Study of Efficacy and Safety of LOU064 in Inadequately Controlled Asthma Patients
Condition: Asthma
MeSH terms: Asthma
Intervention: LOU064 100 mg; Placebo
Intervention description: LOU064 100 mg once daily orally administered as two 50 mg capsules; Placebo once daily administered orally as capsules
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 76.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: asthma; LOU064

Summary:

      This was a proof-of-concept study to evaluate the efficacy of LOU064 in patients with
      inadequately controlled asthma. All subjects were randomized with 3:2 ratio to receive LOU064
      100 mg once daily or LOU064 matching placebo for 12 weeks with standard background therapy of
      budesonide 80 µg/formoterol 4.5 µg two inhalations twice a day (b.i.d).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female adult patients aged ≥ 18 to ≤ 70 years at screening.

          -  Patients must weigh at least 40 kg to participate in the study, and must have a body
             mass index (BMI) <35 kg/m2. BMI = Body weight (kg) / [Height (m)]2 at screening

          -  Patients with a physician-diagnosed history of asthma (according to GINA 2018) for a
             period of at least 6 months prior to screening.

          -  Patients who have been treated with:

               -  Medium or high dose inhaled corticosteroids (ICS), or

               -  ICS plus long-acting beta agonist (LABA), or

               -  ICS plus leukotriene receptor antagonist (LTRA), or

               -  ICS plus long-acting beta agonist (LABA) and long lasting muscarinic antagonist
                  (LAMA) for at least 1 month prior to screening and on the same doses of the above
                  mentioned medications over at least 2 weeks prior to start of the run-in period.

          -  Post-bronchodilator reversibility of FEV1 ≥ 12% and ≥ 200 mL at screening. If
             reversibility is not demonstrated at screening, then two additional attempts are
             permitted (one at the run-in visit and the last one during the run-in period between
             the run-in visit and baseline visit if needed)

          -  Spirometry with pre-bronchodilator FEV1 ≥ 40% of predicted (at screening and baseline)
             and ≤ 85% of predicted at the baseline visit.

          -  ACQ-5 score ≥ 1.5 at baseline visit

          -  ≥ 80% compliance with peak expiratory flow measurement and recording of symptoms in
             the eDiary during the run-in period.

        Exclusion Criteria:

          -  Patients who have had an asthma exacerbation requiring systemic corticosteroids,
             hospitalization, or emergency room visit within 6 weeks prior to screening or during
             the screening period.

          -  Patients who have smoked or inhaled any substance other than asthma medications within
             the 6 month period prior to screening, or who have a smoking history of greater than
             10 pack years (e.g. 10 pack years = 1 pack/day x 10 years or ½ pack/day x 20 years,
             etc.).

          -  History of life-threatening asthma event such as significant hypercarbia (pCO2 > 45
             mmHg), endotracheal intubation, non-invasive positive pressure ventilation (NIPPV),
             respiratory arrest, or seizure as a result of asthma.

          -  Patients with chronic lung diseases other than asthma, including (but not limited to)
             chronic obstructive pulmonary disease, clinically significant bronchiectasis,
             sarcoidosis, interstitial lung disease, cystic fibrosis, Churg-Strauss syndrome,
             allergic broncho-pulmonary aspergillosis, or clinically significant chronic lung
             diseases related to a history of tuberculosis or asbestosis.

          -  History or current diagnosis of ECG abnormalities indicating significant risk of
             safety for subjects participating in the study such as:

               -  Concomitant clinically significant cardiac arrhythmias, e.g. sustained
                  ventricular tachycardia, and clinically significant second or third degree AV
                  block without a pacemaker

               -  History of familial long QT syndrome or known family history of Torsades de
                  Pointes

               -  Resting heart rate (physical exam or 12 lead ECG) < 50 bpm at screening

               -  Resting QTcF ≥ 450 msec (male) or ≥ 460 msec (female) at screening or inability
                  to determine the QTcF interval

               -  Use of agents known to prolong the QT interval unless they can be permanently
                  discontinued for the duration of study

          -  At screening and/or run-in period, any severe, progressive or uncontrolled, acute or
             chronic, medical or psychiatric condition, or other factors such as abnormal vital
             signs, ECG or physical findings, or clinically relevant abnormal laboratory values,
             that in the judgment of the investigator may increase the risk associated with study
             participation/treatment or may interfere with interpretation of study results, and
             thus would make the patient inappropriate for entry into or continuing the study.

          -  Major surgery within 8 weeks prior to screening or surgery planned prior to end of
             study.

          -  History of live attenuated vaccine within 6 weeks prior to randomization or
             requirement to receive vaccinations at any time during the study.

          -  Hematology parameters at screening:

               -  Hemoglobin: < 10 g/dl

               -  Platelets: < 100 000/mm3

               -  White blood cells: < 3 000/mm3

               -  Neutrophils: < 1 500/mm3

          -  Significant bleeding risk or coagulation disorders.

          -  History of gastrointestinal bleeding, e.g. in association with use of Nonsteroidal
             Anti-Inflammatory Drug (NSAID).

          -  Requirement for anti-platelet or anticoagulant medication (e.g., warfarin, or
             clopidogrel or Novel Oral Anti-Coagulant (NOAC)) other than acetylsalicylic acid (up
             to 100 mg/d).

          -  History or presence of thrombotic or thromboembolic event, or increased risk for
             thrombotic or thromboembolic event.