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

Phase 2

Completed

• Conditions: Diabetic Peripheral Neuropathic Pain
• Interventions: Drug: NRD135S.E1; Drug: Placebo to match NRD135S.E1

• Registration Number: NCT02345291
• Lead Sponsor: Novaremed Ltd.

Brief Summary

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.

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 Timeline

• Study First Submitted: 2015-01-19
• Study First Submitted QC: 2015-01-19
• Study First Posted: 2015-01-26
• Study Start: 2015-04
• Status Verified: 2016-07
• Primary Completion: 2016-07
• Study Completion: 2016-07
• Last Update Submitted: 2016-09-21
• Last Update Posted: 2016-09-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 88

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NRD135S.E1 C	NRD135S.E1	C = 150 mg NRD135S.E1 once daily PO for 21 days
NRD135S.E1 B	NRD135S.E1	B = 40 mg NRD135S.E1 once daily PO for 21 days
NRD135S.E1 A	NRD135S.E1	A = 10 mg NRD135S.E1 once daily PO for 21 days
Placebo to match NRD135S.E1 D	Placebo to match NRD135S.E1	D = Placebo once daily PO for 21 days

Primary Outcome Measures

Name	Time	Method
• 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)	three weeks

Secondary Outcome Measures

Name	Time	Method
• 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	three
Incidence of treatment-emergent AEs (TEAEs)	three weeks
Clinician's Global Impression of Change from the baseline week at Day 29 (24 h after last study drug administration)	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)	three weeks
Change from the baseline week to Week 3 in the weekly maximum daily pain intensity as measured on the NPS	three weeks
Change from the baseline week to Week 3 in the weekly Daily Sleep Interference Score	three weeks
Patient's Global Impression of Change from the baseline week at Day 29 (24 h after last study drug administration)	three weeks

Trial Locations

Locations (10)

Sorasky Medical Center, Diabetic unit; 🇮🇱 Tel-Aviv, Israel

Diabetes and Endocrinology clinic, Bat-Yamon Medical center, Clalit health services; 🇮🇱 Bat-Yam, Israel

Rambam Medical Center, Diabetic Endocrine unit; 🇮🇱 Haifa, Israel

Wolfson Medical Center; 🇮🇱 Holon, Israel

Meir Medical Center, Endocrynology, diabetes and metabolism Unit; 🇮🇱 Kfar-Saba, Israel

Diabetes Department Migdal Hamea Clalit health services; 🇮🇱 Tel Aviv, Israel

DMC Medical Center; 🇮🇱 Tel-Aviv, Israel

Diabetes clinic, Lin Medical Center; 🇮🇱 Haifa, Israel

Diabetic and Endocrinology clinic, Clalit health services; 🇮🇱 Jerusalem, Israel

Ziv Medical Center, Endocrinology Unit; 🇮🇱 Zefat, Israel