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: Sodium (R)-8-methyl-2-(3-methylbenzofuran-2-yl)-5-(1-(tetrahydro-2H-pyran-4-yl)ethoxy)quinoline-4-ca
Product Code: PTI-801
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: None
CA
Sponsors
Proteostasis Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 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 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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Part 1 (in US only): Primary safety endpoints for Healthy Volunteer SAD and MAD are: - Clinical laboratory tests: hematology, chemistry, urinalysis, and coagulation - 12-lead electrocardiograms (ECGs) - Physical examinations - Vital signs - Adverse events (AEs) Primary PK endpoints for Healthy Volunteer SAD and MAD are: - For plasma PTI-808: Parameters include, but not limited to, apparent terminal half-life (t1/2), time to reach maximum plasma concentration (Tmax), maximum plasma concentration (Cmax), AUC(0-24), AUC from time 0 to time of last measurable concentration (AUC0-last), AUC from time 0 to infinity (AUC0-inf), percentage of AUC(0-inf) due to extrapolation from time of last measurable concentration to infinity (AUC%extrap), apparent total clearance (CL/F), apparent volume of distribution (V/F), and terminal elimination rate constant (?z) using non compartmental methods as appropriate - For urine PTI-808 (Healthy Volunteer MAD only): Parameters include, but are not limited to, cumulative amount of PTI-808 excreted unchanged in urine (Ae) and renal clearance (CLR) as appropriate Primary PK endpoints for Healthy Volunteer Food Effect are: - For plasma PT-808 with fasting and after a high fat, high calorie meal: parameters include, but not limited to, t1/2, Tmax, Cmax, AUC(0-24), AUC(0-last), AUC(0-inf), AUC(%extrap), CL/F, V/F, and ?z, using noncompartmental methods, as appropriate Part 2 (in US only): Safety and tolerability endpoints are : - Clinical laboratory tests (hematology, serum chemistry, urinalysis, and coagulation), 12-lead ECGs, physical exams, vital signs, and AEs Part 3 (in EU, US and Canada) Primary safety and tolerability endpoints are: - Clinical laboratory tests (hematology, serum chemistry, urinalysis, and coagulation) 12-lead ECGs, physical exams, vital signs, and AEs Part 4 (in EU, US and Canada) Primary safety and tolerability endpoints are: - Clinical laboratory tests (hematology, serum chemistry, urinalysis, | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 (US only): The secondary safety endpoints for HV Food Effect are: - Clinical laboratory tests: hematology, chemistry, urinalysis, and coagulation - 12-lead ECGs - Physical exams - Vital signs - AEs The Pharmacodynamic endpoint for HV SAD, HV MAD and HV Food Effect is: - Holter monitoring Part 2 (in US only): Endpoints to evaluate PK of PTI-808, PTI-801, and PTI-428 in plasma include, but are not limited to: - T1/2, Tmax, Cmax, AUC(0-last), and AUC(0-inf) using noncompartmental methods, as appropriate Exploratory endpoint: - Change in nasal epithelial mRNA and protein expression Part 3 (in EU, US and Canada) Secondary endpoints are: - For plasma PTI-808, PTI-801, and PTI-428: PK parameters including, but not limited to Tmax, Cmax, and AUC(0-last), as appropriate - Change in FEV1 over time Exploratory endpoints are: - Change in sweat chloride concentrations over time - Change in weight and BMI over time - Change in blood glucose over time - Change in nasal epithelial mRNA and protein expression Part 4 (in EU, US and Canada) Secondary endpoints are: - For plasma PTI-808, PTI-801, and PTI-428: PK parameters including, but not limited to Tmax, Cmax, and AUC(0-last), as appropriate - Change in FEV1 over time - Change in sweat chloride concentrations over time Exploratory endpoints are: Weight, BMI, blood glucose, Cystic Fibrosis Questionnaire-Revised (CFQR) respiratory domain, and nasal epithelial mRNA and protein expression ;Timepoint(s) of evaluation of this end point: Part 1: - HV SAD (see Table 15-1 of the protocol) - HV MAD (see Table 15-2 of the protocol) - HV Food Effect (see Table 15-3 of the protocol) Part 2: - HV Co-Administration (see Table 15-4 of the protocol) Part 3: - CF MAD Co-Administration (see Table 15-5 of the protocol) Part 4: - CF Cohorts (see Table 15-6 of the protocol). - Evaluation timepoints are: - For plasma PTI-808, PTI-801, and PTI-428: PK parameters: day 1, 2, 7, 14, 21, 28, 29 - FEV1 and sweat chlorid | — |
Countries
Belgium, Canada, Denmark, France, Germany, United Kingdom, United States
Contacts
Public ContactWalter Fuerst
SFL Regulatory Services GmbH
Outcome results
None listed