A study to investigate the safety and the movement of the study drug VX-121 around the body in healthy people and patients with cystic fibrosis
- Conditions
- Cystic fibrosisMedDRA version: 20.0Level: PTClassification code 10011762Term: Cystic fibrosisSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2018-000126-55-NL
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 115
Parts A, B and C
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 (male subjects and female subjects of non childbearing potential) will be between the ages of 18 and 55 years, inclusive, and healthy, as defined by no clinically relevant abnormalities identified by a detailed medical history, full physical examination (PE), including blood pressure and pulse rate measurement, standard 12 lead ECG, and clinical laboratory tests.
4.Female subjects must have a negative serum pregnancy test at the Screening Visit.
5.Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight >50 kg.
Part D
1.Subject will sign and date an ICF.
2.Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
3.Subjects (male subjects and female subjects of non childbearing potential) aged 18 years or older on the date of informed consent.
4.Female subjects must have a negative serum pregnancy test at the Screening Visit.
5.Body weight =35 kg.
6.Subjects must be able to produce a valid (quantity-sufficient) sweat sample at screening. If the sweat volume at screening is insufficient, then the sweat collection may be repeated once.
7.Confirmed diagnosis of CF as determined by the investigator.
8.Subjects must be heterozygous for F508del with a second CFTR allele carrying a mutation that is not responsive to TEZ, IVA, or TEZ/IVA therapy. If the screening CFTR genotype result is not received before the Run in Period or randomization, as applicable, a previous CFTR genotype laboratory report may be used to establish eligibility. Subjects who have been enrolled and whose screening genotype does not confirm study eligibility must be discontinued from the study (Section 9.9).
9.Subjects must have a forced expiratory volume in 1 second (FEV1) =40% and =90% of predicted normal for age, sex, and height (equations of the Global Lung Function Initiative [GLI])8 at the Screening Visit. Spirometry measurements must meet American Thoracic Society/European Respiratory Society criteria9 for acceptability and repeatability.
10.Stable CF disease as judged by the investigator.
11.Willing to remain on a stable CF treatment regimen (other than protocol specified changes in CFTR modulator regimen) through the Safety Follow up Visit.
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 120
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Parts A, B and C
1. History of any illness or any clinical condition 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.
2. History of febrile illness or other acute illness within 5 days before the first study drug dose.
3. Any condition possibly affecting drug absorption
4. Standard 12 lead ECG demonstrating QTcF >450 msec at screening. If QTcF exceeds 450 msec, the ECG will be repeated 2 more times, and the average of the 3 QTcF values will be used to determine the subject’s eligibility.
5. Blood donation (of approximately 1 pint [500 mL] or more) within 56 days before the first study drug dose or have had any significant loss of blood as determined by the investigator within 60 days before first study drug dose.
6. Use of restricted substances, activities, or devices within the specified duration before the first study drug dose
7. A screen positive for alcohol or drug substances
8. A screen positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) 1 or 2 antibodies.
9. For Part A (Cohorts A3 and A9): a known or suspected lactose intolerance or milk allergy.
10. Subject, or close relative of the subject, is the investigator or a subinvestigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study at that site.
Part D
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 and other ventricular arrhythmias, 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. Abnormal laboratory values at screening, as defined in Section 8.2.2 of the protocol.
5. An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for sinopulmonary disease within 28 days before the first dose of TEZ/IVA in the Run in Period (Day 28) or the first dose of study drug in the Treatment Period, as applicable.
6. Lung infection with organisms associated with a more rapid decline in pulmonary status (e.g., Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus).
7. An acute illness not related to CF (e.g., gastroenteritis) within 14 days before the first dose of TEZ/IVA in the Run in Period (Day 28) or the first dose of study drug in the Treatment Period, as applicable.
8. Standard 12-lead ECG demonstrating QTcF >450 msec at screening. If QTcF exceeds 450 msec, the ECG will be repeated 2 more times, and the average of the 3 QTcF values will be used to determine the subject’s eligibility.
9. History of solid organ or hematological transplantation.
10. History of alcohol or drug abuse in the past year, including, but not limited to, cannabis, cocaine, and opiates, as deemed by the
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method