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

• Sponsor: LEO Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00758862
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Duration (Months): 2
• Patients Per Site Per Month: 9.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Secondarily Infected Traumatic Lesions (SITL); Impetigo	Drug: 2% TD1414 Cream	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Pharmacokinetics of 2% TD1414 Cream in Adults With Secondarily Infected Traumatic Lesions (SITL) or Impetigo
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: 2% TD1414 Cream; Application 3 times daily for 7 days

Outcome Measures

Primary Outcome Measures

1. TD1414 Serum Concentration by Timepoint [From 0 hours to 240 hours]

   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

2. Peak TD1414 Serum Concentration (Cmax ) [From 0 hours to 240 hours]

   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.

3. Peak Serum Concentration by Baseline Lesion Size [From 0 hours to 240 hours]

   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.

4. Peak Serum Concentration by SIRS Score [From 0 hours to 240 hours]

   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.

5. Peak Serum Concentration by Amount of TD1414 Cream Used [From 0 hours to 240 hours]

   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.

6. Time to Reach Peak Serum Concentration (Tmax ) [From 0 hours to 240 hours]

   Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses.

7. Time to Reach Peak Serum Concentration (Tmax ) by Baseline Lesion Size [From 0 hours to 240 hours]

   Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses.

8. Time to Reach Peak Serum Concentration (Tmax ) by SIRS Score [From 0 hours to 240 hours]

   Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses.

9. Time to Reach Peak Serum Concentration (Tmax ) by Amount of TD1414 Cream Used [From 0 hours to 240 hours]

   Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses.

10. Area Under the Curve (AUC(0-t)) [From 0 hours to 240 hours]

    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.

11. Area Under the Curve by Baseline Lesion Size [From 0 hours to 240 hours]

    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.

12. Area Under the Curve by SIRS Score [From 0 hours to 240 hours]

    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.

13. Area Under the Curve (AUC(0-t)) by Amount of TD1414 Cream Used [From 0 hours to 240 hours]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	J&S Studies, Inc.	College Station	Texas	United States	77840

Sponsors and Collaborators

• LEO Pharma

Investigators

• Principal Investigator: Terry Jones, MD, J&S Studies Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT00758862
• Other Study ID Numbers: TD1414-C22
• First Posted: Sep 25, 2008
• Last Update Posted: Jul 23, 2018
• Last Verified: Jun 1, 2018

• Additional relevant MeSH terms: Impetigo

Study Results

Participant Flow

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times on lesions area(s) daily for 7 days. A maximum of 0.5g of cream on a 100 cm2 lesion area was to be used per application.
Period Title: Overall Study
STARTED	20
COMPLETED	19
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.1 (11.8)
Sex: Female, Male (Count of Participants)
Female	8 40%
Male	12 60%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	TD1414 Serum Concentration by Timepoint
Description	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
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

One participant withdrew at day 3 due to the participant being out of range of the inclusion criterion.

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
12 hours Post First Application	624.3 (1255.3)
18 hours Post First Application	864.1 (1635.7)
24 hours Post First Application	1195.7 (2448.1)
36 hours Post First Application	888.4 (1878.6)
Day 3	659.1 (1461.8)
Day 4	309.0 (578.5)
Day 5	344.4 (673.0)
Day 6	178.8 (199.1)
Prior last application	177.4 (220.5)
6 hours Post Last Application	189.9 (231.1)
12 hours Post Last Application	190.6 (214.0)
24 hours Post Last Application	108.6 (135.0)
Day 9	99.2 (125.4)
Day 10	47.2 (60.1)

2. Primary Outcome

Title	Peak TD1414 Serum Concentration (Cmax )
Description	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.
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

Cmax could not be calculated for one participant as all values below lower limit of quantification (TD1414 concentration = 50pg/mL).

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
Geometric Mean (Standard Deviation) [pg/mL]	650.4 (2433.6)

3. Primary Outcome

Title	Peak Serum Concentration by Baseline Lesion Size
Description	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.
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

Cmax could not be calculated for one participant as all values below lower limit of quantification (TD1414 concentration = 50pg/mL).

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
<=15 cm^2	484.1 (1755.1)
>15 cm^2	1233.3 (3545.0)

4. Primary Outcome

Title	Peak Serum Concentration by SIRS Score
Description	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.
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

Cmax could not be calculated for one participant as all values below lower limit of quantification (TD1414 concentration = 50pg/mL).

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
SIRS score <=13	416.2 (1937.5)
SIRS score >13	1068.3 (2931.6)

5. Primary Outcome

Title	Peak Serum Concentration by Amount of TD1414 Cream Used
Description	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.
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

Cmax could not be calculated for one participant as all values below lower limit of quantification (TD1414 concentration = 50pg/mL).

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
<=2 g	323.5 (858.2)
>2 g	1081.0 (2976.6)

6. Primary Outcome

Title	Time to Reach Peak Serum Concentration (Tmax )
Description	Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses.
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

Tmax could not be calculated for one participant as all values below lower limit of quantification (TD1414 concentration = 50pg/mL).

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
Median (Standard Deviation) [hours]	32.08 (59.82)

7. Primary Outcome

Title	Time to Reach Peak Serum Concentration (Tmax ) by Baseline Lesion Size
Description	Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses.
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

Tmax could not be calculated for one participant as all values below lower limit of quantification (TD1414 concentration = 50pg/mL).

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
<=15 cm^2	47.42 (56.91)
>15 cm^2	23.73 (69.77)

8. Primary Outcome

Title	Time to Reach Peak Serum Concentration (Tmax ) by SIRS Score
Description	Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses.
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

AUC(0-t) could not be calculated for one participant as all values below lower limit of quantification (TD1414 concentration = 50pg/mL).

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
<=13 cm^2	42.21 (62.79)
>13 cm^2	24.22 (58.03)

9. Primary Outcome

Title	Time to Reach Peak Serum Concentration (Tmax ) by Amount of TD1414 Cream Used
Description	Please see 1. Primary Outcome for details on collection of blood samples for the Pharmacokinetic analyses.
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

Tmax could not be calculated for one participant as all values below lower limit of quantification (TD1414 concentration = 50pg/mL).

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
<=2 g	28.15 (63.90)
>2 g	33.65 (62.68)

10. Primary Outcome

Title	Area Under the Curve (AUC(0-t))
Description	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.
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

AUC(0-t) could not be calculated for one participant as all values below lower limit of quantification (TD1414 concentration = 50pg/mL).

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
Geometric Mean (Standard Deviation) [h*pg/mL]	32138 (123032)

11. Primary Outcome

Title	Area Under the Curve by Baseline Lesion Size
Description	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.
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

AUC(0-t) could not be calculated for one participant as all values below lower limit of quantification (TD1414 concentration = 50pg/mL).

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
<=15 cm^2	21240 (61954)
>15 cm^2	78836 (192236)

12. Primary Outcome

Title	Area Under the Curve by SIRS Score
Description	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.
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

AUC(0-t) could not be calculated for one participant as all values below lower limit of quantification (TD1414 concentration = 50pg/mL).

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
SIRS score <=13	17923 (69972)
SIRS score >13	61488 (160681)

13. Primary Outcome

Title	Area Under the Curve (AUC(0-t)) by Amount of TD1414 Cream Used
Description	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.
Time Frame	From 0 hours to 240 hours

Outcome Measure Data

Analysis Population Description

AUC(0-t) could not be calculated for one participant as all values below lower limit of quantification (TD1414 concentration = 50pg/mL).

Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
Measure Participants	20
<=2 g	13642 (23828)
>2 g	59932 (150278)

Adverse Events

Time Frame	From Day 1 to Day 10
Arm/Group Title	TD1414
Arm/Group Description	2% TD1414 Cream: Application 3 times daily for 7 days
All Cause Mortality
	TD1414
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	TD1414
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Other (Not Including Serious) Adverse Events
	TD1414
	Affected / at Risk (%)	# Events
Total	0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Company acknowledges the investigator's right to publish the entire results of the study, irrespective of outcome. The Company retains the right to have any publication submitted to the Company for review at least 30 days prior to the same paper being submitted for publication or presentation. Investigators must undertake not to submit any part of their individual data for publication without the prior consent of LEO.