LX9211 for Diabetic Neuropathy

(PROGRESS Trial)

Recruiting at 113 trial locations

Overseen By Tracy Newbold

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Lexicon Pharmaceuticals

Must not be taking: Opioids, Topical analgesics, NSAIDs

Disqualifiers: Other painful conditions, Neurolytic therapy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

496 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test how well a new medication, LX9211, reduces pain caused by diabetic neuropathy (nerve damage from diabetes). Participants will receive either different doses of LX9211 or a placebo (a pill with no active medication) to compare effects. It suits those with type 1 or type 2 diabetes who have experienced ongoing nerve pain for at least six months. The study seeks to find a new way to relieve pain for people living with this condition. For more details, visit: https://diabeticpainstudy.com/.

As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to potential advancements in pain relief.

Will I have to stop taking my current medications?

The trial requires that you stop using opioid medications for diabetic nerve pain at least 2 months before screening and prescription topical pain relievers 3 months before. You also need to stop using NSAIDs at least 2 weeks before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that LX9211 is safe and well tolerated in earlier studies. Tests with healthy participants revealed no serious side effects, suggesting general safety. Additionally, studies on diabetic nerve pain demonstrated that both high and low doses of LX9211 reduced pain more effectively than a placebo. These studies identified no major safety issues, supporting its use in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for diabetic neuropathy?

Unlike the standard treatments for diabetic neuropathy, which often involve managing pain through medications like gabapentin or duloxetine, LX9211 offers a novel approach. LX9211 is unique because it targets a specific protein involved in nerve pain pathways, potentially providing more direct relief. Researchers are excited about this treatment because it could offer a more effective and targeted method of pain management with possibly fewer side effects. Additionally, LX9211's oral administration makes it convenient for daily use, enhancing patient compliance.

What evidence suggests that this trial's treatments could be effective for diabetic neuropathy?

Research shows that LX9211 has promising results for treating pain from diabetic nerve damage. Participants in this trial may receive different doses of LX9211. In earlier studies, the higher dose of LX9211 reduced pain scores by 1.27 points, compared to a 0.72-point reduction with a placebo. The lower dose also achieved important goals, lowering pain by 1.39 points versus 0.72 points for placebo. Additionally, the 10 mg dose provided noticeable pain relief as soon as the first week of treatment. Overall, LX9211 has demonstrated significant pain reduction and is well-tolerated by patients. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

Adults over 18 with a BMI between 18.0 and 40.0 kg/m^2, diagnosed with type 1 or type 2 diabetes and suffering from chronic diabetic peripheral neuropathic pain for at least six months can join this study. They must have stable diabetes management for three months and an A1C level of ≤11%. People using opioids, neurolytic therapies, topical analgesics for neuropathy recently, or NSAIDs within two weeks cannot participate.

Inclusion Criteria

Willing to adhere to the prohibitions and restrictions specified in the protocol.

I have diabetes (type 1 or 2) with chronic nerve pain.

Participant has given written informed consent to participate in the study in accordance with local regulations

Exclusion Criteria

I have other painful conditions besides diabetic peripheral neuropathic pain.

I haven't used prescription creams for nerve pain in the last 3 months.

I have had nerve treatment or surgery for diabetic nerve pain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LX9211 or placebo, orally, once daily during a blinded treatment period

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LX9211
• Placebo

Trial Overview The trial is testing the effectiveness of a new medication called LX9211 against a placebo in reducing pain caused by diabetic peripheral neuropathy. Participants won't know if they're receiving the actual drug or the placebo as both are blinded.

How Is the Trial Designed?

Group I: LX9211 Low Dose Experimental Treatment 1 Intervention

LX9211 low dose, orally, once daily during a blinded treatment period.

Group II: LX9211 High Dose Followed by Low Dose Experimental Treatment 1 Intervention

LX9211 high dose followed by LX9211 low dose, orally, once daily during a blinded treatment period.

Group III: LX9211 High Dose Experimental Treatment 1 Intervention

LX9211 high dose, orally, once daily during a blinded treatment period.

Group IV: LX9211 Placebo Placebo Group 1 Intervention

LX9211 matching placebo, orally, once daily during a blinded treatment period.

Who Is Running the Clinical Trial?

Lexicon Pharmaceuticals

Lead Sponsor

Trials

67

Recruited

24,400+

Dr. Mike Exton

Lexicon Pharmaceuticals

Chief Executive Officer

PhD in Neuroscience from the University of Newcastle and PhD in Immunology from the University of Essen, Germany

Dr. Craig Granowitz

Lexicon Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Pregabalin is strongly recommended as an effective treatment for painful diabetic neuropathy (PDN), based on a systematic review of literature from 1960 to 2008 involving various pharmacological and non-pharmacological interventions.

Other treatments like venlafaxine, duloxetine, and gabapentin are considered probably effective, but many treatments have side effects that may limit their usefulness, highlighting the need for more research on their impact on physical function and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Bril, V., England, J., Franklin, GM., et al.[2022]

Pregabalin is strongly recommended as an effective treatment for painful diabetic neuropathy (PDN), based on a systematic review of literature from 1960 to 2008 involving various pharmacologic and nonpharmacologic therapies.

Other treatments like venlafaxine, duloxetine, and gabapentin are considered probably effective for PDN, but many have side effects that may limit their use, highlighting the need for more research on their impact on physical function and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Bril, V., England, J., Franklin, GM., et al.[2022]

In a 52-week study involving 57 patients with subclinical diabetic neuropathy, tolrestat significantly improved nerve function compared to placebo, with a notable increase in normalized squatting test results (25 patients on tolrestat vs. 6 on placebo).

Patients taking tolrestat also showed a significant improvement in vibration perception thresholds, while those on placebo experienced a deterioration, suggesting tolrestat's potential role in preventing diabetic neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolrestat in the primary prevention of diabetic neuropathy. Giugliano, D., Acampora, R., Marfella, R., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38895916/

Efficacy and Safety of LX9211 for Relief of Diabetic Peripheral ... Results for high-dose LX9211 demonstrated improvement in pain severity versus placebo (-1.27 vs. -0.72 points, respectively).

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111/jdi.14342

LX9211, a rising star for relieving of diabetic peripheral ... LX9211 significantly reduced pain in diabetic peripheral neuropathy (DPN) patients, with the 10 mg dose showing notable relief by the first week.

3. diabetesjournals.figshare.com diabetesjournals.figshare.com/articles/figure/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/25451386

Efficacy and Safety of LX9211 for Relief of Diabetic Peripheral ... Results: Low-dose LX9211 achieved the primary efficacy endpoint: -1.39 versus -0.72 points for placebo; LS mean (SE) difference: -0.67 (0.249), ...

4. investors.lexpharma.com investors.lexpharma.com/news-releases/news-release-details/lexicon-pharmaceuticals-announces-topline-results-phase-2b

Release Details - Investor Relations | Lexicon Pharmaceuticals Pilavapadin achieved meaningful pain reduction versus placebo and was well-tolerated in the 10 mg dose, meeting the Company's objectives for the study.

5. bookcafe.yuntsg.com bookcafe.yuntsg.com/ueditor/jsp/upload/file/20240623/1719134596759025947.pdf

Efficacy and Safety of LX9211 for Relief of Diabetic ... In this double-blind, randomized, multicenter, proof-of-concept study, the primary efficacy end point was achieved for subjects on low-dose ...

6. diabetesjournals.org diabetesjournals.org/care/article/47/8/1325/154530/Efficacy-and-Safety-of-LX9211-for-Relief-of

Efficacy and Safety of LX9211 for Relief of Diabetic Peripheral ... Results for high-dose LX9211 demonstrated improvement in pain severity versus placebo (−1.27 vs. −0.72 points, respectively).

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34108079/

Results of two Phase 1, Randomized, Double-blind ... These studies found that LX9211 was safe and well tolerated in healthy participants. These findings suggest it is appropriate to take LX9211 ...