SNO3: PK Study of N91115 in Cystic Fibrosis Patients

Sponsor

Nivalis Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02227888

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: N91115	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Open-Label Study Evaluating the Pharmacokinetics of N91115 in Cystic Fibrosis Patients

Study Start Date :

Oct 1, 2014

Actual Primary Completion Date :

Jan 1, 2015

Actual Study Completion Date :

Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: N91115 Every 12 hour oral dosing of 50 mg N91115 for 14 days	Drug: N91115 S nitrosoglutathione reductase inhibitor Other Names: Cavosonstat

Arm

Intervention/Treatment

Experimental: N91115

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

Drug: N91115

S nitrosoglutathione reductase inhibitor

Other Names:

Cavosonstat

Outcome Measures

Primary Outcome Measures

Pharmacokinetics [14 Days]
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.

Secondary Outcome Measures

Safety of dosing twice per day over 14 days [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed diagnosis of CF, homozygous for the F508del-CFTR mutation
Weight ≥ 40 kg at screening
FEV1 ≥ 40% of predicted normal for age, gender, and height (Hankinson standards) pre or post-bronchodilator value, at screening
Hematology, clinical chemistry, and urinalysis results with no clinically significant abnormalities that would interfere with the study assessments at screening

Exclusion Criteria:

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
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
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
History, including the screening assessment, of ventricular tachycardia or ventricular arrhythmias
History, including the screening assessment, of prolonged QT and/or QTcF (Fridericia's correction) interval (> 450 msec)
History of solid organ or hematological transplantation
History of alcohol abuse or drug addiction (including cannabis, cocaine, and opioids) in the year prior to screening
Use of continuous (24 hr/day) or nocturnal supplemental oxygen

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama @ Birmingham	Birmingham	Alabama	United States	35294
2	Children's CO	Aurora	Colorado	United States	80045
3	National Jewish Health	Denver	Colorado	United States	80206