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

Sponsor

Gilead Sciences (Industry)

Overall Status

Completed

CT.gov ID

NCT00999531

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis Mucociliary Clearance Airway Hydration	Drug: GS-9411 Drug: Placebo	Phase 1

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, administered twice daily for 14 days.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Feb 1, 2010

Actual Study Completion Date :

Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 GS-9411 9.6 mg	Drug: GS-9411 Inhaled GS-9411 dissolved in sterile saline
Experimental: 2 GS-9411 4.8 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 Saline Placebo	Drug: Placebo Inhaled Placebo, sterile saline

Outcome Measures

Primary Outcome Measures

Safety and tolerability of multiple doses of inhaled GS-9411 in healthy volunteers [21 Days]

Secondary Outcome Measures

Assess the pharmacokinetics of GS-9411 and its metabolites [21 Days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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