LAWAF: Safety Study of Levocetirizine and Fexofenadine

• Sponsor: Charite University, Berlin, Germany (Other)
• Overall Status: Completed
• CT.gov ID: NCT01586091
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 3
• Duration (Months): 12
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

This Study is to comparison of Efficacy and Consistency of Action of Levocetirizine 5 mg once daily with Fexofenadine 60 mg twice daily in the histamine induced wheal, flare and itch Response.

Condition or Disease	Intervention/Treatment	Phase
Pruritus; Chronic Urticaria; Allergic Rhinitis	Drug: Levocetirizine Oral Tablet; Drug: Fexofenadine 60 Mg Oral Tablet; Drug: Placebo Oral Tablet	Phase 4

Detailed Description

This will be a randomized, double-blind, placebo-controlled study with intra-individual comparison of the histamine induced wheal and flare reaction. In September 2009, Fexofenadine was approved as an antihistamine against allergies in Japan and it is currently used widely. It has been approved in 120 countries, including the US, UK, France and Germany [11]. In Europe and the United States, fexofenadine is marketed at 120 mg once daily for allergic rhinitis and 180mg once daily for urticaria. In Japan, fexofenadine is marketed at 60 mg twice daily for both conditions. But is this dosage regimen as effective as levocetirizine, 5 mg once daily? The above described study from Takahashi et al, comparing 60 mg twice daily versus cetirizine 10 mg once daily suggests that it is not [4]. The aim of the study is to compare the efficacy and consistency of action of levocetirizine 5 mg once daily with fexofenadine 60 mg twice daily over a 24 hour period in the histamine induced wheal, flare and itch response. Furthermore, we would like to investigate whether a different between Japanese and Caucasian exists or not. Each volunteer will receive the study medication at time point 0 and 12 hour later. Skin Prick Test (SPT) will be performed in each volunteer using histamine (10 mg/ml), 15 minutes before drug admission (baseline) and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours afterwards. Volumetric optical scanning system and infrared camera will be used for objective evaluation of the wheal- and flare reduction. Additionally, measurement of the erythema diameter with a transparent ruler will be performed. The subjective intensity of itching will be assessed using a Visual Analogue Scale (VAS). To relate the pharmacokinetics of the drugs to their pharmacodynamics, blood samples for assay of drug concentrations will be taken at baseline and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours later. Subjects will undergo the same procedure on three separate occasions to receive each treatment option. The options are: placebo at time 0 hours + placebo at 12 hours, Levocetirizine 5mg at time 0 hours + placebo at 12 hours or fexofenadine 60mg at time 0 hours

• fexofenadine 60mg at 12 hours. There will be a washout period of at least 6 days between the treatments.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparison of Efficacy and Consistency of Action of Levocetirizine 5 mg Once Daily With Fexofenadine 60 mg Twice Daily in the Histamine Induced Wheal, Flare and Itch Response
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo per os at time 0 hours + placebo per os at 12 hours.	Drug: Placebo Oral Tablet; Other Names: Lichtenstein
Active Comparator: Levocetirizin Levocetirizin 5mg at time 0 and placebo per os at 12 hours	Drug: Levocetirizine Oral Tablet; Drug: Placebo Oral Tablet; Other Names: Lichtenstein
Active Comparator: Fexofenadine Fexofenadine 60mg per os at time 0 hours + fexofenadine 60mg per os at 12 hours	Drug: Fexofenadine 60 Mg Oral Tablet; Other Names: Telfast

Outcome Measures

Primary Outcome Measures

1. Pruritus as Assessed by the VAS Score [up to 10 minutes after skin prick test performed 24 hours after drug administration]

   We measured drug concentrations and various aspects of skin provocation testing such as itch intensity and wheal size. Measurements made at each time point were as followed: Pruritus was assessed every 30 s for 10 min after SPT using a visual analogue scale (VAS) score with a "0" and "100" at the two ex- tremes of an unmarked 100 mm line with higher values indicating greater puritus. The mean VAS for each 10 min was calculated and used as a primary end Point.

2. Flaire Diameter (mm) [24 hours per treatment]

   Flaire diameter was measured with a transparent ruler as the mean of the largest diameter and the diameter at right angles to this.

3. Wheal Volume (cm3) [24 hours per treatment]

   Wheal volume was measured by a non-contact three dimensional measurement system (PRIMOS contact, GFM Messtechnik GmbH, Teltow, Germany).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Eighteen (18) healthy male volunteers, including at least 6 persons of Japanese origin, will be recruited for this study

Exclusion Criteria:

• None of the subjects will have taken oral antihistamines, antidepressants, antipsychotics or corticosteroids or applied topical antihistamines, corticosteroids or mast cell stabilizers to the skin for 2 weeks prior to testing.

• No subject shall perform physical exercise for 4 hours prior to the skin prick testing.

• Especially, Bronchial asthma, anaphylactic reactions in the history, use of beta-blockers, skin diseases in the test field are exclusion criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Berlin Charité, Department of Dermatology and Allergy	Berlin		Germany	10117

Sponsors and Collaborators

• Charite University, Berlin, Germany

Investigators

• Principal Investigator: Marcus Maurer, MD, Charite Universitätsmedizin Berlin

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Martin Metz, Prof. Dr. med., Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT01586091
• Other Study ID Numbers: 2010-022747-38
• First Posted: Apr 26, 2012
• Last Update Posted: Oct 4, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Pruritus; Urticaria; Chronic Urticaria; Fexofenadine; Levocetirizine

Study Results

Participant Flow

Arm/Group Title	Day 1	Day 2	Day 3
Arm/Group Description	Intake of Placebo- Fexofenadine 6 mg - Levocetirizin 5 mg	Intake of Fexofenadine 6 mg - Levocetirizin 5 mg - Placebo	Intake of Placebo- Levocetirizin 5 mg- Fexofenadine 60
Period Title: Overall Study
STARTED	6	6	6
COMPLETED	6	6	6
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Day 2	Day 3	Day 1	Total
Arm/Group Description	Intake on 0 hours and 12 hours Intake Levocetirizn	Intake on 0 hours and 12 hours Intake Fexofenadine	Intake on 0 hours and 12 hours Intake Placebo	Total of all reporting groups
Overall Participants	6	6	6	18
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	6 100%	6 100%	18 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	6 100%	6 100%	6 100%	18 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	3 50%	3 50%	3 50%	9 50%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	3 50%	3 50%	3 50%	9 50%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Number) [Number]
Germany	6 100%	6 100%	6 100%	18 100%

Outcome Measures

1. Primary Outcome

Title	Pruritus as Assessed by the VAS Score
Description	We measured drug concentrations and various aspects of skin provocation testing such as itch intensity and wheal size. Measurements made at each time point were as followed: Pruritus was assessed every 30 s for 10 min after SPT using a visual analogue scale (VAS) score with a "0" and "100" at the two ex- tremes of an unmarked 100 mm line with higher values indicating greater puritus. The mean VAS for each 10 min was calculated and used as a primary end Point.
Time Frame	up to 10 minutes after skin prick test performed 24 hours after drug administration

Outcome Measure Data

Analysis Population Description

Please see Outcome Measure Description. Itch was measured using a 10 point VAS.

Arm/Group Title	Levocetirizin	Fexofenadine	Placebo
Arm/Group Description	5 mg once daily	60 mg twice daily	Placebo as comparison to Levocetirizin
Measure Participants	18	18	18
Mean (Standard Error) [mm]	11.5 (16.4)	25.4 (35.3)	46.0 (44.6)

2. Primary Outcome

Title	Flaire Diameter (mm)
Description	Flaire diameter was measured with a transparent ruler as the mean of the largest diameter and the diameter at right angles to this.
Time Frame	24 hours per treatment

Outcome Measure Data

Analysis Population Description

Please see Outcome measure description. Flair Diameter was measured in mm.

Arm/Group Title	Placebo	Levocetirizin	Fexofenadine
Arm/Group Description	Placebo as comparison to Levocetirizin	5 mg once daily	60 mg twice daily
Measure Participants	18	18	18
Mean (Standard Error) [mm]	69.4 (24.8)	20.4 (10.0)	39.9 (13.6)

3. Primary Outcome

Title	Wheal Volume (cm3)
Description	Wheal volume was measured by a non-contact three dimensional measurement system (PRIMOS contact, GFM Messtechnik GmbH, Teltow, Germany).
Time Frame	24 hours per treatment

Outcome Measure Data

Analysis Population Description

Please see Outcome Measure Description. Wheal volume was measured in cm3. The units of measure are provided in the report of the this study protocol.

Arm/Group Title	Placebo	Levocetirizin	Fexofenadine
Arm/Group Description	Placebo as comparison to Levocetirizin	5 mg once daily	60 mg twice daily
Measure Participants	18	18	18
Mean (Standard Error) [cm3]	174.6 (50.9)	35.2 (13.5)	106.3 (39.5)

Adverse Events

Time Frame	Adverse Events were collected on the following time points: 0 (baseline), 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours
Arm/Group Title	Levocetirizine		Fexofenadine		Placebo
Arm/Group Description	5 mg once daily		60 mg twice daily, oral		Placebo against Levocetirzine
All Cause Mortality
	Levocetirizine		Fexofenadine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Levocetirizine		Fexofenadine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Levocetirizine		Fexofenadine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/18 (11.1%)		3/18 (16.7%)		2/18 (11.1%)
Gastrointestinal disorders
fatigue	1/18 (5.6%)	1	0/18 (0%)	0	0/18 (0%)	0
Infections and infestations
bacterial inflammation of the finger	0/18 (0%)	0	1/18 (5.6%)	1	0/18 (0%)	0
Respiratory, thoracic and mediastinal disorders
upper respiratory tract infection	2/18 (11.1%)	2	1/18 (5.6%)	1	0/18 (0%)	0
Skin and subcutaneous tissue disorders
pain at the puncture site of the intravenous catheter	0/18 (0%)	0	1/18 (5.6%)	1	1/18 (5.6%)	1
Social circumstances
pain in the knee joint	0/18 (0%)	0	0/18 (0%)	0	1/18 (5.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.