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

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

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

Study Overview

• Status: Completed
• Conditions: Mild Allergic Asthma
• Intervention / Treatment: Drug: ASM-024; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Hamilton, Quebec, Canada, L8N 3Z5
      • Mc Master University Health Sciences Center
    • Québec, Quebec, Canada, G1V 4G5
      • Centre de Recherche - Institut universitaire de cardiologie et de pneumologie de Québec
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N0W8
      • University of Saskatechewan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late asthmatic response (LAR)	LAR as measured by the peak drop in FEV1 from 3 to 7 hours post-allergen challenge	Day 8 of each treatment period
Early asthmatic response (EAR)	EAR as measured by the peak drop in FEV1 from 0 to 3 hours post-allergen challenge	Day 8 of every treatment period
Airway hyperresponsiveness	Difference between methacholine PC20 measured 24 hours following allergen challenge and methacholine PC20 measured 24 hours before allergen challenge	Days -1, 7 and 9 of each treatment period
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

Outcome Measure	Measure Description	Time Frame
LAR's FEV1 AUC	From 3 to 7 hours post-allergen challenge	Day 8 of every treatment period
FEV1	24 hours post-allergen challenge	Day 9
EAR's FEV1 AUC	From 0 to 3 hours post-allergen challenge	Day 8
Change in FEV1	Before inhalation of ASM-024 and as soon as possible following inhalation of ASM-024	Days 1, 7, 8 and 9
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

Collaborators and Investigators

• Sponsor: Asmacure Ltée

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): January 1, 2012

Study Registration Dates

• First Submitted: March 23, 2010
• First Submitted That Met QC Criteria: March 23, 2010
• First Posted (ESTIMATE): March 25, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): January 26, 2012
• Last Update Submitted That Met QC Criteria: January 25, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: ASM-024/II/STA-01