A Randomized, Double-Blind, Placebo-Controlled Multiple Dose Trial of GS-9411 in Healthy Volunteers

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00999531
• Other study ID #: GS-US-221-0107
• Status: Completed
• Phase: Phase 1
• First received: October 20, 2009
• Last updated: March 8, 2010
• Start date: October 2009
• Est. completion date: March 2010

Study information

• Verified date: March 2010
• 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 repeated doses of GS-9411 in healthy 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 3 dose levels of GS-9411 as an inhaled product, compared to a matched placebo, administered twice daily for 14 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Males and females, 18 to 65 years of age

• No clinically important abnormal physical findings at Screening

• No clinically relevant abnormalities in the results of laboratory evaluation at Screening

• Must test negative for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) at Screening

• Normal electrocardiogram (ECG) at Screening

• Normal blood pressure (BP) and heart rate (HR) in the absence of any medications for body weight between 50 and 125 kg and within ± 15% of ideal body weight or body mass index (BMI) between 18 and 28 kg/m2 at Screening

• 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 of at least 180 days (6 months) duration (< 10 pack/year history) prior to Screening

• 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 hours prior to Day -5 and during the study

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

• Normal intraocular pressure (IOP) between 10 and 21 mm Hg at Screening

• Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condoms) during heterosexual intercourse from Day -5 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 -5 through completion of the study and continuing for at least 90 days from the date of last dose of study drug

• Non-lactating females. Females on hormone replacement therapy (estrogen/progesterone) or contraceptive therapy must be stabilized on a product and dose for at least 90 days prior to Screening

• Females must have a negative serum gonadotropin pregnancy test at Screening and Day -1

• Nonpregnant females of childbearing potential must agree to use highly effective (<1% failure rate) contraception during heterosexual intercourse from Screening, throughout the study, and for at least 30 days following the last dose of study drug

Exclusion Criteria:

• Any prior exposure to GS-9411

• Administration of any investigational drug in the period 84 days (12 weeks) prior to Screening; 112 days (16 weeks) if the previous investigational drug was a new chemical entity

• A need for any medication during the period 0 to 5 days prior to Screening, 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 56 days (8 weeks) of Screening

• Donation or loss of greater than 400 mL of blood in the period 84 days (12 weeks) prior to Screening

• Serious adverse reaction or hypersensitivity to any drug

• Presence or history of any pulmonary diseases (e.g., asthma, emphysema, chronic bronchitis, CF, bronchiectasis)

• Lactating females

• 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) or enzyme-inhibiting agents (e.g., cimetidine) or similar drugs within 28 days (or 5 half-lives of inducing/inhibiting agent, whichever is longer) of Screening

• Major surgery within 180 days (6 months) of the start of this study

• Subjects who have experienced a significant upper or lower respiratory tract infection within the 42 days (6 weeks) prior to Screening

• 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 the 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: Parallel 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, 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 multiple doses of inhaled GS-9411 in healthy volunteers		21 Days	No
Secondary	Assess the pharmacokinetics of GS-9411 and its metabolites		21 Days	No