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Study of Efficacy and Safety of LOU064 in Inadequately Controlled Asthma Patients

  • Clinicaltrials.gov identifier

    NCT03944707

  • Recruitment Status

    Terminated (Company decision)

  • First Posted

    May 9, 2019

  • Result First Posted

    April 27, 2021

  • Last update posted

    April 27, 2021

Study Description

Brief 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).

  • Condition or Disease:Asthma
  • Intervention/Treatment: Drug: LOU064 100 mg
    Drug: Placebo
  • Phase: Phase 2

Detailed Description

This was a non-confirmatory, multi-center, randomized, placebo-controlled, subject- and investigator-blinded, parallel-group study to evaluate the efficacy and safety of LOU064 in patients with inadequately controlled asthma who were on a standardized background therapy of inhaled corticosteroid plus long acting beta-2 agonist (ICS/LABA). The study included: - a Screening period of up to 2 weeks to assess eligibility. - a Run-in period of minimum 3 weeks and maximum 5 weeks where patients discontinued their current asthma therapy and were placed on budesonide 80 μg/formoterol 4.5 μg delivered by dry powder inhaler, two inhalations twice a day (b.i.d). - a Treatment period of 12 weeks. All subjects were randomized 3:2 to receive LOU064 100 mg once daily or placebo for 12 weeks with standard background therapy of budesonide 80 μg/formoterol 4.5 μg, two inhalations b.i.d. - a Follow-up period of 3 weeks following the last dose of study drug. Results from the interim analysis did not provide sufficient evidence of efficacy of LOU064 in inadequately controlled asthma and the sponsor decided to terminate early the study in April 2020. The median duration of exposure (12.0 weeks for LOU064 and 11.7 weeks for placebo) was close to the treatment target, as most of the subjects had completed treatment when the study was terminated.

Study Design

  • Study Type: Interventional
  • Actual Enrollment: 76 participants
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Primary Purpose: Treatment
  • Official Title: A Randomized, Subject- and Investigator-blinded, Placebo-controlled Study to Assess the Efficacy and Safety of LOU064 in Patients With Inadequately Controlled Asthma
  • Actual Study Start Date: July 2019
  • Actual Primary Completion Date: April 2020
  • Actual Study Completion Date: April 2020

Arms and interventions

Arm Intervention/treatment
Experimental: LOU064
LOU064 100 mg once daily orally
Drug: LOU064 100 mg
LOU064 100 mg once daily orally administered as two 50 mg capsules
Placebo Comparator: Placebo
Placebo once daily orally
Drug: Placebo
Placebo once daily administered orally as capsules

Outcome Measures

  • Primary Outcome Measures: 1. Change From Baseline in Pre-dose FEV1 at Week 12 [ Time Frame: Baseline, Week 12 ]
    FEV1 (forced expiratory volume in one second) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Pre-dose FEV1 is defined as average of the two FEV1 measurements taken 45 min and 15 min pre-dose. The baseline pre-dose FEV1 is defined as the average of the FEV1 measurements performed 45 min and 15 min prior to dosing on Day 1. A positive change from baseline in pre-dose FEV1 is considered a favorable outcome. Change from baseline in pre-dose FEV1 was analyzed using a Bayesian model for repeated measures, adjusting for effects of treatment*visit interaction and baseline pre-dose FEV1. A weakly informative prior was considered for the placebo response.
  • Secondary Outcome Measures: 1. Maximum Observed Blood Concentrations (Cmax) of LOU064 at Steady State [ Time Frame: pre-dose, 0.5, 1, 2, 3 and 4 hours after dosing on Days 15 and 85 ]
    Pharmacokinetic (PK) parameters were calculated based on LOU064 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification of 1 ng/mL. Cmax was determined using non-compartmental methods.
  • 2. Time to Reach Maximum Blood Concentrations (Tmax) of LOU064 at Steady State [ Time Frame: pre-dose, 0.5, 1, 2, 3 and 4 hours after dosing on Days 15 and 85 ]
    PK parameters were calculated based on LOU064 blood concentrations determined by a validated LC-MS/MS method with a lower limit of quantification of 1 ng/mL. Tmax was determined using non-compartmental methods.
  • 3. Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24h) of LOU064 at Steady State [ Time Frame: pre-dose, 0.5, 1, 2, 3 and 4 hours after dosing on Days 15 and 85 ]
    PK parameters were calculated based on LOU064 blood concentrations determined by a validated LC-MS/MS method with a lower limit of quantification of 1 ng/mL. AUC0-24h was determined using non-compartmental methods. The linear trapezoidal rule was used for AUC0-24h calculation.
  • 4. Change From Baseline in Asthma Symptom Questionnaire-5 Score (ACQ-5) at Week 12 [ Time Frame: Baseline, Week 12 ]
    The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the overall ACQ-5 score is the mean of all 5 questions, therefore between 0 (totally controlled) and 6 (severely uncontrolled). The baseline values of ACQ-5 were collected at the baseline visit. A negative change from baseline in ACQ-5 is considered a favorable outcome. Change from baseline in ACQ-5 score was analyzed using a Bayesian model for repeated measures, adjusting for effects of treatment*visit interaction and baseline ACQ-5 score. Non-informative priors were considered.
  • 5. Change From Baseline in Mean Morning and Mean Evening Peak Expiratory Flow (PEF) [ Time Frame: Baseline, Weeks 9-12 ]
    PEF (Peak Expiratory Flow) is a person's maximum speed of expiration. All participants were instructed to record PEF twice daily before taking any medication using an electronic peak expiratory flow device (ePEF), once in the morning and once approximately 12 h later in the evening at home. At each timepoint, the participant was instructed to perform 3 consecutive manoeuvres within 10 minutes. These PEF values were captured in the e-PEF/diary. For each day the best value in the morning and in the evening were considered and mean values on 4-week intervals were derived. The baseline values of PEF were the mean values in the run-in period. A positive change from baseline in PEF is considered a favorable outcome. Change from baseline in mean morning and mean evening PEF were analyzed using a Bayesian model for repeated measures, adjusting for effects of treatment*weeks interaction and baseline PEF values. Non-informative priors were considered.
  • 6. Change From Baseline in Number of Puffs of SABA Taken Per Day During the Treatment Period [ Time Frame: Baseline, 12 weeks ]
    Participants were given a short acting β2-agonist (SABA; salbutamol, known also as albuterol) to use as rescue medication throughout the study along with an electronic diary (eDiary) to record rescue medication use. Participants recorded in the eDiary, once in the morning and once in the evening, the use of rescue medication (number of puffs of SABA taken in the previous 12 hours). The total number of puffs of SABA taken per day was calculated and the mean daily use of puffs of SABA over 12 weeks was derived. The baseline values of number of puffs of SABA taken per day were defined as the average from all non-missing records taken during the run-in period. A negative change from baseline is considered a favorable outcome. Change from baseline in number of puffs of SABA taken per day was analyzed using a Bayesian model, adjusting for effects of baseline SABA use, baseline FEV1, baseline asthma daytime symptom score and treatment. Non-informative priors were considered.
  • 7. Change From Baseline in Daytime and Nighttime Asthma Symptom Score [ Time Frame: Baseline, Weeks 9-12 ]
    Participants recorded asthma symptoms twice daily in the eDiary. Daytime asthma symptoms were assessed before bed and nighttime symptoms on awakening. Daytime asthma symptom score included 4 questions. Overall score (0 to 6) was calculated as the average of the 4 questions with higher values indicating more asthma symptoms. Nighttime asthma symptom score included 2 questions. Overall score (0 to 3.5) was calculated as the average of the 2 questions with higher values indicating more asthma symptoms. Mean values of both scores were calculated over 4-week intervals during the treatment period. The baseline values of both asthma symptoms scores were defined as the average score during the run-in period. A negative change from baseline is a favorable outcome. Change from baseline in daytime and nighttime asthma symptom score were analyzed using a Bayesian model for repeated measures, adjusting for effects of treatment*weeks and baseline scores. Non-informative priors were considered.

Eligibility Criteria

  • Ages Eligible for Study: 18 to 70 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No

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) 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.

Contacts and Locations

Contacts

Locations

United States, Colorado
Novartis Investigative Site
Denver

United States, Massachusetts
Novartis Investigative Site
North Dartmouth

United States, Missouri
Novartis Investigative Site
Saint Louis

United States, North Carolina
Novartis Investigative Site
Raleigh

Argentina, Buenos Aires
Novartis Investigative Site
Caba

Argentina, Buenos Aires
Novartis Investigative Site
Caba

Argentina, Santa Fe
Novartis Investigative Site
Rosario

Argentina, Santa Fe
Novartis Investigative Site
Rosario

Germany
Novartis Investigative Site
Berlin

Germany
Novartis Investigative Site
Berlin

Germany
Novartis Investigative Site
Frankfurt

Germany
Novartis Investigative Site
Hamburg

Germany
Novartis Investigative Site
Hannover

Poland
Novartis Investigative Site
Biaystok

Poland
Novartis Investigative Site
Grudziadz

Poland
Novartis Investigative Site
Krakow

Poland
Novartis Investigative Site
Poznan

Russian Federation
Novartis Investigative Site
Saint-Petersburg

Russian Federation
Novartis Investigative Site
Ulyanovsk

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

  • Responsible Party: Novartis Pharmaceuticals
  • ClinicalTrials.gov Identifier: NCT03944707 History of Changes
  • Other Study ID Numbers: CLOU064D12201, 2018-003609-24
  • First Posted: May 9, 2019 Key Record Dates
  • Last Update Posted: April 27, 2021
  • Last Verified: March 2021
  • Individual Participant
    Data (IPD) Sharing
    Statement:

  • Plan to Share IPD: Yes
  • Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Novartis Pharmaceuticals: asthma LOU064
  • Additional relevant MeSH terms: Asthma
  • Study Type: Interventional
  • Study Design: Allocation: Randomized;Intervention Model: Parallel Assignment;Masking: Quadruple;Primary Purpose: Treatment
  • Condition: Asthma
  • Interventions : Drug: LOU064 100 mg
    Drug: Placebo
  • Enrollment: 76

Participant flow

  • Recruitment Details Participants took part in 19 investigative sites in 5 countries.
  • Pre-assignment Details After the screening, participants went through a Run-in period of 3-5 weeks where they discontinued their current asthma therapy and were placed on budesonide 80 μg/formoterol 4.5 μg delivered by dry powder inhaler. Afterwards, patients were randomized in 3:2 ratio to receive LOU064 or placebo and continued to use the budesonide/formoterol inhaler.

  • Arm/Group title Placebo LOU064
  • Arm/Group Description Placebo once daily orally LOU064 100 mg once daily orally
    Period Title: Overall Study
  • Started 29 47
  • Completed 19 35
  • Not Completed 10 12
  • Reason Not Completed
  • Subject decision 1
  • Study terminated by sponsor 7 12
  • Adverse Event 2
Baseline Characteristics
  • Arm/Group title TotalPlaceboLOU064
  • Arm/Group Description Total of all reporting groupsPlacebo once daily orallyLOU064 100 mg once daily orally
  • Overall Number of Baseline Participants 762947
  • Baseline Analysis Population Description [Not Specified]
Outcome Measures

1. PrimaryOutcome

  • Title Change From Baseline in Pre-dose FEV1 at Week 12
  • Description FEV1 (forced expiratory volume in one second) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Pre-dose FEV1 is defined as average of the two FEV1 measurements taken 45 min and 15 min pre-dose. The baseline pre-dose FEV1 is defined as the average of the FEV1 measurements performed 45 min and 15 min prior to dosing on Day 1. A positive change from baseline in pre-dose FEV1 is considered a favorable outcome. Change from baseline in pre-dose FEV1 was analyzed using a Bayesian model for repeated measures, adjusting for effects of treatment*visit interaction and baseline pre-dose FEV1. A weakly informative prior was considered for the placebo response.
  • Time Frame Baseline, Week 12
Outcome Measure Data
  • Analysis Population Description PD analysis set including participants with a valid measurement for the outcome measure.
  •  
  • Arm/Group title PlaceboLOU064
  • Arm/Group Description Placebo once daily orallyLOU064 100 mg once daily orally
  • Overall Number of Participants Analyzed 2032
  • Measure Type: Mean (Standard Deviation)
    Unit of Measure: liters
  • 0.075
    0.105
  • Statistical Analysis Overview
    • Comparison Group Selection Change From Baseline in Pre-dose FEV1 at Week 12
    • Comments
    • Type of Statistical Test Superiority
    • Comments [Not Specified]
  • Statistical Test of Hypothesis
    • P-Value 0.6643
    • Comments Probability LOU064 better than placebo
    • Method Bayesian model for repeated measures
    • Comments
  • Method of Estimation
    • Estimation Parameter Mean Difference (Net)
    • Estimated Value 0.03
    • Confidence Interval (2-Sided ) 80.0%
      -0.06 to 0.119
    • Estimation Comments Posterior mean difference (LOU064 - placebo) and 80% credible interval are presented.

2. SecondaryOutcome

  • Title Change From Baseline in Daytime and Nighttime Asthma Symptom Score
  • Description Participants recorded asthma symptoms twice daily in the eDiary. Daytime asthma symptoms were assessed before bed and nighttime symptoms on awakening. Daytime asthma symptom score included 4 questions. Overall score (0 to 6) was calculated as the average of the 4 questions with higher values indicating more asthma symptoms. Nighttime asthma symptom score included 2 questions. Overall score (0 to 3.5) was calculated as the average of the 2 questions with higher values indicating more asthma symptoms. Mean values of both scores were calculated over 4-week intervals during the treatment period. The baseline values of both asthma symptoms scores were defined as the average score during the run-in period. A negative change from baseline is a favorable outcome. Change from baseline in daytime and nighttime asthma symptom score were analyzed using a Bayesian model for repeated measures, adjusting for effects of treatment*weeks and baseline scores. Non-informative priors were considered.
  • Time Frame Baseline, Weeks 9-12
Outcome Measure Data
  • Analysis Population Description PD analysis set including participants with a valid measurement for the outcome measure.
  •  
  • Arm/Group title PlaceboLOU064
  • Arm/Group Description Placebo once daily orallyLOU064 100 mg once daily orally
  • Overall Number of Participants Analyzed 2947
  • Measure Type: Mean (Standard Deviation)
    Unit of Measure: score on scale
  • Change from baseline in nighttime asthma symptom score -0.195
    -0.120
  • Change from baseline in daytime asthma symptom score -0.175
    -0.225
  • Statistical Analysis Overview
    • Comparison Group Selection Change From Baseline in Pre-dose FEV1 at Week 12, Change From Baseline in Daytime and Nighttime Asthma Symptom Score
    • Comments Change from baseline in nighttime asthma symptom score
    • Type of Statistical Test Superiority
    • Comments [Not Specified]
  • Statistical Test of Hypothesis
    • P-Value 0.1752
    • Comments Probability LOU064 better than placebo
    • Method Bayesian model for repeated measures
    • Comments
  • Method of Estimation
    • Estimation Parameter Mean Difference (Net)
    • Estimated Value 0.075
    • Confidence Interval (2-Sided ) 80.0%
      -0.028 to 0.18
    • Estimation Comments Posterior mean difference (LOU064 - placebo) and 80% credible interval are presented.

3. SecondaryOutcome

  • Title Change From Baseline in Number of Puffs of SABA Taken Per Day During the Treatment Period
  • Description Participants were given a short acting β2-agonist (SABA; salbutamol, known also as albuterol) to use as rescue medication throughout the study along with an electronic diary (eDiary) to record rescue medication use. Participants recorded in the eDiary, once in the morning and once in the evening, the use of rescue medication (number of puffs of SABA taken in the previous 12 hours). The total number of puffs of SABA taken per day was calculated and the mean daily use of puffs of SABA over 12 weeks was derived. The baseline values of number of puffs of SABA taken per day were defined as the average from all non-missing records taken during the run-in period. A negative change from baseline is considered a favorable outcome. Change from baseline in number of puffs of SABA taken per day was analyzed using a Bayesian model, adjusting for effects of baseline SABA use, baseline FEV1, baseline asthma daytime symptom score and treatment. Non-informative priors were considered.
  • Time Frame Baseline, 12 weeks
Outcome Measure Data
  • Analysis Population Description PD analysis set including participants with a valid measurement for the outcome measure.
  •  
  • Arm/Group title PlaceboLOU064
  • Arm/Group Description Placebo once daily orallyLOU064 100 mg once daily orally
  • Overall Number of Participants Analyzed 2641
  • Measure Type: Mean (Standard Deviation)
    Unit of Measure: puffs of SABA
  • -0.059
    -0.192
  • Statistical Analysis Overview
    • Comparison Group Selection Change From Baseline in Pre-dose FEV1 at Week 12, Change From Baseline in Daytime and Nighttime Asthma Symptom Score, Change From Baseline in Number of Puffs of SABA Taken Per Day During the Treatment Period
    • Comments
    • Type of Statistical Test Superiority
    • Comments [Not Specified]
  • Statistical Test of Hypothesis
    • P-Value 0.8022
    • Comments Probability LOU064 better than placebo
    • Method Bayesian model
    • Comments
  • Method of Estimation
    • Estimation Parameter Mean Difference (Net)
    • Estimated Value -0.133
    • Confidence Interval (2-Sided ) 80.0%
      -0.336 to 0.071
    • Estimation Comments Posterior mean difference (LOU064 - placebo) and 80% credible interval are presented.

4. SecondaryOutcome

  • Title Change From Baseline in Mean Morning and Mean Evening Peak Expiratory Flow (PEF)
  • Description PEF (Peak Expiratory Flow) is a person's maximum speed of expiration. All participants were instructed to record PEF twice daily before taking any medication using an electronic peak expiratory flow device (ePEF), once in the morning and once approximately 12 h later in the evening at home. At each timepoint, the participant was instructed to perform 3 consecutive manoeuvres within 10 minutes. These PEF values were captured in the e-PEF/diary. For each day the best value in the morning and in the evening were considered and mean values on 4-week intervals were derived. The baseline values of PEF were the mean values in the run-in period. A positive change from baseline in PEF is considered a favorable outcome. Change from baseline in mean morning and mean evening PEF were analyzed using a Bayesian model for repeated measures, adjusting for effects of treatment*weeks interaction and baseline PEF values. Non-informative priors were considered.
  • Time Frame Baseline, Weeks 9-12
Outcome Measure Data
  • Analysis Population Description PD analysis set including participants with a valid measurement for the outcome measure.
  •  
  • Arm/Group title PlaceboLOU064
  • Arm/Group Description Placebo once daily orallyLOU064 100 mg once daily orally
  • Overall Number of Participants Analyzed 2947
  • Measure Type: Mean (Standard Deviation)
    Unit of Measure: liters/minute
  • Change from baseline in mean evening PEF -6.3
    -9.7
  • Change from baseline in mean morning PEF -2.6
    -2.4
  • Statistical Analysis Overview
    • Comparison Group Selection Change From Baseline in Pre-dose FEV1 at Week 12, Change From Baseline in Daytime and Nighttime Asthma Symptom Score, Change From Baseline in Number of Puffs of SABA Taken Per Day During the Treatment Period, Change From Baseline in Mean Morning and Mean Evening Peak Expiratory Flow (PEF)
    • Comments Change from baseline in mean evening PEF
    • Type of Statistical Test Superiority
    • Comments [Not Specified]
  • Statistical Test of Hypothesis
    • P-Value 0.3611
    • Comments Probability LOU064 better than placebo
    • Method Bayesian model for repeated measures
    • Comments
  • Method of Estimation
    • Estimation Parameter Mean Difference (Net)
    • Estimated Value -3.4
    • Confidence Interval (2-Sided ) 80.0%
      -15.2 to 8.1
    • Estimation Comments Posterior mean difference (LOU064 - placebo) and 80% credible interval are presented.

5. SecondaryOutcome

  • Title Change From Baseline in Asthma Symptom Questionnaire-5 Score (ACQ-5) at Week 12
  • Description The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the overall ACQ-5 score is the mean of all 5 questions, therefore between 0 (totally controlled) and 6 (severely uncontrolled). The baseline values of ACQ-5 were collected at the baseline visit. A negative change from baseline in ACQ-5 is considered a favorable outcome. Change from baseline in ACQ-5 score was analyzed using a Bayesian model for repeated measures, adjusting for effects of treatment*visit interaction and baseline ACQ-5 score. Non-informative priors were considered.
  • Time Frame Baseline, Week 12
Outcome Measure Data
  • Analysis Population Description PD analysis set including participants with a valid measurement for the outcome measure.
  •  
  • Arm/Group title PlaceboLOU064
  • Arm/Group Description Placebo once daily orallyLOU064 100 mg once daily orally
  • Overall Number of Participants Analyzed 2033
  • Measure Type: Mean (Standard Deviation)
    Unit of Measure: score on scale
  • -0.86
    -0.95
  • Statistical Analysis Overview
    • Comparison Group Selection Change From Baseline in Pre-dose FEV1 at Week 12, Change From Baseline in Daytime and Nighttime Asthma Symptom Score, Change From Baseline in Number of Puffs of SABA Taken Per Day During the Treatment Period, Change From Baseline in Mean Morning and Mean Evening Peak Expiratory Flow (PEF), Change From Baseline in Asthma Symptom Questionnaire-5 Score (ACQ-5) at Week 12
    • Comments
    • Type of Statistical Test Superiority
    • Comments [Not Specified]
  • Statistical Test of Hypothesis
    • P-Value 0.6609
    • Comments Probability LOU064 better than placebo
    • Method Bayesian model for repeated measures
    • Comments
  • Method of Estimation
    • Estimation Parameter Median Difference (Net)
    • Estimated Value -0.09
    • Confidence Interval (2-Sided ) 80.0%
      -0.35 to 0.18
    • Estimation Comments Posterior mean difference (LOU064 - placebo) and 80% credible interval are presented.

6. SecondaryOutcome

  • Title Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24h) of LOU064 at Steady State
  • Description PK parameters were calculated based on LOU064 blood concentrations determined by a validated LC-MS/MS method with a lower limit of quantification of 1 ng/mL. AUC0-24h was determined using non-compartmental methods. The linear trapezoidal rule was used for AUC0-24h calculation.
  • Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours after dosing on Days 15 and 85
Outcome Measure Data
  • Analysis Population Description PK analysis set including participants with a valid measurement for the outcome measure.
  •  
  • Arm/Group title PlaceboLOU064
  • Arm/Group Description Placebo once daily orallyLOU064 100 mg once daily orally
  • Overall Number of Participants Analyzed 33
  • Measure Type: Mean (Standard Deviation)
    Unit of Measure: hr*ng/mL

  • 517

  • 471

7. SecondaryOutcome

  • Title Time to Reach Maximum Blood Concentrations (Tmax) of LOU064 at Steady State
  • Description PK parameters were calculated based on LOU064 blood concentrations determined by a validated LC-MS/MS method with a lower limit of quantification of 1 ng/mL. Tmax was determined using non-compartmental methods.
  • Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours after dosing on Days 15 and 85
Outcome Measure Data
  • Analysis Population Description PK analysis set including participants with a valid measurement for the outcome measure.
  •  
  • Arm/Group title PlaceboLOU064
  • Arm/Group Description Placebo once daily orallyLOU064 100 mg once daily orally
  • Overall Number of Participants Analyzed 33
  • Measure Type: Median (Full Range)
    Unit of Measure: hours (hr)

  • 1.00
    (0.483 to 2.0)

  • 1.00
    (0.5 to 3.0)

8. SecondaryOutcome

  • Title Maximum Observed Blood Concentrations (Cmax) of LOU064 at Steady State
  • Description Pharmacokinetic (PK) parameters were calculated based on LOU064 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantification of 1 ng/mL. Cmax was determined using non-compartmental methods.
  • Time Frame pre-dose, 0.5, 1, 2, 3 and 4 hours after dosing on Days 15 and 85
Outcome Measure Data
  • Analysis Population Description PK analysis set including participants with a valid measurement for the outcome measure.
  •  
  • Arm/Group title PlaceboLOU064
  • Arm/Group Description Placebo once daily orallyLOU064 100 mg once daily orally
  • Overall Number of Participants Analyzed 33
  • Measure Type: Mean (Standard Deviation)
    Unit of Measure: ng/mL

  • 222

  • 239
Adverse Events
  • Time Frame From first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to Day 115.
  • Adverse Event Reporting Description Any sign or symptom that occurs during the study treatment plus 30 days post treatment.
  •  
  • Arm/Group Title PlaceboLOU064
  • Arm/Group Description Placebo once daily orallyLOU064 100 mg once daily orally

Show Other (Not Including Serious) Adverse Events

  • LOU064 Placebo
  • Affected at Risk (%) Affected at Risk (%)
  • Total 4/47 (8.51%) 6/29 (20.69%)
  • Infections and infestations
  • Upper respiratory tract infection 4 /47 (8.51%) 4 /29 (13.79%)
  • Nasopharyngitis 4 /47 (8.51%) 6 /29 (20.69%)
  • Respiratory, thoracic and mediastinal disorders
  • Asthma 0 /47 (0.00%) 2 /29 (6.90%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. Novartis does not prohibit any investigator from publishing. Any publications from a single site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.

Results Point of Contact

  • ClinicalTrials.gov Identifier: NCT03944707 History of Changes
  • Other Study ID Numbers: 2018-003609-24
  • First Submitted: May 2, 2019
  • First Posted: May 9, 2019
  • Results First Submitted: March 30, 2021
  • Results First Posted: April 27, 2021
  • Last Update Posted: April 27, 2021