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Study of VX-121 in Healthy Subjects and in Subjects With Cystic Fibrosis

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Placebo (matched to VX-121 suspension)
VX-121 (Suspension)
TEZ/IVA
IVA
Placebo (matched to TEZ/IVA)
Placebo (matched to IVA)
VX-121 (Tablet)
Placebo (matched to VX-121 tablet)
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Key Inclusion Criteria:

  • Part A, B, and C: Healthy Volunteers

    • Female subjects must be of non-childbearing potential
    • Between the ages of 18 and 55 years, inclusive
    • Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight >50 kg

  • Part D: Subjects with CF

    • Heterozygous for F508del and an MF mutation (F/MF)
    • FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height
    • Body weight ≥35 kg

Key Exclusion Criteria:

  • Part A, B and C: Healthy Volunteers

    • Any condition possibly affecting drug absorption
    • History of febrile illness or other acute illness within 5 days before the first study drug dose

  • Part D: Subjects with CF

    • History of clinically significant cirrhosis with or without portal hypertension
    • History of solid organ or hematological transplantation
    • Lung infection with organisms associated with a more rapid decline in pulmonary status

Other protocol defined Inclusion/Exclusion criteria may apply

Sites / Locations

  • Academic Medical Center
  • HagaZiekenhuis van den Haag
  • PRA Health Sciences Onderzoekscentrum UMCG
  • UMC St. Radboud
  • Erasmus Medical Center
  • Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
  • The Medicines Evaluation Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm 18

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Experimental

Experimental

Experimental

Placebo Comparator

Experimental

Arm Label

Part A: Pooled Placebo (Cohorts A1-5; Except A3)

Part A: VX-121 (Cohort A1)

Part A: VX-121 (Cohort A2)

Part A: VX-121 (Cohort A3)

Part A: VX-121 (Cohort A4)

Part A: VX-121 (Cohort A5)

Part A: VX-121 (Cohort A9)

Part B: Pooled Placebo (Cohorts B1-4)

Part B: VX-121 (Cohort B1)

Part B: VX-121 (Cohort B2)

Part B: VX-121 (Cohort B3)

Part B: VX-121 (Cohort B4)

Part C: Pooled Placebo (Cohorts C1-3)

Part C: VX-121 (Cohort C1)

Part C: VX-121 (Cohort C2)

Part C: VX-121 (Cohort C3)

Part D: Placebo

Part D: VX-121/TEZ/IVA

Arm Description

Participants received single dose of placebo matched to VX-121.

Participants received single dose of VX-121 10 milligrams (mg).

Participants received single dose of VX-121 20 mg.

Participants received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk.

Participants received single dose of VX-121 40 mg.

Participants received single dose of VX-121 60 mg.

Participants received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet on Day 9, followed by VX-121 10 mg tablet with milk on Day 17.

Participants received placebo matched to VX-121 for 10 days.

Participants received VX-121 10 mg once daily (qd) for 10 days.

Participants received VX-121 20 mg qd for 10 days.

Participants received VX-121 40 mg qd for 10 days.

Participants received VX-121 60 mg qd for 10 days.

Participants received placebo matched to VX-121/TEZ/IVA for 14 days.

Participants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 14 days.

Participants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.

Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.

Participants received placebo matched to VX-121/TEZ/IVA for 4 weeks.

Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.

Outcomes

Primary Outcome Measures

Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Secondary Outcome Measures

Part A: Maximum Observed Concentration (Cmax) of VX-121
Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121
Part B: Maximum Observed Concentration (Cmax) of VX-121
Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121
Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA)
Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Part D: Absolute Change in Sweat Chloride (SwCl) Concentrations
Sweat samples were collected using an approved collection device.
Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Full Information

First Posted
December 5, 2018
Last Updated
June 17, 2022
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT03768089
Brief Title
Study of VX-121 in Healthy Subjects and in Subjects With Cystic Fibrosis
Official Title
A Phase 1/2 Study of VX-121 in Healthy Subjects and in Subjects With Cystic Fibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
March 20, 2018 (Actual)
Primary Completion Date
May 3, 2019 (Actual)
Study Completion Date
May 3, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate safety and tolerability of VX-121 in healthy subjects and in subjects with cystic fibrosis (CF).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
115 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A: Pooled Placebo (Cohorts A1-5; Except A3)
Arm Type
Placebo Comparator
Arm Description
Participants received single dose of placebo matched to VX-121.
Arm Title
Part A: VX-121 (Cohort A1)
Arm Type
Experimental
Arm Description
Participants received single dose of VX-121 10 milligrams (mg).
Arm Title
Part A: VX-121 (Cohort A2)
Arm Type
Experimental
Arm Description
Participants received single dose of VX-121 20 mg.
Arm Title
Part A: VX-121 (Cohort A3)
Arm Type
Experimental
Arm Description
Participants received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk.
Arm Title
Part A: VX-121 (Cohort A4)
Arm Type
Experimental
Arm Description
Participants received single dose of VX-121 40 mg.
Arm Title
Part A: VX-121 (Cohort A5)
Arm Type
Experimental
Arm Description
Participants received single dose of VX-121 60 mg.
Arm Title
Part A: VX-121 (Cohort A9)
Arm Type
Experimental
Arm Description
Participants received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet on Day 9, followed by VX-121 10 mg tablet with milk on Day 17.
Arm Title
Part B: Pooled Placebo (Cohorts B1-4)
Arm Type
Placebo Comparator
Arm Description
Participants received placebo matched to VX-121 for 10 days.
Arm Title
Part B: VX-121 (Cohort B1)
Arm Type
Experimental
Arm Description
Participants received VX-121 10 mg once daily (qd) for 10 days.
Arm Title
Part B: VX-121 (Cohort B2)
Arm Type
Experimental
Arm Description
Participants received VX-121 20 mg qd for 10 days.
Arm Title
Part B: VX-121 (Cohort B3)
Arm Type
Experimental
Arm Description
Participants received VX-121 40 mg qd for 10 days.
Arm Title
Part B: VX-121 (Cohort B4)
Arm Type
Experimental
Arm Description
Participants received VX-121 60 mg qd for 10 days.
Arm Title
Part C: Pooled Placebo (Cohorts C1-3)
Arm Type
Placebo Comparator
Arm Description
Participants received placebo matched to VX-121/TEZ/IVA for 14 days.
Arm Title
Part C: VX-121 (Cohort C1)
Arm Type
Experimental
Arm Description
Participants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 14 days.
Arm Title
Part C: VX-121 (Cohort C2)
Arm Type
Experimental
Arm Description
Participants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
Arm Title
Part C: VX-121 (Cohort C3)
Arm Type
Experimental
Arm Description
Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
Arm Title
Part D: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo matched to VX-121/TEZ/IVA for 4 weeks.
Arm Title
Part D: VX-121/TEZ/IVA
Arm Type
Experimental
Arm Description
Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo (matched to VX-121 suspension)
Intervention Description
Placebo matched to VX-121 suspension for oral administration.
Intervention Type
Drug
Intervention Name(s)
VX-121 (Suspension)
Intervention Description
Suspension for oral administration.
Intervention Type
Drug
Intervention Name(s)
TEZ/IVA
Other Intervention Name(s)
VX-661/VX-770, tezacaftor/ivacaftor
Intervention Description
Fixed-dose combination tablet for oral administration.
Intervention Type
Drug
Intervention Name(s)
IVA
Other Intervention Name(s)
VX-770, ivacaftor
Intervention Description
Tablet for oral administration.
Intervention Type
Drug
Intervention Name(s)
Placebo (matched to TEZ/IVA)
Intervention Description
Placebo matched to TEZ/IVA for oral administration.
Intervention Type
Drug
Intervention Name(s)
Placebo (matched to IVA)
Intervention Description
Placebo matched to IVA for oral administration.
Intervention Type
Drug
Intervention Name(s)
VX-121 (Tablet)
Intervention Description
Tablet for oral administration.
Intervention Type
Drug
Intervention Name(s)
Placebo (matched to VX-121 tablet)
Intervention Description
Placebo matched to VX-121 tablet for oral administration.
Primary Outcome Measure Information:
Title
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame
From Day 1 Through Safety Follow-up (up to Day 15 for Part A [except Cohorts A3 and A9], up to Day 26 for Cohort A3, up to Day 34 for Cohort A9, up to Day 20 for Part B, up to Day 24 for Part C and up to Week 9 for Part D)
Secondary Outcome Measure Information:
Title
Part A: Maximum Observed Concentration (Cmax) of VX-121
Time Frame
Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose
Title
Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121
Time Frame
Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose
Title
Part B: Maximum Observed Concentration (Cmax) of VX-121
Time Frame
Day 1, Day 5, and Day 10
Title
Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121
Time Frame
Day 1, Day 5, and Day 10
Title
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121
Time Frame
Pre-dose at Day 5 and Day 10
Title
Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA)
Time Frame
Day 1, Day 7, and Day 14
Title
Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Time Frame
Day 1, Day 7, and Day 14
Title
Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Time Frame
Pre-dose at Day 7 and Day 14
Title
Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Time Frame
Day 1 and Day 15
Title
Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Time Frame
Day 1 and Day 15
Title
Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)
Time Frame
Pre-dose at Day 8, Day 15, and Day 29
Title
Part D: Absolute Change in Sweat Chloride (SwCl) Concentrations
Description
Sweat samples were collected using an approved collection device.
Time Frame
From Baseline Through Day 29
Title
Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
From Baseline Through Day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Key Inclusion Criteria: Part A, B, and C: Healthy Volunteers Female subjects must be of non-childbearing potential Between the ages of 18 and 55 years, inclusive Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight >50 kg Part D: Subjects with CF Heterozygous for F508del and an MF mutation (F/MF) FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height Body weight ≥35 kg Key Exclusion Criteria: Part A, B and C: Healthy Volunteers Any condition possibly affecting drug absorption History of febrile illness or other acute illness within 5 days before the first study drug dose Part D: Subjects with CF History of clinically significant cirrhosis with or without portal hypertension History of solid organ or hematological transplantation Lung infection with organisms associated with a more rapid decline in pulmonary status Other protocol defined Inclusion/Exclusion criteria may apply
Facility Information:
Facility Name
Academic Medical Center
City
Amsterdam
Country
Netherlands
Facility Name
HagaZiekenhuis van den Haag
City
Den Haag
Country
Netherlands
Facility Name
PRA Health Sciences Onderzoekscentrum UMCG
City
Groningen
Country
Netherlands
Facility Name
UMC St. Radboud
City
Nijmegen
Country
Netherlands
Facility Name
Erasmus Medical Center
City
Rotterdam
Country
Netherlands
Facility Name
Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
City
Birmingham
Country
United Kingdom
Facility Name
The Medicines Evaluation Unit
City
Manchester
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Study of VX-121 in Healthy Subjects and in Subjects With Cystic Fibrosis

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