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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-001997-16 | EudraCT Number |
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The purpose of this study was to evaluate the safety of ivacaftor treatment, and PK of ivacaftor and metabolites in participants with cystic fibrosis (CF) who are <24 months of age at treatment initiation and have an ivacaftor-responsive CF transmembrane conductance regulator (CFTR) gene mutation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: 3 to <24 months | Experimental | Participants weighing 5 to less than (<) 7 kilogram (kg) received 25 milligram (mg) IVA, 7 to <14 kg received 50 mg IVA, and those weighing 14 to <25 kg received 75 mg IVA administered every 12 hours (q12h) on Days 1 through 3 and 1 morning dose on Day 4. |
|
| Part B + A/B:1 to < 24 months | Experimental | Participants 4 to <6 months of age and weighing greater than or equal to (≥) 5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to <7 kg received 25 mg IVA, 7 to <14 kg received 50 mg IVA, and those weighing 14 to <25 kg received 75 mg IVA q12h for 24 weeks on Part B. For Part A/B, participants 1 to <4 months weighing 3 kg to <5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IVA | Drug | Granules in sachet for oral administration. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs) | Day 1 through Day 70 | |
| Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Pre-dose, 2-4 hours, 6-8 hours, 24-60 hours post-dose | |
| Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs) | Day 1 through Week 38 | |
| Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Day 4 (pre-dose, 2-4 hours, 6-8 hours post-dose); Day 15 (pre-dose); Week 4 (pre-dose); Week 8 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 12 (pre-dose); Week 18 (pre-dose) and Week 24 (pre-dose) |
| Measure | Description | Time Frame |
|---|---|---|
| Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Week 2 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 8 (pre-dose,1 hour, 4-hour post-dose); Week 24 (pre-dose, 2-4 hours post dose) | |
| Part B + A/B: Absolute Change From Baseline in Sweat Chloride |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol defined Inclusion/Exclusion Criteria may apply.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham | Alabama | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33023304 | Derived | Davies JC, Wainwright CE, Sawicki GS, Higgins MN, Campbell D, Harris C, Panorchan P, Haseltine E, Tian S, Rosenfeld M. Ivacaftor in Infants Aged 4 to <12 Months with Cystic Fibrosis and a Gating Mutation. Results of a Two-Part Phase 3 Clinical Trial. Am J Respir Crit Care Med. 2021 Mar 1;203(5):585-593. doi: 10.1164/rccm.202008-3177OC. | |
| 29886024 |
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This study was conducted in participants with cystic fibrosis (CF) who were less than (<) 24 months of age at Day 1 and have an ivacaftor-responsive CF transmembrane conductance regulator (CFTR) mutation.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: 3 to < 24 Months | Participants weighing 5 to less than (<) 7 kilogram (kg) received 25 milligram (mg) IVA (ivacaftor), 7 to <14 kg received 50 mg IVA, and those weighing 14 to <25 kg received 75 mg IVA administered every 12 hours (q12h) on Days 1 through 3 and 1 morning dose on Day 4. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part A (Up to 5 Days) |
|
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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 | Apr 1, 2021 | Jun 19, 2023 |
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Sweat samples were collected using an approved collection device.
| From Baseline at Week 24 |
| Palo Alto |
| California |
| United States |
| Atlanta | Georgia | United States |
| Chicago | Illinois | United States |
| Indianapolis | Indiana | United States |
| Baltimore | Maryland | United States |
| Boston | Massachusetts | United States |
| Kansas City | Missouri | United States |
| Columbus | Ohio | United States |
| Philadelphia | Pennsylvania | United States |
| Houston | Texas | United States |
| Seattle | Washington | United States |
| Madison | Wisconsin | United States |
| Parkville | Victoria | Australia |
| South Brisbane | Australia |
| Westmead | Australia |
| Toronto | Canada |
| Dublin | Ireland |
| Edinburgh | United Kingdom |
| Leicester | United Kingdom |
| London | United Kingdom |
| Manchester | United Kingdom |
| Oxford | United Kingdom |
| Rosenfeld M, Wainwright CE, Higgins M, Wang LT, McKee C, Campbell D, Tian S, Schneider J, Cunningham S, Davies JC; ARRIVAL study group. Ivacaftor treatment of cystic fibrosis in children aged 12 to <24 months and with a CFTR gating mutation (ARRIVAL): a phase 3 single-arm study. Lancet Respir Med. 2018 Jul;6(7):545-553. doi: 10.1016/S2213-2600(18)30202-9. Epub 2018 Jun 7. |
| Part B + A/B: 1 to < 24 Months |
Participants 4 to <6 months of age and weighing greater than or equal to (≥) 5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to <7 kg received 25 mg IVA, 7 to <14 kg received 50 mg IVA, and those weighing 14 to <25 kg received 75 mg IVA q12h for 24 weeks on Part B. For Part A/B, participants 1 to <4 months weighing 3 kg to <5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age. |
| COMPLETED |
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| NOT COMPLETED |
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| Part B + A/B ( Up to 24 Weeks) |
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All participants who received at least one dose of the study drug during the treatment period were included in the baseline analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | Ivacaftor (IVA) | Part A: Participants weighing 5 to <7 kg received 25 mg IVA, 7 to <14 kg received 50 mg IVA, and those weighing 14 to <25 kg received 75 mg IVA administered q12h on Days 1 through 3 and 1 morning dose on Day 4. Participants 4 to <6 months of age and ≥5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to <7 kg received 25 mg IVA, 7 to <14 kg received 50 mg IVA, and those weighing 14 to <25 kg received 75 mg IVA q12h for 24 weeks on Part B. For Part A/B, participants 1 to <4 months weighing 3 kg to <5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study. | Count of Participants | Participants |
| |||||||||||||||||
| Sex: Female, Male | The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study. | Count of Participants | Participants |
| |||||||||||||||||
| Race/Ethnicity, Customized | The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study. | Count of Participants | Participants |
| |||||||||||||||||
| Race/Ethnicity, Customized | The Baseline data were planned to be presented separately for Part A and for the combined Part B+ A/B. Here, "Number Analyzed" signifies participants who were evaluable for specified part of the study. | Count of Participants | Participants |
|
| 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 | Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs) | Safety set included all participants who received at least 1 dose of study drug in Part A. This outcome measure was planned only for Part A: 3 to <24 months arm. | Posted | Count of Participants | Participants | Day 1 through Day 70 |
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| Primary | Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug in Part A. Here the "Number Analyzed" signifies those participants who were evaluable for the specified time point. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/ml) | Pre-dose, 2-4 hours, 6-8 hours, 24-60 hours post-dose |
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| Primary | Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs) | Safety Set included all participants who received at least 1 dose of study drug. The safety and tolerability analyses were assessed for the overall treatment arm. Therefore, the analysis is reported in a overall Part B+ A/B: 1 to <24 months arm. | Posted | Count of Participants | Participants | Day 1 through Week 38 |
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| Primary | Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | PK set included participants who received at least 1 dose of study drug in Part A/B. Here the "Number Analyzed" signifies those participants who were evaluable for the specified time point. | Posted | Mean | Standard Deviation | ng/ml | Day 4 (pre-dose, 2-4 hours, 6-8 hours post-dose); Day 15 (pre-dose); Week 4 (pre-dose); Week 8 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 12 (pre-dose); Week 18 (pre-dose) and Week 24 (pre-dose) |
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| Secondary | Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) | PK set included participants who received at least 1 dose of study drug in Part B. Here the "Number Analyzed" signifies those participants who were evaluable for the specified time point. | Posted | Mean | Standard Deviation | ng/ml | Week 2 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 8 (pre-dose,1 hour, 4-hour post-dose); Week 24 (pre-dose, 2-4 hours post dose) |
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| Secondary | Part B + A/B: Absolute Change From Baseline in Sweat Chloride | Sweat samples were collected using an approved collection device. | The Full Analysis Set (FAS) included all enrolled participants who were exposed to any amount of study drug in Part B + A/B. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome. | Posted | Mean | Standard Deviation | millimole per liter (mmol/L) | From Baseline at Week 24 |
|
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From Day 1 Through Safety Follow-up Period (up to Day 70 for Part A and up to Week 38 for Part B + A/B)
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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 | Part A: 3 to < 24 Months | Participants weighing 5 to <7 kg received 25 mg IVA, weighing 7 to <14 kg received 50 mg IVA, and participants weighing 14 to < 25 kg received 75 mg IVA q12h on days 1 through day 3 and 1 morning dose on day 4. | 0 | 19 | 1 | 19 | 10 | 19 |
| EG001 | Part B + A/B: 1 to <24 Months | Participants 4 to <6 months of age and ≥5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to <7 kg received 25 mg IVA, 7 to <14 kg received 50 mg IVA, and those weighing 14 to <25 kg received 75 mg IVA q12h for 24 weeks on Part B. For Part A/B, participants 1 to <4 months weighing 3 kg to <5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age. | 0 | 43 | 6 | 43 | 34 | 43 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Distal intestinal obstruction syndrome | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Bronchiolitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Eczema Coxsackium | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Eczema herpeticum | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Respiratory tract infection viral | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Infantile spitting up | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Teething | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 25.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 25.1 | Systematic Assessment |
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| Ear infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Hand-foot-and-mouth disease | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Otitis media | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
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| Head injury | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Pseudomonas test positive | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Sleep disorder | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
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| Miliaria | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
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| Flushing | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Monitor | Vertex Pharmaceuticals Incorporated | 617-341-6777 | medicalinfo@vrtx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 7, 2022 | Jun 19, 2023 | SAP_001.pdf |
| 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 |
|---|---|
| C545203 | ivacaftor |
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| Withdrawal of Consent (not due to adverse event) |
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| 4 to <6 months |
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| 1 to <4 months |
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| Part B+ A/B |
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| Male |
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| Part B + A/B |
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| Not Hispanic or Latino |
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| Not collected per local regulations |
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| Part B + A/B |
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| Black or African American |
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| Asian |
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| American Indian or Alaska Native |
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| Native Hawaiian or Other Pacific Islander |
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| Not collected per local Regulations |
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| Part B + A/B |
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