Cystic FibrosisPhase 1NCT01025713
A Phase 1 Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS 9411 in Subjects With Cystic Fibrosis (CF)
A Phase 1 study testing GS-9411 in people with Cystic Fibrosis and Mucociliary Clearance, run by Gilead Sciences at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Cystic Fibrosis, Mucociliary Clearance
- What is being tested?
- GS-9411
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteAustralia
- Study dates
- Dec 2009to Apr 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official 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)
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.
Read the 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 2 dose levels of GS-9411 as an inhaled product, compared to a matched placebo.
- Conditions
- Cystic Fibrosis, Mucociliary Clearance
- Being tested
- GS-9411, Placebo
- Keywords
- Cystic Fibrosis, CF, Mucociliary Clearance, Epithelial Sodium Channel Inhibitor, ENaC Inhibitor, Airway Hydration, Amiloride
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GS-9411Drug
Inhaled GS-9411
PlaceboDrug
Inhaled Placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | GS-9411 2.4 mg Receives: Drug: GS-9411 |
| 2 | Experimental | GS-9411 4.8 mg Receives: Drug: GS-9411 |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety and tolerability of escalating doses of inhaled GS-9411 in subjects with CF.
Measured: 5 Days
Secondary outcomes (1)
To assess the pharmacokinetics (PK) of GS-9411 and its metabolites, in plasma, urine, and sputum after single inhaled doses.
Measured: 5 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2009 (estimated)
- Study startDec 2009
- Primary completionMar 2010
- Study completionApr 2010 (estimated)
Why it stopped: Development program terminated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John Wilson, MD, Principal investigator, The Alfred
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01025713
- Sponsor's protocol ID
- GS-US-221-0106
- Status last verified
- Jul 2015
- First submitted
- 1 Dec 2009
- Last updated
- 9 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT01025713
- Acronym / sponsor ID
- GS-US-221-0106
- Conditions
- Cystic Fibrosis, Mucociliary Clearance
- Keywords
- Cystic Fibrosis, CF, Mucociliary Clearance, Epithelial Sodium Channel Inhibitor, ENaC Inhibitor, Airway Hydration, Amiloride
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Development program terminated.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Mar 2010 (actual)
- Study completion
- Apr 2010 (estimated)
- First posted
- 3 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 2 dose levels of GS-9411 as an inhaled product, compared to a matched placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: GS-9411GS-9411 2.4 mg |
| 2 | Experimental | Drug: GS-9411GS-9411 4.8 mg |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GS-9411Inhaled GS-9411 | Drug | 1, 2 |
| PlaceboInhaled Placebo | Drug | Placebo |
Primary outcome
To evaluate the safety and tolerability of escalating doses of inhaled GS-9411 in subjects with CF.
Time frame: 5 Days
1 secondary outcome
To assess the pharmacokinetics (PK) of GS-9411 and its metabolites, in plasma, urine, and sputum after single inhaled doses.
Time frame: 5 Days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Wilson, MD principal investigator
The Alfred
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GS-9411 in people with Cystic Fibrosis and Mucociliary Clearance, run by Gilead Sciences at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 9 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the safety and tolerability of escalating doses of inhaled GS-9411 in subjects with CF. (time frame: 5 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2015.