Status:

TERMINATED

Safety, Tolerability, Pharmacokinetics, and Preliminary Pharmacodynamics of QBW251 in Healthy Subjects and Cystic Fibrosis Patients

Lead Sponsor:

Novartis Pharmaceuticals

Conditions:

Cystic Fibrosis

Eligibility:

All Genders

18-65 years

Phase:

PHASE1

PHASE2

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 sin...

Eligibility Criteria

Inclusion

  • 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

Exclusion

    Key Trial Info

    Start Date :

    July 31 2012

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    November 30 2015

    Estimated Enrollment :

    153 Patients enrolled

    Trial Details

    Trial ID

    NCT02190604

    Start Date

    July 31 2012

    End Date

    November 30 2015

    Last Update

    December 30 2020

    Active Locations (23)

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    Page 1 of 6 (23 locations)

    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