The Pharmacokinetics of 2% TD1414 Cream in Adults With Secondarily Infected Traumatic Lesions (SITL) or Impetigo

Study Overview
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Brief Summary
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A national, prospective single arm phase II study investigating the pharmacokinetics and safety of the 2% TD1414 cream when applied 3 times daily for 7 days to adult patients with impetigo or Secondarily Infected Traumatic Lesions (SITL). A total of 20 patients will be enrolled.

Official Title
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The Pharmacokinetics of 2% TD1414 Cream in Adults With Secondarily Infected Traumatic Lesions (SITL) or Impetigo

Conditions
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Secondarily Infected Traumatic Lesions (SITL), Impetigo

Intervention / Treatment
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* Drug: 2% TD1414 Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability and willingness to comply with all the study requirements/procedures Age ≥ 18 and ≤65 years Primary bullous/non-bullous impetigo or SITL Patients suffering from primary bullous/non-bullous impetigo must have: Not more than 10 discrete lesions, and A total lesional area ≥ 1 cm2 and ≤ 100 cm2, and Any surrounding erythema must not extend beyond 2 cm from the edge of the lesion, and Total SIRS score equal to or ≥ 8 Patients suffering from SITL must have: A total infected area of the traumatic lesion ≥ 1 cm2 and ≤ 100 cm2, and Any surrounding erythema must not extend beyond 2 cm from the edge of the lesion, and Total SIRS score ≥ 8, and SITL not caused by burns or animal/human bite Amenable for treatment with topical antibiotic alone Body Mass Index ≥18 and ≤ 35 kg/m2. Exclusion Criteria: Immunosuppressed state or other serious systemic disease Signs and/or symptoms of systemic infection, such as malaise and fever or local adenopathy and fever Unwillingness to abstain from use of any other topical products including emollients on the lesional area during the study Systemic treatment with antibacterials or immunosuppressive agents (e.g. corticosteroids) within 2 days before day 1 (inhaled/intranasal steroids may be used) Topical treatment with antibacterials, immunosuppressive agents (e.g. corticosteroids) or antiseptics (e.g. alcohol, chlorhexidine, hydrogen peroxide, iodine) on the lesional area within 2 days before day 1 Indication for surgical or systemic treatment of the SITL/impetigo Known or suspected hypersensitivity to any of the components of the study medication Participation in any other interventional clinical trial or use of an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to day 1 Previously enrolled in this study A blood alcohol content ≥ 0.08% as determined by a Breathalyzer test Known or suspected history of alcohol abuse/alcoholism or drug abuse Known or suspected impairment of liver function Heart rhythm disturbances or clinically significant quantitative or qualitative abnormality in the pretreatment ECG Blood donation in excess of 500mL within 56 days before day 1 or donation during the study or within 3 days of leaving the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: 2% TD1414 Cream<br>* Application 3 times daily for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TD1414 Serum Concentration by Timepoint | On Days 1 and 2(and possibly Day 3 depending on the time of first application on Day 1) a sample was taken for pharmacokinetic(PK) analysis at any time before first application on Day 1, and at 12±1, 18±1, 24±1 and 36±4 hours after first application. If the 36±4 hours sampling time fell on Day 3, then a second sample was also required on Day 3, but was to be obtained at 6pm or afterwards. On Days 3 to 6(and also Day 7 if the very last application fell on Day 8), one sample was taken on each day at any time during the day. On Days 7 and 8(or Days 8 and 9 if very last application was on Day 8), a sample was taken immediately before the very last application and at 6±1, 12±1 and 24±2 hours after the very last application. On Days 9 and 10, one sample was taken on each day at any time during the day. If the participant had already had a sample(s) taken on Day 9 because the timing of some of the post-last application samples fell on this day, then further samples were not required on Day 9 | From 0 hours to 240 hours | 
| Peak TD1414 Serum Concentration (Cmax ) | The Cmax was summarised by lesion size at baseline, by SIRS scores at baseline and by amount of TD1414 cream used. Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses. For description of lesion size, SIRS score and amount of TD1414 cream used please see outcome measure 3, 4 and 5 respectively. | From 0 hours to 240 hours | 
| Peak Serum Concentration by Baseline Lesion Size | On Day 1 (before the first application), the (sub)investigator recorded the size of the lesion(s). For each participant the size of the lesion was allocated to one of two categories: ≤15cm² or >15cm². The Cmax is presented by baseline lesion size category (≤15 cm² and >15 cm²). Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses. | From 0 hours to 240 hours | 
| Peak Serum Concentration by SIRS Score | On Day 1 (before the first application), the (sub)investigator recorded the severity of the lesion(s). The severity was to be recorded using the Severity of Infection Rating Scale (SIRS). For the SIRS, the following seven clinical signs/symptoms of infection were assessed: Exudates/pus Crusting Erythema Oedema Tissue warmth Itching Pain Each of the seven signs/symptoms was scored using the following scale: 0 = absent 2 = mild 4 = moderate 6 = severe The scores for each sign/symptom were summed to give the total SIRS score. The total SIRS score could range from 0 to 42. Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses. | From 0 hours to 240 hours | 
| Peak Serum Concentration by Amount of TD1414 Cream Used | The weight of TD1414 cream used was calculated by subtracting the weight of the used dispensed tube from the mean weight of a full tube. Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses. | From 0 hours to 240 hours | 
| Time to Reach Peak Serum Concentration (Tmax ) | Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses. | From 0 hours to 240 hours | 
| Time to Reach Peak Serum Concentration (Tmax ) by Baseline Lesion Size | Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses. | From 0 hours to 240 hours | 
| Time to Reach Peak Serum Concentration (Tmax ) by SIRS Score | Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses. | From 0 hours to 240 hours | 
| Time to Reach Peak Serum Concentration (Tmax ) by Amount of TD1414 Cream Used | Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses. | From 0 hours to 240 hours | 
| Area Under the Curve (AUC(0-t)) | Area under the concentration-time curve (AUC(0-t)) from time 0 to time of last non-zero observation after dosing, calculated by linear/log trapezoidal method. Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses. | From 0 hours to 240 hours | 
| Area Under the Curve by Baseline Lesion Size | On Day 1 (before the first application), the (sub)investigator recorded the size of the lesion(s). For each participant the size of the lesion was allocated to one of two categories: ≤15cm² or >15cm². Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses. | From 0 hours to 240 hours | 
| Area Under the Curve by SIRS Score | On Day 1 (before the first application), the (sub)investigator recorded the severity of the lesion(s). The severity was to be recorded using the Severity of Infection Rating Scale (SIRS). For the SIRS, the following seven clinical signs/symptoms of infection were assessed: Exudates/pus, Crusting, Erythema, Oedema, Tissue warmth, Itching and Pain. Each of the seven signs/symptoms was scored using the following scale: 0 = absent 2 = mild 4 = moderate 6 = severe The scores for each sign/symptom were summed to give the total SIRS score. The total SIRS score could range from 0 to 42. Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses. | From 0 hours to 240 hours | 
| Area Under the Curve (AUC(0-t)) by Amount of TD1414 Cream Used | The weight of TD1414 cream used was calculated by subtracting the weight of the used dispensed tube from the mean weight of a full tube. Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses. | From 0 hours to 240 hours |