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This study will be a randomized, double blind, placebo controlled, 3-way cross over design in allergic rhinitis subjects. Subjects will receive repeat doses of intra-nasal levocabastine for 7 days in each period and the duration of the study will be about 13 weeks. An Environmental Exposure Chamber (EEC) will be used in this study. The primary objective of the study is to investigate the non-inferiority effect of 7 days treatment with levocabastine on nasal symptoms elicited by an EEC when administered once daily (QD) compared with twice daily (BID). Also study will be conducted to investigate the superiority of effect of 7 days treatment with levocabastine (QD and BID) on nasal symptoms elicited by an EEC in subjects compared to placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Levocabastine Arm | Experimental | Subjects will be assigned to one of six treatment sequences (ABC, BCA, CAB, ACB, BAC, CBA) in accordance with the randomisation schedule. A = Two, 50 microgram (mcg) sprays per nostril of levocabastine QD in the morning. Total dose of 200 mcg. Two, 0 mcg sprays from placebo to match vehicle in the evening; B = Two, 50 mcg sprays per nostril of levocabastine BID in the morning and evening. Total dose of 400 mcg; C = Two, 0 mcg sprays per nostril from placebo vehicle in morning and evenings. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Levocabastine | Drug | Intranasal aqueous 50 mcg microsuspension of levocabastine supplied in an amber glass bottle fitted with a white top actuated plastic metering atomising spray pump filled with a uniform white suspension |
| Measure | Description | Time Frame |
|---|---|---|
| Weighted Mean of the Total Nasal Symptom Score (TNSS) (0-4) Hours (h) Post Start of Allergen Chamber Challenge on Day 8 | The TNSS (score of 0-12) is defined as the sum of the symptom scores for the four individual components (nasal congestion, rhinorrhea, nasal itch, and sneezing, each scored on 0-3 scale [0=none, 1=mild, 2=moderate, 3=severe]). TNSS was measured at the pre-allergen chamber challenge, and then every 15 minutes from 0 to 4 hours post start of the allergen chamber challenge. In the Environmental Exposure Chamber (EEC), aerosolized allergen was administered in a sealed chamber to evaluate the efficacy of antihistamines/other treatments. Weighted mean TNSS was calculated by dividing the value of the area under the response time curve over the 0-4 hours (calculated by trapezoidal rule) by the time interval of available data. | Day 8 of each treatment period (up to 13 Weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Weighted Mean of the Symptom Scores for the Four Individual Components of the Total Nasal Symptom Score (TNSS) (Nasal Congestion, Rhinorrhea, Nasal Itching and Sneezing) (0-4) Hours Post Start of the Allergen Chamber Challenge on Day 8 | TNSS contains symtom scores for the four individual components (nasal congestion [NACG], rhinorrhea [RHSCR], nasal itching [NAITS] and sneezing [SNZS]), each scored on a 0 - 3 scale [0=none, 1=mild, 2=moderate, 3=severe]). TNSS was measured at the pre-allergen chamber challenge, and then every 15 minutes from 0 to 4 hours post start of the allergen chamber challenge. In the Environmental Exposure Chamber (EEC), aerosolized allergen is administered in a sealed chamber to evaluate the efficacy of antihistamines/other treatments. The participants recorded their symptom scores on an e-diary. The mean score for each participant was calculated using the available diary data from the assessment periods, taking the average of non-missing data during the period. Weighted mean of the individual symptoms of theTNSS were calculated by dividing the value of the area under the response time curve over the 0-4 hours (calculated by trapezoidal rule) by the time interval of available data. |
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Inclusion Criteria:
Exclusion Criteria:
Subjects who are using some of the medications below on an as needed basis, may participate in the study if they remain free of medication for the following periods of time prior to screening and prior to dosing (study drugs): Nasal antihistamines: 72 hours, Oral antihistamines A (cetirizine, fexofenadine, loratadine, desloratadine): 72 hours, Oral antihistamines B (all others): 72hours, Eye and Nasal Levocasbastine: 7 days, Nasal decongestants: 24 hours, Oral decongestants: 24 hours, Nasal glucocorticosteroids: 7 days, Inhaled glucocorticoids: 1 week, Oral glucocorticosteroids: 12 weeks, Oral leukotriene receptor antagonists: 7 days, Oral 5-lipoxygenase inhibitors: 7 days, Oral methylxanthines: 7 days
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Mississauga | Ontario | L4W 1A4 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26249767 | Derived | Murdoch RD, Bareille P, Ignar D, Mark S, Miller SR, Gupta A, Salapatek AM, Patel P. Once-daily dosing of levocabastine has comparable efficacy to twice-daily dosing in the treatment of allergic rhinitis assessed in an allergen challenge chamber. Int J Clin Pharmacol Ther. 2015 Oct;53(10):811-8. doi: 10.5414/CP202389. |
| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 200285 | Dataset Specification | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Participants who met the eligibility criteria at Screening were randomized to 1 of 6 treatment sequences. The treatment phase was comprised of three 7-day treatment periods, each separated by a 14- to 20-day washout period.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1: Levo 200 µg, Levo 400µg, Placebo | Participants received levocabastine (Levo) 200 micrograms (µg), Levo 400µg and placebo in Treatment Periods 1, 2, and 3, respectively. Participants received the Levo 200 µg once daily (OD) in the morning as 2 nasal sprays (50 µg per spray) and placebo in the evening into each nostril or placebo/ Levo 400 µg twice daily (BID) in the morning and evening as 2 nasal sprays (50 µg per spray) into each nostril for 7 days. The three treatment periods were separated by a washout period of 14 to 20 days. |
| FG001 | Sequence 2: Levo 400µg, Placebo and Levo 200µg | Participants received Levo 400µg, placebo and Levo 200µg in Treatment Periods 1, 2, and 3, respectively. Participants received the Levo 200 µg OD in the morning as 2 nasal sprays (50 µg per spray) and placebo in the evening into each nostril or placebo/ Levo 400 µg BID in the morning and evening as 2 nasal sprays (50 µg per spray) into each nostril for 7 days. The three treatment periods were separated by a washout period of 14 to 20 days. |
| FG002 | Sequence 3: Placebo, Levo 200µg and Levo 400µg | Participants received placebo, Levo 200µg and Levo 400µg in Treatment Periods 1, 2, and 3, respectively. Participants received the Levo 200 µg OD in the morning as 2 nasal sprays (50 µg per spray) and placebo in the evening into each nostril or placebo/ Levo 400 µg BID in the morning and evening as 2 nasal sprays (50 µg per spray) into each nostril for 7 days. The three treatment periods were separated by a washout period of 14 to 20 days. |
| FG003 | Sequence 4: Levo 200µg, Placebo, and Levo 400µg | Participants received Levo 200µg, placebo, and Levo 400µg in Treatment Periods 1, 2, and 3, respectively. Participants received the Levo 200 µg OD in the morning as 2 nasal sprays (50 µg per spray) and placebo in the evening into each nostril or placebo/ Levo 400 µg BID in the morning and evening as 2 nasal sprays (50 µg per spray) into each nostril for 7 days. The three treatment periods were separated by a washout period of 14 to 20 days. |
| FG004 | Sequence 5: Levo 400µg, Levo 200µg and Placebo | Participants received Levo 400µg, Levo 200µg and placebo in Treatment Periods 1, 2, and 3, respectively. Participants received the Levo 200 µg OD in the morning as 2 nasal sprays (50 µg per spray) and placebo in the evening into each nostril or placebo/ Levo 400 µg BID in the morning and evening as 2 nasal sprays (50 µg per spray) into each nostril for 7 days. The three treatment periods were separated by a washout period of 14 to 20 days. |
| FG005 | Sequence 6: Placebo, Levo 400µg and Levo 200µg | Participants received placebo, Levo 400µg and Levo 200µg in Treatment Periods 1, 2, and 3, respectively. Participants received the Levo 200 µg OD in the morning as 2 nasal sprays (50 µg per spray) and placebo in the evening into each nostril or placebo/ Levo 400 µg BID in the morning and evening as 2 nasal sprays (50 µg per spray) into each nostril for 7 days. The three treatment periods were separated by a washout period of 14 to 20 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (7 Days) |
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| Washout Period 1 (14 to 20 Days) |
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| Treatment Period 2 (7 Days) |
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| Washout Period 2 (14 to 20 Days) |
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| Treatment Period 3 (7 Days) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo/Levocabastine | Participants received placebo/ Levo at a dose of 200 µg OD in the morning as 2 nasal sprays (50 µg per spray) into each nostril or 400 µg BID in the morning and evening as 2 nasal sprays (50 µg per spray) into each nostril for 7 days each, in a crossover design. Treatment was given in one of six sequences in Periods 1, 2, and 3, (14 to 20 day washout period between treatments): ABC, BCA, CAB, ACB, BAC, CBA (A, Levo 200µg; B, Levo 400µg: C, Placebo). On Day 8 of each treatment period (approximately 12 hours post dosing for treatment A and 24 hours post dosing for treatment B and C), participants entered the environmental exposure chamber (EEC) for a 4-hour period, and the assessments were conducted 12-24 hours post-dose. All participants attended a follow-up visit within 7 to 14 day after their final dose, and the overall duration for participation in the study (screening to follow-up) was 13 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Weighted Mean of the Total Nasal Symptom Score (TNSS) (0-4) Hours (h) Post Start of Allergen Chamber Challenge on Day 8 | The TNSS (score of 0-12) is defined as the sum of the symptom scores for the four individual components (nasal congestion, rhinorrhea, nasal itch, and sneezing, each scored on 0-3 scale [0=none, 1=mild, 2=moderate, 3=severe]). TNSS was measured at the pre-allergen chamber challenge, and then every 15 minutes from 0 to 4 hours post start of the allergen chamber challenge. In the Environmental Exposure Chamber (EEC), aerosolized allergen was administered in a sealed chamber to evaluate the efficacy of antihistamines/other treatments. Weighted mean TNSS was calculated by dividing the value of the area under the response time curve over the 0-4 hours (calculated by trapezoidal rule) by the time interval of available data. | Per Protocol Population: all participants in the Intent-to-Treat Population (defined as all participants who were randomized and received >= 1 dose of study medication) and not identified as full protocol deviators with respect to criteria that were considered to impact the primary efficacy analysis. Only those participants contributing data at the | Posted | Least Squares Mean | 95% Confidence Interval | Scores on a scale | Day 8 of each treatment period (up to 13 Weeks) |
Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment until the follow-up contact (up to 13 weeks).
SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all randomized participants who received at least one dose of investigational product , according to the actual treatment received.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received placebo BID as 2 nasal sprays per nostril in the morning and evening for 7 days during one of three treatment periods. Each treatment period was followed by a washout period of 14 to 20 days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D012220 | Rhinitis |
| D065631 | Rhinitis, Allergic |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009668 | Nose Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C047340 | levocabastine |
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| Placebo | Drug | Intranasal aqueous 0 mcg microsuspension supplied in an amber glass bottle fitted with a white top actuated plastic metering atomising spray pump filled with a uniform white suspension |
|
| Day 8 of each treatment period (up to 13 Weeks) |
For additional information about this study please refer to the GSK Clinical Study Register |
| 200285 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200285 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200285 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200285 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200285 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 200285 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| Lost to Follow-up |
|
| COMPLETED |
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| NOT COMPLETED |
|
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Placebo | Participants received placebo BID as 2 nasal sprays per nostril in the morning and evening for 7 days during one of three treatment periods. Each treatment period was followed by a washout period of 14 to 20 days. |
| OG001 | Levocabastine 200µg OD | Participants received levocabastine 200 µg once daily OD as two 50 µg nasal sprays into each nostril in the morning for 7 days during one of the three treatment periods. Each treatment period was followed by a washout period of 14 to 20 days. |
| OG002 | Levocabastine 400µg BID | Participants received levocabastine 400 µg BID as two 50 µg nasal sprays into each nostril in the morning and evening for 7 days during one of the three treatment periods. Each treatment period was followed by a washout period of 14 to 20 days. |
|
|
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| Secondary | Weighted Mean of the Symptom Scores for the Four Individual Components of the Total Nasal Symptom Score (TNSS) (Nasal Congestion, Rhinorrhea, Nasal Itching and Sneezing) (0-4) Hours Post Start of the Allergen Chamber Challenge on Day 8 | TNSS contains symtom scores for the four individual components (nasal congestion [NACG], rhinorrhea [RHSCR], nasal itching [NAITS] and sneezing [SNZS]), each scored on a 0 - 3 scale [0=none, 1=mild, 2=moderate, 3=severe]). TNSS was measured at the pre-allergen chamber challenge, and then every 15 minutes from 0 to 4 hours post start of the allergen chamber challenge. In the Environmental Exposure Chamber (EEC), aerosolized allergen is administered in a sealed chamber to evaluate the efficacy of antihistamines/other treatments. The participants recorded their symptom scores on an e-diary. The mean score for each participant was calculated using the available diary data from the assessment periods, taking the average of non-missing data during the period. Weighted mean of the individual symptoms of theTNSS were calculated by dividing the value of the area under the response time curve over the 0-4 hours (calculated by trapezoidal rule) by the time interval of available data. | ITT Population. Only those participants contributing data at the indicated time points were analyzed. | Posted | Least Squares Mean | 95% Confidence Interval | Scores on a scale | Day 8 of each treatment period (up to 13 Weeks) |
|
|
|
| 0 |
| 75 |
| 2 |
| 75 |
| EG001 | Levocabastine 200µg OD | Participants received levocabastine 200 µg once daily OD as two 50 µg nasal sprays into each nostril in the morning for 7 days during one of the three treatment periods. Each treatment period was followed by a washout period of 14 to 20 days. | 0 | 76 | 3 | 76 |
| EG002 | Levocabastine 400µg BID | Participants received levocabastine 400 µg BID as two 50 µg nasal sprays into each nostril in the morning and evening for 7 days during one of the three treatment periods. Each treatment period was followed by a washout period of 14 to 20 days. | 0 | 74 | 5 | 74 |
| Somnolence | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D010038 |
| Otorhinolaryngologic Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| NAITS |
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| SNZS |
|