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

Cystic Fibrosis Clinical Trial

Official title:

A Phase 1 Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS-9411 in Healthy Male Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00951522
• Other study ID #: GS-US-221-0102
• Status: Completed
• Phase: Phase 1
• First received: August 3, 2009
• Last updated: September 24, 2009
• Start date: September 2009
• Est. completion date: September 2009

Study information

• Verified date: September 2009
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

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.

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 4 dose levels of GS-9411 as an inhaled product, compared to a matched placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Males 18 to 45 years of age

• No clinically important abnormal physical findings at the screening examination

• No clinically relevant abnormalities in the results of laboratory screening evaluation

• 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.

• 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.

• 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 during the study.

• Forced expiratory volume in 1 second (FEV1) = 80% of predicted normal for age, gender, and height at Screening and Pre-dose.

• Normal intraocular pressure between 10 and 21 mm Hg.

• Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condoms) during heterosexual intercourse from Baseline/Day 0 through completion of the study and continuing for at least 90 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 90 days from the date of last dose of study drug.

Exclusion Criteria:

• Any prior exposure to GS-9411.

• 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 at Screening and at Day -1.

• Hemoglobin level < 130 g/L taken at Screening and at Day -1.

• Serum potassium > 5 mEq/L taken at Screening and at Day -1.

• Poor venous access.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Airway Hydration
• Cystic Fibrosis
• Mucociliary Clearance

Intervention

Drug:
• GS-9411
Inhaled GS-9411 dissolved in sterile saline
• Placebo
Inhaled placebo in sterile saline

Locations

Country	Name	City	State
Australia	Nucleus Network, Ltd.	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability of 4 escalating doses of GS-9411 in healthy male volunteers		7 Days	No