A multi-center, double-blind, placebo-controlled, randomized, multiple dose, 2-period cross-over, Phase IIa study to investigate the pharmacodynamics, tolerability and safety, and pharmacokinetics of ACT 129968 in subjects with mild to moderate allergic asthma
- Conditions
- Allergic AsthmaMedDRA version: 9.1Level: LLTClassification code 10001705Term: Allergic asthma
- Registration Number
- EUCTR2008-001209-41-GB
- Lead Sponsor
- Actelion Pharmaceuticals Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 18
•Men and women not of childbearing potential 18–55 years of age (inclusive).
-Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile.
•Signed informed consent prior to any study-mandated procedure.
•Having stable, mild to moderate allergic asthma for at least 1 year and fulfilling all of the following criteria at screening (all assessments should be performed within a period of 1 week):
–No ongoing or recent treatment (see definition below) for allergic airway disease (prescribed or over-the-counter [OTC]) other than stable use of short-acting, inhaled beta2 agonist as needed.
–Asymptomatic hay fever at screening, which is expected to remain asymptomatic during the study.
–No hospital admissions for asthma in the previous year.
–FEV1 >= 70% of predicted value at both of the screening visits, measured >= 8h after any use of a short-acting inhaled beta2 agonist.
–Airway hyperresponsiveness to inhaled methacholine (Mch) with the provocative concentration of Mch causing a fall in baseline FEV1 of 20% (PC20FEV1) (Mch) < 16 mg/mL Mch chloride.
–Early and late allergic reaction (EAR, LAR) airway response with >= 15% minimal reduction in FEV1 during LAR (3–10h) following a standardized bronchial allergen challenge with house dust mite (HDM) extract.
•Positive skin prick test (wheal diameter >= 3 mm) to HDM extract within 1 year before screening.
•Body mass index (BMI) between 18 and 33 kg/m2 (inclusive) at screening.
•Systolic blood pressure (SBP): 100–150 mmHg, diastolic blood pressure (DBP): 50–90 mmHg and heart rate (HR): 40–90 bpm (all inclusive) after 5 minutes in the supine position at screening.
•12-lead electrocardiogram (ECG) without clinically relevant abnormalities at screening.
•Hematology, biochemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening.
•Negative results from drug screen (amphetamines, cocaine, cannabinoids, opiates, benzodiazepines, cotinine) at screening.
•Ability to communicate well with the investigator in the local language and to understand and comply with the requirements of the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
•Ongoing or recent (see below) treatment with medications for allergic airway disease (either prescribed or OTC) other than short-acting, inhaled beta2 agonist.
•Recent treatment for the following medications is defined as:
–Systemic corticosteroids: within 8 weeks prior to screening.
–Inhaled corticosteroids: within 4 weeks prior to screening.
–Intranasal corticosteroids: within 4 weeks prior to screening.
–Leukotriene receptor antagonists: within 2 weeks prior to screening.
–Cromoglycate: within 2 weeks prior to screening.
–Theophylline: within 1 week prior to screening.
–Anti-histamines: within 1 week prior to screening.
–Long-acting beta2 agonists: within 1 week prior to screening.
–Anti-cholinergics: within 1 week prior to screening.
–Anti-immunoglobulin E (IgE): within 6 months prior to screening.
–Immunotherapy: any previous use.
–Other medications: at the discretion of the investigator and with the sponsor’s consent.
•Smoking within the last year or life-time consumption > 10 pack-years
•Symptoms of a clinically relevant lower respiratory tract infection in the 3-week period prior to screening.
•Diagnosis of aspirin or non-steroidal anti-inflammatory drug (NSAID)-induced asthma.
•Planned treatment or treatment with another investigational drug within 3 months prior to screening.
•Loss of 250 mL or more of blood within 3 months before the screening examination.
•Positive HIV serology.
•History of hepatitis B or C and/or positive hepatitis serology, indicating acute or chronic hepatitis B or C.
•History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to the screening examination.
•History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with treatment compliance, study conduct or interpretation, such as any unstable medical abnormality or a disease which could affect the absorption, distribution, metabolism, or excretion of the study drug.
•Known hypersensitivity to any excipients of the study drug formulation.
•Any clinically relevant drug or food allergy.
•Legal incapacity or limited legal capacity at screening.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): •To demonstrate the effect of ACT-129968 vs. placebo on FEV1 during the late allergic reaction (3–10 hours) after a bronchial allergen challenge.;Main Objective: To demonstrate the effect of ACT-129968 vs. placebo on forced expiratory volume, measured in 1 second (FEV1) during the late allergic reaction (3–10 hours) after a bronchial allergen challenge.;Secondary Objective: • To investigate the effect of ACT-129968 on airway inflammation and airway hyperresponsiveness (AHR) after a bronchial allergen challenge.<br>• To investigate the tolerability and safety of ACT-129968.<br>• To investigate the pharmacokinetics (PK) of ACT-129968 in subjects with mild to moderate allergic asthma.<br>
- Secondary Outcome Measures
Name Time Method