Study of Ivacaftor in Cystic Fibrosis Subjects 2 Through 5 Years of Age With a CFTR Gating Mutation
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01705145 |
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Recruitment Status :
Completed
First Posted : October 12, 2012
Results First Posted : April 24, 2015
Last Update Posted : April 5, 2016
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The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD), of ivacaftor in children with cystic fibrosis (CF) who are 2 through 5 years of age and have a CF Transmembrane Conductance Regulator (CFTR) gating mutation in at least 1 allele.
Part A is designed to evaluate the safety and PK of multiple-dose administration of ivacaftor in participants 2 through 5 years of age and to confirm the doses for Part B. Part B is designed to evaluate the safety, PK, PD, and efficacy of ivacaftor in participants 2 through 5 years of age.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cystic Fibrosis | Drug: Ivacaftor | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 35 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, 2-Part, Open-Label Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are 2 Through 5 Years of Age and Have a CFTR Gating Mutation |
| Study Start Date : | January 2013 |
| Actual Primary Completion Date : | March 2014 |
| Actual Study Completion Date : | March 2014 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Ivacaftor
Part A: Ivacaftor 50 milligram (mg) (for participants weighing less than [<] 14 kilograms [kg]) or 75 mg (for participants weighing greater than or equal to [>=] 14 kg) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.. Part B: Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. |
Drug: Ivacaftor
Other Names:
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- Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs [ Time Frame: Part A: Up to 93 Days ]
AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.
Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.
- Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs [ Time Frame: Part B: Up to 28 Weeks ]
AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.
Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.
- Part A: Plasma Concentration of Ivacaftor and Its Metabolites [ Time Frame: Part A: up to 24 hours post-dose on Day 4 ]Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor [M1] and ivacaftor carboxylate [M6]) up to 24 hours post-dose on Day 4 (Hour 0 [pre-dose] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.
- Part B: Plasma Concentration of Ivacaftor and Its Metabolites [ Time Frame: Part B: up to 24 hours post-dose on Day 168 ]Plasma concentration was reported for ivacaftor and its metabolites (M1 and M6) up to 24 hours post-dose on Day 168 (Hour 0 [predose] on Day 1, 14, 56, 112, and 168; 2, 3, 6 hours post-dose on Day 14; 1 hour post-dose on Day 56; 4, 6 hours post-dose on Day 112; 24 hours post-dose on Day 168). Data was planned to be reported for overall participants in the period.
- Part B: Absolute Change From Baseline in Sweat Chloride at Week 24 [ Time Frame: Part B: Baseline, Week 24 ]Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Data was reported as per the dose received and for overall participants.
- Part B: Absolute Change From Baseline in Weight at Week 24 [ Time Frame: Part B: Baseline, Week 24 ]Data was reported as per the dose received and for overall participants.
- Part B: Absolute Change From Baseline in Stature at Week 24 [ Time Frame: Part B: Baseline, Week 24 ]Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Data was reported as per the dose received and for overall participants.
- Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 [ Time Frame: Baseline, Week 24 ]BMI = (Weight [in kg]) divided by (Stature [in meters])^2. Data was reported as per the dose received and for overall participants.
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| Ages Eligible for Study: | 2 Years to 5 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male or female with confirmed diagnosis of CF
- Must have a CFTR gating mutation in at least 1 allele
- Aged 2 through 5 years at screening and Day 1
- Weight >= 8 kg at screening and Day 1
- Hematology, serum chemistry, coagulation, and vital signs results at screening with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator
Exclusion Criteria:
- History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant
- An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks before Day 1
- Abnormal liver function, at screening
- History of solid organ or hematological transplantation
- Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1
- Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives before screening
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01705145
| United States, Alabama | |
| Birmingham, Alabama, United States | |
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| Aurora, Colorado, United States | |
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| Charlottesville, Virginia, United States | |
| Richmond, Virginia, United States | |
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| Seattle, Washington, United States | |
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| Vancouver, Canada | |
| United Kingdom | |
| Edinburgh, United Kingdom | |
| Liverpool, United Kingdom | |
| London, United Kingdom | |
| Principal Investigator: | Margaret Rosenfeld, MD | Seattle Children's Hospital | |
| Principal Investigator: | Jane Davies, MD | Imperial College London |
| Responsible Party: | Vertex Pharmaceuticals Incorporated |
| ClinicalTrials.gov Identifier: | NCT01705145 |
| Other Study ID Numbers: |
VX11-770-108 KIWI |
| First Posted: | October 12, 2012 Key Record Dates |
| Results First Posted: | April 24, 2015 |
| Last Update Posted: | April 5, 2016 |
| Last Verified: | March 2016 |
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Cystic Fibrosis |
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Cystic Fibrosis Fibrosis Pathologic Processes Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases |
Genetic Diseases, Inborn Infant, Newborn, Diseases Ivacaftor Chloride Channel Agonists Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action |