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Study of N91115 in Patients With Cystic Fibrosis Homozygous F508del-CFTR Mutation (SNO4)

3 novembre 2016 aggiornato da: Nivalis Therapeutics, Inc.

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

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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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 di studio

Interventistico

Iscrizione (Effettivo)

51

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • Alabama
      • Birmingham, Alabama, Stati Uniti, 35294
        • University of Alabama @ Birmingham
    • California
      • Palo Alto, California, Stati Uniti, 94304
        • Stanford University
    • Colorado
      • Aurora, Colorado, Stati Uniti, 80045
        • Children's CO
      • Denver, Colorado, Stati Uniti, 80206
        • National Jewish Health
    • Illinois
      • Chicago, Illinois, Stati Uniti, 60611
        • Northwestern University
    • Indiana
      • Indianapolis, Indiana, Stati Uniti, 46202
        • Indiana University
    • Iowa
      • Iowa City, Iowa, Stati Uniti, 52242
        • University of Iowa Children's Hospital
    • Maryland
      • Baltimore, Maryland, Stati Uniti, 21287
        • Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, Stati Uniti, 02115
        • Boston Children's Hospital
    • Minnesota
      • Minneapolis, Minnesota, Stati Uniti, 55455
        • University of Minnesota
    • Missouri
      • St. Louis, Missouri, Stati Uniti, 63110
        • Washington University
    • New York
      • New York, New York, Stati Uniti, 10032
        • Columbia University
      • New York, New York, Stati Uniti, 10032
        • The New York Presbyterian Hospital, Columbia University Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, Stati Uniti, 27599
        • University of North Carolina
    • Ohio
      • Cincinnati, Ohio, Stati Uniti, 45229
        • Cincinnati Children's Hospital
      • Cleveland, Ohio, Stati Uniti, 44106
        • Rainbow Babies and Children's Hospital - Case Medical Center
      • Columbus, Ohio, Stati Uniti, 43205
        • Nationwide Children's Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, Stati Uniti, 19104
        • Children's Hospital of Philadelphia
    • Washington
      • Seattle, Washington, Stati Uniti, 98105
        • Seattle Children's Hospital

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 80 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  1. 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
  2. Sweat chloride ≥ 60 (milliequivalents) mEq/L, by quantitative pilocarpine iontophoresis test (QPIT) at screening
  3. Weight ≥ 40 kg at screening
  4. Forced expiratory volume (FEV1) ≥ 40% of predicted normal for age, gender, and height (Hankinson standards) pre- or post-bronchodilator value, at screening
  5. Oxygen saturation by pulse oximetry ≥ 90% breathing ambient air, at screening
  6. Hematology, clinical chemistry and urinalysis results with no clinically significant abnormalities that would interfere with the study assessments at screening

Exclusion Criteria:

  1. 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
  2. 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
  3. Blood hemoglobin < 10 g/dL at screening
  4. Serum albumin < 2.5 g/dL at screening
  5. 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
  6. History of abnormal renal function (creatinine clearance < 50 mL/min using Cockcroft-Gault equation) within a year of screening
  7. History, including the screening assessment, of ventricular tachycardia or other ventricular arrhythmias
  8. History, including the screening assessment, of prolonged cardiac QT interval and/or QTcF (QT with Fridericia's correction) interval (> 450 msec)
  9. History of solid organ or hematological transplantation
  10. History of alcohol abuse or drug abuse (including cannabis, cocaine, and opioids) in the year prior to screening
  11. Use of continuous (24 hr/day) or nocturnal supplemental oxygen

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Group 1 - 50 mg
Every 12 hour oral dosing of N91115 for 28 days
Droga: N91115
S Nitrosoglutathione Reductase Inhibitor
Altri nomi:
  • Cavosonstat
Sperimentale: Group 2 - 100 mg
Every 12 hour oral dosing of N91115 for 28 days
Droga: N91115
S Nitrosoglutathione Reductase Inhibitor
Altri nomi:
  • Cavosonstat
Sperimentale: Group 3 - 200 mg
Every 12 hour oral dosing of N91115 for 28 days
Droga: N91115
S Nitrosoglutathione Reductase Inhibitor
Altri nomi:
  • Cavosonstat
Comparatore placebo: Group 4 - Placebo
Every 12 hour oral dosing of placebo comparator for 28 days
Droga: N91115
S Nitrosoglutathione Reductase Inhibitor
Altri nomi:
  • Cavosonstat

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Lasso di tempo
Safety assessments based on clinical evaluations, laboratory assessments, and adverse events.
Lasso di tempo: 28 Days
28 Days

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Pharmacokinetic (PK) parameters of N91115 and its glucuronide metabolite in plasma
Lasso di tempo: 28 Days
Area under the curve(AUC) assessments
28 Days
Pharmacokinetic (PK) parameters of N91115 and its glucuronide metabolite in plasma
Lasso di tempo: 28 Days
Maximum plasma concentration (Cmax) determinations
28 Days
Pharmacokinetic (PK) parameters of N91115 and its glucuronide metabolite in plasma
Lasso di tempo: 28 Days
Ratio of parent:glucuronide metabolite
28 Days

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Nivalis Therapeutics, Inc.

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 febbraio 2015

Completamento primario (Effettivo)

1 luglio 2015

Completamento dello studio (Effettivo)

1 luglio 2015

Date di iscrizione allo studio

Primo inviato

14 ottobre 2014

Primo inviato che soddisfa i criteri di controllo qualità

23 ottobre 2014

Primo Inserito (Stima)

27 ottobre 2014

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

6 novembre 2016

Ultimo aggiornamento inviato che soddisfa i criteri QC

3 novembre 2016

Ultimo verificato

1 novembre 2016

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • N91115-1CF-03

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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