Safety, Tolerability and Efficacy of Nefopam Cream in Burn Patients

NCT04685577 | Completed Phase 2

• 3 other identifiers: NEFOPAM-1W81XWH-19-2-0048CDMRP-MB170036
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Burn patients very commonly develop abnormal scars after injury which can be red, raised or elevated, painful and very itchy. They can prevent normal movement of hands and other joints and lead to ugly deformities which makes physical and psychological recovery very difficult. This proposal seeks to test the usefulness of a cream called Nefopam to prevent and treat these bad scars after burns and other injury to the skin. Nefopam is a drug that has been used as a pain medicine in Europe but has been found to have anti-scarring properties in rats and pigs. It has been tested in healthy people and found to be well tolerated and safe. The study purposes to make a scratch in the hip skin in 60 adult burn patients at two burn unit sites, the University of Alberta and the University of California at Davis, Sacramento CA. Burn patients in the study will have a scratch wound in the skin of the each side of the hip, part way through the thickness of the skin which is shallow at first but gets deeper. This scratch is made with a special guide which precisely controls the length and depth of the scratch so that each scratch is the same. Part of the scratch heals without scar and the deeper part heals with a red raised scar over a small region less than 2 inches long. One side will be treated with the drug and the other with a control or placebo are in a white cream that is indistinguishable, where you cannot tell which side contains the drug. Once the wound is nearly healed, usually less than 21 days, the cream will be applied twice daily for three weeks. Measurements will be done about once per month for four months where the healing scratches will be photographed, measurements of the thickness made with ultrasound and mexameter for scar color or pigment and redness. Ultrasound is a painless probe that uses sound waves to measure scar thickness and mexameter is a painless probe on the surface of the scratch to measure color and redness. Both measurements take only minutes to complete. Patients will be asked to answer a scar assessment form about on how they feel each scratch during the treatment and the research staff will also the complete scar form as well. It is the aim of the study to find a cream the works to prevent and reduce scarring after burn injury in military or civilian patients. In the future, an useful cream for scarring in burn patients may also be helpful for other skin damage which leads to scarring.

Conditions

Burn; Multiple Body Regions, Max. Second Degree; Third-Degree Burn; Burn Degree Second

Keywords

Hypertrophic scar, Nefopam,Burn patients.

Outcome Measures

Primary Outcomes (32)

• Assessment of efficacy by measuring scar/wound area at day 1.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Wound area will be measured using images obtained through digital photography on day 1 post operatively. Each image will be analyzed twice and the values averaged to provide an estimate of wound area (mm2) for each wound. Within-subject differences in wound area will be calculated and summarized by treatment group.

  Digital photography of the wound/scar will be performed at day 1.

• Assessment of efficacy by measuring scar/wound area at day 21.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Wound area will be measured using images obtained through digital photography on day 1 post operatively. Each image will be analyzed twice and the values averaged to provide an estimate of wound area (mm2) for each wound. Within-subject differences in wound area will be calculated and summarized by treatment group.

  Digital photography of the wound/scar will be performed at day 21.

• Assessment of efficacy by measuring scar/wound area at day 27.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Wound area will be measured using images obtained through digital photography on day 1 post operatively. Each image will be analyzed twice and the values averaged to provide an estimate of wound area (mm2) for each wound. Within-subject differences in wound area will be calculated and summarized by treatment group.

  Digital photography of the wound/scar will be performed at day 27.

• Assessment of efficacy by measuring scar/wound area at day 48.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Wound area will be measured using images obtained through digital photography on day 1 post operatively. Each image will be analyzed twice and the values averaged to provide an estimate of wound area (mm2) for each wound. Within-subject differences in wound area will be calculated and summarized by treatment group.

  Digital photography of the wound/scar will be performed at day 48.

• Assessment of efficacy by measuring scar/wound area at day 76.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Wound area will be measured using images obtained through digital photography on day 1 post operatively. Each image will be analyzed twice and the values averaged to provide an estimate of wound area (mm2) for each wound. Within-subject differences in wound area will be calculated and summarized by treatment group.

  Digital photography of the wound/scar will be performed at day 76.

• Assessment of efficacy by measuring scar/wound area at day 104.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Wound area will be measured using images obtained through digital photography on day 1 post operatively. Each image will be analyzed twice and the values averaged to provide an estimate of wound area (mm2) for each wound. Within-subject differences in wound area will be calculated and summarized by treatment group.

  Digital photography of the wound/scar will be performed at day 104.

• Assessment of efficacy by measuring scar/wound depth at day 1.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. At each visit there are three (3) measurements of wound depth at three (3) different points (deep end, mid-point, superficial end) will be taken. Scar depth will be measured in mm, based on ultrasound readings taken at scheduled assessment times.

  Dermal ultrasound analysis of the wound/scar will be performed at day 1.

• Assessment of efficacy by measuring scar/wound depth at day 21.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. At each visit there are three (3) measurements of wound depth at three (3) different points (deep end, mid-point, superficial end) will be taken. Scar depth will be measured in mm, based on ultrasound readings taken at scheduled assessment times.

  Dermal ultrasound analysis of the wound/scar will be performed at day 21.

• Assessment of efficacy by measuring scar/wound depth at day 27.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. At each visit there are three (3) measurements of wound depth at three (3) different points (deep end, mid-point, superficial end) will be taken. Scar depth will be measured in mm, based on ultrasound readings taken at scheduled assessment times.

  Dermal ultrasound analysis of the wound/scar will be performed at day 27.

• Assessment of efficacy by measuring scar/wound depth at day 48.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. At each visit there are three (3) measurements of wound depth at three (3) different points (deep end, mid-point, superficial end) will be taken. Scar depth will be measured in mm, based on ultrasound readings taken at scheduled assessment times.

  Dermal ultrasound analysis of the wound/scar will be performed at day 48.

• Assessment of efficacy by measuring scar/wound depth at day 76.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. At each visit there are three (3) measurements of wound depth at three (3) different points (deep end, mid-point, superficial end) will be taken. Scar depth will be measured in mm, based on ultrasound readings taken at scheduled assessment times.

  Dermal ultrasound analysis of the wound/scar will be performed at day 76.

• Assessment of efficacy by measuring scar/wound depth at day 104.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. At each visit there are three (3) measurements of wound depth at three (3) different points (deep end, mid-point, superficial end) will be taken. Scar depth will be measured in mm, based on ultrasound readings taken at scheduled assessment times.

  Dermal ultrasound analysis of the wound/scar will be performed at day 104.

• Assessment of efficacy by measuring scar erythema and pigmentation at day 1.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Once the wound has been determined to be closed, Mexameter® assessments will be performed at scheduled visits to check scar erythema and pigmentation . Mexameter® assessments will be performed at three standardized positions along each scar. At each position, three individual measurements will be taken and the mean and standard deviation will be determined for both erythema and pigmentation at each of the three measurement positions.

  Mexameter® assessments of the wound/scar will be performed at day 1.

• Assessment of efficacy by measuring scar erythema and pigmentation at day 21.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Once the wound has been determined to be closed, Mexameter® assessments will be performed at scheduled visits to check scar erythema and pigmentation . Mexameter® assessments will be performed at three standardized positions along each scar. At each position, three individual measurements will be taken and the mean and standard deviation will be determined for both erythema and pigmentation at each of the three measurement positions.

  Mexameter® assessments of the wound/scar will be performed at day 21.

• Assessment of efficacy by measuring scar erythema and pigmentation at day 27.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Once the wound has been determined to be closed, Mexameter® assessments will be performed at scheduled visits to check scar erythema and pigmentation . Mexameter® assessments will be performed at three standardized positions along each scar. At each position, three individual measurements will be taken and the mean and standard deviation will be determined for both erythema and pigmentation at each of the three measurement positions.

  Mexameter® assessments of the wound/scar will be performed at day 27.

• Assessment of efficacy by measuring scar erythema and pigmentation at day 48.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Once the wound has been determined to be closed, Mexameter® assessments will be performed at scheduled visits to check scar erythema and pigmentation . Mexameter® assessments will be performed at three standardized positions along each scar. At each position, three individual measurements will be taken and the mean and standard deviation will be determined for both erythema and pigmentation at each of the three measurement positions.

  Mexameter® assessments of the wound/scar will be performed at day 48.

• Assessment of efficacy by measuring scar erythema and pigmentation at day 76.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Once the wound has been determined to be closed, Mexameter® assessments will be performed at scheduled visits to check scar erythema and pigmentation . Mexameter® assessments will be performed at three standardized positions along each scar. At each position, three individual measurements will be taken and the mean and standard deviation will be determined for both erythema and pigmentation at each of the three measurement positions.

  Mexameter® assessments of the wound/scar will be performed at day 76.

• Assessment of efficacy by measuring scar erythema and pigmentation at day 104.

  To check the efficacy of the Nefopam cream all comparisons will be made between the Nefopam cream and the Placebo at different time point. Once the wound has been determined to be closed, Mexameter® assessments will be performed at scheduled visits to check scar erythema and pigmentation . Mexameter® assessments will be performed at three standardized positions along each scar. At each position, three individual measurements will be taken and the mean and standard deviation will be determined for both erythema and pigmentation at each of the three measurement positions.

  Mexameter® assessments of the wound/scar will be performed at day 104.

• Assessment of efficacy by assessing scar/wound healing at day 6 (during Nefopam cream treatment).

  Wound healing, defined as 100% epithelialization of the wound with no exudate. Percentage of wounds healed by visit by treatment will be summarized. The difference in proportions of healed wounds will be calculated within treatment group (active treatment against placebo within that group).

  Wound healing will be measured at day 6 (during Nefopam cream treatment).

• Assessment of efficacy by assessing scar/wound healing at day 13 (during Nefopam cream treatment).

  Wound healing, defined as 100% epithelialization of the wound with no exudate. Percentage of wounds healed by visit by treatment will be summarized. The difference in proportions of healed wounds will be calculated within treatment group (active treatment against placebo within that group).

  Wound healing will be measured at day 13 (during Nefopam cream treatment).

• Assessment of efficacy by assessing scar/wound healing at day 20 (during Nefopam cream treatment).

  Wound healing, defined as 100% epithelialization of the wound with no exudate. Percentage of wounds healed by visit by treatment will be summarized. The difference in proportions of healed wounds will be calculated within treatment group (active treatment against placebo within that group).

  Wound healing will be measured at day 20 (during Nefopam cream treatment).

• Assessment of efficacy by assessing scar/wound healing at day 27 (after completion of Nefopam cream application).

  Wound healing, defined as 100% epithelialization of the wound with no exudate. Percentage of wounds healed by visit by treatment will be summarized. The difference in proportions of healed wounds will be calculated within treatment group (active treatment against placebo within that group).

  Wound healing will be measured at day 27 (after completion of Nefopam cream application).

• Assessment of efficacy by assessing scar/wound healing at day 48 (after completion of Nefopam cream application).

  Wound healing, defined as 100% epithelialization of the wound with no exudate. Percentage of wounds healed by visit by treatment will be summarized. The difference in proportions of healed wounds will be calculated within treatment group (active treatment against placebo within that group).

  Wound healing will be measured at day 48 (after completion of Nefopam cream application).

• Assessment of efficacy by assessing scar/wound healing at day 104 (after completion of Nefopam cream application).

  Wound healing, defined as 100% epithelialization of the wound with no exudate. Percentage of wounds healed by visit by treatment will be summarized. The difference in proportions of healed wounds will be calculated within treatment group (active treatment against placebo within that group).

  Wound healing will be measured at day 104 (after completion of Nefopam cream application).

• Assessment of the scar using the Patient and Observer Scar Assessment Scales (POSAS) at day 27 (after completion of Nefopam cream application).

  The POSAS consists of a section completed by the subject and sections completed by three observers - once for each hip, at each post-wound-closure visit. The Patient section consists of seven (7) questions on 10-point scales regarding scar pain, itchiness, colour, stiffness, thickness, irregularity, and an overall assessment. The Observer sections consist of seven (7) 10-point scales regarding vascularity, pigmentation, thickness, relief, pliability, surface area, and overall assessment. On Y axis POSAS scoring will be taken and on X axis outcome from the patients at different time point will be recorded. Each of the seven questions has a 10-point scoring system, with 1 representing normal skin and 10 the worst imaginable scar or sensation. The total score of both scales consists of adding the scores of each of the seven questions (range, 7 to 70). The lowest score, 7, reflects normal skin, whereas the highest score, 70, reflects the worst imaginable scar.

  Patient and Observer Scar Assessment Scales (POSAS) will be performed at day 27 (after completion of Nefopam cream application).

• Assessment of the scar using the Patient and Observer Scar Assessment Scales (POSAS) at day 48 (after completion of Nefopam cream application).

  The POSAS consists of a section completed by the subject and sections completed by three observers - once for each hip, at each post-wound-closure visit. The Patient section consists of seven (7) questions on 10-point scales regarding scar pain, itchiness, colour, stiffness, thickness, irregularity, and an overall assessment. The Observer sections consist of seven (7) 10-point scales regarding vascularity, pigmentation, thickness, relief, pliability, surface area, and overall assessment. On Y axis POSAS scoring will be taken and on X axis outcome from the patients at different time point will be recorded. Each of the seven questions has a 10-point scoring system, with 1 representing normal skin and 10 the worst imaginable scar or sensation. The total score of both scales consists of adding the scores of each of the seven questions (range, 7 to 70). The lowest score, 7, reflects normal skin, whereas the highest score, 70, reflects the worst imaginable scar.

  Patient and Observer Scar Assessment Scales (POSAS) will be performed at day 48 (after completion of Nefopam cream application).

• Assessment of the scar using the Patient and Observer Scar Assessment Scales (POSAS) at day 76 (after completion of Nefopam cream application).

  The POSAS consists of a section completed by the subject and sections completed by three observers - once for each hip, at each post-wound-closure visit. The Patient section consists of seven (7) questions on 10-point scales regarding scar pain, itchiness, colour, stiffness, thickness, irregularity, and an overall assessment. The Observer sections consist of seven (7) 10-point scales regarding vascularity, pigmentation, thickness, relief, pliability, surface area, and overall assessment. On Y axis POSAS scoring will be taken and on X axis outcome from the patients at different time point will be recorded. Each of the seven questions has a 10-point scoring system, with 1 representing normal skin and 10 the worst imaginable scar or sensation. The total score of both scales consists of adding the scores of each of the seven questions (range, 7 to 70). The lowest score, 7, reflects normal skin, whereas the highest score, 70, reflects the worst imaginable scar.

  Patient and Observer Scar Assessment Scales (POSAS) will be performed at day 76 (after completion of Nefopam cream application).

• Assessment of the scar using the Patient and Observer Scar Assessment Scales (POSAS) at day 104 (after completion of Nefopam cream application).

  The POSAS consists of a section completed by the subject and sections completed by three observers - once for each hip, at each post-wound-closure visit. The Patient section consists of seven (7) questions on 10-point scales regarding scar pain, itchiness, colour, stiffness, thickness, irregularity, and an overall assessment. The Observer sections consist of seven (7) 10-point scales regarding vascularity, pigmentation, thickness, relief, pliability, surface area, and overall assessment. On Y axis POSAS scoring will be taken and on X axis outcome from the patients at different time point will be recorded. Each of the seven questions has a 10-point scoring system, with 1 representing normal skin and 10 the worst imaginable scar or sensation. The total score of both scales consists of adding the scores of each of the seven questions (range, 7 to 70). The lowest score, 7, reflects normal skin, whereas the highest score, 70, reflects the worst imaginable scar.

  Patient and Observer Scar Assessment Scales (POSAS) will be performed at day 104 (after completion of Nefopam cream application).

• Assessment of efficacy by performing qPCR of the fibrotic molecules at day 27 (after completion of Nefopam cream application).

  To determine the efficacy of Nefopam cream versus placebo on the fibrotic molecules including type I and type III collagen, β-catenin target gene (AXIN-2), TGF- β1, and decorin, quantitative measures will be performed. TGF-β1, AXIN-2, decorin, and collagen types I and III will be expressed as fold-change values; fold change values will be calculated based on the double delta Ct method (where fold change = 2-∆∆CT).

  Two punch biopsies will be performed on the maximally thick region of each scar on Day 27 (after completion of Nefopam cream application).

• Assessment of efficacy by performing qPCR of the fibrotic molecules at day 104(after completion of Nefopam cream application).

  To determine the efficacy of Nefopam cream versus placebo on the fibrotic molecules including type I and type III collagen, β-catenin target gene (AXIN-2), TGF- β1, and decorin, quantitative measures will be performed. TGF-β1, AXIN-2, decorin, and collagen types I and III will be expressed as fold-change values; fold change values will be calculated based on the double delta Ct method (where fold change = 2-∆∆CT).

  Two punch biopsies will be performed on the maximally thick region of each scar on Day 104 (after completion of Nefopam cream application).

• Assessment of efficacy by performing Immunohistochemistry at day 27(after completion of Nefopam cream application).

  To determine the efficacy of Nefopam cream versus placebo, protein expression of fibrotic molecules will be measured by immunohistochemistry. a-SMA (smooth muscle actin) and β -catenin immunohistochemistry will be performed at day 27.

  Two punch biopsies will be performed on the maximally thick region of each scar on Day 27 (after completion of Nefopam cream application).

• Assessment of efficacy by performing Immunohistochemistry at day 104 (after completion of Nefopam cream application).

  To determine the efficacy of Nefopam cream versus placebo, protein expression of fibrotic molecules will be measured by immunohistochemistry. a-SMA (smooth muscle actin) and β -catenin immunohistochemistry will be performed at day 104.

  Two punch biopsies will be performed on the maximally thick region of each scar on Day 104 (after completion of Nefopam cream application).

Secondary Outcomes (8)

• Assessment of Safety by assessing drug tolerability.

  Treatment tolerability will be assessed regularly during the first 21 days of the trial.

• Assessment of heart rate.

  Hear rate will be measured at day 27, 76, and 104.

• Assessment of temperature.

  Body temperature will be measured at day 27, 76, and 104.

• Assessment of blood pressure.

  Blood pressure will be measured at day 27, 76, and 104.

• Assessment of respiration.

  Respiration will be measured at day 27, 76, and 104.

Study Arms (2)

Nefopam

EXPERIMENTAL

NEFOPAM 3% cream will be applied topically to healing deep dermal scratches in the lateral hip of burn patients daily (twice) for 3 weeks during the proliferative phase of wound healing.

Drug: Nefopam

Placebo

PLACEBO COMPARATOR

This will work as a placebo for the experimental drug.

Other: Placebo (Vehicle)

Interventions

Nefopam DRUG

Nefopam HCl inhibits the proliferation and viability of human mesenchymal fibroblasts with elevated β-catenin expression without affecting normal fibroblasts. Nefopam HCl primarily targets cells in which β-catenin is above normal physiologic levels. This threshold effect makes Nefopam HCl a good prospective therapeutic agent by limiting its effect to abnormal mesenchymal cells.Nefopam HCl has been found safe and effective for the reduction of dermal scarring following standardized human dermal wounds of critical depth that produces HTS in normal human volunteers Phase 1 study. In the current study, it is proposed that the concentration of the cream will be 3% and the timing of application will be delayed until after re-epithelialization at about 21 days to maximize the antiproliferative effects of NEFOPAM during the fibrotic/proliferative phase of healing.

Also known as: Nefopam-HCl

Nefopam

Placebo (Vehicle) OTHER

Participants will receive vehicle with out the investigational product

Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female burn, or trauma patients aged \>18 - \<65 years with 5-70% TBSA deep second or third degree burns who have uninjured skin in both the lateral hip regions and have voluntarily signed the Informed Consent Form (ICF).
• Subjects with clinically acceptable results at screening for the laboratory tests specified in the trial protocol.
• Women of childbearing potential must provide a negative pregnancy serum/urine test at time of screening and have to be compliant with an effective form of birth control throughout the entire study. Non-childbearing potential means subjects have had a history of tubal ligation or a hysterectomy or are post-menopausal with no menses for at least 1 year prior to enrolment in the study.
• Subjects, who are, in the opinion of the Investigator, able to understand the study, co-operate with the study procedures and are willing to return to the clinic for all of the required follow-up visits.
• Subjects must be able to cooperate with requirements of the study (e.g. able to speak, read and write English, and will be expected to be available for adverse event monitoring for the duration of the study).
• Healthy subjects must have ALT and AST \< 2 × ULN and TB \< ULN at entry.
• Subjects with carcinoma in situ or stage 1 cancer of the skin and other tissues will be acceptable once acceptable clinical management of the carcinoma has been established.
• Patients who have well controlled HIV as defined by a viral load amount of HIV in the blood that is undetectable i.e. a: viral load less than 40 to 50 copies/ml and cannot be detected by standard tests for HIV, Hep B or Hep C will be included after consultation with an infectious disease expert.

You may not qualify if:

• Currently Subjects involved any other intervention trial(s) where the intervention could possibly affect wound healing to be eligible for enrolment in the SCX-001 (Nefopam) Cream study.
• Subjects who have scarring from previous interventions or evidence of thermal, electrical or radiation burn scars, tattoos, birthmarks or moles within 5 cm of the treatment site.
• Subjects with a history or family history of abnormal keloid scarring.
• Subjects with additional concurrent illnesses or conditions that may have interfered with wound healing like neoplastic, immune-mediated, or primary infectious disease (e.g. carcinoma, vasculitis, connective tissue disease, immune system disorders, rheumatoid arthritis, chronic renal impairment, significant hepatic impairment, inadequately or uncontrolled congestive heart failure or diabetes mellitus) or any clinically significant medical condition or history of any condition which may impair wound healing.
• Subjects with a skin disorder that is chronic or currently active and which the investigator considers will adversely affect the healing of acute wounds or will involve the areas to be examined in this trial (including psoriasis, dermatitis, eczema)
• Subjects with a body mass index \<15 or \>35 kg/m2.
• A history of radiotherapy to the study scar area.
• Subjects who are positive for HIV, hepatitis B or C.
• Subjects who have known sensitivities to SCX-001 (Nefopam) Cream, structurally related compounds or any of the constituents of SCX-001 (Nefopam) Cream.
• Subjects who have known sensitivities to EMLA cream, chlorhexidine or adhesive dressings.
• Elder patients (\> 65 years), patients with epilepsy, patients with urinary retention, or or when administered with other anticholinergic or sympathomimetic drugs or monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants.
• Subjects with end stage renal disease, where eGFR \</= 30 mL/min.

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

University of Alberta Hospital

Edmonton, Alberta, T6G2B7, Canada

Location

Related Publications (6)

• Case MT, Smith JK, Nelson RA. Reproductive, acute and subacute toxicity studies with nefopam in laboratory animals. Toxicol Appl Pharmacol. 1975 Jul;33(1):46-51. doi: 10.1016/0041-008x(75)90242-2. No abstract available.

  PMID: 1162704 BACKGROUND

• Dunkin CSJ, Pleat JM, Gillespie PH, Tyler MPH, Roberts AHN, McGrouther DA. Scarring occurs at a critical depth of skin injury: precise measurement in a graduated dermal scratch in human volunteers. Plast Reconstr Surg. 2007 May;119(6):1722-1732. doi: 10.1097/01.prs.0000258829.07399.f0.

  PMID: 17440346 BACKGROUND

• Honardoust D, Varkey M, Marcoux Y, Shankowsky HA, Tredget EE. Reduced decorin, fibromodulin, and transforming growth factor-beta3 in deep dermis leads to hypertrophic scarring. J Burn Care Res. 2012 Mar-Apr;33(2):218-27. doi: 10.1097/BCR.0b013e3182335980.

  PMID: 22079916 BACKGROUND

• Poon R, Hong H, Wei X, Pan J, Alman BA. A high throughput screen identifies Nefopam as targeting cell proliferation in beta-catenin driven neoplastic and reactive fibroproliferative disorders. PLoS One. 2012;7(5):e37940. doi: 10.1371/journal.pone.0037940. Epub 2012 May 30.

  PMID: 22666417 BACKGROUND

• Case MT, Smith JK, Nelson RA. Chronic oral toxicity studies of nefopam hydrochloride in rats and dogs. Toxicol Appl Pharmacol. 1976 May;36(2):301-6. doi: 10.1016/0041-008x(76)90009-0. No abstract available.

  PMID: 1273848 BACKGROUND

• Mather GG, Labroo R, Le Guern ME, Lepage F, Gillardin JM, Levy RH. Nefopam enantiomers: preclinical pharmacology/toxicology and pharmacokinetic characteristics in healthy subjects after intravenous administration. Chirality. 2000 Mar;12(3):153-9. doi: 10.1002/(SICI)1520-636X(2000)12:33.0.CO;2-V.

  PMID: 10689295 BACKGROUND

MeSH Terms

Conditions

Burns; Cicatrix, Hypertrophic

Interventions

Nefopam

Condition Hierarchy (Ancestors)

Wounds and Injuries; Cicatrix; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Oxazocines; Azocines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Edward E Tredget, MD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: As this is a 2 arm study. One is experimental drug and other is placebo control. No one will know which side of body part having drug and/or placebo. If required, it will be find out but this study is designed as a double blind.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2020
• First Posted: December 28, 2020
• Study Start: July 10, 2022
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)