A Study to Evaluate Efficacy and Safety of ADC3680 in Subjects With Inadequately-Controlled Asthma

Study Overview
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Brief Summary
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This randomised, double-blind, placebo-controlled study will evaluate the efficacy and safety of ADC3680 administered once daily as an add-on therapy to inhaled corticosteroids and when co-administered with montelukast in patients with inadequately-controlled asthma. Patients will be randomised to 3 Arms to receive ADC3680, placebo or montelukast.

Detailed Description
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This is a multi-centre, randomised, placebo-controlled, double blind, parallel group 3-arm study (including montelukast as an active comparator) designed to compare the efficacy and safety of a once daily dose of ADC3680 with placebo in subjects with inadequately-controlled asthma despite receiving a low to moderate dose of an ICS controller therapy, over a 10 week treatment period. At the end of the 10 week treatment period open label montelukast (10 mg) will be added to ADC3680 and placebo arms for a two week extension period to assess whether efficacy of ADC3680 is enhanced by the addition of montelukast compared with montelukast alone. The montelukast arm will continue with 10 mg montelukast alone.

Official Title
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A Randomised, Double Blind, Placebo-Controlled, Multi-Centre, Parallel Group Study to Evaluate the Efficacy and Safety of ADC3680 Administered Once Daily as an Add-On Therapy to Inhaled Corticosteroids and When Co-Administered With Montelukast in Subjects With Inadequately-Controlled Asthma.

Conditions
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Asthma

Intervention / Treatment
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* Drug: ADC3680
* Drug: Placebo
* Drug: montelukast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18 years to 50 years (inclusive) Diagnosis of asthma (GINA 2011) including a demonstration of reversible airway obstruction Pre-bronchodilator FEV1 value ≥ 40% and ≤ 85% of the predicted normal value at baseline A score of 1.5 or greater on the Asthma Control Questionnaire at baseline Daily use of low to moderate dose of ICS (equivalent to budesonide ≤ 800 µg per day) Prescribed a short-acting inhaled bronchodilator as reliever therapy for relief of symptoms A peripheral blood eosinophil count ≥ 0.25 x 109/L Non-smoker or former smoker who has not smoked in the last six months Body mass index (BMI) ≥ 17 and ≤ 35 kg/m2 Able to comply with the protocol requirements, instructions and restrictions Able to provide signed and dated written informed consent Exclusion Criteria: Subjects with severe asthma exacerbation in the 4 weeks prior to consent Subjects with respiratory tract infection in the 4 weeks prior to consent Subjects with COPD or other relevant lung diseases Subjects with clinically significant condition which may compromise subject safety or interfere with study evaluation Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADC3680<br>ADC3680 oral once daily | Drug: ADC3680<br>* ADC3680 for 12 weeks plus montelukast for the last 2 weeks of the dosing period<br>|
| Placebo Comparator: Placebo<br>Placebo oral once daily | Drug: Placebo<br>* Placebo for 12 weeks plus montelukast for the last 2 weeks of the dosing period<br>|
| Active Comparator: montelukast<br>montelukast oral once daily | Drug: montelukast<br>* montelukast for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of ADC3680 compared with placebo in improving lung function (FEV1) |  | 10 weeks | 
| Adding montelukast to ADC3680 in improving lung function (FEV1) |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of ADC3680 compared with placebo on mean change in Asthma Control Questionnaire (ACQ) from baseline to Week 10 |  | 10 weeks | 
| Efficacy of ADC3680 compared with placebo on mean change in trough pre-bronchodilator FEV1 % predicted from baseline to Week 2 |  | 2 weeks | 
| Efficacy of ADC3680 compared with placebo on mean change in trough pre-bronchodilator FEV1 % predicted from baseline to Week 6 |  | 6 weeks | 
| Efficacy of ADC3680 compared with placebo on mean change in trough pre-bronchodilator FEV1 % predicted from baseline to Week 10 |  | 10 weeks | 
| Efficacy of ADC3680 compared with placebo on mean change in post-bronchodilator FEV1 from baseline to Week 10 |  | 10 weeks | 
| Efficacy of ADC3680 compared with placebo on mean change in pre-bronchodilator PEF (in-clinic) from baseline to Week 2 |  | 2 weeks | 
| Efficacy of ADC3680 compared with placebo on mean change in pre-bronchodilator PEF (in-clinic) from baseline to Week 6 |  | 6 weeks | 
| Efficacy of ADC3680 compared with placebo on mean change in pre-bronchodilator PEF (in-clinic) from baseline to Week 10 |  | 10 weeks | 
| Efficacy of ADC3680 compared with placebo on mean change in blood eosinophils from baseline to Week 10 |  | 10 weeks | 
| Efficacy of ADC3680 compared with placebo on mean change in serum IgE from baseline to Week 10 |  | 10 weeks | 
| Adding montelukast to ADC3680 on mean change in ACQ scores from Week 10 to Week 12 |  | 2 weeks | 
| Adding montelukast to ADC3680 on mean change in trough pre-bronchodilator FEV1 % predicted from Week 10 to Week 12 |  | 2 weeks | 
| Adding montelukast to ADC3680 on mean change in pre-bronchodilator PEF (in-clinic) from Week 10 to Week 12 |  | 2 weeks | 
| Adding montelukast to ADC3680 on mean change in blood eosinophils from Week 10 to Week 12 |  | 2 weeks | 
| Safety of ADC3680 compared to placebo | Safety evaluations will include incidence of Serious Adverse Events (from informed consent), severity & frequency of Adverse Events, change in laboratory values (haematology, clinical chemistry and urinalysis), change in vital signs (pulse, systolic and diastolic blood pressure), change in ECG and change in physical examination from baseline to week 10. | 10 weeks | 
| Safety of a 2 week administration of ADC3680 in combination with montelukast | Safety evaluations will include incidence of Serious Adverse Events, severity & frequency of Adverse Events, change in laboratory values (haematology, clinical chemistry and urinalysis), change in vital signs (pulse, systolic and diastolic blood pressure), change in ECG and change in physical examination from week 10 to week 12. | 2 weeks |