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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/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
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 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
Sex
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
1/12/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2010
Actual
Sample size
Target
Accrual to date
Final
0
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/ct2/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/ct2/show/NCT01025713