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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-001711-67 | EudraCT Number |
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Study discontinued after Part A due to Sponsor's discretion.
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This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-659, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects with F/F or F/MF genotypes.
The study was discontinued after completion of Part A due to Sponsor's discretion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VX-659/TEZ/IVA | Experimental | Participants who received VX-659 120 milligram (mg)/TEZ 50 mg/ IVA 75 mg as fixed-dose combination (FDC) in the morning and IVA 75 mg as a mono tablet in the evening in the triple combination (TC) treatment period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VX-659/TEZ/IVA | Drug | VX-659/TEZ/IVA FDC tablet. |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Concentration (Cmax) of VX-659, TEZ, and IVA | Day 1 and Day 15 | |
| Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVA | Day 8 and Day 15 | |
| Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVA | Day 1 and Day 15 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | Day 1 and Day 15 | |
| Observed Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | Day 8 and Day 15 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Other protocol defined Inclusion/Exclusion criteria may apply.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Colorado | Aurora | Colorado | 80045 | United States | ||
| Ann & Robert Lurie Children's Hospital of Chicago |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37983082 | Derived | Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4. | |
| 33331662 | Derived |
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This study was conducted in participants with cystic fibrosis (CF) 6-11 years of age. The study was terminated before start of Part B at Sponsor's discretion.
A total of 18 participants were enrolled in this study. Two participants were enrolled but were not dosed in triple combination (TC) treatment period. Therefore, results are reported for 16 participants.
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| ID | Title | Description |
|---|---|---|
| FG000 | VX-659/TEZ/IVA | Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | VX-659/TEZ/IVA | Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Concentration (Cmax) of VX-659, TEZ, and IVA | Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug and for whom the primary PK data were considered to be sufficient and interpretable. Here "Number analyzed" signifies those subjects who were evaluable at the specified timepoint. | Posted | Mean | Standard Deviation | microgram per milliliter (mcg/mL) | Day 1 and Day 15 |
|
|
From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | VX-659/TEZ/IVA | Participants who received VX-659 120 mg/TEZ 50 mg/ IVA 75 mg as FDC in the morning and IVA 75 mg as a mono tablet in the evening for 15 days in the TC treatment period. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | Meddra 21.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
The study was terminated before start of Part B due to sponsor discretion.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Monitor | Vertex Pharmaceuticals Incorporated | +1 617 341 6777 | medicalinfo@vrtx.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 14, 2018 | Dec 11, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 13, 2018 | Dec 11, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C545203 | ivacaftor |
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| IVA | Drug | IVA mono tablet. |
|
|
| Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | Day 1 and Day 15 |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks) |
| Chicago |
| Illinois |
| 60611 |
| United States |
| The Children's Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| Clinical Research of Charlotte | Charlotte | North Carolina | 28277 | United States |
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| Texas Children's Hospital | Houston | Texas | 77030 | United States |
| Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Participants |
|
|
| Primary | Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVA | PK set. Here "Number analyzed" signifies those participants who were evaluable at specified timepoints. | Posted | Mean | Standard Deviation | mcg/mL | Day 8 and Day 15 |
|
|
|
| Primary | Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVA | PK set. Here "Number analyzed" signifies those participants who were evaluable at specified timepoints. | Posted | Mean | Standard Deviation | hour*mcg/mL (h*mcg/mL) | Day 1 and Day 15 |
|
|
|
| Secondary | Maximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | PK set. Here "Number analyzed" signifies those subjects who were evaluable at the specified timepoint. | Posted | Mean | Standard Deviation | mcg/mL | Day 1 and Day 15 |
|
|
|
| Secondary | Observed Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | PK set. Here "Number analyzed" signifies those participants who were evaluable at specified timepoints. | Posted | Mean | Standard Deviation | mcg/mL | Day 8 and Day 15 |
|
|
|
| Secondary | Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | PK set. Here "Number analyzed" signifies those participants who were evaluable at specified timepoints. | Posted | Mean | Standard Deviation | h*mcg/mL | Day 1 and Day 15 |
|
|
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Safety set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks) |
|
|
|
| 0 |
| 16 |
| 1 |
| 16 |
| 13 |
| 16 |
| Post-tussive vomiting | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Procedural anxiety | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Bacterial test positive | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Human rhinovirus test positive | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Prothrombin time prolonged | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Pulmonary function test decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Respirovirus test positive | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Nasal discharge discolouration | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Paranasal sinus hypersecretion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Rash vesicular | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
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| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| Title | Measurements |
|---|---|
|
| TEZ: Day 8 |
|
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| TEZ: Day 15 |
|
|
| IVA: Day 8 |
|
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| IVA: Day 15 |
|
|
|
| TEZ: Day 1 |
|
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| TEZ: Day 15 |
|
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| IVA: Day 1 |
|
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| IVA: Day 15 |
|
|
|
| M1-IVA: Day 1 |
|
|
| M1-IVA: Day 15 |
|
|
|
| M1-IVA: Day 8 |
|
|
| M1-IVA: Day 15 |
|
|
|
| M1-IVA: Day 1 |
|
|
| M1-IVA: Day 15 |
|
|