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NCT04455633: RELIEF-DPN 1

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

Completed Phase 2 Results posted Last updated 25 June 2025
What this trial tests

Phase 2 trial testing LX9211 in Diabetic Peripheral Neuropathy in 319 participants. Completed in 28 June 2022.

Timeline
3 September 2020
Primary endpoint
23 May 2022
28 June 2022

Quick facts

Lead sponsorLexicon Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment319
Start date3 September 2020
Primary completion23 May 2022
Estimated completion28 June 2022
Sites44 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Lexicon Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Diabetic Peripheral Neuropathy or Diabetes. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline to Week 6 in ADPS as Measured by the Numerical Rating Scale Primary · Baseline (Week 2 of the Run-in period) to Week 6

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.

GroupValue95% CI
Placebo-0.72-1.08 – -0.36
LX9211 100 mg/10 mg-1.39-1.77 – -1.01
LX9211 200 mg/20 mg-1.27-1.66 – -0.88
Percentage of Participants With ≥30% Reduction in Pain Intensity in ADPS From Baseline to Week 6 Secondary · Baseline (Week 2 of the Run-in period) 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

GroupValue95% CI
Placebo17.8
LX9211 100 mg/10 mg27.4
LX9211 200 mg/20 mg17.0
Percentage of Participants With ≥50% Reduction in Pain Intensity in ADPS From Baseline at Week 6 Secondary · Baseline (Week 2 of the Run-in period) 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 ≤ (-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

GroupValue95% CI
Placebo10.3
LX9211 100 mg/10 mg15.1
LX9211 200 mg/20 mg9.4
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 Secondary · Baseline (Week 2 of the Run-in period) to Week 6

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:0-1

Pain at its Worst
GroupValue95% CI
Placebo-0.69-1.11 – -0.26
LX9211 100 mg/10 mg-1.42-1.87 – -0.97
LX9211 200 mg/20 mg-1.38-1.81 – -0.96
Pain at its Least
GroupValue95% CI
Placebo-0.69-1.13 – -0.26
LX9211 100 mg/10 mg-1.43-1.89 – -0.98
LX9211 200 mg/20 mg-1.38-1.81 – -0.95
Pain Right Now
GroupValue95% CI
Placebo-0.55-1.00 – -0.10
LX9211 100 mg/10 mg-1.42-1.89 – -0.95
LX9211 200 mg/20 mg-1.03-1.47 – -0.59
Interference Score Averaged Over Questions 9A - G
GroupValue95% CI
Placebo-0.74-1.17 – -0.30
LX9211 100 mg/10 mg-1.00-1.46 – -0.53
LX9211 200 mg/20 mg-0.97-1.41 – -0.53
General Activity
GroupValue95% CI
Placebo-0.77-1.25 – -0.28
LX9211 100 mg/10 mg-0.96-1.48 – -0.44
LX9211 200 mg/20 mg-0.82-1.31 – -0.33
Mood
GroupValue95% CI
Placebo-0.71-1.22 – -0.19
LX9211 100 mg/10 mg-0.72-1.27 – -0.16
LX9211 200 mg/20 mg-0.65-1.18 – -0.13
Walking Ability
GroupValue95% CI
Placebo-0.74-1.24 – -0.24
LX9211 100 mg/10 mg-1.36-1.89 – -0.83
LX9211 200 mg/20 mg-1.22-1.73 – -0.72
Normal Work
GroupValue95% CI
Placebo-1.01-1.50 – -0.53
LX9211 100 mg/10 mg-1.07-1.58 – -0.55
LX9211 200 mg/20 mg-1.05-1.54 – -0.56
Percentage of Participants Discontinuing Treatment Due to Lack of Efficacy Secondary · Baseline (Week 2 of the Run-in period) to Week 6

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.

GroupValue95% CI
Placebo0
LX9211 100 mg/10 mg0
LX9211 200 mg/20 mg0
Patient Global Impression of Change (PGIC) Scale Score at Week 6 Secondary · Baseline (Week 2 of the Run-in period) to 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.

GroupValue95% CI
Placebo3.283.04 – 3.52
LX9211 100 mg/10 mg2.932.69 – 3.17
LX9211 200 mg/20 mg3.132.88 – 3.38
Time to Loss of Efficacy From Week 6 to Week 11 Among Participants Achieving a ≥30% Reduction in Pain Intensity at Week 6 Secondary · Weeks 6 to 11

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.

GroupValue95% CI
PlaceboNANA – NA
LX9211 100 mg/10 mgNANA – NA
LX9211 200 mg/20 mgNANA – NA
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Secondary · First dose of study drug after randomization up to the end of study (up to Week 11)

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.

GroupValue95% CI
Placebo (Double-blind Treatment Period)32
LX9211 100 mg/10 mg (Double-blind Treatment Period)57
LX9211 200 mg/20 mg (Double-blind Treatment Period)54
Placebo (Single-blind Follow-up Period)15
LX9211 100 mg/10 mg (Single-blind Follow-up Period)21
LX9211 200 mg/20 mg Single-blind Follow-up Period)18

Adverse events — posted to ClinicalTrials.gov

Time frame: First dose of study drug after randomization up to the end of study (up to Week 11). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo (Double-blind Treatment Period)
Serious: 1/107 (1%)
Deaths: 1/107
LX9211 100 mg/10 mg (Double-blind Treatment Period)
Serious: 0/106 (0%)
Deaths: 0/106
LX9211 200 mg/20 mg (Double-blind Treatment Period)
Serious: 2/106 (2%)
Deaths: 1/106
Placebo (Single-blind Follow-up Period)
Serious: 1/104 (1%)
Deaths: 0/104
LX9211 100 mg/10 mg (Single-blind Follow-up Period)
Serious: 1/99 (1%)
Deaths: 0/99
LX9211 200 mg/20 mg Single-blind Follow-up Period)
Serious: 1/92 (1%)
Deaths: 0/92

Serious adverse events (8 terms)

ReactionSystemPlacebo (Double-blind Trea…LX9211 100 mg/10 mg (Doubl…LX9211 200 mg/20 mg (Doubl…Placebo (Single-blind Foll…LX9211 100 mg/10 mg (Singl…LX9211 200 mg/20 mg Single…
Oedema peripheralGeneral disorders
COVID-19Infections and infestations
Type 1 diabetes mellitusMetabolism and nutrition disorders
OrthopnoeaRespiratory, thoracic and mediastinal disorders
Atrial fibrillationCardiac disorders
Supraventricular tachycardiaCardiac disorders
Abdominal pain lowerGastrointestinal disorders
Coronavirus infectionInfections and infestations
Other adverse events (7 terms — click to expand)

ReactionSystemPlacebo (Double-blind Trea…LX9211 100 mg/10 mg (Doubl…LX9211 200 mg/20 mg (Doubl…Placebo (Single-blind Foll…LX9211 100 mg/10 mg (Singl…LX9211 200 mg/20 mg Single…
DizzinessNervous system disorders
NauseaGastrointestinal disorders
HeadacheNervous system disorders
ConstipationGastrointestinal disorders
SomnolenceNervous system disorders
VomitingGastrointestinal disorders
Balance disorderNervous system disorders

Most-reported serious reactions: Oedema peripheral, COVID-19, Type 1 diabetes mellitus, Orthopnoea, Atrial fibrillation, Supraventricular tachycardia, Abdominal pain lower, Coronavirus infection.

Data from ClinicalTrials.gov NCT04455633 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Diabetic neuropathy: cutting-edge research and future directions.
    Yang Y, Zhao B, Wang Y, Lan H, et al · · 2025 · cited 61× · PMID 40274830 · DOI 10.1038/s41392-025-02175-1
  2. Discovery of (<i>S</i>)-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 Neuropath
    Luo G, Chen L, Kostich WA, Hamman B, et al · · 2022 · cited 24× · PMID 35257579 · DOI 10.1021/acs.jmedchem.1c02131
  3. Potential novel therapeutic strategies for neuropathic pain.
    Du Z, Zhang J, Han X, Yu W, et al · · 2023 · cited 15× · PMID 37152429 · DOI 10.3389/fnmol.2023.1138798
  4. Recent progress in discovery of novel AAK1 inhibitors: from pain therapy to potential anti-viral agents.
    Yuan YH, Mao ND, Duan JL, Zhang H, et al · · 2023 · cited 11× · PMID 37955299 · DOI 10.1080/14756366.2023.2279906
  5. Update on Treating Painful Diabetic Peripheral Neuropathy: A Review of Current US Guidelines with a Focus on the Most Recently Approved Management Options.
    Mallick-Searle T, Adler JA. · · 2024 · cited 9× · PMID 38505500 · DOI 10.2147/jpr.s442595
  6. Development of pyrazolo[1,5-a]pyrimidine based macrocyclic kinase inhibitors targeting AAK1.
    Mensing TE, Kurz CG, Amrhein JA, Ehret TAL, et al · · 2025 · cited 5× · PMID 40882436 · DOI 10.1016/j.ejmech.2025.118076
  7. Efficacy and Safety of LX9211 for Relief of Diabetic Peripheral Neuropathic Pain (RELIEF-DPN 1): Results of a Double-Blind, Randomized, Placebo-Controlled, Proof-of-Concept Study.
    Pop-Busui R, Patel A, Sang CN, Banks PL, et al · · 2024 · cited 5× · PMID 38895916 · DOI 10.2337/dc24-0188
  8. Diabetes and its complications: molecular mechanisms, prevention and treatment.
    Zhao L, Yuan J, Yang Q, Ma J, et al · · 2026 · cited 2× · PMID 41549124 · DOI 10.1038/s41392-025-02401-w

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04455633.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing