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 Code: PTI-428
Pharmaceutical Form: Capsule, hard
Current Sponsor code: PTI-428
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of th
Sponsors
Proteostasis Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General study inclusion criteria: 1. Adult males or females age 18 years and older 2. Confirmed diagnosis of CF, defined as: - A sweat chloride value =60 mmol/L by quantitative pilocarpine iontophoresis and Clinical findings consistent with CF such as chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities. (OR) - 2 CF-causing mutations (all as documented in the subject’s medical record) and Clinical findings consistent with CF such as chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities. 3. FEV1 between 40-90% predicted 4. Pulse Oximetry > 92% at rest 5. Body mass index (BMI) =17 kg/m2 6. Subjects of child-bearing potential and who are sexually active must meet the study contraception requirements. 7. Non-smoker and non-tobacco user for a minimum of 30 days prior to screening and for the duration of the study. 8. Subject understands the full nature and purpose of the study, including possible risks and side effects, and is willing and able to comply with all compulsory study procedures and provides informed consent/permission prior to any study procedures being performed. Stable ORKAMBI® Combination Cohort - Stable on ORKAMBI® dosing for both label indication and per label dosing for a minimum of three months at the time of randomization ORKAMBI® Naïve Combination Cohort - Eligible to take ORKAMBI® in accordance with the label. Stable KALYDECO® Combination Cohort - Stable on KALYDECO® dosing for both label indication and per label dosing for a minimum of three months at the time of randomization. PTI-428 Monotherapy Cohort - Pancreatic sufficiency as defined by lack of need for digestive enzymatic supplementation for at least 3 months and historical (within past year) or screening fecal elastase = 200 mcg/g stool. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 132 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. History or current evidence of any clinically significant cardiac, endocrinologic, hematologic, hepatobiliary, immunologic, metabolic, urologic, pulmonary (besides CF), neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the Investigator. 2. History of prolonged QT/QTc interval with Fridericia’s correction QTcF > 450 msec at screening. 3. Abnormal liver function as defined by: a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) or bilirubin > 3 x upper limit of the normal range. 4. Abnormal renal function at screening defined as: a. Creatinine clearance 120 kg at screening. 12. History of cancer within the past five years (excluding cervical CIS with curative therapy for at least one year prior to screening and non-melanoma skin cancer). 13. History of organ transplantation. 14. History of alcohol or drug abuse or dependence within 12 months of screening as determined by the Investigator. 15. Positive urine screen for prohibited drugs (cocaine, cannabinoids, nicotine [urine cotinine is the detection mechanism for nicotine], opiates, barbiturates, amphetamines, and benzodiazepines) or positive alcohol testing at screening. 16. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCVAb) at screening. 17. Any sinopulmonary infection or CF exacerbation requiring a change or addition of medication (including antibiotics) within 1 month of Study Day 1 or any other clinically significant infection as determined by the investigator within 1 month of Day 1. 18. Known or suspected hypersensitivity or idiosyncratic reaction to study medication or any components thereof. 19. Has donated blood within 3 months of screening or plans to donate blood within 3 months of study completion. 20. Pregnant or nursing women. 21. Any conditions that, in the opinion of the Investigator, would make the subject unsuitable for enrollment or could interfere with the subject’s participation in or completion of the study. 21. Institutionalised because of a legal or regulatory order. 22. Subjects who are employees of the sponsor. 23. Relatives of, or staff directly reporting to, the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PART A SAD Cohorts: · Evaluate the safety and tolerability of a single dose of PTI-428 MAD Cohorts: Stable ORKAMBI® Cohort: · Evaluate the safety and tolerability of multiple doses of PTI-428 in combination with ORKAMBI PTI-428 Monotherapy Cohorts: · Evaluate the safety and tolerability of multiple daily doses of PTI-428 PART B/C: Stable ORKAMBI Cohorts: · Evaluate the safety and tolerability of multiple doses of PTI-428 in combination with ORKAMBI ORKAMBI Naïve Cohort: · Evaluate the safety and tolerability of multiple doses of PTI-428 in combination with ORKAMBI in subjects eligible for ORKAMBI Stable KALYDECO® Cohort: · Evaluate the safety and tolerability of multiple doses of PTI-428 in combination with KALYDECO in subjects on stable KALYDECO PTI-428 Monotherapy Cohort: · Evaluate the safety and tolerability of multiple doses of PTI-428 in adult CF subjects with pancreatic sufficiency not taking either ORKAMBI or KALYDECO ;Secondary Objective: Part A SAD: · Evaluate the PK profile of a single dose of PTI-428 MAD: · Evaluate PK profile of multiple once daily doses of PTI-428 (monotherapy) over time Part A and B Stable ORKAMBI Cohorts: · Evaluate the PK profile of once daily doses of PTI-428 in combination with ORKAMBI over time · Evaluate the PK profile of twice daily doses of ORKAMBI in combination with PTI-428 over time Part C: ORKAMBI Naive or Stable KALYDECO · Evaluate PK profile of once daily doses of PTI-428 in combination with ORKAMBI or KALYDECO over time. · Evaluate PK profile of twice daily doses of ORKAMBI or KALYDECO in combination with PTI-428 PTI-428 Monotherapy Cohort: · Evaluate PK profile of once daily doses of PTI-428 over time All Cohorts in Parts B and C: · Evaluate pulmonary function through FEV1 over time · Evaluate the treatment effect in sweat chloride over time · Evaluate change in weight over time ;Primary end point(s): Safety and Tolerability;Timepoint(s) of evaluation of this end point: Part A SAD: Measured by n | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A SAD: - PK - For plasma PTI-428: PK parameters including, but may not be limited to, t1/2, Tmax, Cmax and AUCt as appropriate MAD: Stable ORKAMBI Cohort: o PK o For plasma PTI-428: PK parameters including, but may not be limited to, t1/2, Tmax, Cmax and AUCt as appropriate o For plasma ORKAMBI (ivacaftor and lumacaftor): PK parameters including, but may not be limited to, t1/2, Tmax, Cmax, and AUCt as appropriate PTI-428 Monotherapy Cohorts: o PK o For plasma PTI-428: PK parameters including, but may not be limited to, t1/2, Tmax, Cmax and AUCt as appropriate Part B Stable ORKAMBI Cohorts: o PK: o For plasma PTI-428: PK parameters including, but may not be limited to, t1/2, Tmax, Cmax and AUCt as appropriate o For plasma ORKAMBI (ivacaftor and lumacaftor): PK parameters including, but may not be limited to, t1/2, Tmax, Cmax,AUCt as appropriate • Change in FEV1 over time • Change in sweat chloride over time • Change in weight over time Part C ORKAMBI Naïve Cohort: PK: o For plasma PTI-428: PK parameters including but may not be limited to t1/2, Tmax, Cmax, AUCt as appropriate. o For plasma ORKAMBI (ivacaftor and lumacaftor): PK parameters including but may not be limited to t1/2, Tmax, Cmax, AUCt as appropriate. • Change in FEV1 over time • Change in sweat chloride over time • Change in weight over time Stable KALYDECO Cohort: PK: o For plasma PTI-428: PK parameters including but may not be limited to t1/2, Tmax, Cmax, AUCt as appropriate. o For plasma KALYDECO: PK parameters including but may not be limited to t1/2, Tmax, Cmax, AUCt as appropriate. • Change in FEV1 over time • Change in sweat chloride over time • Change in weight over time PTI-428 Monotherapy Cohort: o PK: o For plasma PTI-428: PK parameters including but may not be limited to t1/2, Tmax, Cmax, AUCt as appropriate. • Change in FEV1 over time • Change in sweat chloride over time • Change in weight over time ;Timepoint(s) of evaluation of this end point | — |
Countries
Canada, Czech Republic, Denmark, France, Germany, Italy, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Proteostasis Therapeutics
Outcome results
None listed