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

This study has been completed.
Sponsor:
Information provided by:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00800579
First received: November 21, 2008
Last updated: October 20, 2009
Last verified: October 2009
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Drug: GS-9411
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled Trial to Assess the Safety, Tolerability and Pharmacokinetics of GS-9411 in Healthy Male Volunteers

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Safety and Tolerability of 3 escalating doses of GS-9411 in healthy male volunteers [ Time Frame: 11 Days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess pharmacokinetics of GS-9411 and its metabolites [ Time Frame: 11 Days ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: November 2008
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00800579

Locations
Australia, Victoria
Nucleus Network Ltd.
Melbourne, Victoria, Australia, 3004
Sponsors and Collaborators
Gilead Sciences
Investigators
Principal Investigator: Peter Hodsman, MD Nucleus Network Ltd
  More Information

No publications provided

Responsible Party: Thomas O'Riordan, MD, Gilead Sciences, Inc.
ClinicalTrials.gov Identifier: NCT00800579     History of Changes
Other Study ID Numbers: GS-US-221-0101
Study First Received: November 21, 2008
Last Updated: October 20, 2009
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Gilead Sciences:
cystic fibrosis
CF
mucociliary clearance
amiloride
ENaC
ENaC Inhibitor
airway hydration
epithelial sodium channel inhibitor

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Epithelial Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 01, 2014