 sites in 16 countries.
64 sites in 16 countries
Hungary9 sites
Novartis Investigative Site
Balatonfüred, 8230
Novartis Investigative Site
Budapest, 1085
Novartis Investigative Site
Budapest, 1089
Novartis Investigative Site
Debrecen, HUN, 4032
Novartis Investigative Site
Esztergom, HUN, 2500
Novartis Investigative Site
Kistarcsa, 2143
Novartis Investigative Site
Pécs, 7632
Novartis Investigative Site
Szeged, HUN, 6720
Novartis Investigative Site
Szeged, 6725
Germany8 sites
Novartis Investigative Site
Bielefeld, D 33647
Novartis Investigative Site
Düsseldorf, 40225
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Halle, 06120
Novartis Investigative Site
Kassel
Novartis Investigative Site
Kiel, 24119
Novartis Investigative Site
Leipzig, 04109
Novartis Investigative Site
Wiesbaden, 65191
United Kingdom7 sites
Novartis Investigative Site
Bath, BA1 3NG
Novartis Investigative Site
Bournemouth, BH7 7DW
Novartis Investigative Site
Bradford, West Yorkshire, BD9 6RJ
Novartis Investigative Site
Edinburgh, EH4 2XU
Novartis Investigative Site
London, SE1 7EH
Novartis Investigative Site
Middlesbrough, TS4 3BW
Novartis Investigative Site
Oldham, OL1 2JH
Portugal6 sites
Novartis Investigative Site
Caldas da Rainha, 2500 176
Novartis Investigative Site
Lisbon, 1250 203
Novartis Investigative Site
Matosinhos Municipality, 4454 509
Novartis Investigative Site
Porto, 4200 319
Novartis Investigative Site
Viana do Castelo, 4901858
Novartis Investigative Site
Vila Nova de Gaia, 4434 502
Slovakia5 sites
Novartis Investigative Site
Bratislava, 83305
Novartis Investigative Site
Bratislava, 85101
Novartis Investigative Site
Lučenec, Slovak Republic, 98401
Novartis Investigative Site
Prešov, 080 01
Novartis Investigative Site
Prešov, 08001
Australia4 sites
Novartis Investigative Site
Adelaide, South Australia, 5000
Novartis Investigative Site
Broadmeadow, New South Wales, 2292
Novartis Investigative Site
Heidelberg Heights, Victoria, 3081
Novartis Investigative Site
Orange, New South Wales, 2800
Bulgaria4 sites
Novartis Investigative Site
Sofia, Sofia-Grad, 1336
Novartis Investigative Site
Sofia, 1000
Novartis Investigative Site
Sofia, 1407
Novartis Investigative Site
Sofia, 1431
Canada4 sites
Novartis Investigative Site
Laval, Quebec, H7T 2P5
Novartis Investigative Site
Ontario, CAN, L4J 1W3
Novartis Investigative Site
Thornhill, Ontario, L4J 8L7
Novartis Investigative Site
Toronto, Ontario, M4G 3E8
Austria3 sites
Novartis Investigative Site
Graz, A-8036
Novartis Investigative Site
Klagenfurt, 9020
Novartis Investigative Site
Vienna, A-1090
Belgium3 sites
Novartis Investigative Site
Edegem, 2650
Novartis Investigative Site
Liège, 4000
Novartis Investigative Site
Pellenberg, 3212
Denmark3 sites
Novartis Investigative Site
Aarhus, 8000
Novartis Investigative Site
Gentofte Municipality, DK 2820
Novartis Investigative Site
Odense C, DK 5000
Poland3 sites
Novartis Investigative Site
Bialystok, 15-351
Novartis Investigative Site
Krakow, POL, 31 505
Novartis Investigative Site
Warsaw, 00 144
Spain2 sites
Novartis Investigative Site
Madrid, 28222
Novartis Investigative Site
Seville, Andalusia, 41014
About this study
Official 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)
The purpose of this study is to evaluate safety and efficacy of EMA401 compared to placebo in patients with painful diabetic neuropathy (PDN).
Read the 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
- Being tested
- EMA401, Placebo
- Keywords
- Painful diabetic neuropathy, Neuropathic pain, Angiotensin II type 2 receptor antagonist, adult, EMA401, diabetic neuropathy
- Medical subject headings
- Diabetic Neuropathies, Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EMA401Drug
capsules, oral
PlaceboDrug
Placebo to EMA401 capsules, oral
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline up to Week 12
Secondary outcomes (12)
Change in Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 12
The Neuropathic Pain Symptom Inventory (NPSI) is a 12 item patient reported outcome measure that contains 10 descriptors representing 5 dimensions of pain (burning pain, deep/pressing pain, paroxysmal pain, evoked pain and paraesthesia/dysesthesia) and 2 temporal items designed to assess pain duration and the number of pain paroxysms. The sum of the responses to the 10 questions (all except temporal questions) was regarded as the total score and was divided by 10 (10 questions). The range of the total score and of the 5 dimensional scores is 0 to 10. Lower values represent better outcomes.
Measured: Baseline up to Week 12
Change in Brief Pain Inventory-Short Form Interference (BPI-SF) Mean Total Score From Baseline to Week 12
The BPI-SF is a validated, self-administered (at clinic) questionnaire that assesses pain severity and its mpact on daily functions. Patients were asked to complete the 7-item pain interference scale that assessed the degree to which pain interfered with walking and other physical activity, work, mood, relations with others and sleep using a zero to ten scale with zero being "does not interfere" and ten being "completely interferes". The BPI total score is the sum of the 7 items. Each item ranges from 0 to 10, thus the total score ranges from 0 to 70. Lower values indicate a better outcome.
Measured: 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
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.
Measured: Baseline up to Week 12
Number of Participants Per Patient Global Impression of Change Category at Week 12
The Patient Global Impression of Change (PGIC) is a patient-reported instrument that measures change in overall status on a scale ranging from one ("very much improved") to seven ("very much worse"). The PGIC is based on the validated Clinical Global Impression of Change scale. The PGIC was to be completed by patients using the electronic tablet at the site
Measured: Baseline up to Week 12
Percentage of Patients Achieving at Least 30% Pain Reduction at Week 12 on NRS 11 Point Scale
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 number of patients with observed response, i.e. a decrease of 30% units in weekly mean of the 24-hour average pain score NRS. Logistic regression model with region, treatment, sex, use of PHN medications (yes/no) as factors and age and baseline NRS as covariates. An odds ratio >1 = higher chance of a clinically important improvement.
Measured: Baseline up to Week 12
Percentage of Patients Achieving at Least 50% Pain Reduction at Week 12 on NRS 11 Point Scale
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 number of patients with observed response, i.e. a decrease of 50% units in weekly mean of the 24-hour average pain score NRS. Logistic regression model with region, treatment, sex, use of PHN medications (yes/no) as factors and age and baseline NRS as covariates. An odds ratio >1 = higher chance of a clinically important improvement.
Measured: Baseline up to Week 12
Mean Change in Insomnia Severity Index (ISI) From Baseline to Week 12
Patients were asked to complete the ISI using five-point Likert-style scale as a measure of perceived sleep difficulties. The questionnaire assessed the severity of insomnia, satisfaction with current sleep pattern, sleep interference, "noticeability" of sleeping problem to others and concern about sleeping problems. The scale consists of 7 items. The sum of seven items represents the total score. Each of the 7 items is scored using a range from 0 to 4, thus the total score values ranges from zero to 28. Lower values represent better outcomes.
Measured: Baseline up to Week 12
Plasma Pharmacokinetics (PK) Concentrations at Week 8 and 12
Due to the premature termination of the study, the number of patients and observations providing PK data was much smaller than planned, and no PK model was developed. As a consequence, no PK parameters (Cmax, Tmax, AUC) were derived for this study. Only, summary statistics of the plasma concentrations were calculated
Measured: Week 8 (Prior dose, 1-3 hours, 4-6 hours), Week 12 (Prior dose, 1-3 hours, 4-6 hours)
Percentage of Patients Who Required Rescue Medication in Double-blind Treatment Period
Patients were allowed to take acetaminophen/paracetamol up to a maximum of 3 g daily (divided into 4 times/day) for unacceptable pain due to any reason during the study. This medication use was to be recorded in eDiary prior to use. Percentages of patients presented are those who required rescue meds within 7 days prior to visit.
Measured: Baseline and weekly up to 12 weeks, once during double-blind period
Percentage of Patients Who Required Rescue Medication in Treatment Withdrawal Period
Patients were allowed to take acetaminophen/paracetamol up to a maximum of 3 g daily (divided into 4 times/day) for unacceptable pain due to any reason during the study. This medication use was to be recorded in eDiary prior to use. Percentages of patients presented are those who required rescue meds within 7 days prior to visit.
Measured: Week 12 to Week 13 (planned duration subject to varibility in visit scheduling)
Time to First Rescue Medication Intake
Patients were allowed to take acetaminophen/paracetamol up to a maximum of 3 g daily (divided into 4 times/day) for unacceptable pain due to any reason during the study. This medication use was to be recorded in eDiary prior to use. Patients who did not take any rescue medication were censored at the last date of double-blind treatment period.
Measured: Baseline up to day 92
Treatment Emergent Adverse Events During Urgent Safety Measure (USM) Follow-Up
Participants were instructed to stop taking drug immediately upon termination of study and asked to come in for two unscheduled visits for follow up safety assessments
Measured: Approximately from 3 weeks after end of study up to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2017
- Study start14 Mar 2018
- Primary completion25 Mar 2019
- Study completion25 Mar 2019
Why it stopped: Study was terminated due to animal toxicity data
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Painful Diabetic NeuropathyStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03297294
- Sponsor's protocol ID
- CEMA401A2202
- Other IDs
- 2016-000281-39, 2016
- Acronym
- EMPADINE
- Status last verified
- Oct 2021
- First submitted
- 26 Sep 2017
- Last updated
- 8 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
Publications
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.
PubMed 33675631
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT03297294
- Acronym / sponsor ID
- EMPADINE / CEMA401A2202
- Conditions
- Painful Diabetic Neuropathy
- Keywords
- Painful diabetic neuropathy, Neuropathic pain, Angiotensin II type 2 receptor antagonist, adult, EMA401, diabetic neuropathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to animal toxicity data
- Enrolment
- 142 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 14 Mar 2018 (actual)
- Primary completion
- 25 Mar 2019 (actual)
- Study completion
- 25 Mar 2019 (actual)
- First posted
- 29 Sep 2017 (actual)
- Results
- Posted 4 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EMA401 | Experimental | Drug: EMA401, Drug: PlaceboDuring 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 | Placebo comparator | Drug: PlaceboParticipants will receive matching placebo to EMA401 during both the treatment and treatment withdrawal epochs for a total of 13 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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:
- 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.
Key exclusion criteria (12 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EMA401capsules, oral | Drug | EMA401 |
| PlaceboPlacebo to EMA401 capsules, oral | Drug | EMA401, Placebo |
Primary outcome
Change in Weekly Mean 24-hour Average Pain Score Using the 11 Point Numerical Rating Scale (NRS) From Baseline to Week 12
Time frame: Baseline up 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.
12 secondary outcomes
Change in Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 12
Time frame: Baseline up to Week 12
Change in Brief Pain Inventory-Short Form Interference (BPI-SF) Mean Total Score From Baseline to Week 12
Time frame: 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
Time frame: Baseline up to Week 12
Number of Participants Per Patient Global Impression of Change Category at Week 12
Time frame: Baseline up to Week 12
Percentage of Patients Achieving at Least 30% Pain Reduction at Week 12 on NRS 11 Point Scale
Time frame: Baseline up to Week 12
Percentage of Patients Achieving at Least 50% Pain Reduction at Week 12 on NRS 11 Point Scale
Time frame: Baseline up to Week 12
Mean Change in Insomnia Severity Index (ISI) From Baseline to Week 12
Time frame: Baseline up to Week 12
Plasma Pharmacokinetics (PK) Concentrations at Week 8 and 12
Time frame: Week 8 (Prior dose, 1-3 hours, 4-6 hours), Week 12 (Prior dose, 1-3 hours, 4-6 hours)
Percentage of Patients Who Required Rescue Medication in Double-blind Treatment Period
Time frame: Baseline and weekly up to 12 weeks, once during double-blind period
Percentage of Patients Who Required Rescue Medication in Treatment Withdrawal Period
Time frame: Week 12 to Week 13 (planned duration subject to varibility in visit scheduling)
Time to First Rescue Medication Intake
Time frame: Baseline up to day 92
Treatment Emergent Adverse Events During Urgent Safety Measure (USM) Follow-Up
Time frame: Approximately from 3 weeks after end of study up to 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33675631Rice 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.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
64 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EMA401 in people with Painful Diabetic Neuropathy, run by Novartis Pharmaceuticals at 64 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 64 sites in Hungary, Germany, United Kingdom, Portugal, Slovakia and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Weekly Mean 24-hour Average Pain Score Using the 11 Point Numerical Rating Scale (NRS) From Baseline to Week 12 (time frame: Baseline up to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03297294, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2021.