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

Mild Allergic Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01092403
• Other study ID #: ASM-024/II/STA-01
• Status: Completed
• Phase: Phase 2
• First received: March 23, 2010
• Last updated: January 25, 2012
• Start date: April 2010
• Est. completion date: January 2012

Study information

• Verified date: January 2012
• Source: Asmacure Ltée
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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 ß2- 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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma
• Mild Allergic Asthma

Intervention

Drug:
• ASM-024
ASM-024 50 mg of ASM-024 or 200 mg once daily by inhalation
• Placebo
Placebo once daily by inhalation

Locations

Country	Name	City	State
Canada	Mc Master University Health Sciences Center	Hamilton	Quebec
Canada	Centre de Recherche - Institut universitaire de cardiologie et de pneumologie de Québec	Québec	Quebec
Canada	University of Saskatechewan	Saskatoon	Saskatchewan

Sponsors (1)

Lead Sponsor	Collaborator
Asmacure Ltée

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	Yes
Secondary	LAR's FEV1 AUC	From 3 to 7 hours post-allergen challenge	Day 8 of every treatment period	No
Secondary	FEV1	24 hours post-allergen challenge	Day 9	No
Secondary	EAR's FEV1 AUC	From 0 to 3 hours post-allergen challenge	Day 8	No
Secondary	Change in FEV1	Before inhalation of ASM-024 and as soon as possible following inhalation of ASM-024	Days 1, 7, 8 and 9	No
Secondary	Induced sputum eosinophil count and eosinophil and neutrophil percentages		Days -1, 7 and 9 of every Treatment Period	No
Secondary	Blood eosinophil count		Days -1 and 9 of every Treatment Period	No
Secondary	Total and differential WBC count		Days -1 and 9 of every Treatment Period	No