Trial to Assess the Safety, Tolerability and Pharmacokinetics of GS-9411 in Healthy Male Volunteers

A Randomised, Double-blind, Placebo-controlled Trial to Assess the Safety, Tolerability and Pharmacokinetics of GS-9411 in Healthy Male Volunteers

The purpose of this study is to evaluate the safety and tolerability of escalating doses of GS-9411 in healthy male volunteers. GS-9411 is a sodium channel inhibitor, that may restore airway hydration and mucociliary clearance in the lung.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: GS-9411; Drug: Placebo

Detailed Description

GS-9411 is being evaluated as a potential therapy to improve airway hydration and mucociliary clearance in patients with cystic fibrosis. This study is evaluating the safety and tolerability of 3 dose levels of GS-9411 as an inhaled product, compared to a matched placebo.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Males 18 to 45 years of age.
• No clinically important abnormal physical findings at screening.
• No clinically relevant abnormal lab results at screening.
• Normal (or abnormal but not clinically significant) ECG.
• Normal (or abnormal but not clinically significant) blood pressure (BP) and heart rate (HR).
• Body weight between 70 and 125 kg and body mass index (BMI) between 18 and 28 kg/m2, or outside range, but not clinically significant and agreed with sponsor and principal investigator.
• Able to communicate well with the investigator and to comply with the requirements of the entire study.
• Provision of written informed consent.
• Non-smokers of at least 6 months duration (< 10 pack year history) prior to study entry.
• Negative for drugs of abuse (including alcohol) at Screening and Day -5.
• Must be willing to abstain from alcohol and strenuous exercise during the 48-hour period prior to admission and while confined to the clinic.
• Forced expiratory volume in 1 second (FEV1) greater than or equal to 80% of predicted normal for age, gender, and height as per Hankinson et al1 at Screening and Pre-dose.
• Normal intraocular pressure between 10 and 22 mmHg.
• Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condom) during heterosexual intercourse from Baseline/Day 0 through completion of the study and continuing for at least 30 days from date of last dose of study drug.
• Male subjects must refrain from sperm donation from Day 1 through completion of the study and continuing for at least 30 days from the date of last dose of study drug.

Exclusion Criteria:

• Administration of any investigational drug in the period 0 to 12 weeks before entry to the study.
• A need for any medication during the period 0 to 5 days before entry to the study, except those deemed by the principal investigator/clinical investigator not to interfere with the outcome of the study.
• 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.
• Presence or history of allergy requiring treatment. Hay fever is allowed unless it is active or has required treatment within the previous 2 months.
• Donation or loss of greater than 400 mL of blood in the period 0 to 12 weeks before entry to the study.
• Serious adverse reaction or hypersensitivity to any drug.
• Presence or history of any pulmonary diseases (e.g., asthma, emphysema, chronic bronchitis, cystic fibrosis, bronchiectasis).
• 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) or enzyme-inhibiting agents (e.g., cimetidine) or similar drugs within 30 days (or 5 half-lives of inducing/inhibiting agent, whichever is longer) of enrollment in this study.
• Major surgery within 6 months of the start of this study.
• Subjects who have experienced a significant upper or lower respiratory tract infection within the 6 weeks prior to admission.
• Subjects with significant history of respiratory, renal, hepatic, cardiovascular (including history of systemic hypertension requiring therapy), metabolic, neurological, hematological, gastrointestinal, cerebrovascular, or other significant medical illness or disorder which, in the judgment of the investigator, may interfere with the study or require treatment which may affect the evaluation of efficacy and safety of the study drug.
• Subjects with elevated liver enzyme concentrations.
• Haemoglobin level < 130 g/L taken at Screening and at Pre-dose.
• Plasma potassium > 5 mEq/L taken at Screening and at Pre-dose.
• Poor venous access.
• Intraocular pressure > 21 mm Hg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; GS-9411 0.6 mg	Drug: GS-9411; Inhaled GS-9411 dissolved in sterile saline
Experimental: 2; GS-9411 1.2 mg	Drug: GS-9411; Inhaled GS-9411 dissolved in sterile saline
Experimental: 3; GS-9411 2.4 mg	Drug: GS-9411; Inhaled GS-9411 dissolved in sterile saline
Placebo Comparator: 4; Inhaled volume-matched sterile saline placebo	Drug: Placebo; Inhaled volume-matched placebo in sterile saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and Tolerability of 3 escalating doses of GS-9411 in healthy male volunteers	11 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess pharmacokinetics of GS-9411 and its metabolites	11 Days

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Principal Investigator: Peter Hodsman, MD, Nucleus Network Ltd

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: November 21, 2008
• First Submitted That Met QC Criteria: December 1, 2008
• First Posted (Estimate): December 2, 2008

Study Record Updates

• Last Update Posted (Estimate): October 21, 2009
• Last Update Submitted That Met QC Criteria: October 20, 2009
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: cystic fibrosis; CF; mucociliary clearance; amiloride; ENaC; ENaC Inhibitor; airway hydration; epithelial sodium channel inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: GS-US-221-0101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No