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
Visão geral do estudo
Descrição detalhada
Study procedures, frequency and timing are provided in the attached study schema. Adverse events and concomitant medication will be monitored throughout the study from informed consent signing until end of study participation. A Data Monitoring Committee (DMC) will also review unblinded safety data on a monthly basis throughout the study. Limitations on bronchodilators for pulmonary assessments prior to study drug dosing are described below except in emergent situations.
- Short acting β-agonists and anticholinergics will be held for at least 4 hours
- Long acting β-agonists dosed twice daily will be held for at least 12 hours
- Long acting β-agonists dosed once daily and long acting anticholinergics will be held for at least 24 hours
Screening (Day -28 to Day -3):
Patients will sign the informed consent and undergo procedures to determine eligibility including pregnancy testing, demographic information, medical history, and genotype by historical confirmation or blood sample confirmation (as applicable), height and weight, 12-Lead electrocardiogram (ECG), 48-hour Holter monitoring, chemistry, hematology, full physical examination, sweat chloride, smoking and alcohol history, spirometry, sputum microbiology, urinalysis and vital signs.
Day 1 Predose (Day -2 to -1) Patients will return to the clinic to reconfirm eligibility and assess any changes in medical history and pregnancy status. An abbreviated physical examination focusing on cardiovascular, pulmonary and gastrointestinal systems plus an assessment of weight will be conducted. The following will be obtained: 12-lead ECG, abbreviated physical exam, blood for DNA (optional), blood for leukocyte messenger ribonucleic acid (mRNA), blood inflammatory biomarkers, cystic fibrosis questionnaire-revised (CFQ-R), O2 Sat, patient global impression of change (PGIC), safety labs, serum pharmacokinetics (PK), spirometry, sputum microbiology, sweat chloride (SC) (if more than 2 weeks since the screening value was obtained), and vital signs. Sites may choose to perform any of these assessments on Day -2, Day -1 or Day 1 predose except for serum PK that starts Day 1 predose and vital signs that are done Day 1 predose.
Dosing and Food Intake:
Patients will take their dose of study drug every 12 hours at approximately the same time each morning and night. There are no restrictions related to food intake.
Dosing Days 1 and 2:
On Day 1, patients will be observed for at least 4 hours following the first dose of study drug. Patients return to the clinical site on Day 2 for a predose PK sample that is 24 hours after their first dose. Patients will be observed for at least 2 hours after the second dose on Day 2.
Days 3-28:
Patients self-administer study drug at approximately the same time each morning and evening with the exception that the morning doses on clinic Days 7, 14, 21 and 28, which will be administered and witnessed in the clinic.
Day 7 (Dosing in Clinic):
On Day 7, patients will return to the clinic to monitor any changes in health status and for an abbreviated physical exam, 12-Lead ECG, O2 Sat, safety labs, PK, spirometry, study drug compliance, SC and vital signs.
Day 14 (Dosing in Clinic):
On Day 14, patients will return to the clinic to monitor any changes in health status and for an abbreviated physical exam, urine pregnancy, 12-lead ECG, blood inflammatory biomarkers, CFQ-R, O2 Sat, safety labs, PK, spirometry, study drug compliance, SC and vital signs.
Day 21 (Dosing in Clinic):
On Day 21, patients will return to the clinic to monitor any changes in health status and for an abbreviated physical exam, 12-Lead ECG, O2 Sat, safety labs, PK, spirometry, study drug compliance, SC and vital signs.
Day 28 (Dosing in Clinic):
On Day 28 patients will return to the clinic to monitor any changes in health status and for an abbreviated physical exam, 12-Lead ECG, blood for DNA (optional), blood for leukocyte mRNA, blood inflammatory biomarkers, CFQ-R, urine pregnancy, O2 Sat, PGIC, safety labs, PK, spirometry, sputum microbiology, study drug compliance, SC, weight, and vital signs.
Day 42 (Final study day 2 weeks after last dose):
On Day 42 (± 2 days) study follow-up assessments include: abbreviated physical exam, blood inflammatory biomarkers, O2 Sat, PGIC, spirometry, SC, weight, and vital signs.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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Alabama
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Birmingham, Alabama, Estados Unidos, 35294
- University of Alabama @ Birmingham
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California
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Palo Alto, California, Estados Unidos, 94304
- Stanford University
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- Children's CO
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Denver, Colorado, Estados Unidos, 80206
- National Jewish Health
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Illinois
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Chicago, Illinois, Estados Unidos, 60611
- Northwestern University
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Indiana
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Indianapolis, Indiana, Estados Unidos, 46202
- Indiana University
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Iowa
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Iowa City, Iowa, Estados Unidos, 52242
- University of Iowa Children's Hospital
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Maryland
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Baltimore, Maryland, Estados Unidos, 21287
- Johns Hopkins Hospital
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Boston Children's Hospital
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55455
- University of Minnesota
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Missouri
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St. Louis, Missouri, Estados Unidos, 63110
- Washington University
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New York
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New York, New York, Estados Unidos, 10032
- Columbia University
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New York, New York, Estados Unidos, 10032
- The New York Presbyterian Hospital, Columbia University Medical Center
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North Carolina
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Chapel Hill, North Carolina, Estados Unidos, 27599
- University of North Carolina
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45229
- Cincinnati Children's Hospital
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Cleveland, Ohio, Estados Unidos, 44106
- Rainbow Babies and Children's Hospital - Case Medical Center
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Columbus, Ohio, Estados Unidos, 43205
- Nationwide Children's Hospital
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- Children's Hospital of Philadelphia
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Washington
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Seattle, Washington, Estados Unidos, 98105
- Seattle Children's Hospital
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Group 1 - 50 mg
Every 12 hour oral dosing of N91115 for 28 days
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S Nitrosoglutathione Reductase Inhibitor
Outros nomes:
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Experimental: Group 2 - 100 mg
Every 12 hour oral dosing of N91115 for 28 days
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S Nitrosoglutathione Reductase Inhibitor
Outros nomes:
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Experimental: Group 3 - 200 mg
Every 12 hour oral dosing of N91115 for 28 days
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S Nitrosoglutathione Reductase Inhibitor
Outros nomes:
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Comparador de Placebo: Group 4 - Placebo
Every 12 hour oral dosing of placebo comparator for 28 days
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S Nitrosoglutathione Reductase Inhibitor
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
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Safety assessments based on clinical evaluations, laboratory assessments, and adverse events.
Prazo: 28 Days
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28 Days
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Pharmacokinetic (PK) parameters of N91115 and its glucuronide metabolite in plasma
Prazo: 28 Days
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Area under the curve(AUC) assessments
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28 Days
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Pharmacokinetic (PK) parameters of N91115 and its glucuronide metabolite in plasma
Prazo: 28 Days
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Maximum plasma concentration (Cmax) determinations
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28 Days
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Pharmacokinetic (PK) parameters of N91115 and its glucuronide metabolite in plasma
Prazo: 28 Days
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Ratio of parent:glucuronide metabolite
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28 Days
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Colaboradores e Investigadores
Patrocinador
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- N91115-1CF-03
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