Safety, Tolerability and Clinical Activity of ASM-024 in Subjects With Mild Allergic Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Asmacure Ltée
ClinicalTrials.gov Identifier:
NCT01092403
First received: March 23, 2010
Last updated: January 25, 2012
Last verified: January 2012
  Purpose

The study will assess the safety, tolerability and clinical activity of ASM-024 in subjects with mild allergic asthma.


Condition Intervention Phase
Mild Allergic Asthma
Drug: ASM-024
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Three-Way Crossover Study to Evaluate the Safety, Tolerability and Clinical Activity of ASM-024 Administered by Inhalation Once Daily to Subjects With Mild Allergic Asthma

Resource links provided by NLM:


Further study details as provided by Asmacure Ltée:

Primary Outcome Measures:
  • Late asthmatic response (LAR) [ Time Frame: Day 8 of each treatment period ] [ Designated as safety issue: No ]
    LAR as measured by the peak drop in FEV1 from 3 to 7 hours post-allergen challenge

  • Early asthmatic response (EAR) [ Time Frame: Day 8 of every treatment period ] [ Designated as safety issue: No ]
    EAR as measured by the peak drop in FEV1 from 0 to 3 hours post-allergen challenge

  • Airway hyperresponsiveness [ Time Frame: Days -1, 7 and 9 of each treatment period ] [ Designated as safety issue: No ]
    Difference between methacholine PC20 measured 24 hours following allergen challenge and methacholine PC20 measured 24 hours before allergen challenge

  • Safety and tolerability [ Time Frame: 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • LAR's FEV1 AUC [ Time Frame: Day 8 of every treatment period ] [ Designated as safety issue: No ]
    From 3 to 7 hours post-allergen challenge

  • FEV1 [ Time Frame: Day 9 ] [ Designated as safety issue: No ]
    24 hours post-allergen challenge

  • EAR's FEV1 AUC [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    From 0 to 3 hours post-allergen challenge

  • Change in FEV1 [ Time Frame: Days 1, 7, 8 and 9 ] [ Designated as safety issue: No ]
    Before inhalation of ASM-024 and as soon as possible following inhalation of ASM-024

  • Induced sputum eosinophil count and eosinophil and neutrophil percentages [ Time Frame: Days -1, 7 and 9 of every Treatment Period ] [ Designated as safety issue: No ]
  • Blood eosinophil count [ Time Frame: Days -1 and 9 of every Treatment Period ] [ Designated as safety issue: No ]
  • Total and differential WBC count [ Time Frame: Days -1 and 9 of every Treatment Period ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: April 2010
Study Completion Date: January 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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;
  • Diagnosis of mild allergic asthma that meets the following criteria:

    • Stable on inhaled short-acting beta-2-agonists p.r.n. as the only medication for asthma.
    • 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).
    • Baseline methacholine (PC20) ≤ 16 mg/mL.
  • 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;
  • Respiratory tract infections or worsening of asthma within 6 weeks before Screening/Baseline;
  • Baseline methacholine PC20 > 16 mg/mL at Screening / Baseline;
  • 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;
  • Use of any nicotine containing products within 6 months before Pre-Screening;
  • Any of the following concomitant medications:

    • Any medication that are known to prolong QT / QTc interval.
    • Oral or inhaled corticosteroids within 28 days preceding Pre-Screening or systemic corticosteroids within 90 days of Pre-Screening.
    • Long acting beta-2-agonists within one week preceding Baseline.
    • Use of inhaled short-acting β2- agonists or anticholinergics within 8 hours before all study visits to the clinic.
  • Known or suspected allergy or sensitivity to nicotine or cholinergic drugs or any drug with similar chemical structure;
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01092403

Locations
Canada, Quebec
Mc Master University Health Sciences Center
Hamilton, Quebec, Canada, L8N 3Z5
Centre de Recherche - Institut universitaire de cardiologie et de pneumologie de Québec
Québec, Quebec, Canada, G1V 4G5
Canada, Saskatchewan
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
  More Information

No publications provided

Responsible Party: Asmacure Ltée
ClinicalTrials.gov Identifier: NCT01092403     History of Changes
Other Study ID Numbers: ASM-024/II/STA-01
Study First Received: March 23, 2010
Last Updated: January 25, 2012
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on July 20, 2014