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Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (SNO-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
N30 Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01746784
First received: December 6, 2012
Last updated: November 21, 2014
Last verified: November 2014
  Purpose

The purpose of this study is to investigate the safety, tolerability and pharmacokinetics of N6022, and to obtain descriptive information on the effect of N6022 on biomarkers of CFTR function and inflammation in adult cystic fibrosis subjects who are homozygous for the F508del-CFTR mutation.


Condition Intervention Phase
Cystic Fibrosis
Drug: N6022
Drug: Normal saline
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study of N6022 to Evaluate Safety and Pharmacokinetics in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (SNO1)

Resource links provided by NLM:


Further study details as provided by N30 Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Safety and Tolerability [ Time Frame: Over 7 treatment days and 7 days of follow-up ] [ Designated as safety issue: Yes ]
    Assessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events.


Secondary Outcome Measures:
  • Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Change from baseline at Day 7 ] [ Designated as safety issue: No ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson standards were used to calculate percent predicted FEV1 (for age, sex, and height).

  • Change in Biomarkers of CFTR Function [ Time Frame: Change from baseline at Day 7 ] [ Designated as safety issue: No ]
    Sweat chloride millequivalents/Liter (mEq/L)


Enrollment: 66
Study Start Date: February 2014
Study Completion Date: May 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: N6022
Subjects randomized to study drug will receive N6022 by intravenous infusion once per day for 7 days
Drug: N6022
Intravenous solution of N6022 in normal saline administered by infusion pump over 1-8 minutes depending on the dose
Other Name: GSNORi
Placebo Comparator: Normal saline
Subjects randomized to placebo will receive normal saline administered intravenously using the same volume as the active drug group
Drug: Normal saline
Intravenous solution of 0.9% (weight/volume) NaCl administered by infusion pump over 1-8 minutes depending on dose of active drug used in same cohort
Other Name: Placebo

Detailed Description:

This is a double-blind, randomized, placebo-controlled, multicenter, sequential dose-escalation study which will occur in two parts. All selection criteria, assessments and procedures described in this protocol will be applied to both parts. Up to 5 cohorts will be studied with a total of 67 patients at approximately 18 clinical sites in the United States.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Homozygous for F508del-CFTR gene
  • Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis
  • Body weight ≥ 40 kg
  • FEV1 ≥ 40% predicted
  • Oxygen saturation ≥ 90% breathing ambient air
  • Hematology and clinical chemistry of blood and urine results with no clinically significant abnormalities that would interfere with the study assessments
  • Negative pregnancy test for women of child bearing potential
  • Sexually active subjects of child bearing potential willing to follow contraception requirements

Exclusion Criteria:

  • Previous enrollment in another cohort for this study.
  • Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment within 4 weeks of Study Day 1.
  • Any change in chronic therapies for CF lung disease 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 three or more of the following: AST, ALT, GGT, ALP, total bilirubin at screening.
  • History of abnormal renal function (creatinine clearance < 50 mL/min using Cockcroft-Gault equation) within a year at screening.
  • History, including the screening assessment, of ventricular tachycardia or other ventricular arrhythmias.
  • History, including the screening assessment, of prolonged QT and/or QTcF interval (> 450 msec).
  • History of solid organ or hematological transplantation.
  • Intranasal medication changes within 14 days prior to Study Day 1
  • Required Use of continuous (24 hr/d) or nocturnal supplemental oxygen.
  • Concomitant use of any inhibitors or inducers of CYP3A4.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01746784

Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294
United States, Alaska
Providence Alaska Medical Center
Anchorage, Alaska, United States, 99508
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
National Jewish Health
Denver, Colorado, United States, 80206
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Iowa
University of Iowa Children's Hospital
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
Rainbow Babies and Children's Hospital - Case Medical Center
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
Sponsors and Collaborators
N30 Pharmaceuticals, Inc.
Investigators
Principal Investigator: Scott Donaldson, MD University of North Carolina, Chapel Hill
  More Information

Additional Information:
No publications provided

Responsible Party: N30 Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01746784     History of Changes
Other Study ID Numbers: N6022-1CF1-04
Study First Received: December 6, 2012
Results First Received: November 17, 2014
Last Updated: November 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by N30 Pharmaceuticals, Inc.:
Cystic Fibrosis
F508del-CFTR
N6022
S-Nitrosoglutathione

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on November 25, 2014