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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)/ VX-118 or TEZ/ deutivacaftor (D-IVA) in healthy participants and VX-828 in combination with D-IVA with or without TEZ in participants with cystic fibrosis (CF).
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.).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: Single Ascending Dose (SAD) | Experimental | Participants will be randomized to receive a single dose of different dose levels of VX-828. |
|
| Part A: Placebo | Placebo Comparator | Participants will be randomized to receive placebo matched to VX-828. |
|
| Part B: Multiple Ascending Dose (MAD) | Experimental | 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 Comparator | Participants will be randomized to receive placebo matched to VX-828. |
|
| Part C: Drug Drug Interaction | Experimental | 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/D-IVA administration, and concomitant administration of VX-828/TEZ/D-IVA and Midazolam. Part C will be an open-label optional cohort. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VX-828 | Drug | Suspension for Oral Administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | |
| Part B: 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 80) | |
| 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 80) | |
| 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 111) | |
| 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/D-IVA | 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/D-IVA |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Key Inclusion Criteria:
Parts A-D:
Part E:
Key Exclusion Criteria:
Parts A-D:
Part E:
Other protocol defined Inclusion/Exclusion criteria will apply.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Joe DiMaggio Cycstic Fibrosis & Pulmonary Center | Hollywood | Florida | 33021 | United States | ||
| AdventHealth Medical Group Pulmonology at Orlando Ridgewood |
Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/our-science/clinical-trials-data-sharing/
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|
| Part D: VX-828 in combination with TEZ/VX-118 ,TEZ/D-IVA or D-IVA | Experimental | Participants will be randomized to receive VX-828 in combination with TEZ/VX-118, TEZ/D-IVA, or D-IVA. |
|
| Part D: Placebo | Placebo Comparator | Participants will be randomized to receive placebo matched to VX-828/TEZ/VX-118 or placebo matched to VX-828 in combination with TEZ/D-IVA or D-IVA |
|
| Part E: VX-828 in Combination with D-IVA with or without TEZ in CF | Experimental | Participants with cystic fibrosis will receive VX-828 in combination with D-IVA with or without TEZ. |
|
| Placebo | Drug | Suspension for Oral Administration |
|
| Itraconazole | Drug | Solution for Oral Administration |
|
| Midazolam | Drug | Syrup for Oral Administration |
|
| Tezacaftor | Drug | Tablets for Oral Administration |
|
|
| VX-118 | Drug | Tablets for Oral Administration |
|
| Placebo | Drug | Suspension and Tablets for Oral Administration |
|
| Deutivacaftor | Drug | Tablets for Oral Administration |
|
|
| VX-828 | Drug | Tablets for Oral Administration |
|
| From Day 1 up to Day 30 |
| Part B: Maximum Observed Concentration (Cmax) of VX-828 at Day 28 in Plasma | From Day 1 up to Day 80 |
| Part B: Area Under the Concentration Versus Time Curve (AUC) of VX-828 at Day 28 in Plasma | From Day 1 up to Day 80 |
| 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 82) |
| Part D: Maximum Observed Concentration (Cmax) of VX-828, TEZ and D-IVA and their Metabolites at Day 28 in Plasma | Day 28 |
| Part D: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ and D-IVA and their Metabolites at Day 28 in Plasma | Day 28 |
| Part E: Maximum Observed Concentration (Cmax) of VX-828, TEZ, and D-IVA 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 D-IVA and their Metabolites in Plasma | Day 28 |
| Part E: Pre-dose Plasma Concentration (Ctrough) of VX-828, TEZ, D-IVA and its Metabolites | Pre-dose at Day 4, Day 8, Day 15, Day 22, Day 35, Day 49, Day 63, Day 80 |
| Part E: Absolute Change in Sweat Chloride | From Baseline and At Day 28 |
| Orlando |
| Florida |
| 32803 |
| United States |
| Altasciences Clinical Kansas | Overland Park | Kansas | 66212 | United States |
| Kentucky Children's Hospital | Lexington | Kentucky | 40508 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| University of Minnesota -Pulmonology | Minneapolis | Minnesota | 55455 | United States |
| Billings Clinic, Pediatric Pulmonary Dept. | Billings | Montana | 59101 | United States |
| New York Medical College | Hawthorne | New York | 10532 | United States |
| ProMedica Toledo Children's Hospital & ProMedica Central Physicians, LLC | Toledo | Ohio | 43606 | United States |
| Cook Children's Pulmonology | Fort Worth | Texas | 76104 | United States |
| University of Utah Hospital - Pulmonology | Salt Lake City | Utah | 84132 | United States |
| Vermont Lung Center | Colchester | Vermont | 05446 | United States |
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
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| ID | Term |
|---|---|
| D017964 | Itraconazole |
| D008874 | Midazolam |
| C000625213 | tezacaftor |
| C000731138 | deutivacaftor, tezacaftor , vanzacaftor |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010879 | Piperazines |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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