Efficacy, Safety, and PK of LX9211 in Participants With Diabetic Peripheral Neuropathic Pain (RELIEF-DPN 1)

A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of LX9211 in the Treatment of Diabetic Peripheral Neuropathic Pain

Evaluation of the efficacy of a low and high dose of LX9211 compared to placebo in reducing pain related to diabetic peripheral neuropathy (DPNP) over an 11 week assessment period.

Study Overview

• Status: Completed
• Conditions: Diabetes; Diabetic Peripheral Neuropathy
• Intervention / Treatment: Drug: LX9211 Matching Placebo; Drug: LX9211

• Study Type: Interventional
• Enrollment (Actual): 319
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Lexicon Investigational Site
  • Arizona
    • Chandler, Arizona, United States, 85286
      • Lexicon Investigational Site
    • Glendale, Arizona, United States, 85308
      • Lexicon Investigational Site
    • Kingman, Arizona, United States, 86409
      • Lexicon Investigational Site
    • Tucson, Arizona, United States, 85741
      • Lexicon Investigational Site
  • California
    • Anaheim, California, United States, 92801
      • Lexicon Investigational Site
    • Greenbrae, California, United States, 94904
      • Lexicon Investigational Site
    • Los Angeles, California, United States, 90026
      • Lexicon Investigational Site
    • North Hollywood, California, United States, 91606
      • Lexicon Investigational Site
    • Sacramento, California, United States, 95821
      • Lexicon Investigational Site
    • Tustin, California, United States, 92780
      • Lexicon Investigational Site
  • Florida
    • Brandon, Florida, United States, 33511
      • Lexicon Investigational Site
    • Fort Myers, Florida, United States, 33912
      • Lexicon Investigational Site
    • Jacksonville, Florida, United States, 32204
      • Lexicon Investigational Site
    • Lake City, Florida, United States, 32055
      • Lexicon Investigational Site
    • New Port Richey, Florida, United States, 34652
      • Lexicon Investigational Site
    • Ormond Beach, Florida, United States, 32174
      • Lexicon Investigational Site
    • Winter Park, Florida, United States, 32789
      • Lexicon Investigational Site
  • Georgia
    • Macon, Georgia, United States, 31210
      • Lexicon Investigational Site
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Lexicon Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Lexicon Investigational Site
    • South Dartmouth, Massachusetts, United States, 02747
      • Lexicon Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Lexicon Investigational Site
    • Dearborn, Michigan, United States, 48124
      • Lexicon Investigational Site
    • Farmington Hills, Michigan, United States, 48334
      • Lexicon Investigational Site
    • Sterling Heights, Michigan, United States, 48312
      • Lexicon Investigational Site
  • Missouri
    • Hazelwood, Missouri, United States, 63042
      • Lexicon Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Lexicon Investigational Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Lexicon Investigational Site
  • New York
    • Westfield, New York, United States, 14787
      • Lexicon Investigational Site
    • Williamsville, New York, United States, 14221
      • Lexicon Investigational Site
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Lexicon Investigational Site
    • Cary, North Carolina, United States, 27518
      • Lexicon Investigational Site
    • Morehead City, North Carolina, United States, 28557
      • Lexicon Investigational Site
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Lexicon Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • Lexicon Investigational Site
    • Austin, Texas, United States, 78749
      • Lexicon Investigational Site
    • Dallas, Texas, United States, 75231
      • Lexicon Investigational Site
    • Flower Mound, Texas, United States, 75028
      • Lexicon Investigational Site
    • Houston, Texas, United States, 77030
      • Lexicon Investigational Site
    • Houston, Texas, United States, 77074
      • Lexicon Investigational Site
    • Pearland, Texas, United States, 77584
      • Lexicon Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Lexicon Investigational Site
  • Washington
    • Renton, Washington, United States, 98057
      • Lexicon Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has given written informed consent to participate in the study in accordance with local regulations
• Adult male and female participants ≥18 years of age at the time of screening
• Body mass index ≥18.0 to ≤40.0 kg/m2 at Screening
• Diagnosis of diabetic peripheral neuropathic pain (DPNP) at Screening
• Pain from DPN present for at least 6 months
• Haemoglobin A1C ≤11% at screening
• Stable regimen for the treatment of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) for ≥1 month prior to Screening

Exclusion Criteria:

• Presence of other painful conditions that may confound assessment or self-evaluation of DPNP
• History of major depressive episode, active, significant psychiatric disorders
• History of clinically significant drug or alcohol use disorder
• History of neurolytic or neurosurgical therapy for DPNP
• Use of opioid medications for management of DPNP within the 2 months prior to Screening Visit
• Use of non-steroidal anti-inflammatory drugs (NSAIDs) less than 2 weeks prior to the Screening Visit

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Following a 2-week run-in period, participants were randomized to LX9211 matching placebo received as a single loading dose, orally, on Day 1, followed by maintenance doses of LX9211 matching placebo tablets, orally, once daily (QD) from Day 2 up to Week 6. Following completion of the 6-week treatment, all participants were followed for safety and received single oral tablet of LX9211 matching placebo, QD, for 5 weeks during the safety follow-up.	Drug: LX9211 Matching Placebo; Oral Tablets
Experimental: LX9211 100 mg/10 mg; Following a 2-week run-in period, participants were randomized to receive a single loading dose of LX9211, 100 milligrams (mg), tablet, orally, on Day 1, followed by maintenance doses of LX9211 10 mg tablets, orally, QD from Day 2 up to Week 6. Following completion of the 6-week treatment, all participants were followed for safety and received single oral tablet of LX9211 matching placebo, QD, for 5 weeks during safety follow-up.	Drug: LX9211; Oral Tablets
Experimental: LX9211 200 mg/20 mg; Following a 2-week run-in period, participants were randomized to receive a single loading dose of LX9211, 200 mg orally on Day 1, followed by maintenance doses of LX9211, 20 mg, orally, QD from Day 2 up to Week 6. Following completion of the 6-week treatment, all participants were followed for safety and received single oral tablet of LX9211 matching placebo, QD, for 5 weeks during safety follow-up.	Drug: LX9211; Oral Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in ADPS as Measured by the Numerical Rating Scale	ADPS is based on question 5 of Brief Pain Inventory (BPI)-short form for Diabetic Peripheral Neuropathy (BPI-DPN) and is assessed on an 11-point numerical rating scale. Participants were asked to rate their average pain over the past 24 hours, by answering the question 5 "Please rate your pain due to your diabetes by indicating the one number that best describes your pain on the average." on a scale of 0 to 10: 0=no pain, and 10=pain as bad as you can imagine. Higher ADPS scores indicate higher pain intensity. Negative change from baseline indicates improvement.	Baseline (Week 2 of the Run-in period) to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With ≥30% Reduction in Pain Intensity in ADPS From Baseline to Week 6	ADPS is based on question 5 of BPI-DPN and assessed on an 11-point numerical rating scale. Participants were asked to rate their average pain over the past 24 hours, by answering the question 5 "Please rate your pain due to your diabetes by indicating the one number that best describes your pain on the average." on a scale of 0 to 10 where 0 = No Pain and 10 = pain as bad as you can imagine. If % change from Baseline ≤ (-30) then participant was considered a Responder and if missing % change from Baseline or >(-30) participant is considered a Non-responder. Percentage of participants who were responders (who achieved ≥30% reduction in pain intensity in ADPS from Baseline to Week 6) are reported.	Baseline (Week 2 of the Run-in period) to Week 6
Percentage of Participants With ≥50% Reduction in Pain Intensity in ADPS From Baseline at Week 6	ADPS is based on question 5 of BPI-DPN and assessed on an 11-point numerical rating scale. Participants were asked to rate their average pain over the past 24 hours, by answering the question 5 "Please rate your pain due to your diabetes by indicating the one number that best describes your pain on the average." on a scale of 0 to 10 where 0 = No Pain and 10 = pain as bad as you can imagine. If % change from Baseline ≤ (-50) then participant is considered a Responder and if missing % change from Baseline or >(-50) then participant is considered a Non-responder. Percentage of participants who were responders (who achieved ≥50% reduction in pain intensity in ADPS from Baseline to Week 6) are reported.	Baseline (Week 2 of the Run-in period) to Week 6
Change From Baseline to Week 6 in Severity of Pain and Interference of Pain With Sleep and Other Aspects of the Participant's Life Based on the BPI-DPN	BPI-DPN: questionnaire that assesses severity of pain & its impact on functioning in participants with DPN. It consists of 4 questions that measure pain at its "worst,"least","average","now"(current pain) on 11-point numerical scale 0=no pain;10=worst pain.Score range:0-10 for each of these pain questions, higher scores=greater pain severity. Other 7 questions of BPI evaluate level of interference of pain on daily functioning (general activity,walking,work ability,mood,enjoyment of life,relations,sleep) on 11-point numerical scale, 0=does not interfere;10=completely interferes.Score range:0-10 for each of these intensity questions, higher scores=greater interference. Pain severity & pain interference factors are reported as separate categories. Average interference score= mean of 7 interference categories collected in Questions 9A-G, only if 50% (ie at least 4 of 7) of scores were non-missing. Negative change from baseline=improvement. Score range for average interference score: 0-70.	Baseline (Week 2 of the Run-in period) to Week 6
Percentage of Participants Discontinuing Treatment Due to Lack of Efficacy	Lack of efficacy was defined as an increase of 30% from baseline in ADPS based on question 5 of the BPI-DPN. Baseline was defined as the average of the Week 2 Run-in period data collected by participants in the daily pain diary of BPI-DPN. ADPS is based on question 5 of BPI-DPN and assessed on an 11-point numerical rating scale where 0 = No Pain to 10 = pain as bad as you can imagine, higher score indicates higher pain intensity.	Baseline (Week 2 of the Run-in period) to Week 6
Patient Global Impression of Change (PGIC) Scale Score at Week 6	PGIC is a 7-point rating scale that assesses participant's belief about the overall improvement experienced after the end of treatment, where 1= very much improved to 7 = very much worse. Higher score indicates worsening.	Baseline (Week 2 of the Run-in period) to Week 6
Time to Loss of Efficacy From Week 6 to Week 11 Among Participants Achieving a ≥30% Reduction in Pain Intensity at Week 6	For participants who achieved ≥30% reduction in ADPS based on Question 5 of the BPI-DPN at Week 6, the time to loss of efficacy was defined as the time from the date of Week 6 visit to the date of termination of safety follow-up due to lack of efficacy. ADPS is based on question 5 of BPI-DPN and assessed on an 11-point numerical rating scale where, 0 = No Pain to 10 = pain as bad as you can imagine.	Weeks 6 to 11
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Adverse Events (AE) is defined as any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Treatment-emergent AEs are defined as any AEs that occur or worsen after the first dose of study medication.	First dose of study drug after randomization up to the end of study (up to Week 11)

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Investigators: Study Director: Suma Gopinathan, PhD, Lexicon Pharmaceuticals

Publications and helpful links

General Publications

• Luo G, Chen L, Kostich WA, Hamman B, Allen J, Easton A, Bourin C, Gulianello M, Lippy J, Nara S, Maishal TK, Thiyagarajan K, Jalagam P, Pattipati SN, Dandapani K, Dokania M, Vattikundala P, Sharma V, Elavazhagan S, Verma MK, Das ML, Wagh S, Balakrishnan A, Johnson BM, Santone KS, Thalody G, Denton R, Saminathan H, Holenarsipur VK, Kumar A, Rao A, Putlur SP, Sarvasiddhi SK, Shankar G, Louis JV, Ramarao M, Conway CM, Li YW, Pieschl R, Tian Y, Hong Y, Ditta J, Mathur A, Li J, Smith D, Pawluczyk J, Sun D, Yip S, Wu DR, Vetrichelvan M, Gupta A, Wilson A, Gopinathan S, Wason S, Bristow L, Albright CF, Bronson JJ, Macor JE, Dzierba CD. Discovery of (S)-1-((2',6-Bis(difluoromethyl)-[2,4'-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine (BMS-986176/LX-9211): A Highly Selective, CNS Penetrable, and Orally Active Adaptor Protein-2 Associated Kinase 1 Inhibitor in Clinical Trials for the Treatment of Neuropathic Pain. J Med Chem. 2022 Mar 24;65(6):4457-4480. doi: 10.1021/acs.jmedchem.1c02131. Epub 2022 Mar 8.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2020
• Primary Completion (Actual): May 23, 2022
• Study Completion (Actual): June 28, 2022

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (Actual): July 2, 2020

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 20, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Neuralgia; Peripheral Nervous System Diseases
• Other Study ID Numbers: LX9211.1-201-DPN; LX9211.201 (Other Identifier: Lexicon Pharmaceuticals)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No