PK Study of N91115 in Cystic Fibrosis Patients

Nivalis Therapeutics, Inc.6 enrolled

Overview

This Phase 1 study in F508del-CFTR homozygous CF patients is being conducted to assess the pharmacokinetics and absorption dynamics of N91115 compared with healthy subjects in order to identify an initial starting dose for Phase 2 trials.

This is an open-label pharmacokinetic (PK) study of twice daily doses of 50 mg of N91115 administered for 14 days in F508del-CFTR homozygous CF patients. Six patients are planned for enrollment. Each patient will undergo screening (Day 28 to Day 3) and, if eligible, will return to the clinical site on Day 1 or optionally on Day 1. Eligibility will be reconfirmed and the patient will be admitted to a clinical research unit (CRU). Patients will stay overnight from Day 1 to Day 2 and will be discharged on Day 2 after all procedures and assessments are completed. Patients will return to the CRU as outpatients on Days 4, 7, 11, 14, and 15 for PK sample collection and other assessments. They will receive an oral dose of investigational medicinal product (IMP), N91115, twice daily on Days 1 through 14 and will be followed for PK through Day 15. Telephone calls to assess safety and ensure compliance with dosing will be made on days that patients do not make clinic visits (Days 3, 5, 6, 8, 9, 10, 12, and 13). Follow-up safety calls will then be made on Day 21 (adverse events) and Day 28 (serious adverse events only). Participation of an individual patient may last approximately 56 days from the time of screening until the end-of-study (Day 28) follow-up call.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cystic Fibrosis

Interventions

N91115DRUG

S nitrosoglutathione reductase inhibitor

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Confirmed diagnosis of CF, homozygous for the F508del-CFTR mutation 2. Weight ≥ 40 kg at screening 3. FEV1 ≥ 40% of predicted normal for age, gender, and height (Hankinson standards) pre or post-bronchodilator value, at screening 4. Hematology, clinical chemistry, and urinalysis results with no clinically significant abnormalities that would interfere with the study assessments at screening Exclusion Criteria: 1. History of any illness or condition that in the opinion of the investigator could confound the results of the study or pose additional risk when administered IMP 2. Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment or hospitalizations within 4 weeks of Study Day 1 3. 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 4. History, including the screening assessment, of ventricular tachycardia or ventricular arrhythmias 5. History, including the screening assessment, of prolonged QT and/or QTcF (Fridericia's correction) interval (\> 450 msec) 6. History of solid organ or hematological transplantation 7. History of alcohol abuse or drug addiction (including cannabis, cocaine, and opioids) in the year prior to screening 8. Use of continuous (24 hr/day) or nocturnal supplemental oxygen

Locations (3)

University of Alabama @ Birmingham

Birmingham, Alabama, United States

Children's CO

Aurora, Colorado, United States

National Jewish Health

Denver, Colorado, United States

Outcomes

Primary Outcomes

Pharmacokinetics

To assess the pharmacokinetics of N91115 after twice daily (q 12 h) doses given for 14 days by measuring plasma and urine concentrations of N91115 and its primary metabolite.

Time frame: 14 Days

Secondary Outcomes

Safety of dosing twice per day over 14 days

To assess the safety of 14 twice daily (q 12 h) doses of N91115 in F508del-CFTR homozygous CF patients by monitoring, 12 lead ECG, Adverse events, Clinical safety laboratory tests (hematology, clinical chemistry, and urinalysis), Concomitant medications, Abbreviated physical examinations, Hemoglobin oxygen saturation (O2 Sat) by pulse oximetry, Spirometry, Telemetry, Vital signs, Weight

Time frame: 14 Days

Data from ClinicalTrials.gov

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