PK Study of N91115 in Cystic Fibrosis Patients (SNO3)

Nivalis Therapeutics

Status and phase: Completed; Phase 1

Conditions: Cystic Fibrosis

Treatments: Drug: N91115

Study type: Interventional

Funder types: Industry

Identifiers

NCT02227888

N91115-1PK-02

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

N91115

Experimental group

Description:

Every 12 hour oral dosing of 50 mg N91115 for 14 days

Treatment:

Drug: N91115