Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as QBW251
Icenticaftor · 3 trials · 3 indications
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.
Change from baseline to Day 29 in LCI as measured by multiple breath nitrogen washout (MBNW) technique. MBNW is the time taken to wash out nitrogen while breathing 100% oxygen.
Icenticaftor plasma concentrations will be determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Cmax of icenticaftor will be determined with Phoenix WinNonlin (Version 6.4 or higher).
AUClast of icenticaftor will be determined using non-compartment methods with Phoenix WinNonlin (Version 6.4 or higher). The linear trapezoidal rule will be used for AUClast calculation.
AUCinf of icenticaftor will be determined using non-compartment methods with Phoenix WinNonlin (Version 6.4 or higher). The linear trapezoidal rule will be used for AUCinf calculation.
Icenticaftor plasma concentrations will be determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Tmax of icenticaftor will be determined with Phoenix WinNonlin (Version 6.4 or higher).
CL/F of icenticaftor will be determined using non-compartment methods with Phoenix WinNonlin (Version 6.4 or higher).
Vz/F of icenticaftor will be determined using non-compartment methods with Phoenix WinNonlin (Version 6.4 or higher).
T1/2 of icenticaftor will be determined using non-compartment methods with Phoenix WinNonlin (Version 6.4 or higher). Regression analysis of the terminal plasma elimination phase will be used for T1/2 calculation.
| Arm | Type | Description |
|---|---|---|
| QBW251 450 mg | EXPERIMENTAL | QBW251 was orally administered 450 mg b.i.d for 24 weeks |
| QBW251 300 mg | EXPERIMENTAL | QBW251 was orally administered 300 mg b.i.d for 24 weeks |
| QBW251 150 mg | EXPERIMENTAL | QBW251 was orally administered 150 mg b.i.d for 24 weeks |
| QBW251 75 mg | EXPERIMENTAL | QBW251 was orally administered 75 mg b.i.d for 24 weeks |
| QBW251 25 mg | EXPERIMENTAL | QBW251 was orally administered 25 mg b.i.d for 24 weeks |
| Placebo | PLACEBO_COMPARATOR | Placebo was orally administered b.i.d for 24 weeks |
| QBW251 | EXPERIMENTAL | QBW251 will be provided to participants during 70 days |
| Group 1 - Healthy subjects with normal hepatic function | EXPERIMENTAL | Healthy subjects with normal hepatic function - Control |
| Group 2 - Mild Hepatic Impairment | EXPERIMENTAL | Mild hepatic impairment: Child-Pugh A (Score 5-6) |
| Group 3 - Moderate Hepatic Impairment | EXPERIMENTAL | Moderate hepatic impairment: Child-Pugh B (Score 7-9) |
| Group 4 - Severe Hepatic Impairment | EXPERIMENTAL | Severe hepatic impairment: Child-Pugh C (Score 10-15) |
| Name | Type | Description |
|---|---|---|
| QBW251 | DRUG | 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 |
| Placebo | DRUG | Placebo oral capsules administered twice a day for 24 weeks |
| COPD maintenance background therapy | DRUG | Combination of fluticasone furoate, vilanterol and umeclidinium bromide |
| Icenticaftor | DRUG | Single oral dose of 300 mg of icenticaftor (QBW251) |
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 o...
Icenticaftor is an investigational small molecule developed by Novartis AG. It is being studied in hepatic failure, a gastrointestinal therapeutic area, and has been evaluated in a Phase 1 pharmacokinetic study in participants with hepatic impairment. It is not approved and remains in clinical development.
Icenticaftor targets CFTR, the cystic fibrosis transmembrane conductance regulator. It is classified as a CFTR activator, meaning it is designed to increase the activity of the CFTR channel. This mechanism is being explored in the context of hepatic failure.
Icenticaftor is developed by Novartis AG, which trades under the ticker NVS. Novartis is the sponsor of the clinical program evaluating the drug in hepatic failure.
Icenticaftor is in Phase 1 development. It is an investigational drug and has not been approved by the FDA. The only listed trial is a completed Phase 1 pharmacokinetic study in participants with hepatic impairment.
Icenticaftor has been studied in one clinical trial, NCT04587622, titled a pharmacokinetic study of Icenticaftor in participants with hepatic impairment. It was a completed Phase 1 trial with 40 participants, conducted in the United States, and included healthy volunteers.