A Phase 1 Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS 9411 in Subjects With Cystic Fibrosis (CF)

• Register: ClinicalTrials.gov
• Last refreshed on: 3 August 2015
• Main ID: NCT01025713
• Date of registration: 01/12/2009
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences
• 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)
• Date of first enrolment: December 2009
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT01025713
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Australia

Contacts

• Name: John Wilson, MD
• Affiliation: The Alfred Hospital

Key inclusion & exclusion criteria

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.

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



Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Mucociliary Clearance

Cystic Fibrosis

Intervention(s)

Drug: GS-9411

Drug: Placebo

Primary Outcome(s)

To evaluate the safety and tolerability of escalating doses of inhaled GS-9411 in subjects with CF. [Time Frame: 5 Days]

Secondary Outcome(s)

To assess the pharmacokinetics (PK) of GS-9411 and its metabolites, in plasma, urine, and sputum after single inhaled doses. [Time Frame: 5 Days]

Secondary ID(s)

GS-US-221-0106

Source(s) of Monetary Support

Please refer to primary and secondary sponsors