A randomized, double-blind, two way cross-over, proof of concept study to compare the efficacy, safety, pharmacokinetics and pharmacodynamics of two-week oral administration of QAV680 versus placebo, with an extended open-label inhaled corticosteroid period, in steroid-free, mild to moderate persistent asthma patients

• Register: EUCTR
• Last refreshed on: 1 April 2013
• Main ID: EUCTR2008-005168-15-DE
• Date of registration: 24/09/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A randomized, double-blind, two way cross-over, proof of concept study to compare the efficacy, safety, pharmacokinetics and pharmacodynamics of two-week oral administration of QAV680 versus placebo, with an extended open-label inhaled corticosteroid period, in steroid-free, mild to moderate persistent asthma patients
• Scientific title: A randomized, double-blind, two way cross-over, proof of concept study to compare the efficacy, safety, pharmacokinetics and pharmacodynamics of two-week oral administration of QAV680 versus placebo, with an extended open-label inhaled corticosteroid period, in steroid-free, mild to moderate persistent asthma patients
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005168-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: yes Other trial design description: Third period with open-label fluticasone propionate If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female patients aged 18 to 65 years with symptomatic mild to moderate persistent asthma for = 6 months
2. Patients should be steroid naive or off steroids and chromoglycate (by any route) for at least 4 weeks before randomisation. Only use of short-acting ß2-agonists is permissible as rescue medication.
3. Patients should have pre-bronchodilator FEV1 =60% predicted with =12% or 200 mL improvement post short acting ß2-agonist (200µg inhaled Salbutamol).
• Patients who are NOT on ICS during screening need to demonstrate reversibility during screening visit
• Patients who are on steroids need to demonstrate reversibility during the first baseline AFTER their steroid-withdrawal
4. Women must be postmenopausal or surgically sterilized at the time of participation as defined in the protocol.
5. Male subjects must be using a two acceptable methods of contraception as defined in the protocol up to the Study Completion visit and refrain from fathering a child in the 3 months following the last study drug administration.
6. Subjects must weigh at least 45 kg and have a body mass index (BMI) within the range of 20 to 30 kg/m2.
7. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent.

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

Exclusion criteria:
1. Smokers (defined as history of smoking in the previous 2 months)
2. Use of any prescription drugs, herbal supplements, within 4 weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within 2 weeks prior to initial dosing other than short acting inhaled beta-agonists and paracetamol is acceptable but must be documented in the Concomitant CRF.
3. Participation in any clinical investigation within 4 weeks prior to initial dosing.
4. Donation or loss of 400 ml or more of blood within 8) weeks prior to initial dosing. Hemoglobin levels below 12.0 g/dl at screening.
5. Significant illness within 2 weeks prior to initial dosing.
6. Patients with positive stool examination at screening for helminthic, ova or parasitic infections.
7. Past medical history of clinically significant ECG abnormalities, or recent history of hypertension or autonomic dysfunction
8. Recent history (within past three months) of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures.
9. Use of theophylline or long acting ß2 agonists in the last 2 weeks prior to dosing
10. Pregnant or lactating women.
11. Any disease or illness, other than asthma, that may require the use of systemic corticosteroids during the study period.
12. Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the first dose of study medication. Patients with other serious underlying diseases as defined in protocol.
13. History of multiple allergies to drugs or allergy to the investigational compound/compound class being used in this study.
17. Vulnerable patients (e.g. patients kept in detention)

---REFER TO STUDY PROTOCOL FOR FULL LIST OF EXCLUSION CRITERIA---


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Mild to moderate persistent asthma, steroid-free patients
MedDRA version: 9.1 Level: LLT Classification code 10003553 Term: Asthma

Intervention(s)

Product Code: QAV680
Pharmaceutical Form: Capsule, hard
Current Sponsor code: QAV680
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Flutide® mite 100 Diskus
Product Name: Flutide mite 100 Diskus
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Fluticasone propionate
CAS Number: 80474-14-2
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): Trough FEV1 on Day 15 of each treatment period

Main Objective: • To assess the efficacy and safety of multiple doses of QAV680 (500 mg BID over 14 days) compared to placebo in mild to moderate persistent steroid free asthma patients

Secondary Objective: • To assess the pharmacokinetics of multiple doses of QAV680 in asthma patients.

• To assess the pharmacodynamic effect of multiple doses of QAV680 on exhaled NO in asthma patients.

• To assess the effect of QAV680 on asthma control using assessments such as Asthma Control Questionnaire (ACQ) score, FEV1 variability data captured by PIKO-1 home monitoring device and the extent of inhaled salbutamol use as rescue medication.

Secondary ID(s)

CQAV680A2201