Painful Diabetic Neuropathy
Conditions
Brief summary
The purpose of this study is to investigate the safety and efficacy of the current hard gelatin capsule formulation of NRD135S.E1 80 mg once daily in the treatment of PDPN when administered for 13 weeks.
Detailed description
This ISA describes a double-blind Phase II study of the PK/PD, safety, tolerability, and effect of 13 weeks of NRD135S.E1 (80mg/day) as an ISA within the context of the Platform Protocol to Assess Treatments for Painful Diabetic Peripheral Neuropathy, EN21-PP. The ISA is intended to be read and interpreted within the context of the Platform Protocol and focuses on the description of design features that are specific to NRD135S.E1.
Interventions
DRUGNRD135SE.1
The double-blind treatment phase is up to 13 weeks.
OTHERPlacebo
A matching placebo will be taken for up to 13 weeks.
Sponsors
James P. Rathmell, MD
New York University
National Institute of Neurological Disorders and Stroke (NINDS)
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Randomization assignment will be blinded from study participants, staff from clinical sites, investigators, asset owner, IND sponsors, and/or designees.
Intervention model description
This study is an interventional, prospective, parallel-group, multicenter, randomized, double-blind, placebo-controlled, Phase 2 study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
7.1 ISA-Specific Inclusion Criteria (To be used in conjunction with Platform Protocol criteria; note, some ISA criteria may be more stringent than Platform criteria; always follow the more stringent criteria when determining eligibility.) 1. Provides written consent for the EN21-01 ISA. Legally Authorized Representatives (LARs) are not allowed, but impartial witnesses may be utilized as needed for visually impaired participants. 2. Patient-reported daily 11-point NRS (for average pain over the last 24 hours) meets the criteria specified in "Appendix B: Blinded Information" during both the 7-day screening and 7-day baseline periods. The algorithm will be assessed centrally. Waivers to the inclusion criteria will not be allowed. 7.2 ISA-Specific
Exclusion criteria
(To be used in conjunction with Platform Protocol criteria; note, some ISA criteria may be more stringent than Platform criteria; always follow the more stringent criteria when determining eligibility.) Participants fulfilling any of the following criteria are not eligible for the study. 1. Diagnosis of alcohol or substance abuse or dependence (other than nicotine or caffeine) within the 2 years before the Screening visit. \*\*This criterion is more stringent than a related Platform Protocol criterion.\*\* 2. Moderate or severe renal impairment, known (documented) or defined as an estimated/calculated creatinine clearance/estimated glomerular filtration rate (eGFR) \< 45 mL/min/1.73 m2, according to the Chronic Kidney Disease Epidemiology Collaboration formula during the screening process. \*\*This criterion is more stringent than a related Platform Protocol criterion.\*\* 3. Any of the following conditions related to corrected QT intervals using Fridericia's formula (QTcF): 1. A QTcF \> 500 ms prior to starting IP, up to and including the V3 pre-dose ECG. 2. A history of the following additional risk factors for torsade de pointes: heart failure, hypokalemia, history or family history of long QT syndrome. 4. History of myocardial infarction, other clinically active significant heart disease, or stroke. \*\*This criterion is more stringent than a related Platform Protocol criterion.\*\* 5. Participants known to have participated in four or more studies for investigational pain drugs. 6. Participants known to be non-responders to more than three previous neuropathic pain medications at adequate doses over at least 4 weeks. Adequate doses (given as total daily doses) are defined as follows: 1,800 mg gabapentin; 300 mg pregabalin; opioid analgesics 60 mg oxycodone equivalent or 200 mg tramadol; 75 mg amitriptyline or equivalent tricyclic antidepressant; 60 mg duloxetine; 150 mg venlafaxine. 7. Known hypersensitivity or contraindication to any excipients of the study drug formulation. 8. Taking prohibited medications as described in Appendix A, "Prohibited Medications." 9. Major depressive episode within the 6 months before screening and/or a history of diagnosed recurrent major depressive disorder within two years. Any of the following conditions related to suicidality: 1. Any suicidal ideation with intent, with or without a plan, at screening, i.e., answering "yes" to questions 4 or 5 on the Suicidal Ideation section of the Baseline/Screening version of the Columbia-Suicide Severity Rating Scale (C-SSRS); 2. Answering "yes" on any item of the Suicidal Behavior Section (except for the "non-suicidal self-injurious behavior") of the C-SSRS if this behavior occurred in the past 2 years; 3. A lifetime history of suicide attempt (V1). 10. Previous known or possible exposure to NRD135S.E1. Waivers to the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To demonstrate that NRD135S.E1 80 mg daily is superior to placebo in relieving neuropathic pain associated with PDPN, after 13 weeks' treatment. | 13 weeks | Change from Baseline to Week 13 in the weekly mean of the daily 24-hour average pain measured by Numeric Rating Scale (NRS) (abbreviated herein as WAP for weekly average pain). The NRS is a 0-10 scale, with 0 indicating no pain, and 10 being the worst possible pain. |
| The frequency (i.e. number of participants) with treatment emergent adverse events (TEAEs) reported in the time period defined by first administration of IP until 7 days after the last dose of IP. | 13 weeks | A treatment-emergent adverse event (TEAE) is any AE temporally associated with the use of study treatment whether or not considered by the investigator as related to study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of 30% reduction of WAP from Baseline to Week 13. | 13 weeks | Weekly Average Pain is abbreviated as WAP. |
| Occurrence of 50% reduction of WAP from Baseline to Week 13. | 13 weeks | Weekly Average Pain is abbreviated as WAP. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJessica Robinson-Papp, MD
Icahn School of Medicine at Mount Sinai
Outcome results
None listed