Sustained Release Lidocaine for Chronic Pain

Recruiting at 8 trial locations

Overseen By Graeme Boniface

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Sustained Therapeutics Inc.

Must not be taking: Antiarrhythmics, Anticoagulants

Disqualifiers: Allergy to lidocaine, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 4

Duration: 16 weeks

63 Participants Needed

Trial Summary

What is the purpose of this trial?

This multi-center, phase 2, randomized, single-blind, three-arm, active-controlled study is comparing repeat doses, every 28 days, of standard of care (SOC) plus ST-01 against SOC plus 1% lidocaine HCL in men experiencing chronic scrotal content pain (CSCP). The main purpose of this study is to determine if repeat injections of ST-01 are safe and effective in reducing pain. After completing a screening phase participants will be randomized into one of three groups: 1) ST-01 70 mg/mL arm, 2) ST-01 140 mg/mL arm, 3) 1% Lidocaine HCL arm (Control). Participants may receive up to 4 study treatment injections given at a minimum of 28-day intervals. Participants randomized to the Control arm will be given the opportunity to cross over to an ST-01 treatment arm after 2 study treatments.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on antiarrhythmic medication or have a contraindication to lidocaine, you may not be eligible to participate.

What data supports the effectiveness of the drug for chronic pain?

Research shows that lidocaine, a key component of the drug, has been effective in providing pain relief in various medical procedures, such as dental work and skin treatments, due to its rapid action and safety profile. ^{1 2 3 4 5}

Is sustained release lidocaine generally safe for humans?

Lidocaine, used in various forms like Emla cream, is generally safe for humans, but rare cases of allergic reactions such as contact dermatitis (skin rash) have been reported. Studies have shown that lidocaine is effective in reducing pain during procedures like debridement of leg ulcers, indicating its safety in controlled medical use. ^{5 6 7 8 9}

How is the drug 1% Lidocaine HCL, ST-01 unique for treating chronic pain?

The drug 1% Lidocaine HCL, ST-01 offers sustained release of lidocaine, which may provide longer-lasting pain relief compared to other formulations that release the drug more quickly. This sustained release mechanism is particularly beneficial for managing chronic pain, as it can maintain therapeutic levels of the drug over an extended period, potentially reducing the frequency of application. ^{1 10 11 12 13}

Research Team

Graeme Boniface, PhD.

Principal Investigator

Sustained Therapeutics Inc.

Eligibility Criteria

This trial is for adult men (19+) with chronic scrotal pain lasting over 3 months, who've had a positive response to a lidocaine test block. They must have normal-ish blood liver tests and use birth control if sexually active. Men with allergies to lidocaine, other major pain sources, or certain medical conditions can't join.

Inclusion Criteria

I experience significant scrotal pain, averaging a score of 4 or more.

I experienced less pain after a lidocaine test on my spermatic cord.

I have had pain in one or both testicles for more than 3 months.

Exclusion Criteria

I did not respond to a previous nerve block in my groin.

I currently have an infection in my urinary tract or scrotum.

I have pain from another condition that scores 4 or more on a pain scale.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 4 study treatment injections of ST-01 or 1% Lidocaine HCL at a minimum of 28-day intervals

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 1% Lidocaine HCL
• ST-01

Trial Overview The study compares the safety and effectiveness of ST-01 in two different doses against standard care plus 1% Lidocaine HCL in reducing chronic scrotal pain. Participants will be randomly assigned to one of three groups and receive up to four injections every 28 days.

Participant Groups

Group I: ST-01 70 mg/mL Experimental Treatment 1 Intervention

Group II: ST-01 140 mg/mL Experimental Treatment 1 Intervention

Group III: 1% Lidocaine HCL Active Control 1 Intervention

1% Lidocaine HCL is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Lidocaine for:

• Local anesthesia
• Ventricular tachycardia
• Ventricular fibrillation
• Chronic pain
• Acute surgical pain

Approved in European Union as Lignocaine for:

• Local anesthesia
• Ventricular tachycardia
• Ventricular fibrillation
• Chronic pain
• Acute surgical pain

Approved in Canada as Lidocaine for:

• Local anesthesia
• Ventricular tachycardia
• Ventricular fibrillation
• Chronic pain
• Acute surgical pain

Who Is Running the Clinical Trial?

Sustained Therapeutics Inc.

Lead Sponsor

Trials

2

Recruited

180+

Findings from Research

A 24-hour application of EMLA cream (5-10 g) to painful leg ulcers in 10 patients resulted in safe plasma concentrations of lignocaine and prilocaine, well below toxic levels, indicating a low risk of systemic absorption.

The study found that peak plasma levels of lignocaine increased with higher doses, and the cream was well tolerated, suggesting that EMLA could be a safe option for managing chronic ulcer pain, warranting further investigation into its analgesic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma concentrations of lignocaine and prilocaine after a 24-h application of analgesic cream (EMLA) to leg ulcers. Stymne, B., Lillieborg, S.[2019]

In a study involving 40 participants, a topical gel mixture of lidocaine and prilocaine (2.5% each) was found to be significantly more effective than 20% benzocaine in reducing pain from needle insertion in the maxillary vestibule.

The majority of subjects (87.5% to 100% over time) reported that the lidocaine/prilocaine side was less painful, with statistically significant results indicating better pain relief (p < 0.05) compared to benzocaine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of pain from needle stick in the oral mucosa by topical anesthetics: a comparative study between lidocaine/prilocaine and benzocaine. Abu Al-Melh, M., Andersson, L., Behbehani, E.[2022]

A topical gel containing 2.5% lidocaine and 3.5% prilocaine significantly reduced discomfort during 35% trichloroacetic acid (TCA) peels, with 8 out of 10 patients reporting at least a 40% decrease in pain compared to previous peels without anesthesia.

While effective in pain reduction, the gel may increase the depth of the peel, suggesting it should only be used with TCA concentrations below 30% to avoid potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of a topical lidocaine/prilocaine anesthetic gel in 35% trichloroacetic acid peels. Rubin, MG.[2019]

Articaine, introduced in 1976 and widely used since 1986, has become the most popular local anesthetic in dentistry, surpassing lignocaine due to its effective pain control and rapid action.

Compared to older anesthetics, articaine offers enhanced safety and efficacy, making it a valuable addition to the local anesthetic options available to dental practitioners.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New anesthetics]. Malamed, SF.[2013]

In a study involving 30 patients undergoing axillary brachial plexus anaesthesia, both lidocaine and prilocaine provided a similar mean onset time of surgical analgesia at 10 minutes, indicating their effectiveness as local anesthetics.

Pharmacokinetically, while both lidocaine and prilocaine were eliminated rapidly, prilocaine had a higher total body clearance compared to lidocaine, suggesting it may be metabolized more efficiently, making both drugs suitable options for regional anaesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the effects and disposition kinetics of lidocaine and (+/-)prilocaine in patients undergoing axillary brachial plexus block during day case surgery. Simon, MA., Vree, TB., Gielen, MJ., et al.[2021]

In a study of 101 patients, Emla (lignocaine/prilocaine) cream significantly reduced pain during sharp debridement of chronic leg ulcers, with median pain scores of 18 mm for Emla compared to 53.5 mm for placebo (p < 0.0001).

The safety profile of Emla was favorable, with only mild and transient local reactions reported at similar rates in both Emla and placebo groups, indicating it is a safe option for pain management in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using a topical anaesthetic cream to reduce pain during sharp debridement of chronic leg ulcers. Rosenthal, D., Murphy, F., Gottschalk, R., et al.[2018]

Alkalinizing prilocaine with 8.4% NaHCO3 did not change the onset or termination times for sensory block but significantly prolonged the duration of motor block compared to standard prilocaine.

Patients receiving the alkalinized prilocaine reported higher satisfaction and experienced less intense tourniquet pain, suggesting it may be a more effective option for hand-wrist surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the effects of low volume prilocaine and alkalinized prilocaine for the regional intravenous anesthesia technique in hand and wrist surgery. Kapusuz, O., Argun, G., Arikan, M., et al.[2021]

A patient developed an allergic contact dermatitis from prilocaine, confirmed through patch testing, which also showed cross-reactivity with articaine but not with other amide anesthetics like lidocaine or mepivacaine.

The study highlights the importance of testing multiple amide anesthetics in cases of suspected delayed-type allergies, as there are no established rules for cross-reactivity among them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contact allergy and cross-reactions caused by prilocaine. Suhonen, R., Kanerva, L.[2013]

The study found that a methylcellulose-based formulation of lidocaine and prilocaine (P-L) significantly enhances the absorption of these anesthetics through the skin compared to the carbopol-based Eutectic Mixture of Local Anesthesia (EMLA), with higher concentrations detected in the dermis.

Using a microdialysis system, the researchers demonstrated that the P-L formulation resulted in greater area under the concentration-time curve (AUC) and maximal concentrations (Cmax) for both lidocaine and prilocaine, indicating improved efficacy in local anesthesia delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous penetration kinetics of lidocaine and prilocaine in two local anesthetic formulations assessed by in vivo microdialysis in pigs. Wei, H., Chen, Y., Xu, L., et al.[2019]

In a study of 66 patients undergoing hemodialysis, EMLA cream (lidocaine/prilocaine) provided significantly better pain relief during arteriovenous fistula puncture compared to lidocaine tape, with a notable improvement of 10.1 mm on a 100-mm visual analog scale.

Both treatments were safe, with no drug-related adverse events reported, and there was no significant difference in quality of life between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the pain-reducing effects of EMLA cream and of lidocaine tape during arteriovenous fistula puncture in patients undergoing hemodialysis: A multi-center, open-label, randomized crossover trial. Fujimoto, K., Adachi, H., Yamazaki, K., et al.[2020]

The lidocaine/tetracaine medicated plaster effectively reduces pain during minor dermatological and vascular access procedures, showing significantly lower patient-reported pain scores compared to placebo and lidocaine/prilocaine cream in clinical trials.

Systemic absorption of the active ingredients from the plaster is minimal after a 1-hour application, indicating a localized effect with a good safety profile, as the treatment was well tolerated with only minor, self-resolving adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lidocaine/tetracaine medicated plaster: in minor dermatological and needle puncture procedures. Croxtall, JD.[2021]

The modified thermoresponsive poloxamer-based formulation for lidocaine showed sustained release for up to 72 hours, with a significant reduction in burst release when polyvinyl pyrrolidone was added, indicating improved control over drug delivery.

Lidocaine released into ex vivo human intra-articular fluid occurred 1.4 times faster than in phosphate-buffered saline, suggesting that the formulation can effectively target pain relief in the knee joint after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and ex vivo characterisation of an in situ gelling formulation for sustained lidocaine release with potential use following knee arthroplasty. Sharma, M., Chandramouli, K., Curley, L., et al.[2021]

The study found that both the lidocaine-tetracaine (LT cream) and lidocaine-prilocaine (LP cream) formulations are chemically stable for over 3 months and have similar release rates for lidocaine, indicating their potential effectiveness as local anesthetics.

In terms of skin penetration and anesthetic action, LT cream showed comparable results to LP cream in guinea pigs, suggesting that LT cream could be a viable, cost-effective alternative for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local anesthetic cream prepared from lidocaine-tetracaine eutectic mixture. Ohzeki, K., Kitahara, M., Suzuki, N., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Plasma concentrations of lignocaine and prilocaine after a 24-h application of analgesic cream (EMLA) to leg ulcers. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Reduction of pain from needle stick in the oral mucosa by topical anesthetics: a comparative study between lidocaine/prilocaine and benzocaine. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The efficacy of a topical lidocaine/prilocaine anesthetic gel in 35% trichloroacetic acid peels. [2019]

4. Belgium pubmed.ncbi.nlm.nih.gov

[New anesthetics]. [2013]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Comparison of the effects and disposition kinetics of lidocaine and (+/-)prilocaine in patients undergoing axillary brachial plexus block during day case surgery. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Using a topical anaesthetic cream to reduce pain during sharp debridement of chronic leg ulcers. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Comparison of the effects of low volume prilocaine and alkalinized prilocaine for the regional intravenous anesthesia technique in hand and wrist surgery. [2021]

8. Canada pubmed.ncbi.nlm.nih.gov

Contact allergy and cross-reactions caused by prilocaine. [2013]

9. Japan pubmed.ncbi.nlm.nih.gov

Percutaneous penetration kinetics of lidocaine and prilocaine in two local anesthetic formulations assessed by in vivo microdialysis in pigs. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Comparison of the pain-reducing effects of EMLA cream and of lidocaine tape during arteriovenous fistula puncture in patients undergoing hemodialysis: A multi-center, open-label, randomized crossover trial. [2020]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Lidocaine/tetracaine medicated plaster: in minor dermatological and needle puncture procedures. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

In vitro and ex vivo characterisation of an in situ gelling formulation for sustained lidocaine release with potential use following knee arthroplasty. [2021]

13. Japan pubmed.ncbi.nlm.nih.gov

Local anesthetic cream prepared from lidocaine-tetracaine eutectic mixture. [2019]