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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01225211




Registration number
NCT01225211
Ethics application status
Date submitted
15/10/2010
Date registered
20/10/2010
Date last updated
5/10/2015

Titles & IDs
Public title
Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation
Scientific 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
Secondary ID [1] 0 0
2010-020413-90
Secondary ID [2] 0 0
VX09-809-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lumacaftor
Treatment: Drugs - Ivacaftor
Treatment: Drugs - Lumacaftor Placebo
Treatment: Drugs - Ivacaftor Placebo

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).


Treatment: Drugs: Lumacaftor
Tablet

Treatment: Drugs: Ivacaftor
Tablet.

Treatment: Drugs: Lumacaftor Placebo
Matching placebo tablet.

Treatment: Drugs: Ivacaftor Placebo
Matching placebo tablet.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohort 1: Safety and Tolerability Based on Adverse Events (AEs)
Timepoint [1] 0 0
Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21)
Primary outcome [2] 0 0
Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs)
Timepoint [2] 0 0
Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56)
Primary outcome [3] 0 0
Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs
Timepoint [3] 0 0
Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)
Primary outcome [4] 0 0
Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21
Timepoint [4] 0 0
Cohort 1: Day 14, Day 21
Primary outcome [5] 0 0
Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56
Timepoint [5] 0 0
Cohort 2 and 3: Day 28, Day 56
Primary outcome [6] 0 0
Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56
Timepoint [6] 0 0
Cohort 4: Baseline, Day 56
Secondary outcome [1] 0 0
Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14
Timepoint [1] 0 0
Cohort 1: Baseline, Day 14
Secondary outcome [2] 0 0
Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14
Timepoint [2] 0 0
Cohort 2: Baseline, Day 14
Secondary outcome [3] 0 0
Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56
Timepoint [3] 0 0
Cohort 4: Baseline, Day 56
Secondary outcome [4] 0 0
Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21
Timepoint [4] 0 0
Cohort 1: Day 14, Day 21
Secondary outcome [5] 0 0
Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21
Timepoint [5] 0 0
Cohort 1: Day 14, Day 21
Secondary outcome [6] 0 0
Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56
Timepoint [6] 0 0
Cohort 2 and 3: Day 28, Day 56
Secondary outcome [7] 0 0
Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56
Timepoint [7] 0 0
Cohort 2 and 3: Day 28, Day 56
Secondary outcome [8] 0 0
Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56
Timepoint [8] 0 0
Cohort 2 and 3: Baseline, Day 28 and 56
Secondary outcome [9] 0 0
Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56
Timepoint [9] 0 0
Cohort 2 and 3: Baseline, Day 28 and 56
Secondary outcome [10] 0 0
Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56
Timepoint [10] 0 0
Cohort 4: Baseline, Day 56
Secondary outcome [11] 0 0
Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56
Timepoint [11] 0 0
Cohort 2 and 3: Day 28, Day 56
Secondary outcome [12] 0 0
Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56
Timepoint [12] 0 0
Cohort 4: Baseline, Day 56
Secondary outcome [13] 0 0
Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56
Timepoint [13] 0 0
Cohort 4: Baseline, Day 56
Secondary outcome [14] 0 0
Cohort 4: Absolute Change From Baseline in Weight at Day 56
Timepoint [14] 0 0
Cohort 4: Baseline, Day 56

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Factorial
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2014
Sample size
Target
Accrual to date
Final
312
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Brisbane
Recruitment hospital [3] 0 0
- Chermside
Recruitment hospital [4] 0 0
- Nedlands
Recruitment hospital [5] 0 0
- Parkville Victoria
Recruitment hospital [6] 0 0
- Westmead
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Chermside
Recruitment postcode(s) [4] 0 0
- Nedlands
Recruitment postcode(s) [5] 0 0
- Parkville Victoria
Recruitment postcode(s) [6] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Idaho
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Iowa
Country [11] 0 0
United States of America
State/province [11] 0 0
Kansas
Country [12] 0 0
United States of America
State/province [12] 0 0
Kentucky
Country [13] 0 0
United States of America
State/province [13] 0 0
Louisiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Maryland
Country [15] 0 0
United States of America
State/province [15] 0 0
Massachusetts
Country [16] 0 0
United States of America
State/province [16] 0 0
Minnesota
Country [17] 0 0
United States of America
State/province [17] 0 0
Missouri
Country [18] 0 0
United States of America
State/province [18] 0 0
Nebraska
Country [19] 0 0
United States of America
State/province [19] 0 0
New Hampshire
Country [20] 0 0
United States of America
State/province [20] 0 0
New York
Country [21] 0 0
United States of America
State/province [21] 0 0
North Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Ohio
Country [23] 0 0
United States of America
State/province [23] 0 0
Oklahoma
Country [24] 0 0
United States of America
State/province [24] 0 0
Pennsylvania
Country [25] 0 0
United States of America
State/province [25] 0 0
South Carolina
Country [26] 0 0
United States of America
State/province [26] 0 0
South Dakota
Country [27] 0 0
Belgium
State/province [27] 0 0
Leuven
Country [28] 0 0
France
State/province [28] 0 0
Rhone
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
Germany
State/province [30] 0 0
Thueringen
Country [31] 0 0
Germany
State/province [31] 0 0
Berlin
Country [32] 0 0
Germany
State/province [32] 0 0
Bochum
Country [33] 0 0
Germany
State/province [33] 0 0
Essen
Country [34] 0 0
Germany
State/province [34] 0 0
Koeln
Country [35] 0 0
New Zealand
State/province [35] 0 0
Auckland
Country [36] 0 0
New Zealand
State/province [36] 0 0
Christchurch
Country [37] 0 0
United Kingdom
State/province [37] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Vertex Pharmaceuticals Incorporated
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01225211
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01225211