Dose-range Finding Efficacy and Safety Study for QBW251 in COPD Patients

April 6, 2023 updated by: Novartis Pharmaceuticals

A 24-week Multi-center, Double-blind, Placebo Controlled Dose-range Finding Study to Investigate the Efficacy and Safety of Oral QBW251 in COPD Patients on Triple Inhaled Therapy (LABA / LAMA / ICS)

This clinical study was designed to support the dose selection for future studies by evaluating efficacy and safety of different QBW251 doses in Chronic obstructive pulmonary disease (COPD) patients with chronic bronchitis and a history of exacerbations, compared to placebo, when added to a triple inhaled therapy of LABA, LAMA and ICS.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study used a 6 treatment arm, parallel-group, randomized, double-blind study design. 974 male and female COPD patients were randomized into the trial. The study consisted of four distinct study periods:

  • Screening (Weeks -3 to -2): Participants underwent a screening period of 1 week where were assessed for eligibility and tapered off disallowed medications.
  • Run-in (Days -14 to 1): Subsequently, participants entered the run-in period of up to 2 weeks to establish baseline values for symptom assessments, to standardize the COPD background therapy (triple combination LABA/LAMA/ICS), and to complete eligibility assessments.
  • Treatment (Day 1 to Week 24): Eligible participants moved into the Day 1 visit where they were stratified according to their smoking status (current or ex-smoker) and severity of airflow limitation (FEV1 ≥ 30% to < 50% and ≥ 50% to < 80%) and then randomized into 1 of 6 treatment arms with a randomization ratio of 2:2:1:1:1:2 (450 mg b.i.d., 300 mg b.i.d., 150 mg b.i.d., 75 mg b.i.d., 25 mg b.i.d., placebo). The treatment period consisted of 24 weeks, during which the participant returned to the site for regular visits (Day 1 - Week 24). QBW251 450 mg arm was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.
  • Follow-up (Weeks 25-28): Upon completion of the treatment period, participants were followed up for safety assessments for 30 days.

Study Type

Interventional

Enrollment (Actual)

974

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Ciudad Autonoma de Bs As, Argentina, C1425FVH
        • Novartis Investigative Site
      • Mendoza, Argentina, 5500
        • Novartis Investigative Site
      • Mendoza, Argentina, M5500CBA
        • Novartis Investigative Site
      • Salta, Argentina, 4000
        • Novartis Investigative Site
      • Santa Fe, Argentina, S3000FIL
        • Novartis Investigative Site
    • Buenos Aires
      • Berazategui, Buenos Aires, Argentina, 1888
        • Novartis Investigative Site
      • Mar del Plata, Buenos Aires, Argentina, 7600
        • Novartis Investigative Site
    • Entre Ríos
      • Concepcion del Uruguay, Entre Ríos, Argentina, 3260
        • Novartis Investigative Site
    • Santa Fe
      • Rosario, Santa Fe, Argentina, S2000DBS
        • Novartis Investigative Site
      • Rosario, Santa Fe, Argentina, S2000AII
        • Novartis Investigative Site
  • Australia
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Novartis Investigative Site
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Novartis Investigative Site
      • Footscray, Victoria, Australia, 3011
        • Novartis Investigative Site
    • Western Australia
      • Spearwood, Western Australia, Australia, 6163
        • Novartis Investigative Site
  • Austria
      • Feldbach, Austria, 8330
        • Novartis Investigative Site
      • Grieskirchen, Austria, 4710
        • Novartis Investigative Site
      • Thalheim bei Wels, Austria, 4600
        • Novartis Investigative Site
  • Belgium
      • Erpent, Belgium, 5100
        • Novartis Investigative Site
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
      • Liege, Belgium, 4000
        • Novartis Investigative Site
  • Canada
    • Alberta
      • Sherwood Park, Alberta, Canada, T8H 0N2
        • Novartis Investigative Site
    • Quebec
      • Sainte Foy, Quebec, Canada, G1V 4G5
        • Novartis Investigative Site
      • St-Charles-Borromee, Quebec, Canada, J6E 2B4
        • Novartis Investigative Site
  • Colombia
    • Cundinamarca
      • Zipaquira, Cundinamarca, Colombia, 250252
        • Novartis Investigative Site
  • Czechia
      • Varnsdorf, Czechia, 40747
        • Novartis Investigative Site
    • Czech Republic
      • Liberec, Czech Republic, Czechia, 460 05
        • Novartis Investigative Site
      • Ostrava Poruba, Czech Republic, Czechia, 708 68
        • Novartis Investigative Site
      • Teplice, Czech Republic, Czechia, 415 01
        • Novartis Investigative Site
  • Denmark
      • Aalborg, Denmark, DK 9000
        • Novartis Investigative Site
      • Copenhagen, Denmark, DK-2400
        • Novartis Investigative Site
      • Hvidovre, Denmark, 2650
        • Novartis Investigative Site
  • France
      • Lyon Cedex 04, France, 69317
        • Novartis Investigative Site
      • Pessac Cedex, France, 33604
        • Novartis Investigative Site
      • Reims, France, 51092
        • Novartis Investigative Site
    • Herault
      • Montpellier cedex 5, Herault, France, 34059
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 12157
        • Novartis Investigative Site
      • Berlin, Germany, 12159
        • Novartis Investigative Site
      • Berlin, Germany, 10119
        • Novartis Investigative Site
      • Frankfurt, Germany, 60596
        • Novartis Investigative Site
      • Halle, Germany, 06108
        • Novartis Investigative Site
      • Hamburg, Germany, 20354
        • Novartis Investigative Site
      • Landsberg, Germany, 86899
        • Novartis Investigative Site
      • Leipzig, Germany, 04207
        • Novartis Investigative Site
      • Leipzig, Germany, D-04299
        • Novartis Investigative Site
      • Leipzig, Germany, D-04347
        • Novartis Investigative Site
      • Mainz, Germany, 55131
        • Novartis Investigative Site
      • Marburg, Germany, 35037
        • Novartis Investigative Site
      • Mittweida, Germany, 09648
        • Novartis Investigative Site
      • Witten, Germany, 58452
        • Novartis Investigative Site
  • Greece
      • Heraklion Crete, Greece, 711 10
        • Novartis Investigative Site
    • GR
      • Thessaloniki, GR, Greece, 570 10
        • Novartis Investigative Site
  • Guatemala
      • Guatemala City, Guatemala, 01011
        • Novartis Investigative Site
    • GTM
      • Guatemala City, GTM, Guatemala, 01010
        • Novartis Investigative Site
      • Guatemala City, GTM, Guatemala, 01011
        • Novartis Investigative Site
  • Hong Kong
      • New Territories, Hong Kong
        • Novartis Investigative Site
      • Pokfulam, Hong Kong
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, 1106
        • Novartis Investigative Site
      • Godollo, Hungary, 2100
        • Novartis Investigative Site
      • Komarom, Hungary, 2900
        • Novartis Investigative Site
      • Mako, Hungary, 6900
        • Novartis Investigative Site
      • Pecs, Hungary, 7635
        • Novartis Investigative Site
  • Italy
    • GE
      • Genova, GE, Italy, 16132
        • Novartis Investigative Site
    • SI
      • Siena, SI, Italy, 53100
        • Novartis Investigative Site
    • VR
      • Negrar, VR, Italy, 37024
        • Novartis Investigative Site
  • Japan
      • Osaka, Japan, 531-0073
        • Novartis Investigative Site
    • Aichi
      • Nagoya, Aichi, Japan, 457-8511
        • Novartis Investigative Site
      • Nagoya, Aichi, Japan, 457 8510
        • Novartis Investigative Site
    • Fukuoka
      • Fukuoka city, Fukuoka, Japan, 811-1394
        • Novartis Investigative Site
      • Fukuoka-city, Fukuoka, Japan, 819-8555
        • Novartis Investigative Site
      • Kasuga-city, Fukuoka, Japan, 816-0813
        • Novartis Investigative Site
      • Koga city, Fukuoka, Japan, 811 3195
        • Novartis Investigative Site
      • Yanagawa-city, Fukuoka, Japan, 832-0059
        • Novartis Investigative Site
    • Gifu
      • Mizunami-city, Gifu, Japan, 509 6134
        • Novartis Investigative Site
    • Hokkaido
      • Asahikawa-city, Hokkaido, Japan, 070-8644
        • Novartis Investigative Site
      • Sapporo, Hokkaido, Japan, 062-8618
        • Novartis Investigative Site
    • Ibaraki
      • Naka-gun, Ibaraki, Japan, 319-1113
        • Novartis Investigative Site
    • Kanagawa
      • Kawasaki-city, Kanagawa, Japan, 210-0852
        • Novartis Investigative Site
      • Sagamihara-city, Kanagawa, Japan, 252-0392
        • Novartis Investigative Site
      • Yokohama-city, Kanagawa, Japan, 223-0059
        • Novartis Investigative Site
    • Mie
      • Matsusaka-city, Mie, Japan, 515-8544
        • Novartis Investigative Site
    • Miyagi
      • Sendai-shi, Miyagi, Japan, 983 8520
        • Novartis Investigative Site
    • Osaka
      • Kawachinagano, Osaka, Japan, 586-8521
        • Novartis Investigative Site
      • Kishiwada-city, Osaka, Japan, 596-8501
        • Novartis Investigative Site
      • Toyonaka, Osaka, Japan, 560-8552
        • Novartis Investigative Site
    • Tokyo
      • Chuo ku, Tokyo, Japan, 104-0031
        • Novartis Investigative Site
      • Chuo-ku, Tokyo, Japan, 103-0003
        • Novartis Investigative Site
      • Chuo-ku, Tokyo, Japan, 103-0028
        • Novartis Investigative Site
      • Kodaira, Tokyo, Japan, 187-0024
        • Novartis Investigative Site
      • Setagaya-Ku, Tokyo, Japan, 157-0072
        • Novartis Investigative Site
      • Setagaya-ku, Tokyo, Japan, 158-8531
        • Novartis Investigative Site
      • Shinagawa, Tokyo, Japan, 140-8522
        • Novartis Investigative Site
      • Toshima ku, Tokyo, Japan, 170 0003
        • Novartis Investigative Site
    • Yamagata
      • Yamagata city, Yamagata, Japan, 990-8533
        • Novartis Investigative Site
  • Korea, Republic of
      • Daegu, Korea, Republic of, 705703
        • Novartis Investigative Site
      • Incheon, Korea, Republic of, 21431
        • Novartis Investigative Site
    • Seocho Gu
      • Seoul, Seocho Gu, Korea, Republic of, 06591
        • Novartis Investigative Site
  • Netherlands
      • Eindhoven, Netherlands, 5623 EJ
        • Novartis Investigative Site
      • Harderwijk, Netherlands, 3840 AC
        • Novartis Investigative Site
  • Philippines
      • Bulacan, Philippines, 3020
        • Novartis Investigative Site
      • Iloilo City, Philippines, 5000
        • Novartis Investigative Site
      • Manila, Philippines, 1000
        • Novartis Investigative Site
    • Batangas
      • Lipa City, Batangas, Philippines, 4217
        • Novartis Investigative Site
    • Iloilo
      • Iloilo city, Iloilo, Philippines, 5000
        • Novartis Investigative Site
  • Poland
      • Grudziadz, Poland, 86-300
        • Novartis Investigative Site
      • Katowice, Poland, 40-648
        • Novartis Investigative Site
      • Zawadzkie, Poland, 47-120
        • Novartis Investigative Site
  • Slovakia
      • Poprad, Slovakia, 058 01
        • Novartis Investigative Site
      • Presov, Slovakia, 080 01
        • Novartis Investigative Site
      • Spisska Nova Ves, Slovakia, 052 01
        • Novartis Investigative Site
      • Vysne Hagy, Slovakia, 5984
        • Novartis Investigative Site
    • Slovak Republic
      • Bardejov, Slovak Republic, Slovakia, 085 01
        • Novartis Investigative Site
      • Bojnice, Slovak Republic, Slovakia, 972 01
        • Novartis Investigative Site
      • Humenne, Slovak Republic, Slovakia, 066 01
        • Novartis Investigative Site
  • Spain
      • Girona, Spain, 17005
        • Novartis Investigative Site
    • Andalucia
      • Marbella, Andalucia, Spain, 29603
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Alzira, Comunidad Valenciana, Spain, 46600
        • Novartis Investigative Site
  • Thailand
      • Bangkok, Thailand, 10330
        • Novartis Investigative Site
      • Bangkok, Thailand, 10400
        • Novartis Investigative Site
    • Hat Yai
      • Songkhla, Hat Yai, Thailand, 90110
        • Novartis Investigative Site
    • THA
      • Khon Kaen, THA, Thailand, 40002
        • Novartis Investigative Site
  • Turkey
      • Adana, Turkey, 01330
        • Novartis Investigative Site
      • Mersin, Turkey, 33079
        • Novartis Investigative Site
  • United Kingdom
      • London, United Kingdom, EC1A 7BE
        • Novartis Investigative Site
  • United States
    • Alabama
      • Andalusia, Alabama, United States, 36420
        • Novartis Investigative Site
    • California
      • Los Angeles, California, United States, 90025
        • Novartis Investigative Site
      • Westminster, California, United States, 92683
        • Novartis Investigative Site
    • Florida
      • Ormond Beach, Florida, United States, 32174
        • Novartis Investigative Site
      • Sarasota, Florida, United States, 34233
        • Novartis Investigative Site
      • Winter Park, Florida, United States, 32789
        • Novartis Investigative Site
    • Kentucky
      • Florence, Kentucky, United States, 41042
        • Novartis Investigative Site
    • Louisiana
      • Crowley, Louisiana, United States, 70526
        • Novartis Investigative Site
      • New Orleans, Louisiana, United States, 70115
        • Novartis Investigative Site
      • Zachary, Louisiana, United States, 70791
        • Novartis Investigative Site
    • Michigan
      • Livonia, Michigan, United States, 48152
        • Novartis Investigative Site
    • Minnesota
      • Edina, Minnesota, United States, 55435
        • Novartis Investigative Site
      • Minneapolis, Minnesota, United States, 55407
        • Novartis Investigative Site
    • Missouri
      • Saint Charles, Missouri, United States, 63301
        • Novartis Investigative Site
      • Saint Louis, Missouri, United States, 63141
        • Novartis Investigative Site
    • Nebraska
      • Omaha, Nebraska, United States, 68134
        • Novartis Investigative Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28207
        • Novartis Investigative Site
      • Gastonia, North Carolina, United States, 28054
        • Novartis Investigative Site
      • Shelby, North Carolina, United States, 28150
        • Novartis Investigative Site
    • Ohio
      • Columbus, Ohio, United States, 43215
        • Novartis Investigative Site
    • Oregon
      • Medford, Oregon, United States, 97504
        • Novartis Investigative Site
    • Texas
      • El Paso, Texas, United States, 79903
        • Novartis Investigative Site
      • Houston, Texas, United States, 77030
        • Novartis Investigative Site
      • McKinney, Texas, United States, 75069
        • Novartis Investigative Site
    • Virginia
      • Midlothian, Virginia, United States, 23114
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male and female COPD patients aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.
  • Current or ex-smokers who have a smoking history of at least 10 pack years.
  • Patients who have been treated with a triple combination of LABA/LAMA/ICS for the last 3 months prior to screening.
  • Patients featuring chronic bronchitis

Exclusion Criteria:

  • Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization, or a respiratory tract infection in the 4 weeks prior to screening, or between screening and randomization.
  • Patients with any documented history of asthma, or with an onset of chronic respiratory symptoms, including a COPD diagnosis, prior to age 40 years.
  • Patients with a body mass index (BMI) of more than 40 kg/m2.
  • Use of other investigational drugs (approved or unapproved) within 30 days or 5 half-lives prior to screening, or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations.
  • Pregnant or nursing (lactating) women, and women of childbearing potential not willing to use acceptable effective methods of contraception during study participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: QBW251 450 mg
QBW251 was orally administered 450 mg b.i.d for 24 weeks
Drug: QBW251
QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks
Drug: COPD maintenance background therapy
Combination of fluticasone furoate, vilanterol and umeclidinium bromide
Experimental: QBW251 300 mg
QBW251 was orally administered 300 mg b.i.d for 24 weeks
Drug: QBW251
QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks
Drug: COPD maintenance background therapy
Combination of fluticasone furoate, vilanterol and umeclidinium bromide
Experimental: QBW251 150 mg
QBW251 was orally administered 150 mg b.i.d for 24 weeks
Drug: QBW251
QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks
Drug: COPD maintenance background therapy
Combination of fluticasone furoate, vilanterol and umeclidinium bromide
Experimental: QBW251 75 mg
QBW251 was orally administered 75 mg b.i.d for 24 weeks
Drug: QBW251
QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks
Drug: COPD maintenance background therapy
Combination of fluticasone furoate, vilanterol and umeclidinium bromide
Experimental: QBW251 25 mg
QBW251 was orally administered 25 mg b.i.d for 24 weeks
Drug: QBW251
QBW251 oral capsules (450, 300, 150, 75 and 25 mg) of identical appearance to ensure blinding administered twice a day (b.i.d) for 24 weeks
Drug: COPD maintenance background therapy
Combination of fluticasone furoate, vilanterol and umeclidinium bromide
Placebo Comparator: Placebo
Placebo was orally administered b.i.d for 24 weeks
Drug: Placebo
Placebo oral capsules administered twice a day for 24 weeks
Drug: COPD maintenance background therapy
Combination of fluticasone furoate, vilanterol and umeclidinium bromide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 12
Time Frame: Baseline and Week 12

The primary efficacy analysis assessed the effect of QBW251 on the absolute change from baseline in trough FEV1 in liters on Week 12. Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline measurement was defined as the baseline visit pre-bronchodilator spirometry assessment.

Change from baseline in the FEV1 mean scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in FEV1 + airflow limitation severity + region + time interval + treatment*time interval interaction + baseline score*time interval interaction.
Baseline and Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Forced Expiratory Volume in One Second (FEV1)
Time Frame: Baseline, weeks 4, 8, 16, 20 and 24
The primary efficacy analysis assessed the effect of QBW251 on the absolute change from baseline in trough FEV1 in liters compared to placebo on Weeks 4, 8, 16, 20 and 24. Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline measurement was defined as the baseline visit pre-bronchodilator spirometry assessment. A positive trend for change from baseline in FEV1 across the dose range is considered a favorable outcome.
Baseline, weeks 4, 8, 16, 20 and 24
Change From Baseline in Evaluating Respiratory Symptoms (E-RS); Total Score
Time Frame: Baseline, weeks 12 and 24

The E-RS assesses overall daily respiratory COPD symptoms (Total score) and it is derived as the sum of 11 severity items; a higher scores indicate more severe symptoms. E-RS total score has a range of 0 to 40.

Change from baseline in the E-RS Total weekly mean scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in E-RS + airflow limitation severity + region + time interval + treatment*time interval interaction + baseline score*time interval interaction.

The mean baseline E-RS Total score was the average of the corresponding daily scores from the run-in period.

A negative change from baseline corresponds to improvement in symptoms severity.
Baseline, weeks 12 and 24
Change From Baseline in Evaluating Respiratory Symptoms (E-RS); Cough and Sputum Score
Time Frame: Baseline, weeks 12 and 24

The E-RS assesses both overall daily respiratory COPD symptoms (Total score) and specific respiratory symptoms using 3 subscales (Breathlessness, Cough & Sputum, and Chest Symptoms). The E-RS comprises 11 severity items and higher scores indicate more severe symptoms. The Cough and Sputum subscale score has a range of 0 to 11 and was derived as the sum of items 2 - 4.

Change from baseline in the E-RS Cough and Sputum weekly mean scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in E-RS + airflow limitation severity + region + time interval + treatment*time interval interaction + baseline score*time interval interaction.

The mean baseline E-RS Cough & Sputum subscale score was the average of the corresponding daily scores from the run-in period. Lower scores in the change from baseline correspond to lower symptom severity.
Baseline, weeks 12 and 24
Number of Participants With a "Better" Change in the Patient Global Impression of Severity (PGI-S) From Baseline
Time Frame: Baseline, weeks 12 and 24
The PGI-S questionnaire is a patient-reported outcomes score that rates the severity of the respiratory symptoms and of cough and mucus. The change in severity scores (Better, No change and Worse) from baseline were reported at weeks 12 and 24. Thus, the number of participants with a Better change in the severity score are reported in the table below.
Baseline, weeks 12 and 24
Change From Baseline in the Cough and Sputum Assessment Questionnaire (CASA-Q)
Time Frame: Baseline, weeks 12 and 24

The CASA-Q is a validated questionnaire instrument used to measure cough and sputum production, and their impact in patients COPD and/or chronic bronchitis. It contains a total of 20 items on a 5-step scale distributed in 4 domains: Cough symptoms, Cough impact, Sputum symptoms and Sputum impact. All items are rescored from 1-5 to 0-4 and then reverse scored such that better responses have higher scores. The four domains are ranged from 0-100 where higher scores associated with fewer symptoms/less impact due to cough or sputum.

Change from baseline in the CASA-Q cough and symptoms scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in E-RS + airflow limitation severity + region + time interval + treatment*time interval interaction + baseline score*time interval interaction.
Baseline, weeks 12 and 24
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ)
Time Frame: Baseline, weeks 12 and 24

SGRQ measures health impairment and contains 50 items divided into three components: Symptoms, Activity and Impacts. A score was calculated for each component and a "Total" score was also calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of quality of life.

Change from baseline in the SGRQ scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + baseline SGRQ score + airflow limitation severity + region + time interval + treatment*time interval interaction + baseline score*time interval interaction.
Baseline, weeks 12 and 24
Minimum Plasma Concentration (Cmin) for QBW251
Time Frame: Pre-dose on Days 15, 29, 57, 85, 113, 141 and 169
Venous whole blood samples were collected for pharmacokinetics characterization. Cmin was measured pre dose at all visits and was summarized using descriptive statistics. All concentrations below the lower limit of quantification (LLOQ) were treated as zero.
Pre-dose on Days 15, 29, 57, 85, 113, 141 and 169
Maximum Plasma Concentration (Cmax) for QBW251
Time Frame: Days 1, 15 and 169
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax was calculated from plasma concentration data using non-compartmental methods and summarized using descriptive statistics. Cmax was measured in the samples taken at 3 hours post-dose with the exception of the participants included in the Serial PK set on Days 1 and 15 for whom all samples (1, 2, 4, 6, and 8 hours post-dose) were taken into consideration for the measurement of Cmax. All concentrations below the lower limit of quantification (LLOQ) were treated as zero.
Days 1, 15 and 169
Maximum Plasma Concentration (Cmax) for QBW251 in Serial PK Set
Time Frame: 1, 2, 4, 6, and 8 hours post-dose on Days 1 and 15
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax was calculated from plasma concentration data using non-compartmental methods and summarized using descriptive statistics. All concentrations below the lower limit of quantification (LLOQ) were treated as zero.
1, 2, 4, 6, and 8 hours post-dose on Days 1 and 15
Area Under the Curve From Time 0 to 24 Hours (AUC0-24h) of QBW251 in Serial PK Set
Time Frame: 1, 2, 4, 6, and 8 hours post-dose on Days 1 and 15
Venous whole blood samples were collected for pharmacokinetics characterization. AUC0-24h was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. All concentrations below the lower limit of quantification (LLOQ) were treated as zero.
1, 2, 4, 6, and 8 hours post-dose on Days 1 and 15

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 12, 2019

Primary Completion (Actual)

October 8, 2021

Study Completion (Actual)

February 1, 2022

Study Registration Dates

First Submitted

August 7, 2019

First Submitted That Met QC Criteria

August 27, 2019

First Posted (Actual)

August 28, 2019

Study Record Updates

Last Update Posted (Actual)

April 28, 2023

Last Update Submitted That Met QC Criteria

April 6, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CQBW251B2201
  • 2018-003197-28 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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