Safety, Tolerability and Clinical Activity of ASM-024 in Subjects With Mild Allergic Asthma
Study Details
Study Description
Brief Summary
The study will assess the safety, tolerability and clinical activity of ASM-024 in subjects with mild allergic asthma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ASM-024 ASM-024 once daily by inhalation |
Drug: ASM-024
ASM-024 50 mg of ASM-024 or 200 mg once daily by inhalation
|
| Placebo Comparator: Placebo Placebo once daily by inhalation |
Drug: Placebo
Placebo once daily by inhalation
|
Outcome Measures
Primary Outcome Measures
- Late asthmatic response (LAR) [Day 8 of each treatment period]
LAR as measured by the peak drop in FEV1 from 3 to 7 hours post-allergen challenge
- Early asthmatic response (EAR) [Day 8 of every treatment period]
EAR as measured by the peak drop in FEV1 from 0 to 3 hours post-allergen challenge
- Airway hyperresponsiveness [Days -1, 7 and 9 of each treatment period]
Difference between methacholine PC20 measured 24 hours following allergen challenge and methacholine PC20 measured 24 hours before allergen challenge
- Safety and tolerability [Physical examination: Day 9, vital signs: Days -1, 1, 7, 8 and 9; twelve-lead ECG: Days 1, 7, 8 and 9 , AEs throughout the study, safety laboratory assessments Day 1 and 9 and Chest X-Ray: Day 9 of the final treatment period]
Secondary Outcome Measures
- LAR's FEV1 AUC [Day 8 of every treatment period]
From 3 to 7 hours post-allergen challenge
- FEV1 [Day 9]
24 hours post-allergen challenge
- EAR's FEV1 AUC [Day 8]
From 0 to 3 hours post-allergen challenge
- Change in FEV1 [Days 1, 7, 8 and 9]
Before inhalation of ASM-024 and as soon as possible following inhalation of ASM-024
- Induced sputum eosinophil count and eosinophil and neutrophil percentages [Days -1, 7 and 9 of every Treatment Period]
- Blood eosinophil count [Days -1 and 9 of every Treatment Period]
- Total and differential WBC count [Days -1 and 9 of every Treatment Period]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Able and willing to provide written informed consent;
-
Male or female subjects, ≥18 years and ≤ 50 years of age;
-
Female subjects of childbearing potential must have a negative pregnancy test (serum b-HCG) at Pre-Screening, and a negative urine pregnancy test immediately before the first administration of the study drug for each of the three Treatment Periods. Sexually active females must be willing to use adequate contraception.
-
Male subjects must be willing to use a condom with a spermicide for the duration of their participation in the study, plus an additional 30 days following study drug administration and ensure that their partner is using a highly effective method of birth control such as combined oral contraceptives, implants, injectables or a IUD. Male subjects must ensure that their female partner is willing to use adequate contraception;
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Diagnosis of mild allergic asthma that meets the following criteria:
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Stable on inhaled short-acting beta-2-agonists p.r.n. as the only medication for asthma.
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Presence of both early asthmatic response (EAR) (at least 20 % fall in FEV1 within 3 hours after allergen inhalation) and late asthmatic response (LAR) (at least 15 % fall in FEV1).
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Baseline methacholine (PC20) ≤ 16 mg/mL.
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FEV1 of at least 70 % of the predicted value at Pre-Screening and Screening / Baseline;
-
BMI ≥ 19 and ≤ 35 kg/m²;
-
Body weight ≥ 40 kg;
-
Positive skin prick test to at least one common aeroallergen.
Exclusion Criteria:
-
Any lung disease other than mild allergic asthma;
-
Pregnant or nursing women or women intending to conceive during the course of the study or have a positive serum pregnancy test at Pre-Screening or a positive urine pregnancy test during the study;
-
Women of childbearing potential (unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years) not using a highly effective method of birth control. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e., less than 1 % per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, intra-uterine devices (IUDs), sexual abstinence or a partner who has undergone a vasectomy;
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Respiratory tract infections or worsening of asthma within 6 weeks before Screening/Baseline;
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Baseline methacholine PC20 > 16 mg/mL at Screening / Baseline;
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Current cigarette smokers or former smokers with a smoking history of greater than 10 pack years or who stopped smoking within the 12 months preceding enrolment in the study;
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Use of any nicotine containing products within 6 months before Pre-Screening;
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Any of the following concomitant medications:
-
Any medication that are known to prolong QT / QTc interval.
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Oral or inhaled corticosteroids within 28 days preceding Pre-Screening or systemic corticosteroids within 90 days of Pre-Screening.
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Long acting beta-2-agonists within one week preceding Baseline.
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Use of inhaled short-acting β2- agonists or anticholinergics within 8 hours before all study visits to the clinic.
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Known or suspected allergy or sensitivity to nicotine or cholinergic drugs or any drug with similar chemical structure;
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Clinically significant ECG abnormalities at Pre-Screening including clinically significant or marked baseline prolongation of QT / QTc interval (e.g. repeated demonstration of a QTc interval of > 450 ms). Other non clinically significant findings such as sinus bradycardia, sinus arrhythmia, borderline first degree AV block (up to 205 ms), left ventricular hypertrophy (on voltage criteria for a subject less than 40 years old for instance) are permissible if judged to be acceptable by the Qualified investigator;
-
Family history of additional risk factors for TdP (e.g., family history of Long QT Syndrome.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mc Master University Health Sciences Center | Hamilton | Quebec | Canada | L8N 3Z5 |
| 2 | Centre de Recherche - Institut universitaire de cardiologie et de pneumologie de Québec | Québec | Quebec | Canada | G1V 4G5 |
| 3 | University of Saskatechewan | Saskatoon | Saskatchewan | Canada | S7N0W8 |
Sponsors and Collaborators
- Asmacure Ltée
Investigators
- Principal Investigator: Louis-Philippe Boulet, MD, Institut universitaire de cardiologie et de pneumologie de Québec
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ASM-024/II/STA-01