Effect of NRD135S.E1 in Peripheral Neuropathic Pain in Diabetic Patients

September 21, 2016 updated by: Novaremed Ltd.

A Phase 2a, Randomized, Double-blind, Placebo (Vehicle)-Controlled, Dose Finding Trial to Assess the Safety, Tolerability and Efficacy of NRD135S.E1 in Patients With Neuropathic Pain Associated With Diabetes Mellitus

A multicenter, Phase 2a, randomized, double-blind, placebo (vehicle)-controlled, parallel-group, dose-finding study designed to evaluate the efficacy, safety and tolerability of NRD135S.E1 in adult patients with diabetes mellitus type 1 or 2 with neuropathic pain. Potential study patients will sign informed consent prior to undergoing any study-related procedure.

Study Overview

Detailed Description

Following screening, eligible patients will be enrolled and go through a week of washout of analgesic treatment. Patients who are still eligible following the washout will be randomized to one of four treatment groups: NRD135S.E1 at 10, 40, or 150 mg per day or placebo (vehicle).

All four treatment groups will start study treatment with 1 week of single blind placebo (baseline week) followed by 3 weeks of the allocated double blind treatment (Weeks 1, 2, and 3). All patients will be followed for 30 days after the last study drug administration. The total study duration per patient is 9 to10 weeks.

Visit schedule: Screening (Days minus 14 to minus 8, Visit 1). Washout visit (Day minus 7, Visit 2). Randomization and start of placebo treatment (Day 1, Visit 3). Double blind treatment visits on Days 8 (Visit 4), 15 (Visit 5) and 29 (Visit 6). Follow up visit by telephone (Day 59, Visit 7).

Study Type

Interventional

Enrollment (Actual)

88

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Bat-Yam, Israel
        • Diabetes and Endocrinology clinic, Bat-Yamon Medical center, Clalit health services
      • Haifa, Israel, 35152
        • Diabetes clinic, Lin Medical Center
      • Haifa, Israel
        • Rambam Medical Center, Diabetic Endocrine unit
      • Holon, Israel
        • Wolfson Medical Center
      • Jerusalem, Israel, 9310609
        • Diabetic and Endocrinology clinic, Clalit health services
      • Kfar-Saba, Israel, 44821
        • Meir Medical Center, Endocrynology, diabetes and metabolism Unit
      • Tel Aviv, Israel, 62038
        • Diabetes Department Migdal Hamea Clalit health services
      • Tel-Aviv, Israel, 6937947
        • DMC Medical Center
      • Tel-Aviv, Israel
        • Sorasky Medical Center, Diabetic unit
      • Zefat, Israel
        • Ziv Medical Center, Endocrinology Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. -Males agree to use condoms throughout treatment and follow up study periods.

    • Females must not be of childbearing potential as evidenced by at least one of the following:

      ≥ 62 years old and amenorrheic for ≥ 1 year

    • Amenorrheic ≥ 12 consecutive months and a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
    • Irregular menstrual periods and a documented FSH level > 35 mIU/mL
    • On hormone replacement therapy and prior clinical evidence of menopause based on any of the criteria above
    • Surgically sterile
  2. Known stable diabetes mellitus for the last 3 months. (No oral hypoglycemic medications change allowed. Maximum insulin change allowed is ± 20%).
  3. Evidence of peripheral neuropathy associated with diabetes mellitus diagnosed by DN4 criteria.
  4. Presence of ongoing pain due to DPN for at least 3 months.
  5. Mean DPN pain intensity of 4 to 9 on the NPS at screening.
  6. HbA1c ≤ 9% of total hemoglobin at screening.
  7. Willing to stop pain medications for DPN (except for limited use of paracetamol).
  8. Signed written informed consent.

    • Subjects must have signed and dated an Institutional Review Board / Independent Ethics Committee approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
    • Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.

Exclusion Criteria

  1. Female of childbearing potential.
  2. Neurologic disorders unrelated to DPN that may interfere with the assessment of DPN.
  3. Known allergy or intolerance to paracetamol.
  4. Evidence of non-DPN polyneuropathy.
  5. The presence of severe pain associated with conditions other than DPN (e.g., peripheral vascular disease, phantom pain, etc.) that could confound the self-evaluation of pain due to DPN.
  6. Any anti-epileptic or anti-depressive treatment. Amityptiline (Elatrol/Elatrolet) or duloxetine (Cymbalta) are permitted at screening but not later.
  7. Constant use of non-steroidal anti-inflammatory drugs or opiates that cannot be withdrawn during the washout period and the whole study duration.
  8. Participation in another clinical trial in the last 3 months.
  9. Poor compliance with prescribed medication or alcohol or drug abuse within 2 years before screening.
  10. Hypersensitivity to paracetamol or any of the inactive ingredients in NRD135S.E1 capsules.
  11. Any serious medical condition, including the presence of laboratory abnormalities, that places the patient at an unacceptable risk if he or she participates in this study or confounds the ability to interpret data from the study.
  12. Patients with any hematological disorder.
  13. Prisoners or subjects who are involuntarily incarcerated.
  14. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.
  15. Patients whose judgment has been impaired by their physical ir mental condition

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NRD135S.E1 A
A = 10 mg NRD135S.E1 once daily PO for 21 days
A small chemical entity for treatment of neuropathic pain NRD135S.E1
Other Names:
  • E1
Experimental: NRD135S.E1 B
B = 40 mg NRD135S.E1 once daily PO for 21 days
A small chemical entity for treatment of neuropathic pain NRD135S.E1
Other Names:
  • E1
Experimental: NRD135S.E1 C
C = 150 mg NRD135S.E1 once daily PO for 21 days
A small chemical entity for treatment of neuropathic pain NRD135S.E1
Other Names:
  • E1
Placebo Comparator: Placebo to match NRD135S.E1 D
D = Placebo once daily PO for 21 days
Placebo capsule to match NRD135S.E1 capsules
Other Names:
  • Placebo for E1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
• Change from the baseline week to Week 3 in the weekly average daily pain intensity as measured on an 11-point numerical pain scale (NPS)
Time Frame: three weeks
three weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Change from the baseline week to Week 3 in the weekly maximum daily pain intensity as measured on the NPS
Time Frame: three weeks
three weeks
Change from the baseline week to Week 3 in the weekly consumption of rescue analgesic (i.e., number of paracetamol 500 mg tablets taken per week)
Time Frame: three weeks
three weeks
• Change from Day 8 (end of baseline week) to Day 29 (24 h after last study drug administration) in Short-Form McGill Pain Questionnaire (SF-MPQ) score
Time Frame: three
three
Clinician's Global Impression of Change from the baseline week at Day 29 (24 h after last study drug administration)
Time Frame: three weeks
three weeks
Patient's Global Impression of Change from the baseline week at Day 29 (24 h after last study drug administration)
Time Frame: three weeks
three weeks
Change from the baseline week to Week 3 in the weekly Daily Sleep Interference Score
Time Frame: three weeks
three weeks
Incidence of treatment-emergent AEs (TEAEs)
Time Frame: three weeks
three weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Eli Kaplan, MD, Novaremed Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2015

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

January 19, 2015

First Submitted That Met QC Criteria

January 19, 2015

First Posted (Estimate)

January 26, 2015

Study Record Updates

Last Update Posted (Estimate)

September 22, 2016

Last Update Submitted That Met QC Criteria

September 21, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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