Trial Outcomes & Findings for Efficacy of Co-administration of Bilastine and Montelukast in Patients With SARC and Asthma (NCT NCT02761252)

Last Updated: 2019-07-12

Results Overview

To demonstrate that concomitant administration of montelukast and bilastine is superior to bilastine monotherapy in SARC symptoms, as assessed by Total Symptoms Scores (TSS) after 4 weeks of treatment. Total Symptoms Scores (TSS) assesses nasal (nasal congestion, rhinorrhea, nasal itching, sneezing) and non nasal symptoms (ocular redness, ocular itching, tearing) of rhinoconjuctivits. Each of the 7 symptoms is scored from 0 (absent) to 3 (severe) as follows: * 0 (absent) Symptom not present * 1 (mild) Symptom is clearly present but easily tolerated, a nuisance, minimal awareness * 2 (moderate) Symptom is bothersome but tolerable, does not interfere with daily activities or sleep * 3 (severe) Symptom is hard to tolerate and interferes with daily activities or sleep. TSS assessment comprises of scoring (0-3) of all 7 above mentioned symptoms. Final TSS scores is in a range from 0-21.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

454 participants

Primary outcome timeframe

4 weeks of treatment (from baseline to 4 weeks of treatment)

Results posted on

2019-07-12

Participant Flow

The recruitment started on 13 April 2016 and termineted on 23 November 2016. 454 patients with SARC and mild to moderate asthma as comorbidity were screened. 420 patients were randomised of which 388 patients completed the study.

454 patients were enrolled but 34 patients did not met inclusion/exclusion critera.

Participant milestones

Participant milestones
Measure	Bilastine+Montelukast Bilastine 20mg Montelukast 10mg	Bilastine Monotherapy Bilastine 20mg Placebo Montelukast 10mg	Montelukast Monotherapy Montelukast 10mg Placebo Bilastine 20mg
Overall Study STARTED	143	140	137
Overall Study COMPLETED	133	132	123
Overall Study NOT COMPLETED	10	8	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy of Co-administration of Bilastine and Montelukast in Patients With SARC and Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bilastine+Montelukast n=143 Participants Bilastine 20mg Montelukast 10mg	Bilastine Monotherapy n=140 Participants Bilastine 20mg Placebo Montelukast 10mg	Montelukast Monotherapy n=137 Participants Montelukast 10mg Placebo Bilastine 20mg	Total n=420 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	143 Participants n=5 Participants	140 Participants n=7 Participants	137 Participants n=5 Participants	420 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	34.9 years STANDARD_DEVIATION 11.1 • n=5 Participants	35.5 years STANDARD_DEVIATION 11.0 • n=7 Participants	35.4 years STANDARD_DEVIATION 10.7 • n=5 Participants	35.2 years STANDARD_DEVIATION 10.9 • n=4 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	83 Participants n=7 Participants	73 Participants n=5 Participants	225 Participants n=4 Participants
Sex: Female, Male Male	74 Participants n=5 Participants	57 Participants n=7 Participants	64 Participants n=5 Participants	195 Participants n=4 Participants

PRIMARY outcome

Timeframe: 4 weeks of treatment (from baseline to 4 weeks of treatment)

Outcome measures

Outcome measures
Measure	Bilastine+Montelukast n=143 Participants Bilastine 20mg+Montelukast 10mg	Bilastine Monotherapy n=140 Participants Bilastine 20mg Placebo Montelukast 10mg	Montelukast Monotherapy Montelukast 10mg Placebo Bilastine 20mg
Change From Baseline With Montelukast+Bilastine Compared With Bilastine Monotherapy in SARC Symptoms	-3.2522 score on a scale Interval -3.8718 to -2.6327	-3.4462 score on a scale Interval -4.0708 to -2.8217	—

SECONDARY outcome

Timeframe: After 4 weeks of treatments

Population: The Intention To Treat population (used for statistical analysis) was 419 patients because 1 patient in Montekukast Monotherapy arm was a drop-out. The drop-out patient was, instead, included in a Safety Population (420 patients).

To evaluate the efficacy of concomitant montelukast and bilastine compared with montelukast and bilastine monotherapies in asthma control, as assessed by Asthma Quality of Life Questionnaire (AQLQ) after 4 weeks. The AQLQ was developed to measure the functional problems (physical, emotional, social and occupational) that are most troublesome to adults (17-70 years) with asthma. Each of the 32 questionnaire's items will be scored on a 7-point scale (where 7 means "not impaired at all" and 1 means "severely impaired"). The overall AQLQ score is the mean of all 32 responses (https://www.qoltech.co.uk/aqlq.html). The change in AQLQ score from baseline to 4 weeks after treatment - AQLQ score at baseline for patients with both available values has been the secondary endpoint.

Outcome measures

Outcome measures
Measure	Bilastine+Montelukast n=143 Participants Bilastine 20mg+Montelukast 10mg	Bilastine Monotherapy n=140 Participants Bilastine 20mg Placebo Montelukast 10mg	Montelukast Monotherapy n=136 Participants Montelukast 10mg Placebo Bilastine 20mg
Change From Baseline With Montelukast+Bilastine Compared With Montelukast and Bilastine Monotherapies in Asthma Control	0.6250 score on a scale Interval 0.4788 to 0.7712	0.6399 score on a scale Interval 0.4929 to 0.787	0.5849 score on a scale Interval 0.4344 to 0.7353

SECONDARY outcome

Timeframe: After 4 weeks of treatment (from baseline)

To evaluate the efficacy of concomitant montelukast and bilastine compared with montelukast and bilastine monotherapies in daytime symptoms of SARC, as assessed by Daytime Nasal Symptom Score (DNSS) after 4 weeks of treatment. Daytime Nasal Symptom Score (DNSS) is the average of individual scores of nasal congestion, rhinorrhea, nasal itching, sneezing of rhinoconjuctivits. Each of the 4 symptoms is scored from 0 (absent) to 3 (severe) as follows: * 0 (absent) Symptom not present * 1 (mild) Symptom is clearly present but easily tolerated, a nuisance, minimal awareness * 2 (moderate) Symptom is bothersome but tolerable, does not interfere with daily activities or sleep * 3 (severe) Symptom is hard to tolerate and interferes with daily activities or sleep. DNSS assessment comprises of scoring (0-3) of all 4 above mentioned symptoms. Final DNSS scores is in a range from 0-12.

Outcome measures

Outcome measures
Measure	Bilastine+Montelukast n=143 Participants Bilastine 20mg+Montelukast 10mg	Bilastine Monotherapy n=140 Participants Bilastine 20mg Placebo Montelukast 10mg	Montelukast Monotherapy n=136 Participants Montelukast 10mg Placebo Bilastine 20mg
Change From Baseline With Montelukast+Bilastine Compared With Montelukast and Bilastine Monotherapies in SARC Symptoms (DNSS)	-1.9713 score on a scale Interval -2.3442 to -1.5984	-2.1106 score on a scale Interval -2.4863 to -1.7349	-1.8678 score on a scale Interval -2.2468 to -1.4888

SECONDARY outcome

Timeframe: After 4 weeks of treatment (from baseline)

To evaluate the efficacy of concomitant montelukast and bilastine compared with montelukast and bilastine monotherapies in daytime symptoms of SARC, as assessed by Daytime Non Nasal Symptom Score (DNNSS) after 4 weeks of treatment. Daytime Non Nasal Symptom Score (DNSS) is the average of individual scores of ocular redness, ocular itching and tearing of rhinoconjuctivits. Each of the 3 symptoms is scored from 0 (absent) to 3 (severe) as follows: * 0 (absent) Symptom not present * 1 (mild) Symptom is clearly present but easily tolerated, a nuisance, minimal awareness * 2 (moderate) Symptom is bothersome but tolerable, does not interfere with daily activities or sleep * 3 (severe) Symptom is hard to tolerate and interferes with daily activities or sleep. DNNSS assessment comprises of scoring (0-3) of all 3 above mentioned symptoms. Final DNNSS scores is in a range from 0-9.

Outcome measures

Outcome measures
Measure	Bilastine+Montelukast n=143 Participants Bilastine 20mg+Montelukast 10mg	Bilastine Monotherapy n=140 Participants Bilastine 20mg Placebo Montelukast 10mg	Montelukast Monotherapy n=136 Participants Montelukast 10mg Placebo Bilastine 20mg
Change From Baseline With Montelukast + Bilastine Compared With Montelukast and Bilastine Monotherapies in SARC Symptoms (DNNSS)	-1.2824 score on a scale Interval -1.5667 to -0.998	-1.3185 score on a scale Interval -1.6051 to -1.032	-1.1574 score on a scale Interval -1.4462 to -0.8687

SECONDARY outcome

Timeframe: From baseline to 4 weeks of treatment

Number of days without any relief medication for SARC

Outcome measures

Outcome measures
Measure	Bilastine+Montelukast n=143 Participants Bilastine 20mg+Montelukast 10mg	Bilastine Monotherapy n=140 Participants Bilastine 20mg Placebo Montelukast 10mg	Montelukast Monotherapy n=136 Participants Montelukast 10mg Placebo Bilastine 20mg
Usage of Relief Medication for SARC	15.0057 Days Standard Error 0.8260	15.8416 Days Standard Error 0.8326	15.4179 Days Standard Error 0.8411

SECONDARY outcome

Timeframe: From baseline to 4 weeks of treatment

Number of days without any relief medication for Asthma.

Outcome measures

Outcome measures
Measure	Bilastine+Montelukast n=143 Participants Bilastine 20mg+Montelukast 10mg	Bilastine Monotherapy n=140 Participants Bilastine 20mg Placebo Montelukast 10mg	Montelukast Monotherapy n=136 Participants Montelukast 10mg Placebo Bilastine 20mg
Usage of Relief Medication for Asthma	53.2548 Days Standard Error 2.0193	52.4177 Days Standard Error 2.0212	50.7146 Days Standard Error 2.0768

Adverse Events

Bilastine+Montelukast

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Bilastine+Placebo Montelukast

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Montelukast+Placebo Bilastine

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bilastine+Montelukast n=143 participants at risk Bilastine 20 mg, 10 blister containing 10 tablets + Montelukast 10 mg, 10 blister containing 10 film coated tablets each for treatment Bilastine 20mg Montelukast 10mg	Bilastine+Placebo Montelukast n=140 participants at risk Bilastine 20 mg, 10 blister containing 10 tablets + Placebo Montelukast, 10 blister containing 10 film coated tablets each. Bilastine 20mg Placebo Montelukast 10mg	Montelukast+Placebo Bilastine n=137 participants at risk Placebo Bilastine, 10 blister containing 10 tablets + Montelukast 10 mg, 10 blister containing 10 film coated tablets each. Montelukast 10mg Placebo Bilastine 20mg
Gastrointestinal disorders Abdominal Pain	0.00% 0/143	0.00% 0/140	0.73% 1/137 • Number of events 1

Other adverse events

Other adverse events
Measure	Bilastine+Montelukast n=143 participants at risk Bilastine 20 mg, 10 blister containing 10 tablets + Montelukast 10 mg, 10 blister containing 10 film coated tablets each for treatment Bilastine 20mg Montelukast 10mg	Bilastine+Placebo Montelukast n=140 participants at risk Bilastine 20 mg, 10 blister containing 10 tablets + Placebo Montelukast, 10 blister containing 10 film coated tablets each. Bilastine 20mg Placebo Montelukast 10mg	Montelukast+Placebo Bilastine n=137 participants at risk Placebo Bilastine, 10 blister containing 10 tablets + Montelukast 10 mg, 10 blister containing 10 film coated tablets each. Montelukast 10mg Placebo Bilastine 20mg
Investigations Alanine Aminotransferase Increased	1.4% 2/143 • Number of events 2	0.00% 0/140	0.00% 0/137
Investigations Aspartate Aminotransferase Increased	0.70% 1/143 • Number of events 1	0.00% 0/140	0.00% 0/137
Investigations Gamma-glutamytrasferase Increased	0.70% 1/143 • Number of events 1	0.00% 0/140	0.73% 1/137 • Number of events 1
Nervous system disorders Dizziness	0.00% 0/143	0.00% 0/140	1.5% 2/137 • Number of events 2
Nervous system disorders Headache	0.70% 1/143 • Number of events 1	0.00% 0/140	0.73% 1/137 • Number of events 1
Nervous system disorders Hypoaesthesia	0.00% 0/143	0.00% 0/140	0.73% 1/137 • Number of events 1
Nervous system disorders Sedation	0.70% 1/143 • Number of events 1	0.00% 0/140	0.73% 1/137 • Number of events 1
Nervous system disorders Somnolence	1.4% 2/143 • Number of events 2	1.4% 2/140 • Number of events 2	1.5% 2/137 • Number of events 2
General disorders Fatigue	0.00% 0/143	0.71% 1/140 • Number of events 1	0.00% 0/137
Ear and labyrinth disorders Vertigo	0.00% 0/143	0.71% 1/140 • Number of events 1	0.00% 0/137
Psychiatric disorders Anxiety	0.00% 0/143	0.00% 0/140	0.73% 1/137 • Number of events 1
Psychiatric disorders Insomnia	0.70% 1/143 • Number of events 1	0.00% 0/140	0.00% 0/137
Psychiatric disorders Irritability	0.00% 0/143	0.00% 0/140	0.73% 1/137 • Number of events 1
Gastrointestinal disorders Gastrooesophageal Reflux Disease	0.00% 0/143	0.00% 0/140	0.73% 1/137 • Number of events 1
Gastrointestinal disorders Gingival Bleeding	0.00% 0/143	0.00% 0/140	0.73% 1/137 • Number of events 1
Gastrointestinal disorders Hypoaesthesia oral	0.00% 0/143	0.00% 0/140	0.73% 1/137 • Number of events 1
Metabolism and nutrition disorders Increased appetite	0.70% 1/143 • Number of events 1	0.71% 1/140 • Number of events 1	0.00% 0/137
General disorders Oedema Peripheral	0.00% 0/143	0.00% 0/140	0.73% 1/137 • Number of events 1

Additional Information

Medical Director

Menarini International Operations Luxembourg SA

Phone: +352 2649761

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place