Cystic fibrosis MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: VX-659
Product Code: VX-659
Pharmaceutical Form: Tablet
INN or Proposed INN: VX-659
Current Sponsor code: VX-659
Other descriptive name: VX-659
Concentration unit: mg milligram(s)
Concen
Sponsors
Vertex Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject will sign and date an informed consent form (ICF). 2. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures. 3. Subjects will be aged 18 years or older on the date of informed consent. 4. Body weight =35 kg. 5. Subjects must be able to produce a valid (quantity-sufficient) sweat sample at screening. If the initial screening collection results in insufficient sweat volume, then the sweat chloride collection may be repeated once, after approval by the medical monitor. -Parts 1 and 3: Subjects must have a sweat chloride value =60 mmol/L at screening or documented in the form of a laboratory report in the subject’s medical record. If the sweat chloride value cannot be determined from the screening test for a reason other than insufficient sweat volume (i.e., because of laboratory error, damaged specimen, or equipment malfunction), it is acceptable to use a sweat chloride value that was obtained before previous treatment with IVA, LUM/IVA, or an investigational CFTR modulator. -Part 2: For subjects with a sweat chloride value =60 mmol/L at screening or documented in the form of a laboratory report in the subject’s medical record, medical monitor approval is not required. For subjects with a sweat chloride value =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of any comorbidity 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. 2. History of clinically significant cirrhosis with or without portal hypertension. 3. Risk factors for Torsade de Pointes, including but not limited to, history of any of the following: familial long QT syndrome, chronic hypokalemia, heart failure, left ventricular hypertrophy, chronic bradycardia, myocardial infarction, cardiomyopathy, history of arrhythmia (ventricular or atrial fibrillation), obesity, acute neurologic events (subarachnoid hemorrhage, intracranial hemorrhage, cerebrovascular accident, or intracranial trauma), or autonomic neuropathy. 4. Current or past history of peptic ulcer disease. 5. History of hemolysis. 6. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, defined as G6PD activity less than the lower limit of normal (LLN) or 70% of the mean of the LLN and the upper limit of normal (ULN), whichever is greater. 7. Any of the following abnormal laboratory values at screening: -Hemoglobin 450 msec at screening. If QTc exceeds 450 msec for the screening ECG, the ECG should be repeated 2 more times during the Screening Period, and the subject will be excluded if the average of the 3 QTc values is >450 msec. Study sites should use QTcF unless they receive approval in advance from the medical monitor to use QTcB 12. History of solid organ or hematological transplantation. 13. History of alcohol or drug of abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator. 14. Ongoing or prior participation in a study of an investigational treatment other than a CFTR modulator within 28 days or 5 terminal half-lives (whichever is longer) before screening. The duration of the elapsed time may be longer if required by local regulations. 15. Use of prohibited medications as defined in Table 9-3, within the specified window before the first dose of study drug. 16. Pregnant or nursing females. Females of childbearing potential must have a negativ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Parts 1 and 2: To evaluate the safety and tolerability of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) Part 3 (optional): To evaluate the safety and tolerability of VX-659 in TC with TEZ and VX-561 (also known as CTP-656, deuterated IVA) All parts: To evaluate the efficacy of VX-659 in TC with TEZ and either IVA or VX-561;Secondary Objective: Parts 1 and 2: To evaluate the pharmacodynamic (PD) effects of VX-659 in TC with TEZ and IVA on CFTR function Part 3 (optional): To evaluate the PD effects of VX-659 in TC with TEZ and VX-561 on CFTR function All parts: • To evaluate the pharmacokinetics (PK) of VX-659 when administered in TC with TEZ and either IVA or VX-561 • To evaluate the PK of TEZ, IVA, VX-561 and their respective metabolites when administered with VX-659 (as applicable);Primary end point(s): • Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values, standard 12 lead ECGs, vital signs, and pulse oximetry • Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) from baseline through the Day 29 Visit ;Timepoint(s) of evaluation of this end point: 1. Screening Visit, Treatment Period, ETT Visit, Safety Follow-up 2. from baseline through the Day 29 Visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Absolute change in sweat chloride concentrations from baseline through the Day 29 Visit •Relative change in ppFEV1 from baseline through the Day 29 Visit •Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ R) respiratory domain score from baseline at the Day 29 Visit •PK parameters of VX 659, TEZ, M1 TEZ, IVA, M1 IVA , and VX-561;Timepoint(s) of evaluation of this end point: 1. from baseline through the Day 29 Visit 2. from baseline through the Day 29 Visit 3. from baseline at the Day 29 Visit 4. Treatment Period, ETT Visit | — |
Countries
Ireland, Israel, United Kingdom, United States
Contacts
Public ContactClinical Trials and Medical Info
Vertex Pharmaceuticals Incorporated
Outcome results
None listed