cystic fibrosis MedDRA version: 9.1 Level: LLT Classification code 10011762 Term: Cystic fibrosis
Conditions
Interventions
Product Name: VX-770
Product Code: VX-770, VRT-813077
Pharmaceutical Form: Tablet
INN or Proposed INN: NA
Current Sponsor code: VX-770
Other descriptive name: VRT-813077
Concentration unit: mg milligr
Sponsors
Vertex Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female with confirmed diagnosis of cystic fibrosis, and must be accompanied by either chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities and a positive sweat chloride value greater or equal to 60 mmol/L [by quantitative pilocarpine iontophoresis] or a sweat sodium greater or equal to 60 mmol/L on at least 1 occasion. 2. In Part 1, must have the G551D mutation in at least 1 allele (any known or unknown mutations allowed in second allele with the exception of R117H or 2789 + 5G-->A, mutation) or, in Part 2, must have the G551D, R117H, or 2789 + 5G-->A mutation in at least 1 allele (any known or unknown mutations allowed in the second allele). The CF mutations must be appropriately documented in the medical record. 3. Age 18 years or older. 4. Weight 40 kg. 5. Negative pregnancy test (for women of childbearing potential). 6. Forced expiratory volume in 1 second being 40% of predicted normal for age, gender, and height (Hankinson standards): prebronchodilator value. 7. Oxygen saturation (pulse oximetry) ³92% on room air. 8. Hematology and clinical chemistry of blood and urine results with no clinically significant abnormalities that would interfere with the study assessments (as judged by the medical investigator). 9. Able to understand and comply with protocol requirements, restrictions and instructions and likely to complete the study as planned. 10. Willing to use at least 1 effective method of birth control (excluding hormonal contraceptives) during the study and for 90 days after the last dose of study drug. 11. Willing to remain on a stable medication regimen for the duration of study participation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of any illness that, in the opinion of the investigator or the subject’ s general practitioner, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include but is not limited to a history of cirrhosis; a history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; history or presence of clinically significant pathology; or history of mental illness. 2. Ongoing acute illness including acute respiratory or lower respiratory infections. Subjects should not have a pulmonary exacerbation (see Section 23 of protocol for definition) or changes in therapy for pulmonary disease within 14 days before the first dose of study drug. 3. Pregnant, planning a pregnancy, or breast-feeding. 4. Hemoglobin 450 msec). 9. History of solid organ or hematological transplantation. 10. History of alcohol abuse or drug addiction (including cannabis, cocaine and opiates) during the past year. 11. Ongoing participation in another therapeutic clinical trial, or prior participation in an investigational drug study without appropriate washout (washout period should be discussed with the Vertex medical monitor on a case-by-case basis, but in no instance shall it be <5 half-lives of the previous investigational study drug). 12. Illness within 14 days before receiving the first dose of study drug (“illness” is defined as a recent non-serious, non-acute condition, e.g., common cold). 13. Intranasal medication changes within 14 days prior to start of dosing (including corticosteroids, cromolyn, phenylephrine, etc). 14. Change of treatment with systemic antibiotics within 14 days prior to study drug dosing. 15. Required use of continuous (24 hr/d) supplemental oxygen by nasal cannula. 16. Concomitant use of any inhibitors or inducers of CYP3A4 including: acetazolamide, azole antifungals, clarithromycin, dalfopristin, diltiazem, erythromycin, fluoxetine, fluvoxamine, grapefruit juice, itraconazole, ketoconazole, voriconazole, loratadine, nefazadone, niacinamide, nicotinamide, propoxyphene, quinine, quinupristin, troleandomycin, valproate, verapamil, zileuton, felbamate, methsuximide, theophylline, and St. John’ s Wort. 17. Not able to have Nasal potential differences performed due to physical or other constraints.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Evaluate the safety and tolerability of multiple dose administrations of orally administered VX-770 given to cystic fibrosis (CF) subjects with genotype G551D.;Secondary Objective: - Examine biomarkers of CFTR activity following multiple dose administrations of orally administered VX-770 given to CF subjects with genotype G551D. - Investigate the pharmacokinetics (PK) of VX-770, following multiple dose administrations of orally administered VX-770 given to CF subjects with genotype G551D. - To select a dose of VX-770 for further study.;Primary end point(s): Primary endpoint: Safety and tolerability assessments based on clinical evaluations, laboratory assessments, and adverse events during administration of VX-770 for 14 or 28 days. Secondary endpoint: Nasal Potential Difference (NPD) Sweat Chloride Forced expiratory volume in 1 second VX-770 pharmacokinetic parameters | — |
Countries
Germany
Outcome results
None listed