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

Phase 2

Completed

Conditions: Diabetic Peripheral Neuropathy
Diabetes

Interventions: Drug: LX9211 Matching Placebo
Drug: LX9211

Registration Number: NCT04455633

Lead Sponsor: Lexicon Pharmaceuticals

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 319

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	LX9211 Matching 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.
LX9211 100 mg/10 mg	LX9211	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.
LX9211 200 mg/20 mg	LX9211	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 6 in ADPS as Measured by the Numerical Rating Scale	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.

Secondary Outcome Measures

Name	Time	Method
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	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.
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	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.
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	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.
Percentage of Participants Discontinuing Treatment Due to Lack of Efficacy	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.
Patient Global Impression of Change (PGIC) Scale Score at Week 6	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.
Time to Loss of Efficacy From Week 6 to Week 11 Among Participants Achieving a ≥30% Reduction in Pain Intensity at Week 6	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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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.