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.

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.