Safety, Tolerability, Pharmacokinetics, and Preliminary P... | NCT02190604 | Trialant
NCT02190604
Sponsor
Novartis Pharmaceuticals
Status
Terminated
Last Update Posted
Dec 30, 2020Actual
Enrollment
153Actual
Phase
Phase 1Phase 2
Conditions
Cystic Fibrosis
Interventions
Placebo
QBW251
Countries
United States
Belgium
France
Germany
Ireland
Romania
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02190604
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CQBW251X2101
Secondary IDs
ID
Type
Description
Link
2011-005085-37
EudraCT Number
Brief Title
Safety, Tolerability, Pharmacokinetics, and Preliminary Pharmacodynamics of QBW251 in Healthy Subjects and Cystic Fibrosis Patients
Official Title
A Randomized, Double Blind Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Pharmacodynamics of Single and Multiple Ascending Doses of QBW251 in Healthy Subjects and Multiple Doses in Cystic Fibrosis Patients
Acronym
Not provided
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Mar 2019
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jul 31, 2012Actual
Primary Completion Date
Nov 30, 2015Actual
Completion Date
Nov 30, 2015Actual
First Submitted Date
Jul 11, 2014
First Submission Date that Met QC Criteria
Jul 14, 2014
First Posted Date
Jul 15, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Nov 23, 2016
Results First Submitted that Met QC Criteria
Jul 18, 2017
Results First Posted Date
Jul 19, 2017Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Dec 9, 2020
Last Update Posted Date
Dec 30, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This study is designed to assess the safety, tolerability, pharmacokinetics and preliminary pharmacodynamics (proof of concept) of QBW251 in healthy subjects and cystic fibrosis patients following single and multiple doses. This first-in-human and proof of concept study will consist of 4 parts, with Parts 1 and 2 in healthy volunteers and Parts 3 and 4 in cystic fibrosis patients.
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Drug: QBW251
Part 1 Cohort 2: QBW251
Experimental
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Drug: QBW251
Part 1 Cohort 3: QBW251
Experimental
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Drug: QBW251
Part 1 Cohort 4: QBW251
Experimental
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Placebo
Drug
Capsule- oral dose
Part 1 Placebo
Part 2 Placebo
Part 3 Placebo
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part 1 and 2:Number of Participants (Healthy Volunteers) With Reported Adverse Events Receiving QBW251
All adverse events (in healthy volunteers) reported.
Day 1 to Day 36
Part 3: Change in Lung Clearance Index (LCI) From Baseline to Day 15
Change in Lung Clearance Index (LCI) will be conducted according to international standards in cystic fibrosis patients. Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test, A reduction in mean change from baseline for LCI2.5 indicates improvement.
Baseline and Day 15
Part 3: Number of Participants (Patients) With Reported Adverse Events Receiving QBW251
All adverse events and serious adverse events (in patients) reported.
Day 1 to Day 56
Secondary Outcomes
Measure
Description
Time Frame
Part 3:Change in Forced Expiratory Volume in 1 Second (FEV1) at Day 15
Forced Expiratory Volume in 1 second (FEV1) will be measured via spirometer according to international standards. Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation
Baseline and Day 15
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Key inclusion criteria (Parts 1 and 2)
Healthy female (of non-childbearing potential) and male subjects of 18 to 55 years of age (inclusive)
Body mass index (BMI) must be within the range of 15 to 30 kg/m2
Oxygen saturation (O2) at screening must be ≥ 96% on room air.
Key exclusion criteria (Parts 1 and 2)
Use of any prescription drugs or herbal supplements within four (4) weeks prior to dosing or within 5 half-lives of the drug, whichever is longer
Over-the-counter (OTC) medication (including vitamins, dietary supplements) within two (2) weeks prior to dosing
Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
Unwilling to avoid direct sun exposure by covering exposed skin, using topical sun block and wearing sunglasses from the first dose of study drug to the end of participation in the study
Pregnant or nursing (lactating) women.
Key inclusion criteria (Parts 3 and 4):
Male and female patients of 18 to 65 years of age (inclusive) with a confirmed diagnosis of cystic fibrosis as per the Cystic Fibrosis Foundation (CFF) consensus guidelines
Heterozygous with one allele represented as any CFTR mutation and the other allele must represent a class III, IV, V, VI CFTR mutation (Note: since the CFTR mutation, F508del, can be considered either a class II or III mutation, heterozygous CF patients that have one allele that contains F508del, must have the other allele contain a class III (i.e., not F508del), IV, V, or VI mutation). Patients with F508del/F508del mutation should only be included in Part 3 Cohort 3.
Body mass index (BMI) must be within the range of 15-35 kg/m2
FEV1 at Screening must be 40 to 100% predicted (inclusive) by NHANES/Hankinson standards
Oxygen saturation (O2) at screening must be > 90% on room air.
Key exclusion criteria (Parts 3 and 4)
Use of herbal supplements within four (4) weeks prior to dosing or within 5 half-lives of the supplement, whichever is longer
Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
Unwilling to avoid direct sun exposure by covering exposed skin, using topical sun block and wearing sunglasses from the first dose of study drug to the end of participation in the study
Pregnant or nursing (lactating) women
Women of child-bearing potential, UNLESS they are using highly effective contraception
Any changes in concomitant medications for 14 days prior to screening
History or clinical evidence of pancreatic injury or pancreatitis; clinical evidence of liver disease or liver injury as indicated by clinically significant abnormal liver function tests as judged by the investigator such as SGOT, SGPT, GGT, alkaline phosphatase, or serum bilirubin
History or presence of impaired renal function as indicated by abnormal creatinine or BUN values or abnormal urinary constituents (e.g., albuminuria)
History of Burkholderia cepacia respiratory tract infection (must have at least two negative cultures and no positive cultures in the past 18 months prior to screening to be eligible for enrollment)
Sexually active males unless they use a condom during intercourse while taking drug and for condom is required to be used also by vasectomized men in order to prevent delivery of drug via seminal fluid.
Patient is currently receiving (or has received within 4 weeks of baseline visit) VX-770/Ivacaftor.
In parts 1 and 2, participants (Healthy Volunteers) were randomized 3:1 to receive QBW251X or placebo. In part 3, participants (cystic fibrosis (CF) patients) were randomized 3:1 to receive QBW251X or placebo.
Recruitment Details
For Cohort 6 continuing into the food effect part of the study the subjects remained on the same treatment assignment that was required during the fed state. Therefore no randomization f the subject occurred during the food effect arm. Only 5 of the 6 subjects went into the fed cohort.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part 1 Cohort 1: QBW251
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
FG001
Periods
Title
Milestones
Reasons Not Completed
Part 1 and 2 (Healthy Volunteers)
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Netherlands
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Triple
Masking Description
Not provided
Who Masked
ParticipantCare ProviderInvestigator
Drug: QBW251
Part 1 Cohort 5: QBW251
Experimental
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Drug: QBW251
Part 1 Cohort 6: QBW251
Experimental
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Drug: QBW251
Part 1 Cohort 6: QBW251(fed)
Experimental
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Drug: QBW251
Part 1 Cohort 7: QBW251
Experimental
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Drug: QBW251
Part 1 Cohort 8: QBW251
Experimental
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Drug: QBW251
Part 1 Placebo
Placebo Comparator
Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Drug: Placebo
Part 2 Cohort 1: QBW251
Experimental
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Drug: QBW251
Part 2 Cohort 2: QBW251
Experimental
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Drug: QBW251
Part 2 Cohort 3: QBW251
Experimental
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Drug: QBW251
Part 2 Cohort 4: QBW251
Experimental
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Drug: QBW251
Part 2 Cohort 5: QBW251
Experimental
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Drug: QBW251
Part 2 Placebo
Placebo Comparator
Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Drug: Placebo
Part 3 Cohort 1: QBW251
Experimental
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Drug: QBW251
Part 3 Cohort 2: QBW251
Experimental
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Drug: QBW251
Part 3 Cohort 3: QBW251
Experimental
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Drug: QBW251
Part 3 Placebo
Placebo Comparator
Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Drug: Placebo
QBW251
Drug
Capsule - oral dose
Part 1 Cohort 1: QBW251
Part 1 Cohort 2: QBW251
Part 1 Cohort 3: QBW251
Part 1 Cohort 4: QBW251
Part 1 Cohort 5: QBW251
Part 1 Cohort 6: QBW251
Part 1 Cohort 6: QBW251(fed)
Part 1 Cohort 7: QBW251
Part 1 Cohort 8: QBW251
Part 2 Cohort 1: QBW251
Part 2 Cohort 2: QBW251
Part 2 Cohort 3: QBW251
Part 2 Cohort 4: QBW251
Part 2 Cohort 5: QBW251
Part 3 Cohort 1: QBW251
Part 3 Cohort 2: QBW251
Part 3 Cohort 3: QBW251
Part 3: Change in Cystic Fibrosis Questionnaire-Revised Reported Outcomes
Change in Cystic Fibrosis Questionnaire data will be obtained from patient reported outcomes (CFQ-R PRO). Respiratory Domain, cores range from 0 to 100, with higher scores indicating better health, a change of 4 is considered clinically relevant
Baseline and Day 14
Part 1: AUC0-t in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration (AUC0-t). In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUC0-t goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 2-5)
Part 1: Maximum Concentration (Cmax) in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Days 1- 5 are from healthy volunteers
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
Part 1: Time to Maximum Concentration (Tmax) in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In this part of the study a single dose was administered and samples were collected up to 5 days. As a result the Tmax is one value as the concentration-time curve goes to Day 5 (for some lower does QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
Part 1: T1/2 in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: terminal elimination half-life. In this analysis T1/2 will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the T1/2 goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
Part 1: AUCinf in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: area under the plasma concentration time curve from time zero to infinity. In this analysis AUCinf will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUCinf goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
Part 1: CL/F in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the CL/F goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
Part 1: Vz/F in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers.
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
Part 2: AUCtau in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma after multiple doses: the area under the plasma concentration-time curve from time zero to end of the dosing interval tau. In this analysis AUCtau will be reported. Samples taken on Days 1 and 14 from healthy volunteers
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
Part 2: Maximum Concentration (Cmax) in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma after multiple doses: observed maximum plasma concentration following QBW251 at steady state. In this analysis Cmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
Part 2: Time to Maximum Concentration (Tmax) in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
Part 2: AUC0-t
Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration. In this analysis AUC0-t will be reported using blood samples taken on Day 14 are from healthy volunteers.
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
Part 2: Cav in Healthy Volunteers
The average drug concentration in plasma during multiple dosing. In this analysis Cav will be reported using blood samples taken on Days 1 and 14 are from healthy volunteers.
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
Part 2: CL/F in Healthy Volunteers
apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Day 14 from healthy volunteers.
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
Part 2: Vz/F in Healthy Volunteers
Apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Day 14 from healthy volunteers.
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
Part 2: Racc in Healthy Volunteers
Accumulation ratio (Racc). In this analysis Racc will be reported using blood samples taken on Days 1 - 14 from healthy volunteers.
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 - 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
Part 2: T1/2 in Healthy Volunteers
terminal elimination half-life (T1/2). In this analysis T1/2 will be reported using blood samples taken on Day 14 from healthy volunteers.
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
Part 3: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of QBW251 in CF Patients
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
Part 3: Plasma Concentration at the Last Quantifiable Time Point (Clast) of QBW251 in CF Patients
Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day2
Part 3: Maximum Concentration (Cmax) in CF Patients
Observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Day 1and day 14 from patients
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
Part 3: Tlast in CF Patients
Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable day 1 and day 14
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
Part 3: Time to Maximum Concentration (Tmax)
Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 in patients
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
Part 2: Ae0-t in Healthy Volunteers
Pharmacokinetics of QBW251 in urine: amount of drug excreted in urine from time zero until last measurable concentration. In this analysis Ae0-t will be reported using urine samples taken on Day 1 from healthy volunteers.
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1
Part 2: CLr in Healthy Volunteers
Pharmacokinetics of QBW251 in urine: renal clearance following drug administration. In this analysis CLr will be reported using urine samples taken on Day 1 from healthy volunteers.
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1; Day 14 was calculated as urine was only collected up to 12 hours on Day 1 thus CLr cannot be calculated.
Denver
Colorado
80206
United States
Novartis Investigative Site
Chicago
Illinois
60611
United States
Novartis Investigative Site
Louisville
Kentucky
40202
United States
Novartis Investigative Site
Boston
Massachusetts
02114
United States
Novartis Investigative Site
Boston
Massachusetts
02115
United States
Novartis Investigative Site
St Louis
Missouri
63110
United States
Novartis Investigative Site
Chapel Hill
North Carolina
27514
United States
Novartis Investigative Site
Columbus
Ohio
43205
United States
Novartis Investigative Site
Brussels
1090
Belgium
Novartis Investigative Site
Ghent
9000
Belgium
Novartis Investigative Site
Montpellier
34059
France
Novartis Investigative Site
Paris
75014
France
Novartis Investigative Site
Pierre-Bénite
69495
France
Novartis Investigative Site
Cologne
North Rhine-Westphalia
50937
Germany
Novartis Investigative Site
Berlin
10098
Germany
Novartis Investigative Site
Dublin
4
Ireland
Novartis Investigative Site
Bucharest
050159
Romania
Novartis Investigative Site
Livingston
West Lothian
EH54 6PP
United Kingdom
Novartis Investigative Site
Belfast
BT9 7AB
United Kingdom
Novartis Investigative Site
London
SW 6NP
United Kingdom
Novartis Investigative Site
Manchester
M23 9QZ
United Kingdom
Novartis Investigative Site
Mid Glamorgan
CF484DR
United Kingdom
Part 1 Cohort 2: QBW251
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
FG002
Part 1 Cohort 3: QBW251
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
FG003
Part 1 Cohort 4: QBW251
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
FG004
Part 1 Cohort 5: QBW251
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
FG005
Part 1 Cohort 6: QBW251 (Fasting/Fed), Same Subjects
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
FG006
Part 1 Cohort 7: QBW251
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
FG007
Part 1 Cohort 8: QBW251
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
FG008
Part 1 Placebo
Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
FG009
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
FG010
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
FG011
Part 2 Cohort 3: QBW251
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
FG012
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
FG013
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
FG014
Part 2 Placebo
Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
FG015
Part 3 Cohort 1: QBW251
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
FG016
Part 3 Cohort 2: QBW251
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
FG017
Part 3 Cohort 3: QBW251
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
FG018
Part 3 Placebo
Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG0046 subjects
FG0056 subjects
FG0066 subjects
FG0076 subjects
FG00816 subjects
FG0096 subjects
FG0106 subjects
FG0116 subjects
FG0126 subjects
FG0136 subjects
FG01410 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
FG0180 subjects
COMPLETED
FG0006 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG0046 subjects
FG0056 subjects
FG0066 subjects
FG0076 subjects
FG00816 subjects
FG0096 subjects
FG0106 subjects
FG0116 subjects
FG0126 subjects
FG0135 subjects
FG0148 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
FG0180 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0131 subjects
FG0142 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
FG0180 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0142 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
FG0180 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Part 3 (Patients)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0156 subjects
FG01612 subjects
FG01719 subjects
FG01812 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part 1 Cohort 1: QBW251
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
BG001
Part 1 Cohort 2: QBW251
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
BG002
Part 1 Cohort 3: QBW251
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
BG003
Part 1 Cohort 4: QBW251
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
BG004
Part 1 Cohort 6: QBW251
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
BG005
Part 1 Cohort 6: QBW251 (Fastin / Fed), Same Subjects
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
BG006
Part 1 Cohort 7: QBW251
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
BG007
Part 1 Cohort 8: QBW251
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
BG008
Part 1 Placebo
Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
BG009
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
BG010
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
BG011
Part 2 Cohort 3: QBW251
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
BG012
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
BG013
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
BG014
Part 2 Placebo
Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
BG015
Part 3 Cohort 1: QBW251
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
BG016
Part 3 Cohort 2: QBW251
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
BG017
Part 3 Cohort 3: QBW251
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
BG018
Part 3 Placebo
Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
BG019
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0006
BG0016
BG0026
BG0036
BG0046
BG0056
BG0066
BG0076
BG00816
BG0096
BG0106
BG0116
BG0126
BG0136
BG01410
BG0156
BG01612
BG01719
BG01812
BG019153
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Part 1, HV (n= 64)
Title
Measurements
BG00036.3± 8.69
BG00135± 14.25
BG00243.5± 3.39
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Part 1 and 2:Number of Participants (Healthy Volunteers) With Reported Adverse Events Receiving QBW251
All adverse events (in healthy volunteers) reported.
All treated subjects were included in the data analysis. Subjects were analyzed according to the study treatment(s) received.
Posted
Number
Participants
Day 1 to Day 36
ID
Title
Description
OG000
Part 1 Cohort 4: QBW251
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG001
Part 1 Cohort 5: QBW251
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG002
Part 1 Cohort 6: QBW251
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG003
Part 1 Cohort 6: QBW251(Fed)
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG004
Part 1 Cohort 7: QBW251
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG005
Part 1 Cohort 8: QBW251
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG006
Part 1 Placebo
Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG007
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG008
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG009
Part 2 Cohort 3: QBW251
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG010
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG011
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG012
Part 2 Placebo
Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG013
Part 1 Cohort 1: QBW251
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15
OG014
Part 1 Cohort 2: QBW251
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG015
Part 1 Cohort 3: QBW251
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Adverse events
Title
Measurements
OG0001
OG0012
OG0022
OG003
Primary
Part 3: Change in Lung Clearance Index (LCI) From Baseline to Day 15
Change in Lung Clearance Index (LCI) will be conducted according to international standards in cystic fibrosis patients. Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test, A reduction in mean change from baseline for LCI2.5 indicates improvement.
Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis
Posted
Mean
Standard Deviation
Ratio
Baseline and Day 15
ID
Title
Description
OG000
Part 3 Cohort 1: QBW251
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG001
Part 3 Cohort 2: QBW251
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG002
Part 3 Cohort 3: QBW251
Primary
Part 3: Number of Participants (Patients) With Reported Adverse Events Receiving QBW251
All adverse events and serious adverse events (in patients) reported.
Safety analysis set: All randomized patients were included in the safety analysis
Posted
Number
Participants
Day 1 to Day 56
ID
Title
Description
OG000
Part 3 Cohort 1: QBW251
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG001
Part 3 Cohort 2: QBW251
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG002
Part 3 Cohort 3: QBW251
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Secondary
Part 3:Change in Forced Expiratory Volume in 1 Second (FEV1) at Day 15
Forced Expiratory Volume in 1 second (FEV1) will be measured via spirometer according to international standards. Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation
Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis
Posted
Least Squares Mean
Standard Error
Liters
Baseline and Day 15
ID
Title
Description
OG000
Part 3 Cohort 1: QBW251
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG001
Part 3 Cohort 2: QBW251
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG002
Part 3 Cohort 3: QBW251
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Secondary
Part 3: Change in Cystic Fibrosis Questionnaire-Revised Reported Outcomes
Change in Cystic Fibrosis Questionnaire data will be obtained from patient reported outcomes (CFQ-R PRO). Respiratory Domain, cores range from 0 to 100, with higher scores indicating better health, a change of 4 is considered clinically relevant
Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis
Posted
Least Squares Mean
Standard Error
Units on a scale
Baseline and Day 14
ID
Title
Description
OG000
Part 3 Cohort 1: QBW251
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG001
Part 3 Cohort 2: QBW251
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG002
Part 3 Cohort 3: QBW251
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Secondary
Part 1: AUC0-t in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration (AUC0-t). In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUC0-t goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis.
Posted
Mean
Standard Deviation
hr*ng/mL
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 2-5)
ID
Title
Description
OG000
Part 1 Cohort 1: QBW251
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG001
Part 1 Cohort 2: QBW251
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Secondary
Part 1: Maximum Concentration (Cmax) in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Days 1- 5 are from healthy volunteers
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
ug/L
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
ID
Title
Description
OG000
Part 1 Cohort 1: QBW251
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG001
Part 1 Cohort 2: QBW251
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Secondary
Part 1: Time to Maximum Concentration (Tmax) in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In this part of the study a single dose was administered and samples were collected up to 5 days. As a result the Tmax is one value as the concentration-time curve goes to Day 5 (for some lower does QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
hr
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
ID
Title
Description
OG000
Part 1 Cohort 1: QBW251
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG001
Part 1 Cohort 2: QBW251
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Secondary
Part 1: T1/2 in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: terminal elimination half-life. In this analysis T1/2 will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the T1/2 goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
hr
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
ID
Title
Description
OG000
Part 1 Cohort 1: QBW251
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG001
Part 1 Cohort 2: QBW251
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Secondary
Part 1: AUCinf in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: area under the plasma concentration time curve from time zero to infinity. In this analysis AUCinf will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUCinf goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
hr*ng/mL
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
ID
Title
Description
OG000
Part 1 Cohort 1: QBW251
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG001
Part 1 Cohort 2: QBW251
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Secondary
Part 1: CL/F in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the CL/F goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
L/hr
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
ID
Title
Description
OG000
Part 1 Cohort 1: QBW251
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG001
Part 1 Cohort 2: QBW251
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Secondary
Part 1: Vz/F in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma: apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers.
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
Liters
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
ID
Title
Description
OG000
Part 1 Cohort 1: QBW251
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG001
Part 1 Cohort 2: QBW251
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Secondary
Part 2: AUCtau in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma after multiple doses: the area under the plasma concentration-time curve from time zero to end of the dosing interval tau. In this analysis AUCtau will be reported. Samples taken on Days 1 and 14 from healthy volunteers
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
hr*ng/mL
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
ID
Title
Description
OG000
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG001
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG002
Part 2 Cohort 3: QBW251
Secondary
Part 2: Maximum Concentration (Cmax) in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma after multiple doses: observed maximum plasma concentration following QBW251 at steady state. In this analysis Cmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
ug/L
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
ID
Title
Description
OG000
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG001
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG002
Part 2 Cohort 3: QBW251
Secondary
Part 2: Time to Maximum Concentration (Tmax) in Healthy Volunteers
Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
hr
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
ID
Title
Description
OG000
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG001
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG002
Part 2 Cohort 3: QBW251
Secondary
Part 2: AUC0-t
Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration. In this analysis AUC0-t will be reported using blood samples taken on Day 14 are from healthy volunteers.
Posted
Mean
Standard Deviation
hr*ng/mL
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
ID
Title
Description
OG000
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG001
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG002
Part 2 Cohort 3: QBW251
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG003
Part 2 Cohort 4: QBW251
Secondary
Part 2: Cav in Healthy Volunteers
The average drug concentration in plasma during multiple dosing. In this analysis Cav will be reported using blood samples taken on Days 1 and 14 are from healthy volunteers.
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
ug/L
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
ID
Title
Description
OG000
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG001
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG002
Part 2 Cohort 3: QBW251
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Secondary
Part 2: CL/F in Healthy Volunteers
apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Day 14 from healthy volunteers.
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
L/hr
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
ID
Title
Description
OG000
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG001
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG002
Part 2 Cohort 3: QBW251
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Secondary
Part 2: Vz/F in Healthy Volunteers
Apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Day 14 from healthy volunteers.
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
Liters
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
ID
Title
Description
OG000
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG001
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG002
Part 2 Cohort 3: QBW251
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Secondary
Part 2: Racc in Healthy Volunteers
Accumulation ratio (Racc). In this analysis Racc will be reported using blood samples taken on Days 1 - 14 from healthy volunteers.
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
Ratio
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 - 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
ID
Title
Description
OG000
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG001
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG002
Part 2 Cohort 3: QBW251
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Secondary
Part 2: T1/2 in Healthy Volunteers
terminal elimination half-life (T1/2). In this analysis T1/2 will be reported using blood samples taken on Day 14 from healthy volunteers.
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
hr
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
ID
Title
Description
OG000
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG001
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG002
Part 2 Cohort 3: QBW251
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Secondary
Part 3: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of QBW251 in CF Patients
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
ng × hr /mL
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
ID
Title
Description
OG000
Part 3 Cohort 1: QBW251
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG001
Part 3 Cohort 2: QBW251
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG002
Part 3 Cohort 3: QBW251
Secondary
Part 3: Plasma Concentration at the Last Quantifiable Time Point (Clast) of QBW251 in CF Patients
Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
ng/mL
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day2
ID
Title
Description
OG000
Part 3 Cohort 1: QBW251
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG001
Part 3 Cohort 2: QBW251
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG002
Part 3 Cohort 3: QBW251
Secondary
Part 3: Maximum Concentration (Cmax) in CF Patients
Observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Day 1and day 14 from patients
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
ng/mL
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
ID
Title
Description
OG000
Part 3 Cohort 1: QBW251
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG001
Part 3 Cohort 2: QBW251
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG002
Part 3 Cohort 3: QBW251
Secondary
Part 3: Tlast in CF Patients
Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable day 1 and day 14
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
hr
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
ID
Title
Description
OG000
Part 3 Cohort 1: QBW251
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG001
Part 3 Cohort 2: QBW251
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG002
Part 3 Cohort 3: QBW251
Secondary
Part 3: Time to Maximum Concentration (Tmax)
Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 in patients
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
hr
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
ID
Title
Description
OG000
Part 3 Cohort 1: QBW251
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG001
Part 3 Cohort 2: QBW251
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG002
Part 3 Cohort 3: QBW251
Secondary
Part 2: Ae0-t in Healthy Volunteers
Pharmacokinetics of QBW251 in urine: amount of drug excreted in urine from time zero until last measurable concentration. In this analysis Ae0-t will be reported using urine samples taken on Day 1 from healthy volunteers.
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
L/hr
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1
ID
Title
Description
OG000
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG001
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG002
Part 2 Cohort 3: QBW251
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Secondary
Part 2: CLr in Healthy Volunteers
Pharmacokinetics of QBW251 in urine: renal clearance following drug administration. In this analysis CLr will be reported using urine samples taken on Day 1 from healthy volunteers.
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Posted
Mean
Standard Deviation
L/hr
Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1; Day 14 was calculated as urine was only collected up to 12 hours on Day 1 thus CLr cannot be calculated.
ID
Title
Description
OG000
Part 2 Cohort 1: QBW251
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG001
Part 2 Cohort 2: QBW251
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG002
Part 2 Cohort 3: QBW251
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Time Frame
Not provided
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part 1 Placebo
Part 1 Placebo
0
16
8
16
EG001
Part 1 QBW251 10mg
Part 1 QBW251 10mg
0
6
3
6
EG002
Part 1 QBW251 25mg
Part 1 QBW251 25mg
0
6
2
6
EG003
Part 1 QBW251 150mg
Part 1 QBW251 150mg
0
6
1
6
EG004
Part 1 QBW251 300mg
Part 1 QBW251 300mg
0
6
2
6
EG005
Part 1 QBW251 500mg
Part 1 QBW251 500mg
0
6
2
6
EG006
Part 1 QBW251 500mg (Fed)
Part 1 QBW251 500mg (fed)
0
5
1
5
EG007
Part 1 QBW251 750mg
Part 1 QBW251 750mg
0
6
1
6
EG008
Part 1 QBW251 1000mg
Part 1 QBW251 1000mg
0
6
4
6
EG009
Part 2 Placebo
Part 2 Placebo
0
10
7
10
EG010
Part 2 QBW251 150mg
Part 2 QBW251 150mg
0
6
3
6
EG011
Part 2 QBW251 400mg
Part 2 QBW251 400mg
0
6
6
6
EG012
Part 2 QBW251 750mg
Part 2 QBW251 750mg
0
6
3
6
EG013
Part 2 QBW251 450mg BID
Part 2 QBW251 450mg BID
0
6
6
6
EG014
Part 2 QBW251 750mg BID
Part 2 QBW251 750mg BID
0
6
4
6
EG015
Part 3 Placebo C1/C2/C3
Part 3 Placebo C1/C2/C3
0
12
8
12
EG016
Part 3 QBW251 150mg BID C1
Part 3 QBW251 150mg BID C1
1
6
5
6
EG017
Part 3 QBW251 450mg BID C2
Part 3 QBW251 450mg BID C2
1
12
8
12
EG018
Part 3 QBW251 450mg BID C3
Part 3 QBW251 450mg BID C3
1
19
18
19
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG0030 affected6 at risk
EG004
SINUSITIS
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
PALPITATIONS
Cardiac disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG0030 affected6 at risk
EG0040 affected6 at risk
EG0050 affected6 at risk
EG0060 affected5 at risk
EG0070 affected6 at risk
EG0080 affected6 at risk
EG0090 affected10 at risk
EG0100 affected6 at risk
EG0110 affected6 at risk
EG0120 affected6 at risk
EG0130 affected6 at risk
EG0140 affected6 at risk
EG0151 affected12 at risk
EG0161 affected6 at risk
EG0170 affected12 at risk
EG0180 affected19 at risk
ICHTHYOSIS
Congenital, familial and genetic disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
EAR DISCOMFORT
Ear and labyrinth disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
EAR PAIN
Ear and labyrinth disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
TINNITUS
Ear and labyrinth disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
ABDOMINAL DISCOMFORT
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
ABDOMINAL DISTENSION
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0021 affected6 at risk
EG003
ABDOMINAL PAIN
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
ABDOMINAL PAIN LOWER
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
APHTHOUS STOMATITIS
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
DIARRHOEA
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0001 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
FAECES DISCOLOURED
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
FLATULENCE
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
GASTROOESOPHAGEAL REFLUX DISEASE
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0021 affected6 at risk
EG003
GINGIVAL DISORDER
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
NAUSEA
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
SALIVA ALTERED
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
SALIVARY GLAND PAIN
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
VOMITING
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
ASTHENIA
General disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
CHEST DISCOMFORT
General disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
CHEST PAIN
General disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
FATIGUE
General disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
INFLUENZA LIKE ILLNESS
General disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PAIN
General disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PERIPHERAL SWELLING
General disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PYREXIA
General disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
SENSATION OF FOREIGN BODY
General disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
THIRST
General disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
VESSEL PUNCTURE SITE BRUISE
General disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
BRONCHITIS
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
BRONCHOPULMONARY ASPERGILLOSIS ALLERGIC
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
FOLLICULITIS
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
FUNGAL INFECTION
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
GASTROENTERITIS
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
NASOPHARYNGITIS
Infections and infestations
MedDRA
Systematic Assessment
EG0001 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
ORAL HERPES
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PHARYNGITIS
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
SINUSITIS
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
UPPER RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
VIRAL UPPER RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
ARTHROPOD BITE
Injury, poisoning and procedural complications
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
LIGAMENT SPRAIN
Injury, poisoning and procedural complications
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
SKIN WOUND
Injury, poisoning and procedural complications
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
ADENOVIRUS TEST POSITIVE
Investigations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
BLOOD ALKALINE PHOSPHATASE INCREASED
Investigations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
BLOOD POTASSIUM DECREASED
Investigations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
BREATH SOUNDS ABNORMAL
Investigations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
CORONAVIRUS TEST POSITIVE
Investigations
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
DECREASED APPETITE
Metabolism and nutrition disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
HYPOGLYCAEMIA
Metabolism and nutrition disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
VITAMIN D DEFICIENCY
Metabolism and nutrition disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
BACK PAIN
Musculoskeletal and connective tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0021 affected6 at risk
EG003
JOINT SWELLING
Musculoskeletal and connective tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
MUSCLE SPASMS
Musculoskeletal and connective tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
MUSCULOSKELETAL CHEST PAIN
Musculoskeletal and connective tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
MUSCULOSKELETAL PAIN
Musculoskeletal and connective tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
MUSCULOSKELETAL STIFFNESS
Musculoskeletal and connective tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
NECK PAIN
Musculoskeletal and connective tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PAIN IN EXTREMITY
Musculoskeletal and connective tissue disorders
MedDRA
Systematic Assessment
EG0001 affected16 at risk
EG0010 affected6 at risk
EG0021 affected6 at risk
EG003
BALANCE DISORDER
Nervous system disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
DIZZINESS
Nervous system disorders
MedDRA
Systematic Assessment
EG0003 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
HEADACHE
Nervous system disorders
MedDRA
Systematic Assessment
EG0002 affected16 at risk
EG0012 affected6 at risk
EG0020 affected6 at risk
EG003
HYPERAESTHESIA
Nervous system disorders
MedDRA
Systematic Assessment
EG0001 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PRESYNCOPE
Nervous system disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
SCIATICA
Nervous system disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
SYNCOPE
Nervous system disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
TREMOR
Nervous system disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
AGITATION
Psychiatric disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
DEPRESSION
Psychiatric disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
INSOMNIA
Psychiatric disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
STRESS
Psychiatric disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
CHROMATURIA
Renal and urinary disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
GLYCOSURIA
Renal and urinary disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PROTEINURIA
Renal and urinary disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
BRONCHIAL OBSTRUCTION
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
COUGH
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
DYSPNOEA
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
EPISTAXIS
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
HAEMOPTYSIS
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
NASAL CONGESTION
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0001 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
NASAL DISCOMFORT
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
OROPHARYNGEAL PAIN
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PAINFUL RESPIRATION
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PRODUCTIVE COUGH
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PULMONARY CONGESTION
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
RHINORRHOEA
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
SINUS CONGESTION
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
SNEEZING
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
SPUTUM INCREASED
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
THROAT IRRITATION
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
TONSILLAR DISORDER
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
ERYTHEMA
Skin and subcutaneous tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
HEAT RASH
Skin and subcutaneous tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
NIGHT SWEATS
Skin and subcutaneous tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PHOTOSENSITIVITY REACTION
Skin and subcutaneous tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PRURITUS
Skin and subcutaneous tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
PRURITUS GENERALISED
Skin and subcutaneous tissue disorders
MedDRA
Systematic Assessment
EG0001 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
RASH
Skin and subcutaneous tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
RASH ERYTHEMATOUS
Skin and subcutaneous tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0010 affected6 at risk
EG0020 affected6 at risk
EG003
RASH PRURITIC
Skin and subcutaneous tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0011 affected6 at risk
EG0020 affected6 at risk
EG003
URTICARIA
Skin and subcutaneous tissue disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0011 affected6 at risk
EG0020 affected6 at risk
EG003
HOT FLUSH
Vascular disorders
MedDRA
Systematic Assessment
EG0000 affected16 at risk
EG0011 affected6 at risk
EG0020 affected6 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Point of Contact
Title
Organization
Phone
Extension
Email
Study Director
Novartis
862-778-8300
ID
Term
D003550
Cystic Fibrosis
D001229
Aspergillosis, Allergic Bronchopulmonary
Ancestor Terms
ID
Term
D010182
Pancreatic Diseases
D004066
Digestive System Diseases
D008171
Lung Diseases
D012140
Respiratory Tract Diseases
D030342
Genetic Diseases, Inborn
D009358
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232
Infant, Newborn, Diseases
D055732
Pulmonary Aspergillosis
D001228
Aspergillosis
D009181
Mycoses
D001423
Bacterial Infections and Mycoses
D007239
Infections
D008172
Lung Diseases, Fungal
D012141
Respiratory Tract Infections
D012130
Respiratory Hypersensitivity
D006969
Hypersensitivity, Immediate
D006967
Hypersensitivity
D007154
Immune System Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C000722274
icenticaftor
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0131 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
FG0180 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0156 subjects
FG01612 subjects
FG01719 subjects
FG01812 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
FG0180 subjects
33.3
± 9.61
BG00444.2± 8.23
BG00543.6± 9.07
BG00628.2± 9.28
BG00733.2± 9.47
BG00830.3± 9.18
BG009NA± NAThis row is for Part 1 HV
BG010NA± NAThis row is for Part 1 HV
BG011NA± NAThis row is for Part 1 HV
BG012NA± NAThis row is for Part 1 HV
BG013NA± NAThis row is for Part 1 HV
BG014NA± NAThis row is for Part 1 HV
BG015NA± NAThis row is for Part 1 HV
BG016NA± NAThis row is for Part 1 HV
BG017NA± NAThis row is for Part 1 HV
BG018NA± NAThis row is for Part 1 HV
BG01934.4± 9.92
Part 2, HV (n=40)
Title
Measurements
BG000NA± NAThis row is for Part 2 HV
BG001NA± NAThis row is for Part 2 HV
BG002NA± NAThis row is for Part 2 HV
BG003NA± NAThis row is for Part 2 HV
BG004NA± NAThis row is for Part 2 HV
BG005NA± NAThis row is for Part 2 HV
BG006NA± NAThis row is for Part 2 HV
BG007NA± NAThis row is for Part 2 HV
BG008NA± NAThis row is for Part 2 HV
BG00930.3± 5.13
BG01030.5± 5.89
BG01129.2± 11.62
BG01231.7± 13.22
BG01327.8± 5
BG01429± 6.22
BG015NA± NAThis row is for Part 2 HV
BG016NA± NAThis row is for Part 2 HV
BG017NA± NAThis row is for Part 2 HV
BG018NA± NAThis row is for Part 2 HV
BG01929.7± 7.82
Part 3, CF patients (n=49)
Title
Measurements
BG000NA± NAThis row is for Part 3 HV
BG001NA± NAThis row is for Part 3 HV
BG002NA± NAThis row is for Part 3 HV
BG003NA± NAThis row is for Part 3 HV
BG004NA± NAThis row is for Part 3 HV
BG005NA± NAThis row is for Part 3 HV
BG006NA± NAThis row is for Part 3 HV
BG007NA± NAThis row is for Part 3 HV
BG008NA± NAThis row is for Part 3 HV
BG009NA± NAThis row is for Part 3 HV
BG010NA± NAThis row is for Part 3 HV
BG011NA± NAThis row is for Part 3 HV
BG012NA± NAThis row is for Part 3 HV
BG013NA± NAThis row is for Part 3 HV
BG014NA± NAThis row is for Part 3 HV
BG01539.3± 5.47
BG01632.7± 13.77
BG01727± 5.44
BG01827.9± 6.37
BG01930.1± 9.18
0
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
BG0090
BG0100
BG0110
BG0120
BG0130
BG0140
BG0151
BG0165
BG0179
BG0184
BG01919
Male
BG0006
BG0016
BG0026
BG0036
BG0046
BG0056
BG0066
BG0076
BG00816
BG0096
BG0106
BG0116
BG0126
BG0136
BG01410
BG0155
BG0167
BG01710
BG0188
BG019134
5
OG0046
OG0056
OG00616
OG0076
OG0086
OG0096
OG0106
OG0116
OG01210
OG0136
OG0146
OG0156
1
OG0041
OG0054
OG0068
OG0073
OG0086
OG0093
OG0106
OG0114
OG0127
OG0133
OG0142
OG0150
Serious adverse events
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
OG0080
OG0090
OG0100
OG0110
OG0120
OG0130
OG0140
OG0150
Death
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
OG0080
OG0090
OG0100
OG0110
OG0120
OG0130
OG0140
OG0150
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
OG003
Part 3 Placebo
Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Units
Counts
Participants
OG0005
OG00111
OG00217
OG00311
Title
Denominators
Categories
Title
Measurements
OG0000.27± 0.769
OG001-0.85± 1.798
OG002-0.13± 2.276
OG0030.28± 1.959
OG003
Part 3 Placebo
Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Units
Counts
Participants
OG0006
OG00112
OG00219
OG00312
Title
Denominators
Categories
Adverse Events (AE)
Title
Measurements
OG0006
OG0018
OG00218
OG0038
Serious Adverse Events (SAE)
Title
Measurements
OG0001
OG0011
OG0021
OG003
OG003
Part 3 Placebo
Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Units
Counts
Participants
OG0005
OG00111
OG00216
OG00312
Title
Denominators
Categories
Title
Measurements
OG0000.58± 2.476
OG0015.99± 1.648
OG002-1.16± 1.059
OG003-1.46± 1.229
OG003
Part 3 Placebo
Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Units
Counts
Participants
OG0005
OG00111
OG00219
OG00312
Title
Denominators
Categories
Title
Measurements
OG00016.06± 6.872
OG0015.04± 4.617
OG002-2.62± 2.853
OG003-2.06± 4.415
OG002
Part 1 Cohort 3: QBW251
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG003
Part 1 Cohort 4: QBW251
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG004
Part 1 Cohort 5: QBW251
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG005
Part 1 Cohort 6: QBW251
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG006
Part 1 Cohort 6: QBW251(Fed)
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG007
Part 1 Cohort 7: QBW251
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG008
Part 1 Cohort 8: QBW251
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG009
Part 1 Placebo
Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0065
OG0076
OG0086
OG00916
Title
Denominators
Categories
Title
Measurements
OG00052.5± 28.1
OG00173.7± 51.8
OG002692± 389
OG0031650± 907
OG0045470± 1070
OG0059450± 1740
OG0067470± 2190
OG00720200± 11500
OG00835900± 9100
OG009NA± NANot calculated
OG002
Part 1 Cohort 3: QBW251
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG003
Part 1 Cohort 4: QBW251
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG004
Part 1 Cohort 5: QBW251
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG005
Part 1 Cohort 6: QBW251
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG006
Part 1 Cohort 6: QBW251(Fed)
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG007
Part 1 Cohort 7: QBW251
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG008
Part 1 Cohort 8: QBW251
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0065
OG0076
OG0086
Title
Denominators
Categories
Title
Measurements
OG00021.1± 11.9
OG00124.7± 15.9
OG002186± 82.3
OG003459± 267
OG0041110± 330
OG0051910± 413
OG0061090± 449
OG0072680± 1000
OG0084540± 930
OG002
Part 1 Cohort 3: QBW251
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG003
Part 1 Cohort 4: QBW251
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG004
Part 1 Cohort 5: QBW251
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG005
Part 1 Cohort 6: QBW251
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG006
Part 1 Cohort 6: QBW251(Fed)
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG007
Part 1 Cohort 7: QBW251
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG008
Part 1 Cohort 8: QBW251
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0065
OG0076
OG0086
Title
Denominators
Categories
Title
Measurements
OG0000.756± 0.268
OG0011.25± 0.612
OG0021.33± 0.516
OG0031.50± 0.548
OG0041.50± 0.837
OG0052.17± 1.17
OG0063.40± 0.894
OG0072.52± 0.850
OG0081.83± 0.753
OG002
Part 1 Cohort 3: QBW251
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG003
Part 1 Cohort 4: QBW251
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG004
Part 1 Cohort 5: QBW251
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG005
Part 1 Cohort 6: QBW251
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG006
Part 1 Cohort 6: QBW251(Fed)
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG007
Part 1 Cohort 7: QBW251
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG008
Part 1 Cohort 8: QBW251
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0065
OG0076
OG0086
Title
Denominators
Categories
Title
Measurements
OG000NA± NAThere were not enough time points to calculated the T1/2
OG001NA± NAThere were not enough time points to calculated the T1/2
OG00210.3± 4.24
OG00310.1± 3.35
OG00412.0± 2.26
OG00512.7± 1.99
OG00615.6± 5.03
OG00712.8± 3.85
OG00810.7± 2.19
OG002
Part 1 Cohort 3: QBW251
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG003
Part 1 Cohort 4: QBW251
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG004
Part 1 Cohort 5: QBW251
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG005
Part 1 Cohort 6: QBW251
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG006
Part 1 Cohort 6: QBW251(Fed)
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG007
Part 1 Cohort 7: QBW251
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG008
Part 1 Cohort 8: QBW251
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0065
OG0076
OG0086
Title
Denominators
Categories
Title
Measurements
OG000NA± NANot calculated due to insufficient data
OG001NA± NANot calculated due to insufficient data
OG002731± 387
OG0031680± 903
OG0045510± 1080
OG0059480± 1740
OG0067540± 2220
OG00720300± 11500
OG00836000± 9120
OG002
Part 1 Cohort 3: QBW251
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG003
Part 1 Cohort 4: QBW251
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG004
Part 1 Cohort 5: QBW251
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG005
Part 1 Cohort 6: QBW251
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG006
Part 1 Cohort 6: QBW251(Fed)
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG007
Part 1 Cohort 7: QBW251
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG008
Part 1 Cohort 8: QBW251
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0065
OG0076
OG0086
Title
Denominators
Categories
Title
Measurements
OG000NA± NANot calculated due to insufficient data
OG001NA± NANot calculated due to insufficient data
OG002123± 49.0
OG003114± 63.9
OG00456.2± 11.0
OG00554.5± 11.9
OG00671.6± 22.6
OG00745.9± 19.9
OG00829.7± 9.00
OG002
Part 1 Cohort 3: QBW251
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG003
Part 1 Cohort 4: QBW251
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG004
Part 1 Cohort 5: QBW251
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG005
Part 1 Cohort 6: QBW251
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG006
Part 1 Cohort 6: QBW251(Fed)
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG007
Part 1 Cohort 7: QBW251
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
OG008
Part 1 Cohort 8: QBW251
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0065
OG0076
OG0086
Title
Denominators
Categories
Title
Measurements
OG000NA± NANot calculated due to insufficient data
OG001NA± NANot calculated due to insufficient data
OG0021700± 772
OG0031490± 622
OG004957± 151
OG005995± 235
OG0061580± 587
OG007827± 375
OG008447± 112
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG003
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG004
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
Title
Denominators
Categories
Day1
Title
Measurements
OG0001800± 794
OG0016170± 1250
OG00216100± 8170
OG0037160± 1960
OG00418800± 6360
Day 14
Title
Measurements
OG0002060± 708
OG0017620± 1470
OG00228300± 5570
OG003
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG003
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG004
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
Title
Denominators
Categories
Day 1
Title
Measurements
OG000541± 338
OG0011650± 343
OG0022790± 1040
OG0031650± 188
OG0043720± 1530
Day 14
Title
Measurements
OG000430± 145
OG0011500± 442
OG0023840± 868
OG003
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG003
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG004
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
Title
Denominators
Categories
Day 1
Title
Measurements
OG0001.67± 0.816
OG0011.17± 0.408
OG0022.33± 1.21
OG0032.68± 0.813
OG0043.67± 0.516
Day 2
Title
Measurements
OG0002.17± 1.17
OG0012.17± 0.408
OG0022.33± 1.03
OG003
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG004
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG005
Part 2 Placebo
Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0045
OG00514
Title
Denominators
Categories
Title
Measurements
OG0002060± 708
OG0017620± 1470
OG00228300± 5570
OG00312100± 4930
OG00480300± 56300
OG005NA± NANot calculated
OG003
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG004
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
Title
Denominators
Categories
Title
Measurements
OG00085.8± 29.5
OG001318± 61.1
OG0021180± 232
OG003NA± NANot calculated due to insufficient data
OG004NA± NANot calculated due to insufficient data
OG003
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG004
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
Title
Denominators
Categories
Title
Measurements
OG00080.8± 29.7
OG00154.0± 9.40
OG00227.5± 5.98
OG003NA± NANot calculated due to insufficient data
OG004NA± NANot calculated due to insufficient data
OG003
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG004
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
Title
Denominators
Categories
Title
Measurements
OG0001330± 550
OG0011120± 395
OG002608± 255
OG003NA± NANot calculated due to insufficient data
OG004NA± NANot calculated due to insufficient data
OG003
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG004
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
Title
Denominators
Categories
Title
Measurements
OG0001.27± 0.425
OG0011.25± 0.199
OG0022.08± 0.913
OG0031.66± 0.386
OG0043.88± 2.07
OG003
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG004
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
Title
Denominators
Categories
Title
Measurements
OG00011.3± 1.44
OG00114.1± 3.80
OG00215.1± 4.40
OG003NA± NANot calculated due to insufficient data
OG004NA± NANot calculated due to insufficient data
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Units
Counts
Participants
OG0006
OG00112
OG00219
Title
Denominators
Categories
Day 1
Title
Measurements
OG0001110± 709
OG0017530± 2480
OG0026020± 2960
Day 14
Title
Measurements
OG0001760± 943
OG00118900± 6850
OG002NA± NAPK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose.
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Units
Counts
Participants
OG0006
OG00112
OG00219
Title
Denominators
Categories
Day 1
Title
Measurements
OG00042.3± 14.1
OG001423± 275
OG002653± 318
Day 14
Title
Measurements
OG00086.4± 16.3
OG0011570± 813
OG002NA± NAPK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Units
Counts
Participants
OG0006
OG00112
OG00219
Title
Denominators
Categories
Day 1
Title
Measurements
OG000419± 316
OG0011950± 715
OG0022380± 1240
Day 14
Title
Measurements
OG000632± 438
OG0014080± 1780
OG002NA± NAPK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Units
Counts
Participants
OG0006
OG00112
OG00219
Title
Denominators
Categories
Day 1
Title
Measurements
OG0007.99± 0.0136
OG0017.95± 0.149
OG0025.80± 0.639
Day 14
Title
Measurements
OG0007.97± 0.0667
OG0017.96± 0.0554
OG002NA± NAPK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Units
Counts
Participants
OG0006
OG00112
OG00219
Title
Denominators
Categories
Day 1
Title
Measurements
OG0003.17± 2.47
OG0013.08± 1.68
OG0023.18± 0.838
Day 14
Title
Measurements
OG0001.82± 0.750
OG0012.39± 0.973
OG002NA± NAPK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose
OG003
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG004
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG005
Part 2 Placebo
Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0035
OG0045
OG00514
Title
Denominators
Categories
Title
Measurements
OG0002.36± 1.84
OG0012.20± 1.26
OG0021.21± 0.697
OG0030.419± 0.271
OG0040.140± 0.0936
OG005NA± NANot calculated
OG003
Part 2 Cohort 4: QBW251
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
OG004
Part 2 Cohort 5: QBW251
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).