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

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ClinicalTrials.gov Identifier: NCT03297294
Recruitment Status : Terminated (for safety reasons)
First Posted : September 29, 2017
Last Update Posted : May 2, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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).

Condition or disease Intervention/treatment Phase
Painful Diabetic Neuropathy Drug: EMA401 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 137 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 14, 2018
Actual Primary Completion Date : March 25, 2019
Actual Study Completion Date : March 25, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: EMA401
capsules, oral

Drug: Placebo
Placebo to EMA401 capsules, oral

Placebo Comparator: Placebo
Participants will receive matching placebo to EMA401 during both the treatment and treatment withdrawal epochs for a total of 13 weeks.
Drug: Placebo
Placebo to EMA401 capsules, oral




Primary Outcome Measures :
  1. Change in weekly mean 24-hour average pain score (using the 11 point Numeric Rating Scale) from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]

    The Numeric Rating Scale (NRS) is an 11-point scale for patient self-reporting of pain.

    11-point numeric rating scale (NRS) ranges from zero to ten. Patients will evaluate their average pain during the past 24 hours in the evening prior to sleep by touching the appropriate corresponding number between zero ("no pain") and ten ("pain as bad as you can imagine") on the eDiary device.



Secondary Outcome Measures :
  1. Change in Neuropathic Pain Symptom Inventory (NPSI) total score from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
    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

  2. Change in Brief Pain Inventory-Short Form (BPI-SF) interference total score from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]

    The Brief Pain Inventory-Short Form (BPI-SF) is a validated, self-administered questionnaire that assesses pain severity and its impact on daily functions.

    Patients will be asked to complete the 7-item pain interference scale which assesses the degree to which pain interferes with walking and other physical activity, work, mood, relations with others and sleep using a zero to ten numeric rating scale, with zero being "does not interfere" and ten being "completely interferes."


  3. Change in weekly mean of the 24-hour worst pain score, using an 11-point Numeric Rating Scale, from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]

    The Numeric Rating Scale (NRS) is an 11-point scale for patient self-reporting of pain.

    11-point numeric rating scale (NRS) ranges from zero to ten. Patients will evaluate their average pain during the past 24 hours in the evening prior to sleep by touching the appropriate corresponding number between zero ("no pain") and ten ("pain as bad as you can imagine") on the eDiary device.


  4. Patient Global Impression of Change (PGIC) at Week 12 [ Time Frame: 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.


  5. Number of patients meeting responder criteria from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
    The responder status for each patient will be calculated based on the continuous weekly score measurements of the Numeric Rating Scale.

  6. Change in Insomnia Severity Index (ISI) from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]

    The Insomnia Severity Index (ISI) is a validated seven-item patient questionnaire used to quantify perceived insomnia severity.

    Patients will be asked to complete the ISI using five-point Likert-style scale as a measure of perceived sleep difficulties. Scores can range from zero to 28, with a cut-off score of eight suggesting the presence of sub-threshold insomnia. The questionnaire assesses the severity of insomnia, satisfaction with current sleep pattern, sleep interference, "noticeability" of sleeping problem to others and concern about sleeping problems.


  7. Plasma pharmacokinetics of EMA401 will be characterized by population non-linear mixed effects modeling techniques [ Time Frame: Baseline, Week 8, Week 12 ]
    Plasma concentration of EMA401

  8. Number of patients who need rescue medication separately for the double blind treatment epoch and treatment withdrawal epoch [ Time Frame: from Baseline to Week 12, from Week 12 to Week 13 ]
    Rescue medication usage

  9. Time to first intake of rescue medication during the double blind treatment epoch [ Time Frame: Week 12 ]
    Time to first rescue medication will be assessed during the double blind treatment epoch.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At the time of Screening, have 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.)
  • Be 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 are using highly effective methods of contraception during dosing and for 3 days after stopping of study medication. Highly effective contraception methods include:

    • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are 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 has 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 be 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.
  • Have evidence of significant renal insufficiency or pre-existing liver condition.
  • Have 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 has 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 with 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 is unwilling or unable to complete daily eDiary.

Other protocol-defined inclusion/exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03297294


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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03297294     History of Changes
Other Study ID Numbers: CEMA401A2202
First Posted: September 29, 2017    Key Record Dates
Last Update Posted: May 2, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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.

URL: http://www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Painful diabetic neuropathy
Neuropathic pain
Angiotensin II type 2 receptor antagonist

Additional relevant MeSH terms:
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Peripheral Nervous System Diseases
Pain
Diabetic Neuropathies
Neuromuscular Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Angiotensin II Type 2 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action