<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03029455</url>
  </required_header>
  <id_info>
    <org_study_id>VX16-659-001</org_study_id>
    <secondary_id>2016-003048-35</secondary_id>
    <nct_id>NCT03029455</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Adults With Cystic Fibrosis</brief_title>
  <official_title>A Phase 1, Randomized, Double Blind, Placebo Controlled, Dose Escalation, and Bioavailability Study Evaluating the Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Subjects With Cystic Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vertex Pharmaceuticals Incorporated</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vertex Pharmaceuticals Incorporated</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Evaluate the safety and tolerability of VX-659 in healthy subjects&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">August 2017</completion_date>
  <primary_completion_date type="Actual">August 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs)</measure>
    <time_frame>from baseline up to Day 50</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed concentration (Cmax) of VX-659 and selected metabolites (μg/mL)</measure>
    <time_frame>from baseline up to Day 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of TEZ and selected metabolites (μg/mL)</measure>
    <time_frame>from baseline up to Day 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of IVA and selected metabolites (μg/mL)</measure>
    <time_frame>from baseline up to Day 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-659 and selected metabolites (μg,h/mL)</measure>
    <time_frame>from baseline up to Day 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCtau of TEZ and selected metabolites (μg,h/mL)</measure>
    <time_frame>from baseline up to Day 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCtau of IVA and selected metabolites (μg,h/mL)</measure>
    <time_frame>from baseline up to Day 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed pre-dose concentration (Ctrough) of VX-659 and selected metabolites (μg/mL)</measure>
    <time_frame>from baseline up to Day 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ctrough of TEZ and selected metabolites (μg/mL)</measure>
    <time_frame>from baseline up to Day 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ctrough of IVA and selected metabolites (μg/mL)</measure>
    <time_frame>from baseline up to Day 18</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">163</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Part A: VX-659 or Matching Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part A includes single-dose escalation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: VX-659 or Matching Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part B includes multiple-dose escalation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part D includes subjects with CF. Participants will receive TC or matching placebos.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>VX-659</intervention_name>
    <arm_group_label>Part A: VX-659 or Matching Placebo</arm_group_label>
    <arm_group_label>Part B: VX-659 or Matching Placebo</arm_group_label>
    <arm_group_label>Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo</arm_group_label>
    <arm_group_label>Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tezacaftor</intervention_name>
    <arm_group_label>Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo</arm_group_label>
    <arm_group_label>Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo</arm_group_label>
    <other_name>VX-661</other_name>
    <other_name>TEZ</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivacaftor</intervention_name>
    <arm_group_label>Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo</arm_group_label>
    <arm_group_label>Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo</arm_group_label>
    <other_name>VX-770</other_name>
    <other_name>IVA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>VX-659 Matching Placebo</intervention_name>
    <arm_group_label>Part A: VX-659 or Matching Placebo</arm_group_label>
    <arm_group_label>Part B: VX-659 or Matching Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Triple Combination (TC) Matching Placebos</intervention_name>
    <arm_group_label>Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo</arm_group_label>
    <arm_group_label>Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Healthy Volunteers: PARTS A, B, and C&#xD;
&#xD;
          -  Males and Females of non-childbearing potential.&#xD;
&#xD;
          -  Between the ages of 18 and 60 years inclusive&#xD;
&#xD;
          -  Healthy, as defined per protocol.&#xD;
&#xD;
          -  Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive&#xD;
&#xD;
          -  Body weight &gt;50 kg&#xD;
&#xD;
        CF Patients: PART D&#xD;
&#xD;
          -  Body weight ≥35 kg.&#xD;
&#xD;
          -  Males and Females of non-childbearing potential.&#xD;
&#xD;
          -  Sweat chloride value ≥ 60 mmol/L at screening.&#xD;
&#xD;
          -  Heterozygous for F508del and a minimal function CFTR mutation&#xD;
&#xD;
          -  Forced expiratory volume in 1 second (FEV1) ≥40% and ≤90% of predicted at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Healthy Volunteers: PARTS A, B, and C&#xD;
&#xD;
          -  History of any illness or any clinical condition that in the opinion of the&#xD;
             investigator might confound the results of the study or pose additional risk to the&#xD;
             subject.&#xD;
&#xD;
          -  Any condition possibly affecting drug absorption.&#xD;
&#xD;
          -  History of febrile illness within 14 days before the first study drug dose.&#xD;
&#xD;
          -  Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.&#xD;
&#xD;
        CF Patients: PART D&#xD;
&#xD;
          -  History of any comorbidity that, in the opinion of the investigator, might confound&#xD;
             the results of the study or pose an additional risk to the subject.&#xD;
&#xD;
          -  History of cirrhosis with portal hypertension.&#xD;
&#xD;
          -  Risk factors for Torsade de Pointes.&#xD;
&#xD;
          -  G6PD deficiency assessed at Screening.&#xD;
&#xD;
          -  Abnormal Laboratory Values.&#xD;
&#xD;
          -  Lung infection with organisms associated with a more rapid decline in pulmonary status&#xD;
&#xD;
          -  History of solid organ or hematological transplantation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cambridge</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Exeter</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Glasgow</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Leeds</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Newcastle upon Tyne</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Southampton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <last_update_submitted>September 1, 2017</last_update_submitted>
  <last_update_submitted_qc>September 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ivacaftor</mesh_term>
    <mesh_term>VX-659</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03029455
org study id: VX16-659-001
secondary id: 2016-003048-35
nct id: NCT03029455
lead sponsor: 
has dmc: Yes
Evaluate the safety and tolerability of VX-659 in healthy subjects
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs)
time frame: from baseline up to Day 50
measure: Maximum observed concentration (Cmax) of VX-659 and selected metabolites (μg/mL)
time frame: from baseline up to Day 18
measure: Cmax of TEZ and selected metabolites (μg/mL)
time frame: from baseline up to Day 18
measure: Cmax of IVA and selected metabolites (μg/mL)
time frame: from baseline up to Day 18
measure: Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-659 and selected metabolites (μg,h/mL)
time frame: from baseline up to Day 18
measure: AUCtau of TEZ and selected metabolites (μg,h/mL)
time frame: from baseline up to Day 18
measure: AUCtau of IVA and selected metabolites (μg,h/mL)
time frame: from baseline up to Day 18
measure: Observed pre-dose concentration (Ctrough) of VX-659 and selected metabolites (μg/mL)
time frame: from baseline up to Day 18
measure: Ctrough of TEZ and selected metabolites (μg/mL)
time frame: from baseline up to Day 18
measure: Ctrough of IVA and selected metabolites (μg/mL)
time frame: from baseline up to Day 18
arm group label: Part A: VX-659 or Matching Placebo
arm group type: Experimental
description: Part A includes single-dose escalation.
arm group label: Part B: VX-659 or Matching Placebo
arm group type: Experimental
description: Part B includes multiple-dose escalation.
arm group label: Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
arm group type: Experimental
description: Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).
arm group label: Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
arm group type: Experimental
description: Part D includes subjects with CF. Participants will receive TC or matching placebos.
intervention type: Drug
intervention name: VX-659
arm group label: Part A: VX-659 or Matching Placebo
arm group label: Part B: VX-659 or Matching Placebo
arm group label: Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
arm group label: Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
intervention type: Drug
intervention name: Tezacaftor
arm group label: Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
arm group label: Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
other name: VX-661
other name: TEZ
intervention type: Drug
intervention name: Ivacaftor
arm group label: Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
arm group label: Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
other name: VX-770
other name: IVA
intervention type: Drug
intervention name: VX-659 Matching Placebo
arm group label: Part A: VX-659 or Matching Placebo
arm group label: Part B: VX-659 or Matching Placebo
intervention type: Drug
intervention name: Triple Combination (TC) Matching Placebos
arm group label: Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
arm group label: Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis
mesh term: Ivacaftor
mesh term: VX-659