Efficacy and Safety of NYX-2925 in Subjects With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy (DPN)

• ClinicalTrials.gov Identifier: NCT03219320
• Recruitment Status: Completed
• First Posted: July 17, 2017
• Results First Posted: June 9, 2020
• Last Update Posted: June 9, 2020
• Sponsor: Aptinyx
• Collaborator: Syneos Health
• Information provided by (Responsible Party): Aptinyx

Study Description

Brief Summary:

To evaluate the efficacy of multiple dose levels of NYX-2925 versus placebo in treating the neuropathic pain associated with Diabetic Peripheral Neuropathy.

Condition or disease	Intervention/treatment	Phase
Diabetic Peripheral Neuropathy	Drug: NYX-2925; Drug: Placebo	Phase 2

Detailed Description:

This is a randomized, double-blind, parallel-group, placebo-controlled, multiple-dose study to assess the efficacy and safety of NYX-2925 in subjects with neuropathic pain associated with diabetic peripheral neuropathy.

The study will be a 6 to 9-week study, including a 1 to 4-week (dependent on duration of washout period) Screening Period, followed by a 4-week double-blind, randomized, placebo-controlled Treatment Period, and a 1-week Follow Up Period. Subjects eligible for the study will randomize to receive either NYX-2925 or placebo for 4 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 301 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Subjects will be randomized to receive placebo or NYX-2925.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Treatment arms, dose levels, and randomization algorithm are masked.
• Primary Purpose: Supportive Care
• Official Title: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multiple-Dose Study to Assess the Efficacy and Safety of NYX-2925 in Subjects With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
• Actual Study Start Date: June 27, 2017
• Actual Primary Completion Date: November 2, 2018
• Actual Study Completion Date: November 2, 2018

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo Oral Capsule; Up to 300 subjects: Placebo	Drug: Placebo; Matching Placebo capsules.
Experimental: NYX-2925; Up to 300 subjects: Multiple dose levels of NYX-2925 daily for 28 days	Drug: NYX-2925; NYX-2925 is a novel small molecule that modulates the N-methyl-D-aspartate receptor (NMDAR).

Outcome Measures

Primary Outcome Measures :

1. Numeric Rating Scale (NRS) Average Pain Intensity [ Time Frame: From baseline (average of -7 to -1) to Week 4 (average of Days 22 through 28) ]
   Change in the NRS score assessing average pain intensity in the past 24 hours; 0=no pain, 10=worst pain imaginable

Secondary Outcome Measures :

1. Numeric Rating Scale (NRS) Average Pain Intensity in Patients Who Did Not Use a Concomitant Medication at Baseline [ Time Frame: baseline to week 4 ]
   Change in the NRS score assessing average pain intensity in the past 24 hours for patients who did not use a concomitant medication at baseline; 0=no pain, 10=worst pain imaginable

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. An Institutional Review Board-approved written informed consent and privacy language (Health Insurance Portability and Accountability Act) authorization must be obtained from the subject prior to performing any study-related procedures.
2. Subjects who consent to being included in a subject registry database.
3. Male and female subjects ≥18 and ≤75 years of age.
4. Subjects with a diagnosis of Type 2 diabetes.
5. Subjects with a score of ≥4 and ≤9 on the 11-point numeric rating scale (NRS) for average pain intensity over the past 24 hours at Visit 1.
6. Hemoglobin A1c (HbA1c) ≤11% (measured at Visit 1).
7. Stable use of diabetic medications beginning 1 month prior to Visit 1 (Adequate glycemic control with only diet and exercise is also permitted.).
8. Subjects with diabetic peripheral neuropathy, of symmetrical nature and in lower extremities for ≥6 months to ≤10 years, and diagnosed by a score of ≥3 on Michigan Neuropathy Screening Instrument.
9. Body mass index of <40 kg/m^2
10. Calculated creatinine clearance of ≥60 mL/minute (Cockcroft-Gault formula).
11. Clinical laboratory values must be within normal limits or deemed not clinically significant by the investigator and sponsor-designated medical monitor.

Inclusion Criteria: Randomization Daily pain scores and diary compliance will be transferred into the interactive response technology system, which will assess the criteria for randomization. Subjects whose mean of the daily average pain intensity score during the preceding 7 (±1) days is within the protocol-defined algorithm and with adequate compliance with daily diary completion will be eligible for randomization.

Waivers to the inclusion criteria will NOT be allowed.

Exclusion Criteria:

1. Subjects who have a current diagnosis of major psychiatric disorder (including schizophrenia, bipolar disorder, or panic disorder), including those who have required an antipsychotic or mood stabilizer (e.g., lithium, carbamazepine, valproate) for a psychiatric condition in the past year, or subjects who have had a major depressive episode (MDE) in the past 6 months. Subjects with major depressive disorder (MDD) or generalized anxiety disorder (GAD) who have been on stable medications for the past 3 months (and are expected to remain stable for the duration of the trial) and whose condition is currently well-controlled may be included.
2. Subjects who have pain that cannot be clearly differentiated from, or could interfere with the assessment of peripheral diabetic neuropathy, as measured by the Masquerading Disorders Tool at Visit 1.
3. Neurologic disorders unrelated to diabetic neuropathy (e.g., phantom limb from amputation), skin condition in the area of neuropathy that could alter sensation (e.g., plantar ulcer), or other painful conditions (e.g., arthritis) that, in the judgment of the investigators, could interfere with reporting of pain due to diabetic neuropathy.
4. History of hypoglycemia that disturbed consciousness, or ketoacidosis requiring hospitalization within past 3 months.
5. Subjects with history of severe renal impairment.
6. Impaired hepatic function.
7. Known history of significant cardiovascular condition.
8. History of Huntington's disease, Parkinson's disease, Alzheimer's disease, Multiple Sclerosis, or a history of seizures, epilepsy, or strokes.
9. HIV infection, hepatitis, or other ongoing infectious disease that the investigator considers clinically significant.
10. Concomitant use of antiepileptic drugs, non-steroidal anti-inflammatory drugs (except cardiac preventive acetylsalicylic acid), opioids, muscle relaxants, dextromethorphan (except low dose intermittent use for cough), tramadol, topical lidocaine, topical capsaicin, and selective norepinephrine reuptake inhibitors. Subjects are allowed to enter with a maximum of 1 allowed analgesic medication for neuropathic pain that has been taken at stable dose for at least 1 month (30 days) prior to Visit 1. Allowed analgesics may not be N-methyl-D-aspartate receptor ligands, must be non-opioid and non-sedative and must not interfere with subjects' pain reporting. Tricyclic antidepressants may be continued if designated as the single analgesic medication for the treatment of pain.
11. Sensitivity to, allergy to, or concomitant use of N-methyl-D-aspartate receptor ligands including ketamine, amantadine, dextromethorphan (except low dose intermittent use for cough), memantine, methadone, dextropropoxyphene, and/or ketobemidone.
12. Amputations of lower extremities (toe amputation is allowed).
13. Any condition, including serious medical conditions that could interfere with the ability of the subject to participate in the study or could confound study assessments.
14. Subjects who meet the criteria for suicidal intent, plan and/or behavior by scoring 3 or 4 on Questions 2 or 13, or 2 or higher on any Questions 1a (only if 1b is coded YES), 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 14 based on the Sheehan - Suicidality Tracking Scale at Visit 1 or Visit 2.

Waivers to the exclusion criteria will NOT be allowed.

Contacts and Locations

Locations

United States, Arizona

Aptinyx Clinical Site

Phoenix, Arizona, United States, 85053

United States, California

Aptinyx Clinical Site

Anaheim, California, United States, 92801

Aptinyx Clinical Site

Fresno, California, United States, 93710

Aptinyx Clinical Site

Norco, California, United States, 92860

Aptinyx Clinical Site

Santa Monica, California, United States, 90404

Aptinyx Clinical Site

Tustin, California, United States, 92480

United States, Connecticut

Aptinyx Clinical Site

New London, Connecticut, United States, 06320

United States, Florida

Aptinyx Clinical Site

Bradenton, Florida, United States, 34201

Aptinyx Clinical Site

Brandon, Florida, United States, 33511

Aptinyx Clinical Site

Fort Myers, Florida, United States, 33912

Aptinyx Clinical Site

Hallandale Beach, Florida, United States, 33009

Aptinyx Clinical Site

Jupiter, Florida, United States, 33458

Aptinyx Clinical Site

Miami, Florida, United States, 33012

Aptinyx Clinical Site

Miami, Florida, United States, 33126

Aptinyx Clinical Site

Miami, Florida, United States, 33175

Aptinyx Clinical Site

Ocoee, Florida, United States, 34761

Aptinyx Clinical Site

Orlando, Florida, United States, 32801

Aptinyx Clinical Site

Orlando, Florida, United States, 32806

Aptinyx Clinical Site

Tampa, Florida, United States, 33603

Aptinyx Clinical Site

West Palm Beach, Florida, United States, 33401

United States, Georgia

Aptinyx Clinical Site

Columbus, Georgia, United States, 31904

Aptinyx Clinical Site

Decatur, Georgia, United States, 30033

United States, Idaho

Aptinyx Clinical Site

Meridian, Idaho, United States, 83642

United States, Illinois

Aptinyx Clinical Site

Flossmoor, Illinois, United States, 60422

United States, Missouri

Aptinyx Clinical Site

Hazelwood, Missouri, United States, 63042

United States, New Jersey

Aptinyx Clinical Site

Berlin, New Jersey, United States, 08009

United States, New York

Aptinyx Clinical Site

Rochester, New York, United States, 14618

United States, Ohio

Aptinyx Clinical Site

Dayton, Ohio, United States, 45439

United States, Tennessee

Aptinyx Clinical Site

Knoxville, Tennessee, United States, 37909

Aptinyx Clinical Site

Memphis, Tennessee, United States, 38119

Aptinyx Clinical Site

Tullahoma, Tennessee, United States, 37388

United States, Texas

Aptinyx Clinical Site

Austin, Texas, United States, 78731

Aptinyx Clinical Site

Houston, Texas, United States, 77058

Aptinyx Clinical Site

Plano, Texas, United States, 75024

United States, Virginia

Aptinyx Clinical Site

Norfolk, Virginia, United States, 23510

Sponsors and Collaborators

Aptinyx

Syneos Health

  Study Documents (Full-Text)

Documents provided by Aptinyx:

Study Protocol  [PDF] February 28, 2018

Statistical Analysis Plan  [PDF] December 14, 2018

More Information

• Responsible Party: Aptinyx
• ClinicalTrials.gov Identifier: NCT03219320
• Other Study ID Numbers: NYX-2925-2001
• First Posted: July 17, 2017
• Results First Posted: June 9, 2020
• Last Update Posted: June 9, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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

Keywords provided by Aptinyx:

Type 2 Diabetes; Neuropathic Pain; Peripheral Nervous System

Additional relevant MeSH terms:

Peripheral Nervous System Diseases; Neuralgia; Diabetic Neuropathies; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases