E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the efficacy of single doses of 40 mg and 400 mg CRD007 in subjects with asthma |
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E.2.2 | Secondary objectives of the trial |
•To determine the protective effect of CRD007 on release of mast cell mediators by measuring urine excretion of biomarkers (9α,11ß-PGF2; LTE4; N-methylhistamine) before and after mannitol challenge
•To investigate the safety profile of single doses of 40 mg and 400 mg CRD007
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Written informed consent must be obtained before any trial related procedures are performed
2) Age ≥18 and <50 years
3) Diagnosis of asthma according to the GINA Guidelines
4) Fractional exhaled nitric oxide (FENO) >20 ppb (calculated average of 2 independent FENO measurements) at Visit 1
5) Baseline FEV1 >80% of the predicted normal value at Visit 1
6) Demonstration of PD15 at ≤315 mg mannitol <4 weeks prior to Visit 2
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E.4 | Principal exclusion criteria |
- Lower respiratory tract infection <6 weeks prior to Visit 1 (subjects may be re-screened 6 weeks after resolution of respiratory infection)
- Current smokers and ex-smokers
- Treatment with any of the medications listed below <3 weeks prior to Visit 1:
• Inhaled steroids in a dose equivalent to >2 x 400 µg budesonide /day (dose must not be changed <4 weeks prior to Visit 1 and during the trial)
• Oral corticosteroids
• Any systemic immunomodulatory therapy
• Any systemic anti-rheumatic therapy
• Anti-IL-4 therapy
- Clinically significant comorbidities that may be compromised by induced bronchospasm or repeated spirometry as judged by Investigator
- Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, cardiac, haematological, gastrointestinal, endocrine, inflammatory, autoimmune, pulmonary, neurological, cerebral or psychiatric disease evaluated by the Investigator to interfere with effect of the trial drug |
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E.5 End points |
E.5.1 | Primary end point(s) |
PD15 for mannitol after treatment with CRD007 and placebo |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 hours after administration of IMP/Placebo a mannitol challenge test will be performed to evaluate the primary endpoint |
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E.5.2 | Secondary end point(s) |
• PD15 for mannitol after treatment with CRD007 in relation to pemirolast blood concentration
a) Response Dose Ratio after treatment with CRD007 and placebo
b) Response Dose Ratio induced by mannitol challenge after treatment with CRD007 in relation to pemirolast blood concentrations
c) Change in urine excretion of biomarkers for mast cell mediators (9α,11ß-PGF2; LTE4; N-methylhistamine) in relation to CRD007 treatment
d) Adverse events
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 hours after administration of IMP/Placebo a mannitol challenge test will be performed to evaluate the secondary endpoints (a,b)
Less than 10 minutes before the mannitol challenge test and 30 and 60 minutes after the test (c)
During the trial (visit 1-5) (d) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |