Study Assessing the Safety, Tolerability and Pharmacokinetics of PTI-808 in Healthy Adult Subjects and in Adults 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] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2017-003319-21-DE
- Lead Sponsor
- Proteostasis Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 240
Study part 1 (in US only): A list of inclusion criteria for part 1 of the Study is available in the clinical study protocol number PTI-808-01 version 6.6; dated 07 August 2019 (section 3.4.1).
Study part 2 (in US only): A list of inclusion criteria for part 2 of the Study is available in the clinical study protocol number PTI-808-01 version 6.6; dated 07 August 2019 (section 4.4.1).
Study part 3 (in EU, US and Canada):
Inclusion criteria are: A list of inclusion criteria for part 3 of the Study is available in the clinical study protocol number PTI-808-01 version 6.6; dated 07 August 2019 (section 5.4.1).
Study part 4 (in EU, US and Canada):
Inclusion criteria are:
1. Understands the full nature and purpose of the study, including possible risks and side effects, is willing and able to comply with all compulsory study procedures, and provides written informed consent/permission prior to any study procedures being performed
2. Adult male or female, =18 years of age, at the time of informed consent
3. Confirmed diagnosis of CF as follows:
a. For homozygous subjects: Confirmed diagnosis of CF with the F508del CFTR homozygous genotype on record, along with clinical findings consistent with CF, such as, chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities. The medical monitor's approval is not required for homozygous 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. For subjects with a sweat chloride value <60 mmol/L at screening and no documented historical value of =60 mmol/L, medical monitor approval is required based on documented evidence of chronic sinopulmonary disease manifested by at least 1 of the following:
- Persistent colonization/infection with typical CF pathogens, including but not limited to, Staphylococcus aureus, Haemophilus influenzae, and/or Pseudomonas aeruginosa
- Chronic cough and sputum production
- Persistent chest radiograph abnormalities (eg, bronchiectasis, atelectasis, infiltrates, hyperinflation)
- Nasal polyps, chronic sinusitis, or radiographic or computed tomographic abnormalities of the paranasal sinuses
b. For heterozygous subjects: Confirmed diagnosis of CF with only one copy of the F508del CFTR mutation on record, along with clinical findings consistent with CF, such as, chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities;
AND
a sweat chloride value of =60 mmol/L based on quantitative pilocarpine iontophoresis (as documented in the subject's medical record or as confirmed at the screening visit)
4. Subject must be able to produce a valid sweat sample (quantitysufficient; ie, >15 µL) at the screening visit. If the sweat volume is insufficient then the sweat chloride collection may be repeated once with approval from the medical monitor.
5. Clinically stable CF disease in the opinion of the investigator with no significant changes in health status within 14 days prior to Day 1
6. FEV1 40% to 90%, predicted, inclusive (subjects with FEV1 <40% or >90% predicted at Day -1 must be reviewed with the medical monitor to ensure subject meets criteria to continue in the study)
7. Pulse oximetry >92% at rest
8. BMI =16 and <30 kg/m2
9. Subjects of childbearing potential must meet contraception requirements (Section 8.24.2)
10. Non-smoker and non-tobacco user for a minimum of 30 days prior to screening, and agrees not to smoke or use tobacco for the duration of the study
Are
Study part 1 (in US only): A list of exclusion criteria for part 1 of the Study is available in the clinical study protocol number PTI-808-01 version 6.6; dated 07 August 2019 (section 3.4.2).
Study part 2 (in US only): A list of exclusion criteria for part 2 of the Study is available in the clinical study protocol number PTI-808-01 version 6.6; dated 07 August 2019 (section 4.4.2).
Study part 3 (in EU, US and Canada): A list of exclusion criteria for part 3 of the Study is available in the clinical study protocol number PTI-808-01 version 6.6; dated 07 August 2019 (section 5.4.2).
Study part 4 (in EU, US and Canada):
Exclusion criteria are:
1. History or current evidence of any clinically significant cardiac (eg, heart failure, left ventricular hypertrophy, myocardial infarction, and arrhythmia), endocrinologic, hematologic, hepatobiliary (eg, clinically significant cirrhosis with or without portal hypertension), immunologic, metabolic, urologic, pulmonary (besides CF), neurologic (eg, subarachnoid hemorrhage, intracranial hemorrhage, cerebrovascular accident, intracranial trauma, and autonomic neuropathy), dermatologic, psychiatric, renal, or other major disease, that is unstable or could interfere with the subject's participation in or completion of the study, in the opinion of the investigator (eg, subjects with CFRD can participate in the study if the CFRD is well controlled using a stable medication
regimen)
2. Clinically significant screening results that would exclude subject from the study (eg, medical histories, physical exams, ECGs, vital signs, pulse oximetry, laboratory profiles) or any conditions that, would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study, in the opinion of the investigator. The medical monitor must be contacted for review of any subjects with screening results or conditions that may make them unsuitable for enrollment or could interfere with participation in or completion of the study.
3. Prolonged QTcF >450 msec at screening
4. Abnormal liver function as defined by AST, ALT, gamma-glutamyl transferase (GGT), or alkaline phosphatase =3 times or total bilirubin =2 times upper limit of the normal range
5. Hemoglobin <10 g/dL
6. Platelet count <150,000 cells/mm3
7. Abnormal renal function at screening defined as creatinine clearance <60 mL/min using the Modified Diet in Renal Disease (MDRD)
8. Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically significant infection or illness (in the opinion of the investigator) requiring an increase or addition of medication, such as antibiotics or corticosteroids, within 28 days of Day 1
9. Lung infection with organisms associated with a more rapid decline in pulmonary status (eg, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus). For subjects who have had a history of a positive culture in the past, the investigator will apply the following criteria to establish whether the subject is free of infection with such organisms:
- The subject has had 2 respiratory tract cultures negative for these organisms within the 12 months before the screening visit, with no subsequent positive cultures.
- These 2 respiratory tract cultures were separated by at least 3 months, and 1 of them was obtained within 6 months before the screening visit.
10. Subject is currently taking or has taken a CFTR modulator within 14 days prior to the screening visit
11. Pa
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