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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01025713




Registration number
NCT01025713
Ethics application status
Date submitted
1/12/2009
Date registered
3/12/2009
Date last updated
9/07/2015

Titles & IDs
Public title
A Phase 1 Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS 9411 in Subjects With Cystic Fibrosis (CF)
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS 9411 in Subjects With Cystic Fibrosis (CF)
Secondary ID [1] 0 0
GS-US-221-0106
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
Condition category
Condition code
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
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

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

Experimental: 1 - GS-9411 2.4 mg

Experimental: 2 - GS-9411 4.8 mg

Placebo Comparator: Placebo - Placebo


Treatment: Drugs: GS-9411
Inhaled GS-9411

Treatment: Drugs: Placebo
Inhaled Placebo

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate the safety and tolerability of escalating doses of inhaled GS-9411 in subjects with CF.
Timepoint [1] 0 0
5 Days
Secondary outcome [1] 0 0
To assess the pharmacokinetics (PK) of GS-9411 and its metabolites, in plasma, urine, and sputum after single inhaled doses.
Timepoint [1] 0 0
5 Days

Eligibility
Key inclusion criteria
- Males and females aged 18 to 65 years

- Patients with diagnosis of CF as confirmed by at least one of the following:

- Documented sweat chloride = 60 mEq/L by quantitative pilocarpine iontophoresis test OR

- Documented sweat sodium test = 60 mmol/L OR

- Abnormal nasal potential difference test OR

- At least one well-characterized disease-causing genetic mutation in the CF
transmembrane conductance regulatory (CFTR) gene AND

- Accompanying symptoms characteristic of CF

- Normal (or abnormal but not clinically significant) electrocardiogram (ECG)

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

- Normal (or abnormal but not clinically significant) blood pressure (BP) and heart rate
(HR) in the absence of any medications for hypertension; these will be measured after
the subject has rested supine for 3 minutes; normal BP is taken to be 90 to 140 mm Hg
systolic and 50 to 89 mm Hg diastolic; normal HR is taken to be 40 to 100 beats per
minute (bpm)

- 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 for at least 180 days (6 months) prior to Screening

- Must be willing to abstain from alcohol and strenuous exercise during the 48 hours
prior to Screening, 72 hours prior to initial dosing, and during the study

- Forced expiratory volume in 1 second (FEV1) = 50% predicted normal for age, gender,
and height at Screening as per Knudson et al

- Stable regimen of oral CF medications, dornase alfa, and physiotherapies for the
period 28 days prior to Screening; those subjects taking continuous (non-cycling)
inhaled antibiotics for prophylaxis must be on a stable regimen of these drugs for at
least 90 days prior to Screening

- Subjects must be in the off-phase of any cyclical inhaled antibiotic treatment regimen

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

- Male subjects who are sexually active must be willing to use effective barrier
contraception (e.g., condom) during heterosexual intercourse from Day -1 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

- Nonlactating 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

- Glomerular filtration rate (GFR) of < 60 mL/min/1.73m2 at Screening (GFR to be
calculated using the Cockcroft-Gault equation), and alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) less than or equal to 3× upper limits of normal (ULN)

- Chest radiograph at Screening without significant acute findings (e.g., infiltrates
[lobar or diffuse interstitial], pleural effusion, pneumothorax); or chest radiograph,
CT, or MRI obtained within the 90 days prior to Screening without acute findings or
significant intercurrent illness; chronic, stable findings (e.g., chronic scarring or
atelectasis) are allowed. A chest radiograph obtained and interpreted between
Screening and Day 1 is also acceptable for determining eligibility.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Administration of any investigational drug or device in the 28 days prior to Screening

- A need for any new medication during the period 28 days before first dosing with study
drug, except those deemed by the principal investigator/clinical investigator not to
interfere with the outcome of the study

- Subjects who routinely use inhaled hypertonic saline must discontinue use for at least
14 days prior to clinic admission and for the duration of the study

- Use of trimethoprim or high dose ibuprofen (> 800 mg/day) during the 28 days prior to
first dosing

- Serious adverse reaction or hypersensitivity to any drug

- 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

- Lactating females

- History of airway intolerance to hypertonic saline

- History of lung transplantation

- History of a positive test for Burkholderia cepacia

- History of cirrhosis or ascites

- History of clinically significant adrenal disease

- History of congestive heart failure diagnosed clinically or with documented left
ventricular ejection fraction (LVEF) = 40%

- 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) within 28 days (or 5 half-lives of inducing agent, whichever is
longer) of Screening

- Subjects requiring any of the following drugs in the 28 days prior to Screening:
diuretics (e.g., spironolactone, amiloride, thiazide), ACE inhibitors, angiotensin
receptor blockers, oral corticosteroids, or medicines for hypertension

- Donation or loss of greater than 400 mL of blood in the period 90 days (3 months)
prior to Screening

- Major surgery within 180 days (6 months) of Screening

- Hemoglobin levels < 120 g/L in females or < 130 g/L in males 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
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
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 GS-9411 in patients
with Cystic Fibrosis. GS-9411 is a sodium channel inhibitor, that may restore airway
hydration and mucociliary clearance in the lung.
Trial website
https://clinicaltrials.gov/show/NCT01025713
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
John Wilson, MD
Address 0 0
The Alfred
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/show/NCT01025713