Evaluation of VX-828 in Healthy Participants and in Participants With Cystic Fibrosis
Phase 1
Recruiting
- Conditions
- Cystic Fibrosis
- Interventions
- Registration Number
- NCT06154447
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
The purpose of the study is to evaluate safety, tolerability, and pharmacokinetics of VX-828 and VX-828 in triple combination (TC) with Tezacaftor (TEZ) and VX-118 in healthy participants and in participants with cystic fibrosis (CF).
- Detailed Description
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 225
Inclusion Criteria
Parts A-D:
- Body mass index (BMI) of 18.0 to 32.0 kilogram per meter square (kg/m^2)
- A total body weight of more than (>) 50 kg
- Nonsmoker or ex-smoker for at least 3 months before screening with current nonsmoking status confirmed by urine or blood cotinine at screening
Part E:
- Confirmed diagnosis of CF as determined by the investigator
- A total body weight of more than or equal to (>=) 35 kg
- Participants must be heterozygous for F508del with a second CFTR allele carrying a minimal function mutation that is not responsive to ELX/TEZ/IVA therapy
- Participants must have a forced expiratory volume in 1 second (FEV1) of greater than or equal to (≥) 40% of predicted normal for age, sex, and height
Key
Exclusion Criteria
Parts A-D:
- History of febrile illness or other acute illness within 14 days before the first dose of study drug
- Any condition possibly affecting drug absorption
Part E:
- An acute illness not related to CF (e.g., gastroenteritis) within 14 days before the first dose of study drug
- History of solid organ or hematological transplantation
- History of clinically significant cirrhosis with or without portal hypertension
- Lung infection with organisms associated with a more rapid decline in pulmonary status
Other protocol defined Inclusion/Exclusion criteria will apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: Single Ascending Dose (SAD) VX-828 Participants will be randomized to receive a single dose of different dose levels of VX-828. Part A: Placebo Placebo Participants will be randomized to receive placebo matched to VX-828. Part B: Multiple Ascending Dose (MAD) VX-828 Participants will be randomized to receive multiple doses of different dose levels of VX-828. The dose levels will be determined based on the data from Part A. Part B: Placebo Placebo Participants will be randomized to receive placebo matched to VX-828. Part C: Drug Drug Interaction Itraconazole Participants will receive a single dose of VX-828, followed by a washout period, Itraconazole administration, and concomitant administration of itraconazole and VX-828; or participants will receive Midazolam followed by VX-828/TEZ/VX-118 administration, and concomitant administration of VX-828/TEZ/VX-118 and Midazolam. Part C will be an open-label optional cohort. Part C: Drug Drug Interaction Midazolam Participants will receive a single dose of VX-828, followed by a washout period, Itraconazole administration, and concomitant administration of itraconazole and VX-828; or participants will receive Midazolam followed by VX-828/TEZ/VX-118 administration, and concomitant administration of VX-828/TEZ/VX-118 and Midazolam. Part C will be an open-label optional cohort. Part C: Drug Drug Interaction Tezacaftor Participants will receive a single dose of VX-828, followed by a washout period, Itraconazole administration, and concomitant administration of itraconazole and VX-828; or participants will receive Midazolam followed by VX-828/TEZ/VX-118 administration, and concomitant administration of VX-828/TEZ/VX-118 and Midazolam. Part C will be an open-label optional cohort. Part D: VX-828 in Triple Combination (TC) with TEZ/VX-118 VX-828 Participants will be randomized to receive VX-828 in TC with TEZ/VX-118. Part D: VX-828 in Triple Combination (TC) with TEZ/VX-118 Tezacaftor Participants will be randomized to receive VX-828 in TC with TEZ/VX-118. Part D: Placebo Placebo Participants will be randomized to receive placebo matched to VX-828 in TC with TEZ/VX-118. Part E: VX-828 in Triple Combination (TC) with TEZ/VX-118 in CF Tezacaftor Participants with cystic fibrosis will receive VX-828 in TC with TEZ/VX-118. Part E: VX-828 in Triple Combination (TC) with TEZ/VX-118 in CF VX-118 Participants with cystic fibrosis will receive VX-828 in TC with TEZ/VX-118. Part C: Drug Drug Interaction VX-828 Participants will receive a single dose of VX-828, followed by a washout period, Itraconazole administration, and concomitant administration of itraconazole and VX-828; or participants will receive Midazolam followed by VX-828/TEZ/VX-118 administration, and concomitant administration of VX-828/TEZ/VX-118 and Midazolam. Part C will be an open-label optional cohort. Part E: VX-828 in Triple Combination (TC) with TEZ/VX-118 in CF VX-828 Participants with cystic fibrosis will receive VX-828 in TC with TEZ/VX-118. Part C: Drug Drug Interaction VX-118 Participants will receive a single dose of VX-828, followed by a washout period, Itraconazole administration, and concomitant administration of itraconazole and VX-828; or participants will receive Midazolam followed by VX-828/TEZ/VX-118 administration, and concomitant administration of VX-828/TEZ/VX-118 and Midazolam. Part C will be an open-label optional cohort. Part D: VX-828 in Triple Combination (TC) with TEZ/VX-118 VX-118 Participants will be randomized to receive VX-828 in TC with TEZ/VX-118.
- Primary Outcome Measures
Name Time Method Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 67) Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 61) Part D: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 61) Part E: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Signing of Informed Consent Form (ICF) up to End of Study (Up to Day 66) Part C: Maximum Observed Concentration (Cmax) of VX-828 in Plasma in the Absence and Presence of Itraconazole From Day 1 up to Day 71 Part C: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma in the Absence and Presence of Itraconazole From Day 1 up to Day 71 Part C: Maximum Observed Concentration (Cmax) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/VX-118 From Day 1 up to Day 30 Part C: Area Under the Concentration Versus Time Curve (AUC) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/VX-118 From Day 1 up to Day 30
- Secondary Outcome Measures
Name Time Method Part D: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ, and VX-118 and their Metabolites at Steady State in Plasma Day 28 Part C: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 71) Part A: Maximum Observed Concentration (Cmax) of VX-828 in Plasma From Day 1 up to Day 67 Part A: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma From Day 1 up to Day 67 Part B: Maximum Observed Concentration (Cmax) of VX-828 at Steady State in Plasma From Day 1 up to Day 61 Part B: Area Under the Concentration Versus Time Curve (AUC) of VX-828 at Steady State in Plasma From Day 1 up to Day 61 Part D: Maximum Observed Concentration (Cmax) of VX-828, TEZ, and VX-118 and their Metabolites at Steady State in Plasma Day 28 Part E: Maximum Observed Concentration (Cmax) of VX-828, TEZ, and VX-118 and their Metabolites in Plasma Day 1 and Day 28 Part E: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ, and VX-118 and their Metabolites in Plasma Day 28 Part E: Pre-dose Plasma Concentration (Ctrough) of VX-828, TEZ, and its Metabolites Pre-dose at Day 4, Day 8, Day 15, Day 22, Day 35, Day 49, Day 63 Part E: Absolute Change in Sweat Chloride From Baseline At Day 28
Trial Locations
- Locations (1)
Altasciences Clinical Kansas
🇺🇸Overland Park, Kansas, United States