Efficacy, Safety, and PK of LX9211 in Participants With Diabetic Peripheral Neuropathic Pain

NCT04455633 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: LX9211.1-201-DPNLX9211.201
• Study Type: interventional
• Target: 319
• Locations: 1 country
• Sites: 44

Brief Summary

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.

Conditions

Diabetic Peripheral Neuropathy; Diabetes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Percentage of Participants With ≥30% Reduction in Pain Intensity in ADPS From Baseline to Week 6

  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

  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

  Baseline (Week 2 of the Run-in period) to Week 6

• Percentage of Participants Discontinuing Treatment Due to Lack of Efficacy

  Baseline (Week 2 of the Run-in period) to Week 6

• Patient Global Impression of Change (PGIC) Scale Score at Week 6

  Baseline (Week 2 of the Run-in period) to Week 6

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

LX9211 100 mg/10 mg

EXPERIMENTAL

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

LX9211 200 mg/20 mg

EXPERIMENTAL

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

Interventions

LX9211 DRUG

Oral Tablets

LX9211 100 mg/10 mg; LX9211 200 mg/20 mg

LX9211 Matching Placebo DRUG

Oral Tablets

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead

Study Sites (44)

Lexicon Investigational Site

Mobile, Alabama, 36608, United States

Location

Lexicon Investigational Site

Chandler, Arizona, 85286, United States

Location

Lexicon Investigational Site

Glendale, Arizona, 85308, United States

Location

Lexicon Investigational Site

Kingman, Arizona, 86409, United States

Location

Lexicon Investigational Site

Tucson, Arizona, 85741, United States

Location

Lexicon Investigational Site

Anaheim, California, 92801, United States

Location

Lexicon Investigational Site

Greenbrae, California, 94904, United States

Location

Lexicon Investigational Site

Los Angeles, California, 90026, United States

Location

Lexicon Investigational Site

North Hollywood, California, 91606, United States

Location

Lexicon Investigational Site

Sacramento, California, 95821, United States

Location

Lexicon Investigational Site

Tustin, California, 92780, United States

Location

Lexicon Investigational Site

Brandon, Florida, 33511, United States

Location

Lexicon Investigational Site

Fort Myers, Florida, 33912, United States

Location

Lexicon Investigational Site

Jacksonville, Florida, 32204, United States

Location

Lexicon Investigational Site

Lake City, Florida, 32055, United States

Location

Lexicon Investigational Site

New Port Richey, Florida, 34652, United States

Location

Lexicon Investigational Site

Ormond Beach, Florida, 32174, United States

Location

Lexicon Investigational Site

Winter Park, Florida, 32789, United States

Location

Lexicon Investigational Site

Macon, Georgia, 31210, United States

Location

Lexicon Investigational Site

Evansville, Indiana, 47714, United States

Location

Lexicon Investigational Site

Boston, Massachusetts, 02115, United States

Location

Lexicon Investigational Site

South Dartmouth, Massachusetts, 02747, United States

Location

Lexicon Investigational Site

Ann Arbor, Michigan, 48109, United States

Location

Lexicon Investigational Site

Dearborn, Michigan, 48124, United States

Location

Lexicon Investigational Site

Farmington Hills, Michigan, 48334, United States

Location

Lexicon Investigational Site

Sterling Heights, Michigan, 48312, United States

Location

Lexicon Investigational Site

Hazelwood, Missouri, 63042, United States

Location

Lexicon Investigational Site

Omaha, Nebraska, 68130, United States

Location

Lexicon Investigational Site

Berlin, New Jersey, 08009, United States

Location

Lexicon Investigational Site

Westfield, New York, 14787, United States

Location

Lexicon Investigational Site

Williamsville, New York, 14221, United States

Location

Lexicon Investigational Site

Asheville, North Carolina, 28803, United States

Location

Lexicon Investigational Site

Cary, North Carolina, 27518, United States

Location

Lexicon Investigational Site

Morehead City, North Carolina, 28557, United States

Location

Lexicon Investigational Site

Greenville, South Carolina, 29607, United States

Location

Lexicon Investigational Site

Austin, Texas, 78731, United States

Location

Lexicon Investigational Site

Austin, Texas, 78749, United States

Location

Lexicon Investigational Site

Dallas, Texas, 75231, United States

Location

Lexicon Investigational Site

Flower Mound, Texas, 75028, United States

Location

Lexicon Investigational Site

Houston, Texas, 77030, United States

Location

Lexicon Investigational Site

Houston, Texas, 77074, United States

Location

Lexicon Investigational Site

Pearland, Texas, 77584, United States

Location

Lexicon Investigational Site

Salt Lake City, Utah, 84107, United States

Location

Lexicon Investigational Site

Renton, Washington, 98057, United States

Location

Related Publications (1)

• 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.

  PMID: 35257579 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Medical Affairs
• Organization: Lexicon Pharmaceuticals, Inc.

medical-information@lexpharma.com

510-338-6064

Study Officials

• Suma Gopinathan, PhD

  Lexicon Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2020
• First Posted: July 2, 2020
• Study Start: September 3, 2020
• Primary Completion: May 23, 2022
• Study Completion: June 28, 2022
• Last Updated: June 25, 2025
• Results First Posted: June 25, 2025

Record last verified: 2025-06

Locations

US (44)