Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation
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| ClinicalTrials.gov Identifier: NCT01225211 |
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Recruitment Status :
Completed
First Posted : October 20, 2010
Results First Posted : October 5, 2015
Last Update Posted : October 5, 2015
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Sponsor:
Vertex Pharmaceuticals Incorporated
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
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Brief Summary:
The purpose of this study is to evaluate of the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of lumacaftor (VX-809) alone and when coadministered with ivacaftor (VX-770) in participants with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cystic Fibrosis | Drug: Lumacaftor Drug: Ivacaftor Drug: Lumacaftor Placebo Drug: Ivacaftor Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 312 participants |
| Allocation: | Randomized |
| Intervention Model: | Factorial Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2, Multicenter, Double-Blinded, Placebo-Controlled, Multiple-Dose Study to Evaluate Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Lumacaftor Monotherapy, and Lumacaftor and Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation |
| Study Start Date : | October 2010 |
| Actual Primary Completion Date : | April 2014 |
| Actual Study Completion Date : | April 2014 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Cystic fibrosis
MedlinePlus related topics:
Cystic Fibrosis
Drug Information available for:
Ivacaftor
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: Cohort 1: Placebo
Participants homozygous (HO) for the F508del-CF transmembrane conductance regulator gene (CFTR) mutation received lumacaftor matched placebo once daily (qd) (Day 1 through Day 14), followed by lumacaftor matched placebo qd in combination with ivacaftor matched placebo every 12 hours (q12h) (Day 15 through Day 21).
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Drug: Lumacaftor Placebo
Matching placebo tablet. Drug: Ivacaftor Placebo Matching placebo tablet. |
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Experimental: Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h
Participants homozygous for the F508del-CFTR mutation received 200 milligram (mg) of lumacaftor (LUM) qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor (IVA) q12h (Day 15 through Day 21).
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Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM Drug: Ivacaftor Tablet.
Other Name: VX-770, IVA |
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Experimental: Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h
Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21).
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Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM Drug: Ivacaftor Tablet.
Other Name: VX-770, IVA |
|
Placebo Comparator: Cohort 2 and 3: Placebo (HO and HE)
Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).
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Drug: Lumacaftor Placebo
Matching placebo tablet. Drug: Ivacaftor Placebo Matching placebo tablet. |
|
Experimental: Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO)
Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
|
Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM Drug: Ivacaftor Tablet.
Other Name: VX-770, IVA |
|
Experimental: Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO)
Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
|
Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM Drug: Ivacaftor Tablet.
Other Name: VX-770, IVA |
|
Experimental: Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE)
Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
|
Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM Drug: Ivacaftor Tablet.
Other Name: VX-770, IVA |
|
Experimental: Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO)
Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
|
Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM Drug: Ivacaftor Tablet.
Other Name: VX-770, IVA |
|
Placebo Comparator: Cohort 4: Placebo
Participants heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 1 through Day 56).
|
Drug: Lumacaftor Placebo
Matching placebo tablet. Drug: Ivacaftor Placebo Matching placebo tablet. |
|
Experimental: Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
|
Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM Drug: Ivacaftor Tablet.
Other Name: VX-770, IVA |
Primary Outcome Measures :
- Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) [ Time Frame: Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21) ]AE: any untoward medical occurrence in a participant during study; irrespective of relationship with treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent. AE includes serious AEs (SAEs) as well as Non-SAEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. AE that started at/after initial dosing of study drug, or increased in severity after initial dosing of study drug is considered treatment-emergent. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 14) and combination therapy period (Period 2: Day 15 to Day 21).
- Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) [ Time Frame: Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56) ]Detailed description is provided in Outcome Measure 1. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 28) and combination therapy period (Period 2: Day 29 to Day 56).
- Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs [ Time Frame: Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56) ]AEs and SAEs are defined in Outcome Measure 1.
- Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21 [ Time Frame: Cohort 1: Day 14, Day 21 ]
- Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56 [ Time Frame: Cohort 2 and 3: Day 28, Day 56 ]
- Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56 [ Time Frame: Cohort 4: Baseline, Day 56 ]FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Hankinson method.
Secondary Outcome Measures :
- Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14 [ Time Frame: Cohort 1: Baseline, Day 14 ]
- Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14 [ Time Frame: Cohort 2: Baseline, Day 14 ]
- Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56 [ Time Frame: Cohort 4: Baseline, Day 56 ]
- Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21 [ Time Frame: Cohort 1: Day 14, Day 21 ]FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
- Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21 [ Time Frame: Cohort 1: Day 14, Day 21 ]FEV1 and ppFEV1 are defined in Outcome Measure 6.
- Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56 [ Time Frame: Cohort 2 and 3: Day 28, Day 56 ]FEV1 and ppFEV1 are defined in Outcome Measure 6.
- Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56 [ Time Frame: Cohort 2 and 3: Day 28, Day 56 ]FEV1 and ppFEV1 are defined in Outcome Measure 6.
- Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 [ Time Frame: Cohort 2 and 3: Baseline, Day 28 and 56 ]FEV1 and ppFEV1 are defined in Outcome Measure 6.
- Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 [ Time Frame: Cohort 2 and 3: Baseline, Day 28 and 56 ]FEV1 and ppFEV1 are defined in Outcome Measure 6.
- Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56 [ Time Frame: Cohort 4: Baseline, Day 56 ]FEV1 and ppFEV1 are defined in Outcome Measure 6.
- Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56 [ Time Frame: Cohort 2 and 3: Day 28, Day 56 ]The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
- Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56 [ Time Frame: Cohort 4: Baseline, Day 56 ]CFQ-R respiratory domain is defined in Outcome Measure 17.
- Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56 [ Time Frame: Cohort 4: Baseline, Day 56 ]BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).
- Cohort 4: Absolute Change From Baseline in Weight at Day 56 [ Time Frame: Cohort 4: Baseline, Day 56 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Male or female participants with confirmed diagnosis of CF
- Must have the F508del-CFTR mutation on at least 1 allele.
- FEV1 greater than equal (>=) 40% of predicted normal for age, gender, and height (Knudson standards)(Cohort 1, 2, and 3); FEV1 40-90% of predicted normal for age, gender, and height (Hankinson standards (Cohort 4)
- Participant of child-bearing potential and who are sexually active must meet the contraception requirements
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 (e.g., cirrhosis with portal hypertension).
- An acute illness including acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 14 days (Cohort 1, 2, and 3) or 28 days (Cohort 4) before receiving the first dose of study drug.
- History of solid organ or hematological transplantation.
- History of alcohol abuse or drug addiction in the past year, including cannabis, cocaine, and opiates.
- Ongoing participation in another therapeutic clinical study, or prior participation in an investigational drug study without appropriate washout
- Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception
- Participants enrolled in Cohort 1 or Cohort 2 will not be eligible for Cohort 3
- Ongoing or prior participation in an investigational drug study within 30 days of the Screening Visit
- Heterozygous participants who participated in Cohort 2 and meet the eligibility criteria for Cohort 4 may participate in Cohort 4
- Evidence of lens opacity or cataract as determined by the ophthalmologic examination (Cohort 4 only)
Information from the National Library of Medicine
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): NCT01225211
Locations
Show 56 study locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Vertex Pharmaceuticals Incorporated |
| ClinicalTrials.gov Identifier: | NCT01225211 |
| Other Study ID Numbers: |
VX09-809-102 2010-020413-90 ( EudraCT Number ) |
| First Posted: | October 20, 2010 Key Record Dates |
| Results First Posted: | October 5, 2015 |
| Last Update Posted: | October 5, 2015 |
| Last Verified: | September 2015 |
Additional relevant MeSH terms:
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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 |