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A Study to Evaluate Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Adults With Cystic Fibrosis

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ClinicalTrials.gov Identifier: NCT03029455
Recruitment Status : Completed
First Posted : January 24, 2017
Last Update Posted : September 5, 2017
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Brief Summary:
Evaluate the safety and tolerability of VX-659 in healthy subjects

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: VX-659 Drug: Tezacaftor Drug: Ivacaftor Drug: VX-659 Matching Placebo Drug: Triple Combination (TC) Matching Placebos Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 163 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : November 2016
Actual Primary Completion Date : August 2017
Actual Study Completion Date : August 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: Part A: VX-659 or Matching Placebo
Part A includes single-dose escalation.
Drug: VX-659
Drug: VX-659 Matching Placebo
Experimental: Part B: VX-659 or Matching Placebo
Part B includes multiple-dose escalation.
Drug: VX-659
Drug: VX-659 Matching Placebo
Experimental: Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).
Drug: VX-659
Drug: Tezacaftor
Other Names:
  • VX-661
  • TEZ

Drug: Ivacaftor
Other Names:
  • VX-770
  • IVA

Drug: Triple Combination (TC) Matching Placebos
Experimental: Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
Part D includes subjects with CF. Participants will receive TC or matching placebos.
Drug: VX-659
Drug: Tezacaftor
Other Names:
  • VX-661
  • TEZ

Drug: Ivacaftor
Other Names:
  • VX-770
  • IVA

Drug: Triple Combination (TC) Matching Placebos



Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Maximum observed concentration (Cmax) of VX-659 and selected metabolites (μg/mL) [ Time Frame: from baseline up to Day 18 ]
  2. Cmax of TEZ and selected metabolites (μg/mL) [ Time Frame: from baseline up to Day 18 ]
  3. Cmax of IVA and selected metabolites (μg/mL) [ Time Frame: from baseline up to Day 18 ]
  4. 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 ]
  5. AUCtau of TEZ and selected metabolites (μg,h/mL) [ Time Frame: from baseline up to Day 18 ]
  6. AUCtau of IVA and selected metabolites (μg,h/mL) [ Time Frame: from baseline up to Day 18 ]
  7. Observed pre-dose concentration (Ctrough) of VX-659 and selected metabolites (μg/mL) [ Time Frame: from baseline up to Day 18 ]
  8. Ctrough of TEZ and selected metabolites (μg/mL) [ Time Frame: from baseline up to Day 18 ]
  9. Ctrough of IVA and selected metabolites (μg/mL) [ Time Frame: from baseline up to Day 18 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Healthy Volunteers: PARTS A, B, and C

  • Males and Females of non-childbearing potential.
  • Between the ages of 18 and 60 years inclusive
  • Healthy, as defined per protocol.
  • Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive
  • Body weight >50 kg

CF Patients: PART D

  • Body weight ≥35 kg.
  • Males and Females of non-childbearing potential.
  • Sweat chloride value ≥ 60 mmol/L at screening.
  • Heterozygous for F508del and a minimal function CFTR mutation
  • Forced expiratory volume in 1 second (FEV1) ≥40% and ≤90% of predicted at screening

Exclusion Criteria:

Healthy Volunteers: PARTS A, B, and C

  • History of any illness or any clinical condition that in the opinion of the investigator might confound the results of the study or pose additional risk to the subject.
  • Any condition possibly affecting drug absorption.
  • History of febrile illness within 14 days before the first study drug dose.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.

CF Patients: PART D

  • History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the subject.
  • History of cirrhosis with portal hypertension.
  • Risk factors for Torsade de Pointes.
  • G6PD deficiency assessed at Screening.
  • Abnormal Laboratory Values.
  • Lung infection with organisms associated with a more rapid decline in pulmonary status
  • History of solid organ or hematological transplantation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03029455


Locations
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United Kingdom
Birmingham, United Kingdom
Cambridge, United Kingdom
Exeter, United Kingdom
Glasgow, United Kingdom
Leeds, United Kingdom
Liverpool, United Kingdom
London, United Kingdom
Manchester, United Kingdom
Newcastle upon Tyne, United Kingdom
Southampton, United Kingdom
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03029455     History of Changes
Other Study ID Numbers: VX16-659-001
2016-003048-35 ( EudraCT Number )
First Posted: January 24, 2017    Key Record Dates
Last Update Posted: September 5, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
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Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action