Safety, Tolerability, Pharmacokinetics, and Preliminary Pharmacodynamics of QBW251 in Healthy Subjects and Cystic Fibrosis Patients
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT02190604
Collaborator
(none)
153
23
20
40
6.7
0.2
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
153 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Jul 31, 2012
Actual Primary Completion Date
:
Nov 30, 2015
Actual Study Completion Date
:
Nov 30, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Placebo Comparator: 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). |
Drug: Placebo
Capsule- oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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). |
Drug: QBW251
Capsule - oral dose
|
| Placebo Comparator: 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). |
Drug: Placebo
Capsule- oral dose
|
| Experimental: 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. |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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. |
Drug: QBW251
Capsule - oral dose
|
| Experimental: 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. |
Drug: QBW251
Capsule - oral dose
|
| Placebo Comparator: 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. |
Drug: Placebo
Capsule- oral dose
|
Outcome Measures
Primary Outcome Measures
- Part 1 and 2:Number of Participants (Healthy Volunteers) With Reported Adverse Events Receiving QBW251 [Day 1 to Day 36]
All adverse events (in healthy volunteers) reported.
- Part 3: Change in Lung Clearance Index (LCI) From Baseline to Day 15 [Baseline and 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.
- Part 3: Number of Participants (Patients) With Reported Adverse Events Receiving QBW251 [Day 1 to Day 56]
All adverse events and serious adverse events (in patients) reported.
Secondary Outcome Measures
- Part 3:Change in Forced Expiratory Volume in 1 Second (FEV1) at Day 15 [Baseline and 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
- Part 3: Change in Cystic Fibrosis Questionnaire-Revised Reported Outcomes [Baseline and Day 14]
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
- Part 1: AUC0-t in 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 2-5)]
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)
- Part 1: Maximum Concentration (Cmax) in 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)]
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
- Part 1: Time to Maximum Concentration (Tmax) in 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)]
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).
- Part 1: T1/2 in 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)]
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).
- Part 1: AUCinf in 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)]
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)
- Part 1: CL/F in 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)]
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)
- Part 1: Vz/F in 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)]
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.
- Part 2: AUCtau in 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)]
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
- Part 2: Maximum Concentration (Cmax) in 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)]
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.
- Part 2: Time to Maximum Concentration (Tmax) in 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)]
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.
- Part 2: AUC0-t [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)]
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.
- Part 2: Cav in 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)]
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.
- Part 2: CL/F in 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)]
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.
- Part 2: Vz/F in 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)]
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.
- Part 2: Racc in 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)]
Accumulation ratio (Racc). In this analysis Racc will be reported using blood samples taken on Days 1 - 14 from healthy volunteers.
- Part 2: T1/2 in 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)]
terminal elimination half-life (T1/2). In this analysis T1/2 will be reported using blood samples taken on Day 14 from healthy volunteers.
- Part 3: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of QBW251 in CF Patients [Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14]
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
- Part 3: Plasma Concentration at the Last Quantifiable Time Point (Clast) of QBW251 in CF Patients [Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day2]
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
- Part 3: Maximum Concentration (Cmax) in CF Patients [Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14]
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
- Part 3: Tlast in CF Patients [Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14]
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
- Part 3: Time to Maximum Concentration (Tmax) [Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14]
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
- Part 2: Ae0-t in 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]
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.
- Part 2: CLr in 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.]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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.
-
History of lung transplant
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Birmingham | Alabama | United States | 35294-0006 |
| 2 | Novartis Investigative Site | Denver | Colorado | United States | 80206 |
| 3 | Novartis Investigative Site | Chicago | Illinois | United States | 60611 |
| 4 | Novartis Investigative Site | Louisville | Kentucky | United States | 40202 |
| 5 | Novartis Investigative Site | Boston | Massachusetts | United States | 02114 |
| 6 | Novartis Investigative Site | Boston | Massachusetts | United States | 02115 |
| 7 | Novartis Investigative Site | Saint Louis | Missouri | United States | 63110 |
| 8 | Novartis Investigative Site | Chapel Hill | North Carolina | United States | 27514 |
| 9 | Novartis Investigative Site | Columbus | Ohio | United States | 43205 |
| 10 | Novartis Investigative Site | Brussel | Belgium | 1090 | |
| 11 | Novartis Investigative Site | Gent | Belgium | 9000 | |
| 12 | Novartis Investigative Site | Montpellier | France | 34059 | |
| 13 | Novartis Investigative Site | Paris | France | 75014 | |
| 14 | Novartis Investigative Site | PIERRE BENITE Cedex | France | 69495 | |
| 15 | Novartis Investigative Site | Koeln | Nordrhein-Westfalen | Germany | 50937 |
| 16 | Novartis Investigative Site | Berlin | Germany | 10098 | |
| 17 | Novartis Investigative Site | Dublin 4 | Ireland | 4 | |
| 18 | Novartis Investigative Site | Bucuresti | Romania | 050159 | |
| 19 | Novartis Investigative Site | Livingston | West Lothian | United Kingdom | EH54 6PP |
| 20 | Novartis Investigative Site | Belfast | United Kingdom | BT9 7AB | |
| 21 | Novartis Investigative Site | London | United Kingdom | SW 6NP | |
| 22 | Novartis Investigative Site | Manchester | United Kingdom | M23 9QZ | |
| 23 | Novartis Investigative Site | Mid Glamorgan | United Kingdom | CF484DR |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02190604
Other Study ID Numbers:
- CQBW251X2101
- 2011-005085-37
First Posted:
Jul 15, 2014
Last Update Posted:
Dec 30, 2020
Last Verified:
Mar 1, 2019
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| 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. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | 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 (Fasting/Fed), Same Subjects | Part 1 Cohort 7: QBW251 | Part 1 Cohort 8: QBW251 | Part 1 Placebo | 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 2 Placebo | Part 3 Cohort 1: QBW251 | Part 3 Cohort 2: QBW251 | Part 3 Cohort 3: QBW251 | Part 3 Placebo |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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. | 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. | 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. | 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. |
| Period Title: Part 1 and 2 (Healthy Volunteers) | |||||||||||||||||||
| STARTED | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 16 | 6 | 6 | 6 | 6 | 6 | 10 | 0 | 0 | 0 | 0 |
| COMPLETED | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 16 | 6 | 6 | 6 | 6 | 5 | 8 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
| Period Title: Part 1 and 2 (Healthy Volunteers) | |||||||||||||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 12 | 19 | 12 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 12 | 19 | 12 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Part 1 Cohort 1: QBW251 | Part 1 Cohort 2: QBW251 | Part 1 Cohort 3: QBW251 | Part 1 Cohort 4: QBW251 | Part 1 Cohort 6: QBW251 | Part 1 Cohort 6: QBW251 (Fastin / Fed), Same Subjects | Part 1 Cohort 7: QBW251 | Part 1 Cohort 8: QBW251 | Part 1 Placebo | 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 2 Placebo | Part 3 Cohort 1: QBW251 | Part 3 Cohort 2: QBW251 | Part 3 Cohort 3: QBW251 | Part 3 Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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. | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 16 | 6 | 6 | 6 | 6 | 6 | 10 | 6 | 12 | 19 | 12 | 153 |
| Age (Years) [Mean (Standard Deviation) ] | ||||||||||||||||||||
| Part 1, HV (n= 64) |
36.3
(8.69)
|
35
(14.25)
|
43.5
(3.39)
|
33.3
(9.61)
|
44.2
(8.23)
|
43.6
(9.07)
|
28.2
(9.28)
|
33.2
(9.47)
|
30.3
(9.18)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
34.4
(9.92)
|
| Part 2, HV (n=40) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
30.3
(5.13)
|
30.5
(5.89)
|
29.2
(11.62)
|
31.7
(13.22)
|
27.8
(5)
|
29
(6.22)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
29.7
(7.82)
|
| Part 3, CF patients (n=49) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
39.3
(5.47)
|
32.7
(13.77)
|
27
(5.44)
|
27.9
(6.37)
|
30.1
(9.18)
|
| Sex: Female, Male (Count of Participants) | ||||||||||||||||||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
5
41.7%
|
9
47.4%
|
4
33.3%
|
19
12.4%
|
| Male |
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
16
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
10
100%
|
5
83.3%
|
7
58.3%
|
10
52.6%
|
8
66.7%
|
134
87.6%
|
Outcome Measures
| Title | Part 1 and 2:Number of Participants (Healthy Volunteers) With Reported Adverse Events Receiving QBW251 |
|---|---|
| Description | All adverse events (in healthy volunteers) reported. |
| Time Frame | Day 1 to Day 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated subjects were included in the data analysis. Subjects were analyzed according to the study treatment(s) received. |
| Arm/Group Title | 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 1 Placebo | 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 2 Placebo | Part 1 Cohort 1: QBW251 | Part 1 Cohort 2: QBW251 | Part 1 Cohort 3: QBW251 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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 | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 5 | 6 | 6 | 16 | 6 | 6 | 6 | 6 | 6 | 10 | 6 | 6 | 6 |
| Adverse events |
1
16.7%
|
2
33.3%
|
2
33.3%
|
1
16.7%
|
1
16.7%
|
4
66.7%
|
8
133.3%
|
3
50%
|
6
37.5%
|
3
50%
|
6
100%
|
4
66.7%
|
7
116.7%
|
3
50%
|
2
20%
|
0
0%
|
| Serious adverse events |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Death |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Part 3: Change in Lung Clearance Index (LCI) From Baseline to Day 15 |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis |
| Arm/Group Title | Part 3 Cohort 1: QBW251 | Part 3 Cohort 2: QBW251 | Part 3 Cohort 3: QBW251 | Part 3 Placebo |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 5 | 11 | 17 | 11 |
| Mean (Standard Deviation) [Ratio] |
0.27
(0.769)
|
-0.85
(1.798)
|
-0.13
(2.276)
|
0.28
(1.959)
|
| Title | Part 3: Number of Participants (Patients) With Reported Adverse Events Receiving QBW251 |
|---|---|
| Description | All adverse events and serious adverse events (in patients) reported. |
| Time Frame | Day 1 to Day 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set: All randomized patients were included in the safety analysis |
| Arm/Group Title | Part 3 Cohort 1: QBW251 | Part 3 Cohort 2: QBW251 | Part 3 Cohort 3: QBW251 | Part 3 Placebo |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 12 | 19 | 12 |
| Adverse Events (AE) |
6
100%
|
8
133.3%
|
18
300%
|
8
133.3%
|
| Serious Adverse Events (SAE) |
1
16.7%
|
1
16.7%
|
1
16.7%
|
0
0%
|
| Title | Part 3:Change in Forced Expiratory Volume in 1 Second (FEV1) at Day 15 |
|---|---|
| Description | 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 |
| Time Frame | Baseline and Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis |
| Arm/Group Title | Part 3 Cohort 1: QBW251 | Part 3 Cohort 2: QBW251 | Part 3 Cohort 3: QBW251 | Part 3 Placebo |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 5 | 11 | 16 | 12 |
| Least Squares Mean (Standard Error) [Liters] |
0.58
(2.476)
|
5.99
(1.648)
|
-1.16
(1.059)
|
-1.46
(1.229)
|
| Title | Part 3: Change in Cystic Fibrosis Questionnaire-Revised Reported Outcomes |
|---|---|
| Description | 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 |
| Time Frame | Baseline and Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis |
| Arm/Group Title | Part 3 Cohort 1: QBW251 | Part 3 Cohort 2: QBW251 | Part 3 Cohort 3: QBW251 | Part 3 Placebo |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 5 | 11 | 19 | 12 |
| Least Squares Mean (Standard Error) [Units on a scale] |
16.06
(6.872)
|
5.04
(4.617)
|
-2.62
(2.853)
|
-2.06
(4.415)
|
| Title | Part 1: AUC0-t in Healthy Volunteers |
|---|---|
| Description | 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) |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | 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 1 Placebo |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 5 | 6 | 6 | 16 |
| Mean (Standard Deviation) [hr*ng/mL] |
52.5
(28.1)
|
73.7
(51.8)
|
692
(389)
|
1650
(907)
|
5470
(1070)
|
9450
(1740)
|
7470
(2190)
|
20200
(11500)
|
35900
(9100)
|
NA
(NA)
|
| Title | Part 1: Maximum Concentration (Cmax) in Healthy Volunteers |
|---|---|
| Description | 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 |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 5 | 6 | 6 |
| Mean (Standard Deviation) [ug/L] |
21.1
(11.9)
|
24.7
(15.9)
|
186
(82.3)
|
459
(267)
|
1110
(330)
|
1910
(413)
|
1090
(449)
|
2680
(1000)
|
4540
(930)
|
| Title | Part 1: Time to Maximum Concentration (Tmax) in Healthy Volunteers |
|---|---|
| Description | 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). |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 5 | 6 | 6 |
| Mean (Standard Deviation) [hr] |
0.756
(0.268)
|
1.25
(0.612)
|
1.33
(0.516)
|
1.50
(0.548)
|
1.50
(0.837)
|
2.17
(1.17)
|
3.40
(0.894)
|
2.52
(0.850)
|
1.83
(0.753)
|
| Title | Part 1: T1/2 in Healthy Volunteers |
|---|---|
| Description | 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). |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 5 | 6 | 6 |
| Mean (Standard Deviation) [hr] |
NA
(NA)
|
NA
(NA)
|
10.3
(4.24)
|
10.1
(3.35)
|
12.0
(2.26)
|
12.7
(1.99)
|
15.6
(5.03)
|
12.8
(3.85)
|
10.7
(2.19)
|
| Title | Part 1: AUCinf in Healthy Volunteers |
|---|---|
| Description | 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) |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 5 | 6 | 6 |
| Mean (Standard Deviation) [hr*ng/mL] |
NA
(NA)
|
NA
(NA)
|
731
(387)
|
1680
(903)
|
5510
(1080)
|
9480
(1740)
|
7540
(2220)
|
20300
(11500)
|
36000
(9120)
|
| Title | Part 1: CL/F in Healthy Volunteers |
|---|---|
| Description | 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) |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 5 | 6 | 6 |
| Mean (Standard Deviation) [L/hr] |
NA
(NA)
|
NA
(NA)
|
123
(49.0)
|
114
(63.9)
|
56.2
(11.0)
|
54.5
(11.9)
|
71.6
(22.6)
|
45.9
(19.9)
|
29.7
(9.00)
|
| Title | Part 1: Vz/F in Healthy Volunteers |
|---|---|
| Description | 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. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 6 | 5 | 6 | 6 |
| Mean (Standard Deviation) [Liters] |
NA
(NA)
|
NA
(NA)
|
1700
(772)
|
1490
(622)
|
957
(151)
|
995
(235)
|
1580
(587)
|
827
(375)
|
447
(112)
|
| Title | Part 2: AUCtau in Healthy Volunteers |
|---|---|
| Description | 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 |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Day1 |
1800
(794)
|
6170
(1250)
|
16100
(8170)
|
7160
(1960)
|
18800
(6360)
|
| Day 14 |
2060
(708)
|
7620
(1470)
|
28300
(5570)
|
12100
(4930)
|
80300
(56300)
|
| Title | Part 2: Maximum Concentration (Cmax) in Healthy Volunteers |
|---|---|
| Description | 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. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Day 1 |
541
(338)
|
1650
(343)
|
2790
(1040)
|
1650
(188)
|
3720
(1530)
|
| Day 14 |
430
(145)
|
1500
(442)
|
3840
(868)
|
2190
(769)
|
9420
(4330)
|
| Title | Part 2: Time to Maximum Concentration (Tmax) in Healthy Volunteers |
|---|---|
| Description | 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. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Day 1 |
1.67
(0.816)
|
1.17
(0.408)
|
2.33
(1.21)
|
2.68
(0.813)
|
3.67
(0.516)
|
| Day 2 |
2.17
(1.17)
|
2.17
(0.408)
|
2.33
(1.03)
|
3.25
(1.41)
|
3.80
(0.447)
|
| Title | Part 2: AUC0-t |
|---|---|
| Description | 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. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 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 2 Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 5 | 14 |
| Mean (Standard Deviation) [hr*ng/mL] |
2060
(708)
|
7620
(1470)
|
28300
(5570)
|
12100
(4930)
|
80300
(56300)
|
NA
(NA)
|
| Title | Part 2: Cav in Healthy Volunteers |
|---|---|
| Description | 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. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [ug/L] |
85.8
(29.5)
|
318
(61.1)
|
1180
(232)
|
NA
(NA)
|
NA
(NA)
|
| Title | Part 2: CL/F in Healthy Volunteers |
|---|---|
| Description | 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. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [L/hr] |
80.8
(29.7)
|
54.0
(9.40)
|
27.5
(5.98)
|
NA
(NA)
|
NA
(NA)
|
| Title | Part 2: Vz/F in Healthy Volunteers |
|---|---|
| Description | 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. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [Liters] |
1330
(550)
|
1120
(395)
|
608
(255)
|
NA
(NA)
|
NA
(NA)
|
| Title | Part 2: Racc in Healthy Volunteers |
|---|---|
| Description | Accumulation ratio (Racc). In this analysis Racc will be reported using blood samples taken on Days 1 - 14 from healthy volunteers. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [Ratio] |
1.27
(0.425)
|
1.25
(0.199)
|
2.08
(0.913)
|
1.66
(0.386)
|
3.88
(2.07)
|
| Title | Part 2: T1/2 in Healthy Volunteers |
|---|---|
| Description | terminal elimination half-life (T1/2). In this analysis T1/2 will be reported using blood samples taken on Day 14 from healthy volunteers. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [hr] |
11.3
(1.44)
|
14.1
(3.80)
|
15.1
(4.40)
|
NA
(NA)
|
NA
(NA)
|
| Title | Part 3: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of QBW251 in CF Patients |
|---|---|
| Description | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Time Frame | Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | Part 3 Cohort 1: QBW251 | Part 3 Cohort 2: QBW251 | Part 3 Cohort 3: QBW251 |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 6 | 12 | 19 |
| Day 1 |
1110
(709)
|
7530
(2480)
|
6020
(2960)
|
| Day 14 |
1760
(943)
|
18900
(6850)
|
NA
(NA)
|
| Title | Part 3: Plasma Concentration at the Last Quantifiable Time Point (Clast) of QBW251 in CF Patients |
|---|---|
| Description | 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 |
| Time Frame | Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | Part 3 Cohort 1: QBW251 | Part 3 Cohort 2: QBW251 | Part 3 Cohort 3: QBW251 |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 6 | 12 | 19 |
| Day 1 |
42.3
(14.1)
|
423
(275)
|
653
(318)
|
| Day 14 |
86.4
(16.3)
|
1570
(813)
|
NA
(NA)
|
| Title | Part 3: Maximum Concentration (Cmax) in CF Patients |
|---|---|
| Description | 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 |
| Time Frame | Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | Part 3 Cohort 1: QBW251 | Part 3 Cohort 2: QBW251 | Part 3 Cohort 3: QBW251 |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 6 | 12 | 19 |
| Day 1 |
419
(316)
|
1950
(715)
|
2380
(1240)
|
| Day 14 |
632
(438)
|
4080
(1780)
|
NA
(NA)
|
| Title | Part 3: Tlast in CF Patients |
|---|---|
| Description | 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 |
| Time Frame | Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | Part 3 Cohort 1: QBW251 | Part 3 Cohort 2: QBW251 | Part 3 Cohort 3: QBW251 |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 6 | 12 | 19 |
| Day 1 |
7.99
(0.0136)
|
7.95
(0.149)
|
5.80
(0.639)
|
| Day 14 |
7.97
(0.0667)
|
7.96
(0.0554)
|
NA
(NA)
|
| Title | Part 3: Time to Maximum Concentration (Tmax) |
|---|---|
| Description | 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 |
| Time Frame | Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | Part 3 Cohort 1: QBW251 | Part 3 Cohort 2: QBW251 | Part 3 Cohort 3: QBW251 |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 6 | 12 | 19 |
| Day 1 |
3.17
(2.47)
|
3.08
(1.68)
|
3.18
(0.838)
|
| Day 14 |
1.82
(0.750)
|
2.39
(0.973)
|
NA
(NA)
|
| Title | Part 2: Ae0-t in Healthy Volunteers |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 2 Placebo |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 5 | 5 | 14 |
| Mean (Standard Deviation) [L/hr] |
2.36
(1.84)
|
2.20
(1.26)
|
1.21
(0.697)
|
0.419
(0.271)
|
0.140
(0.0936)
|
NA
(NA)
|
| Title | Part 2: CLr in Healthy Volunteers |
|---|---|
| Description | 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. |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [L/hr] |
2.36
(1.84)
|
2.20
(1.26)
|
1.21
(0.697)
|
0.419
(0.271)
|
0.140
(0.0936)
|
Adverse Events
| Time Frame | ||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||||||||||||||||
| Arm/Group Title | Part 1 Placebo | Part 1 QBW251 10mg | Part 1 QBW251 25mg | Part 1 QBW251 150mg | Part 1 QBW251 300mg | Part 1 QBW251 500mg | Part 1 QBW251 500mg (Fed) | Part 1 QBW251 750mg | Part 1 QBW251 1000mg | Part 2 Placebo | Part 2 QBW251 150mg | Part 2 QBW251 400mg | Part 2 QBW251 750mg | Part 2 QBW251 450mg BID | Part 2 QBW251 750mg BID | Part 3 Placebo C1/C2/C3 | Part 3 QBW251 150mg BID C1 | Part 3 QBW251 450mg BID C2 | Part 3 QBW251 450mg BID C3 | |||||||||||||||||||
| Arm/Group Description | Part 1 Placebo | Part 1 QBW251 10mg | Part 1 QBW251 25mg | Part 1 QBW251 150mg | Part 1 QBW251 300mg | Part 1 QBW251 500mg | Part 1 QBW251 500mg (fed) | Part 1 QBW251 750mg | Part 1 QBW251 1000mg | Part 2 Placebo | Part 2 QBW251 150mg | Part 2 QBW251 400mg | Part 2 QBW251 750mg | Part 2 QBW251 450mg BID | Part 2 QBW251 750mg BID | Part 3 Placebo C1/C2/C3 | Part 3 QBW251 150mg BID C1 | Part 3 QBW251 450mg BID C2 | Part 3 QBW251 450mg BID C3 | |||||||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||||||||||||
| Part 1 Placebo | Part 1 QBW251 10mg | Part 1 QBW251 25mg | Part 1 QBW251 150mg | Part 1 QBW251 300mg | Part 1 QBW251 500mg | Part 1 QBW251 500mg (Fed) | Part 1 QBW251 750mg | Part 1 QBW251 1000mg | Part 2 Placebo | Part 2 QBW251 150mg | Part 2 QBW251 400mg | Part 2 QBW251 750mg | Part 2 QBW251 450mg BID | Part 2 QBW251 750mg BID | Part 3 Placebo C1/C2/C3 | Part 3 QBW251 150mg BID C1 | Part 3 QBW251 450mg BID C2 | Part 3 QBW251 450mg BID C3 | ||||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||||||||||||
| Part 1 Placebo | Part 1 QBW251 10mg | Part 1 QBW251 25mg | Part 1 QBW251 150mg | Part 1 QBW251 300mg | Part 1 QBW251 500mg | Part 1 QBW251 500mg (Fed) | Part 1 QBW251 750mg | Part 1 QBW251 1000mg | Part 2 Placebo | Part 2 QBW251 150mg | Part 2 QBW251 400mg | Part 2 QBW251 750mg | Part 2 QBW251 450mg BID | Part 2 QBW251 750mg BID | Part 3 Placebo C1/C2/C3 | Part 3 QBW251 150mg BID C1 | Part 3 QBW251 450mg BID C2 | Part 3 QBW251 450mg BID C3 | ||||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 1/19 (5.3%) | |||||||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||||||||||||
| INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/19 (5.3%) | |||||||||||||||||||
| SINUSITIS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||||||||||||||
| Part 1 Placebo | Part 1 QBW251 10mg | Part 1 QBW251 25mg | Part 1 QBW251 150mg | Part 1 QBW251 300mg | Part 1 QBW251 500mg | Part 1 QBW251 500mg (Fed) | Part 1 QBW251 750mg | Part 1 QBW251 1000mg | Part 2 Placebo | Part 2 QBW251 150mg | Part 2 QBW251 400mg | Part 2 QBW251 750mg | Part 2 QBW251 450mg BID | Part 2 QBW251 750mg BID | Part 3 Placebo C1/C2/C3 | Part 3 QBW251 150mg BID C1 | Part 3 QBW251 450mg BID C2 | Part 3 QBW251 450mg BID C3 | ||||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/16 (50%) | 3/6 (50%) | 2/6 (33.3%) | 1/6 (16.7%) | 2/6 (33.3%) | 2/6 (33.3%) | 1/5 (20%) | 1/6 (16.7%) | 4/6 (66.7%) | 7/10 (70%) | 3/6 (50%) | 6/6 (100%) | 3/6 (50%) | 6/6 (100%) | 4/6 (66.7%) | 8/12 (66.7%) | 5/6 (83.3%) | 8/12 (66.7%) | 18/19 (94.7%) | |||||||||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||||||||||||||||
| PALPITATIONS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| Congenital, familial and genetic disorders | ||||||||||||||||||||||||||||||||||||||
| ICHTHYOSIS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||||||||||||||||||||
| EAR DISCOMFORT | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| EAR PAIN | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| TINNITUS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||||||||||||
| ABDOMINAL DISCOMFORT | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/19 (5.3%) | |||||||||||||||||||
| ABDOMINAL DISTENSION | 0/16 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| ABDOMINAL PAIN | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| ABDOMINAL PAIN LOWER | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| APHTHOUS STOMATITIS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| DIARRHOEA | 1/16 (6.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 2/19 (10.5%) | |||||||||||||||||||
| FAECES DISCOLOURED | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/19 (0%) | |||||||||||||||||||
| FLATULENCE | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 2/10 (20%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 4/6 (66.7%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/19 (0%) | |||||||||||||||||||
| GASTROOESOPHAGEAL REFLUX DISEASE | 0/16 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/19 (0%) | |||||||||||||||||||
| GINGIVAL DISORDER | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| NAUSEA | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 1/6 (16.7%) | 4/12 (33.3%) | 2/19 (10.5%) | |||||||||||||||||||
| SALIVA ALTERED | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| SALIVARY GLAND PAIN | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| VOMITING | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 2/19 (10.5%) | |||||||||||||||||||
| General disorders | ||||||||||||||||||||||||||||||||||||||
| ASTHENIA | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/19 (5.3%) | |||||||||||||||||||
| CHEST DISCOMFORT | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/12 (16.7%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| CHEST PAIN | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| FATIGUE | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 3/12 (25%) | 2/19 (10.5%) | |||||||||||||||||||
| INFLUENZA LIKE ILLNESS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| PAIN | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/19 (5.3%) | |||||||||||||||||||
| PERIPHERAL SWELLING | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/19 (0%) | |||||||||||||||||||
| PYREXIA | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/19 (5.3%) | |||||||||||||||||||
| SENSATION OF FOREIGN BODY | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| THIRST | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| VESSEL PUNCTURE SITE BRUISE | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||||||||||||
| BRONCHITIS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| BRONCHOPULMONARY ASPERGILLOSIS ALLERGIC | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/19 (5.3%) | |||||||||||||||||||
| FOLLICULITIS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| FUNGAL INFECTION | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| GASTROENTERITIS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 3/12 (25%) | 1/6 (16.7%) | 0/12 (0%) | 2/19 (10.5%) | |||||||||||||||||||
| NASOPHARYNGITIS | 1/16 (6.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/5 (20%) | 0/6 (0%) | 1/6 (16.7%) | 1/10 (10%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| ORAL HERPES | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| PHARYNGITIS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| SINUSITIS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| UPPER RESPIRATORY TRACT INFECTION | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| VIRAL UPPER RESPIRATORY TRACT INFECTION | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||||||||||||
| ARTHROPOD BITE | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| LIGAMENT SPRAIN | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| SKIN WOUND | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| Investigations | ||||||||||||||||||||||||||||||||||||||
| ADENOVIRUS TEST POSITIVE | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| BLOOD ALKALINE PHOSPHATASE INCREASED | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| BLOOD POTASSIUM DECREASED | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| BREATH SOUNDS ABNORMAL | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| CORONAVIRUS TEST POSITIVE | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||||||||||||
| DECREASED APPETITE | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| HYPOGLYCAEMIA | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| VITAMIN D DEFICIENCY | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||||||||||||
| BACK PAIN | 0/16 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| JOINT SWELLING | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/19 (0%) | |||||||||||||||||||
| MUSCLE SPASMS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| MUSCULOSKELETAL CHEST PAIN | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| MUSCULOSKELETAL PAIN | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| MUSCULOSKELETAL STIFFNESS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| NECK PAIN | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| PAIN IN EXTREMITY | 1/16 (6.3%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||||||||||||||
| BALANCE DISORDER | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| DIZZINESS | 3/16 (18.8%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 2/6 (33.3%) | 2/10 (20%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 2/12 (16.7%) | 1/19 (5.3%) | |||||||||||||||||||
| HEADACHE | 2/16 (12.5%) | 2/6 (33.3%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/5 (0%) | 0/6 (0%) | 2/6 (33.3%) | 4/10 (40%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/12 (0%) | 1/6 (16.7%) | 3/12 (25%) | 4/19 (21.1%) | |||||||||||||||||||
| HYPERAESTHESIA | 1/16 (6.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| PRESYNCOPE | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| SCIATICA | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/19 (0%) | |||||||||||||||||||
| SYNCOPE | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| TREMOR | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||||||||||||||||
| AGITATION | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| DEPRESSION | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| INSOMNIA | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| STRESS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||||||||||||||||
| CHROMATURIA | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| GLYCOSURIA | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| PROTEINURIA | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||||||||||||
| BRONCHIAL OBSTRUCTION | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| COUGH | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 4/6 (66.7%) | 0/6 (0%) | 2/12 (16.7%) | 1/6 (16.7%) | 1/12 (8.3%) | 4/19 (21.1%) | |||||||||||||||||||
| DYSPNOEA | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| EPISTAXIS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/10 (10%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| HAEMOPTYSIS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/12 (0%) | 2/19 (10.5%) | |||||||||||||||||||
| NASAL CONGESTION | 1/16 (6.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 2/19 (10.5%) | |||||||||||||||||||
| NASAL DISCOMFORT | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| OROPHARYNGEAL PAIN | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/19 (0%) | |||||||||||||||||||
| PAINFUL RESPIRATION | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| PRODUCTIVE COUGH | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| PULMONARY CONGESTION | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 2/12 (16.7%) | 1/19 (5.3%) | |||||||||||||||||||
| RHINORRHOEA | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 2/19 (10.5%) | |||||||||||||||||||
| SINUS CONGESTION | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| SNEEZING | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| SPUTUM INCREASED | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/12 (16.7%) | 3/6 (50%) | 0/12 (0%) | 5/19 (26.3%) | |||||||||||||||||||
| THROAT IRRITATION | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| TONSILLAR DISORDER | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||||||||||||
| ERYTHEMA | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| HEAT RASH | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| NIGHT SWEATS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 1/12 (8.3%) | 0/19 (0%) | |||||||||||||||||||
| PHOTOSENSITIVITY REACTION | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| PRURITUS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 2/19 (10.5%) | |||||||||||||||||||
| PRURITUS GENERALISED | 1/16 (6.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| RASH | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 1/19 (5.3%) | |||||||||||||||||||
| RASH ERYTHEMATOUS | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| RASH PRURITIC | 0/16 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/10 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| URTICARIA | 0/16 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
| Vascular disorders | ||||||||||||||||||||||||||||||||||||||
| HOT FLUSH | 0/16 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/10 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | 0/12 (0%) | 0/19 (0%) | |||||||||||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. 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.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis |
| Phone | 862-778-8300 |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02190604
Other Study ID Numbers:
- CQBW251X2101
- 2011-005085-37
First Posted:
Jul 15, 2014
Last Update Posted:
Dec 30, 2020
Last Verified:
Mar 1, 2019