Study of N91115 in Patients With Cystic Fibrosis Homozygous F508del-CFTR Mutation
SNO4
A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Parallel, Group Study of N91115 to Evaluate Safety and Pharmacokinetics in Patients With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation
1 other identifier
interventional
51
1 country
19
Brief Summary
This Phase 1b study in F508del-CFTR homozygous CF patients is being conducted to assess the safety of N91115 as the sole cystic fibrosis transmembrane conductance regulator (CFTR) modulator at doses near the expected therapeutic exposure level in preparation for Phase 2 studies of N91115 added to the CFTR modulator combination lumacaftor/ivacaftor when launched.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2015
Shorter than P25 for phase_1
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 14, 2014
CompletedFirst Posted
Study publicly available on registry
October 27, 2014
CompletedStudy Start
First participant enrolled
February 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2015
CompletedNovember 7, 2016
November 1, 2016
5 months
October 14, 2014
November 3, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Safety assessments based on clinical evaluations, laboratory assessments, and adverse events.
28 Days
Secondary Outcomes (3)
Pharmacokinetic (PK) parameters of N91115 and its glucuronide metabolite in plasma
28 Days
Pharmacokinetic (PK) parameters of N91115 and its glucuronide metabolite in plasma
28 Days
Pharmacokinetic (PK) parameters of N91115 and its glucuronide metabolite in plasma
28 Days
Study Arms (4)
Group 1 - 50 mg
EXPERIMENTALEvery 12 hour oral dosing of N91115 for 28 days
Group 2 - 100 mg
EXPERIMENTALEvery 12 hour oral dosing of N91115 for 28 days
Group 3 - 200 mg
EXPERIMENTALEvery 12 hour oral dosing of N91115 for 28 days
Group 4 - Placebo
PLACEBO COMPARATOREvery 12 hour oral dosing of placebo comparator for 28 days
Interventions
S Nitrosoglutathione Reductase Inhibitor
Eligibility Criteria
You may qualify if:
- Male or female, age ≥ 18 years with confirmed diagnosis of CF, homozygous for the F508del-CFTR mutation based on historical results generated by Ambry Genetics within the past two years or if unavailable, confirmed by testing done within the past 28 days
- Sweat chloride ≥ 60 (milliequivalents) mEq/L, by quantitative pilocarpine iontophoresis test (QPIT) at screening
- Weight ≥ 40 kg at screening
- Forced expiratory volume (FEV1) ≥ 40% of predicted normal for age, gender, and height (Hankinson standards) pre- or post-bronchodilator value, at screening
- Oxygen saturation by pulse oximetry ≥ 90% breathing ambient air, at screening
- Hematology, clinical chemistry and urinalysis results with no clinically significant abnormalities that would interfere with the study assessments at screening
You may not qualify if:
- Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment or hospitalization within 2 weeks of Study Day 1
- Any change in chronic therapies for CF lung disease (e.g., Ibuprofen, Pulmozyme®, hypertonic saline, Azithromycin, Tobi®, Cayston®) within 4 weeks of Study Day 1
- Blood hemoglobin \< 10 g/dL at screening
- Serum albumin \< 2.5 g/dL at screening
- Abnormal liver function defined as ≥ 3 x upper limit of normal (ULN) in 3 or more of the following: aspartate aminotransferase (AST), alanine aminotransferase (ALT), g-glutamyl transferase (GGT), alkaline phosphatase (ALP), or total bilirubin at screening
- History of abnormal renal function (creatinine clearance \< 50 mL/min using Cockcroft-Gault equation) within a year of screening
- History, including the screening assessment, of ventricular tachycardia or other ventricular arrhythmias
- History, including the screening assessment, of prolonged cardiac QT interval and/or QTcF (QT with Fridericia's correction) interval (\> 450 msec)
- History of solid organ or hematological transplantation
- History of alcohol abuse or drug abuse (including cannabis, cocaine, and opioids) in the year prior to screening
- Use of continuous (24 hr/day) or nocturnal supplemental oxygen
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (19)
University of Alabama @ Birmingham
Birmingham, Alabama, 35294, United States
Stanford University
Palo Alto, California, 94304, United States
Children's CO
Aurora, Colorado, 80045, United States
National Jewish Health
Denver, Colorado, 80206, United States
Northwestern University
Chicago, Illinois, 60611, United States
Indiana University
Indianapolis, Indiana, 46202, United States
University of Iowa Children's Hospital
Iowa City, Iowa, 52242, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21287, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Washington University
St Louis, Missouri, 63110, United States
Columbia University
New York, New York, 10032, United States
The New York Presbyterian Hospital, Columbia University Medical Center
New York, New York, 10032, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229, United States
Rainbow Babies and Children's Hospital - Case Medical Center
Cleveland, Ohio, 44106, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Related Publications (1)
Donaldson SH, Solomon GM, Zeitlin PL, Flume PA, Casey A, McCoy K, Zemanick ET, Mandagere A, Troha JM, Shoemaker SA, Chmiel JF, Taylor-Cousar JL. Pharmacokinetics and safety of cavosonstat (N91115) in healthy and cystic fibrosis adults homozygous for F508DEL-CFTR. J Cyst Fibros. 2017 May;16(3):371-379. doi: 10.1016/j.jcf.2017.01.009. Epub 2017 Feb 13.
PMID: 28209466DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Scott Donaldson, MD
University of North Carolina
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 14, 2014
First Posted
October 27, 2014
Study Start
February 1, 2015
Primary Completion
July 1, 2015
Study Completion
July 1, 2015
Last Updated
November 7, 2016
Record last verified: 2016-11