Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00999531




Registration number
NCT00999531
Ethics application status
Date submitted
20/10/2009
Date registered
21/10/2009
Date last updated
10/03/2010

Titles & IDs
Public title
A Randomized, Double-Blind, Placebo-Controlled Multiple Dose Trial of GS-9411 in Healthy Volunteers
Scientific 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
Secondary ID [1] 0 0
GS-US-221-0107
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Mucociliary Clearance 0 0
Airway Hydration 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GS-9411
Treatment: Drugs - Placebo

Experimental: 1 - GS-9411 9.6 mg

Experimental: 2 - GS-9411 4.8 mg

Experimental: 3 - GS-9411 2.4 mg

Placebo Comparator: 4 - Saline Placebo


Treatment: Drugs: GS-9411
Inhaled GS-9411 dissolved in sterile saline

Treatment: Drugs: Placebo
Inhaled Placebo, sterile saline
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability of multiple doses of inhaled GS-9411 in healthy volunteers
Timepoint [1] 0 0
21 Days
Secondary outcome [1] 0 0
Assess the pharmacokinetics of GS-9411 and its metabolites
Timepoint [1] 0 0
21 Days

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2010
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Nucleus Network, Ltd. - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00999531
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Peter Hodsman, MD
Address 0 0
Nucleus Network Ltd
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00999531