A Phase 2, Multicenter, Double Blinded, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 Monotherapy and VX-661/Ivacaftor Cotherapy in Subjects with Cystic Fibrosis, Homozygous or Heterozygous for the F508del CFTR Mutatio

Phase 1

Conditions: Cystic Fibrosis
MedDRA version: 16.0Level: PTClassification code 10011762Term: Cystic fibrosisSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: EUCTR2011-003821-93-DE

Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 220

Inclusion Criteria

-For Groups 1 through 8: Male or female with confirmed diagnosis of CF, defined as:
a sweat chloride value 60 mmol/L by quantitative pilocarpine iontophoresis
OR 2 CF-causing mutations (all as documented in the subject’s medical record)
AND
chronic sinopulmonary disease
OR gastrointestinal/nutritional abnormalities.
-For Groups 1 through 6: homozygous subjects must have the F508del-CFTR mutation in both alleles.
- For Group 7: heterozygous subjects must have the F508del-CFTR mutation on 1 allele, and the second CFTR allele must encode a mutation predicted to result in the gating mutation G551D in the CFTR gene. The CFTR mutations for Group 7 must be confirmed before randomization after reviewing the report provided by the central laboratory.
-For group 8: heterozygous subjects must have the F508del-CFTR
mutation on 1 allele, and a copy of a CFTR mutation associated with
residual CFTR function or defective mRNA splicing on the other allele.
The CFTR mutations for Group 8 must be confirmed before
randomization after reviewing the report provided by the central
laboratory AND
Subjects must have clinical evidence of residual CFTR function based on
any 1 of the following:
- Fecal elastase-1 >200 µg/g stool at screening
- Sweat chloride =80 mmol/L at screening
- =12 years of age at the time of diagnosis
The following inclusion criteria are applicable to Groups 1 through 8.
-FEV1 40% to 90% (inclusive) of predicted normal for age, gender, and height (Knudson standards ) at screening.
-If sexually active, male subjects who can father a child and female subjects of child bearing potential must meet the contraception requirements.
- For Groups 1 through 6 and Group 8: Eighteen years of age or older and able to read, understand, sign, and date a written informed consent form (ICF) before study participation at screening
OR
For Group 7: Twelve of age or older on the date of signed ICF, and where appropriate, date of assent.
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 215
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-History of any illness 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 subject.
-An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Study Day 1.
-Pregnant, breast-feeding, or not willing to follow contraception requirements.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: -To evaluate the safety and tolerability of VX-661 monotherapy and VX-661/VX-770 cotherapy<br>-To evaluate the effect of VX-661 monotherapy and VX-661/VX-770 cotherapy on CFTR function<br>;Secondary Objective: -To evaluate the efficacy of VX-661 monotherapy and VX-661/VX-770 cotherapy <br>-To evaluate the PK of VX-661 monotherapy<br>-To assess the PK of VX-661 and VX-770 when the 2 drugs are administered together<br>;Primary end point(s): -Safety as determined by adverse events, clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis), standard digital ECGs, and vital signs<br>-Change in sweat chloride from baseline through Study Day 28 <br>;Timepoint(s) of evaluation of this end point: 28 Days

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -Change in sweat chloride from baseline to each visit up to Study Day 28 <br>-Change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline to each visit and from baseline through Study Day 28 <br>-Change in FEV1 (L) from baseline to each visit and from baseline through Study Day 28 <br>-Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score from baseline to each visit up to Study Day 28 <br>-PK parameters of VX-661,VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together<br>;Timepoint(s) of evaluation of this end point: 28 Days

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