Safety, Tolerability, and Pharmacokinetics of GS-5745 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02077465
First received: February 28, 2014
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

This study is to assess the safety, tolerability, and pharmacokinetics (PK) of multiple infusions of GS-5745 in participants with chronic obstructive pulmonary disease (COPD) as assessed by adverse events (AEs) and laboratory abnormalities.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: GS-5745
Drug: Placebo to match GS-5745
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1 Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GS-5745 in Subjects With Chronic Obstructive Pulmonary Disease

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Incidence of adverse events, change from screening in laboratory tests and vital signs, and development of immunogenicity after dosing [ Time Frame: Baseline to Day 29 plus 30 days ] [ Designated as safety issue: No ]
    This composite endpoint will measure the safety and tolerability profile of GS-5745.


Secondary Outcome Measures:
  • PK parameters of GS-5745 as measured by AUC and Cmax [ Time Frame: Baseline to Day 29 ] [ Designated as safety issue: No ]
    • AUC represents the total amount of drug absorbed by the body by comparing plasma concentration over time
    • Cmax is defined as the maximum concentration of drug

  • PK parameters of GS-5745 as measured by Tmax, Clast, Tlast, Ctau, λz, CL, and Vz [ Time Frame: Baseline to Day 29 ] [ Designated as safety issue: No ]
    • Tmax is defined as the time of Cmax
    • Clast is defined as the last observable concentration of drug
    • Tlast is defined as the time of Clast
    • Ctau is defined as the observed drug concentration at the end of the dosing interval
    • λz is defined as the terminal elimination rate constant
    • CL is defined as systemic clearance following intravenous (IV) administration
    • Vz is defined as apparent volume of distribution following IV administration


Estimated Enrollment: 12
Study Start Date: March 2014
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GS-5745
Participants will receive GS-5745 every 2 weeks for a total of 3 infusions.
Drug: GS-5745
400 mg GS-5745 administered intravenously
Placebo Comparator: Placebo to match GS-5745
Participants will receive placebo to match GS-5745 every 2 weeks for a total of 3 infusions.
Drug: Placebo to match GS-5745
Placebo to match GS-5745 administered intravenously

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Weight: ≥ 45 kg to < 120 kg at screening
  • Males or non-pregnant, non-lactating females
  • Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception. Male subjects must refrain from sperm donation for 90 days post last infusion of the study drug
  • Diagnosis of COPD per Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for at least 6 months prior to screening and anticipated to remain on stable therapy for the duration of the study
  • Post-bronchodilator forced expiratory volume in one second (FEV1) ≥ 40% predicted
  • No changes in COPD medications within 30 days prior to randomization
  • Hepatic panel [aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin, alkaline phosphatase, lactate dehydrogenase (LDH)] ≤ 2 times the upper limit of the normal range (ULN)
  • Serum creatinine ≤ 2.0
  • Hemoglobin ≥ 8.5 g/dL (both males and females)
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1,500 mm^3)
  • Platelets ≥ 100 x 10^9/L

Exclusion Criteria:

  • Clinically significant active infection as judged by the investigator during screening
  • Known history of HIV, hepatitis B or C during screening. Subjects who are hepatitis B surface antigen positive, but who received a successful series of hepatitis B vaccinations and never had the disease remain eligible
  • A positive QuantiFERON-TB GOLD test during screening
  • History of malignancy within the last 5 years except for patients who have been treated locally for non-melanoma skin cancer or cervical carcinoma in situ
  • Any serious cardiac event such as myocardial infarction, unstable or life-threatening arrhythmia, hospitalization for cardiac failure within 6 months prior to randomization or any significant or new electrocardiogram (ECG) finding at Visit 1 as judged by the Investigator
  • A hospitalization for a respiratory event such as, but not limited to, COPD, pneumonia, bronchiolitis, within the previous 6 months prior to randomization
  • Chronic lung disease other than COPD such as: asthma, cystic fibrosis or fibrotic disease, α-1-antitrypsin deficiency, interstitial lung disease, pulmonary thromboembolic disease, or bronchiectasis
  • Chronic use of systemic corticosteroids and/or treatment with systemic corticosteroids for an acute exacerbation of COPD (AECOPD) event, or other medical condition not requiring hospitalization, within 90 days of randomization.
  • Treatment with antibiotics for an AECOPD event, or other medical condition not requiring hospitalization within 90 days of randomization, or any minor medical event not requiring hospitalization within 14 days of randomization.
  • Treatment with any marketed or investigational biologic within 5 half-lives of the molecule or if unknown within 90 days of screening
  • Subjects currently on nonbiologic immune modulator medications such as: azathioprine, cyclosporine, hydroxychloroquine, leflunomide, methotrexate, mycophenolate mofetil, sulfasalazine, tofacitinib, within 90 days of randomization
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02077465

Locations
United States, Florida
Advanced Pharma CR, LLC
Miami, Florida, United States, 33136
Elite Research Institute
Miami, Florida, United States, 33169
Compass Research, LLC
Orlando, Florida, United States, 32806
United States, New York
University at Buffalo CTRC
Buffalo, New York, United States, 14203
United States, Tennessee
Volunteer Research Group
Knoxville, Tennessee, United States, 37920
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: David Gossage, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02077465     History of Changes
Other Study ID Numbers: GS-US-368-1212
Study First Received: February 28, 2014
Last Updated: September 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
COPD, chronic obstructive pulmonary disease; Phase 1b, Safety, Pharmacokinetics

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 29, 2014