Clinical trial NCT03768089: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2018-12-07
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: 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 outcomes:
measure: Part A: Maximum Observed Concentration (Cmax) of VX-121
timeFrame: 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
measure: 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
timeFrame: 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
measure: Part B: Maximum Observed Concentration (Cmax) of VX-121
timeFrame: Day 1, Day 5, and Day 10
measure: Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121
timeFrame: Day 1, Day 5, and Day 10
measure: Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121
timeFrame: Pre-dose at Day 5 and Day 10
measure: 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)
timeFrame: Day 1, Day 7, and Day 14
measure: 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)
timeFrame: Day 1, Day 7, and Day 14
measure: 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)
timeFrame: Pre-dose at Day 7 and Day 14
measure: 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)
timeFrame: Day 1 and Day 15
measure: 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)
timeFrame: Day 1 and Day 15
measure: 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)
timeFrame: Pre-dose at Day 8, Day 15, and Day 29
measure: Part D: Absolute Change in Sweat Chloride (SwCl) Concentrations
timeFrame: From Baseline Through Day 29
measure: Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: From Baseline Through Day 29
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis van den Haag
city: Groningen
country: Netherlands
facility: PRA Health Sciences Onderzoekscentrum UMCG
city: Nijmegen
country: Netherlands
facility: UMC St. Radboud
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Birmingham
country: United Kingdom
facility: Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
city: Manchester
country: United Kingdom
facility: The Medicines Evaluation Unit
Study officials:
References: