A Phase 1 Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS 9411 in Subjects With Cystic Fibrosis (CF)

NCT01025713 | Withdrawn Phase 1

• 1 other identifier: GS-US-221-0106
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of GS-9411 in patients with Cystic Fibrosis. GS-9411 is a sodium channel inhibitor, that may restore airway hydration and mucociliary clearance in the lung.

Conditions

Cystic Fibrosis; Mucociliary Clearance

Keywords

Cystic Fibrosis; CF; Mucociliary Clearance; Epithelial Sodium Channel Inhibitor; ENaC Inhibitor; Airway Hydration; Amiloride

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of escalating doses of inhaled GS-9411 in subjects with CF.

  5 Days

Secondary Outcomes (1)

• To assess the pharmacokinetics (PK) of GS-9411 and its metabolites, in plasma, urine, and sputum after single inhaled doses.

  5 Days

Study Arms (3)

1

EXPERIMENTAL

GS-9411 2.4 mg

Drug: GS-9411

2

EXPERIMENTAL

GS-9411 4.8 mg

Drug: GS-9411

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

GS-9411 DRUG

Inhaled GS-9411

1; 2

Placebo DRUG

Inhaled Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females aged 18 to 65 years
• Patients with diagnosis of CF as confirmed by at least one of the following:
• Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test OR
• Documented sweat sodium test ≥ 60 mmol/L OR
• Abnormal nasal potential difference test OR
• At least one well-characterized disease-causing genetic mutation in the CF transmembrane conductance regulatory (CFTR) gene AND
• Accompanying symptoms characteristic of CF
• Normal (or abnormal but not clinically significant) electrocardiogram (ECG)
• Normal intraocular pressure (IOP) between 10 and 21 mm Hg at Screening.
• Normal (or abnormal but not clinically significant) blood pressure (BP) and heart rate (HR) in the absence of any medications for hypertension; these will be measured after the subject has rested supine for 3 minutes; normal BP is taken to be 90 to 140 mm Hg systolic and 50 to 89 mm Hg diastolic; normal HR is taken to be 40 to 100 beats per minute (bpm)
• Able to communicate well with the investigator and to comply with the requirements of the entire study
• Provision of written informed consent to participate as shown by a signature on the volunteer consent form
• Nonsmokers for at least 180 days (6 months) prior to Screening
• Must be willing to abstain from alcohol and strenuous exercise during the 48 hours prior to Screening, 72 hours prior to initial dosing, and during the study
• Forced expiratory volume in 1 second (FEV1) ≥ 50% predicted normal for age, gender, and height at Screening as per Knudson et al

You may not qualify if:

• Administration of any investigational drug or device in the 28 days prior to Screening
• A need for any new medication during the period 28 days before first dosing with study drug, except those deemed by the principal investigator/clinical investigator not to interfere with the outcome of the study
• Subjects who routinely use inhaled hypertonic saline must discontinue use for at least 14 days prior to clinic admission and for the duration of the study
• Use of trimethoprim or high dose ibuprofen (\> 800 mg/day) during the 28 days prior to first dosing
• Serious adverse reaction or hypersensitivity to any drug
• Existence of any surgical or medical condition which, in the judgment of the clinical investigator, might interfere with the absorption, distribution, metabolism, or excretion of the drug
• Lactating females
• History of airway intolerance to hypertonic saline
• History of lung transplantation
• History of a positive test for Burkholderia cepacia
• History of cirrhosis or ascites
• History of clinically significant adrenal disease
• History of congestive heart failure diagnosed clinically or with documented left ventricular ejection fraction (LVEF) ≤ 40%
• History of glaucoma
• Consumption of drugs and/or herbal preparations capable of inducing hepatic enzyme metabolism (e.g., barbiturates, rifampicin, carbamazepine, phenytoin, primidone, or St. John's Wort) within 28 days (or 5 half-lives of inducing agent, whichever is longer) of Screening

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Nucleus Network, Ltd.

Melbourne, Victoria, Australia

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• John Wilson, MD

  The Alfred

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2009
• First Posted: December 3, 2009
• Study Start: December 1, 2009
• Primary Completion: March 1, 2010
• Study Completion: April 1, 2010
• Last Updated: July 9, 2015

Record last verified: 2015-07

Locations

AU (1)