Cystic FibrosisPhase 2NCT00903201
28 Day Repeat Dose in Cystic Fibrosis Patients
A Phase 2 study testing SB656933 in people with Cystic Fibrosis, run by GlaxoSmithKline at 33 sites in 5 countries.
Trial summary
The purpose of this study is to determine whether the safety, tolerability and pharmacodynamics of SB656933 in patients that have cystic fibrosis Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- SB656933
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 146 participants
- Where
- 33 sitesin 5 countries
- Study dates
- 28 Sep 2009to 29 Dec 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of CF based on the following: sweat chloride > 60 mEq/L and/or genotype with 2 identifiable mutations consistent with CF; (ΔF508 homozygote, or ΔF508 heterozygote with a second allele known to cause the disease, or two alleles known to cause a class I, II, or III mutation) and one or more clinical features consistent with CF.
- Male and female subjects aged ≥18 years of age
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory].
- Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until one week after the last dose.
- Patients are non-smokers or former smokers by history. Former smokers will be defined as those who have not smoked for ≥6 months. Subjects who only use chewing tobacco products may be enrolled at the discretion of the Investigator and after consultation with the GSK medical monitor.
Show all 17Show fewer
- In the judgement of the investigator the patient is clinically stable with no change in symptoms or medication, no admissions to hospital, and no intravenous antibiotic therapy for at least 1 month prior to dosing.
- Able to perform lung function tests reliably.
- FEV1 >40% and <110% predicted.
- Excluding periods of exacerbation, FEV1 has not decreased by >15% over the past 12 months
- Clinically colonized by a bacterial organism commonly seen in cystic fibrosis other than Burkholderia cepacia (i.e. Pseudomonas spp., Staphylococcus aureus, Stenotrophomonas, B. Gladioli) as evidenced by identification in sputum culture within the past year. To be eligible a CF patient must have colonization of at least one typical CF organism.
- To be eligible, female patients must have a negative pregnancy test (urine or serum) and not be nursing at screening or prior to dosing.
- Subjects must have a QTcB or QTcF < 450 msec at screening as determined by the investigators review.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) within twice (2x) the upper limit of normal at screening and bilirubin within 1.25x ULN at screening. AST, ALT, alkaline phosphatase and bilirubin >2.0 xULN (isolated bilirubin >2.0xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Male subjects must agree to use one of the contraception methods listed in Section 8.1.2. This criterion must be followed from the time of the first dose of study medication until one week after the last dose.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
Who cannot join
- Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination, or ECG, that is not associated with cystic fibrosis.
- Neutrophil count <1.5x109 /L
- In the judgment of the PI, the patient:
- suffers from clinically unstable pancreatic function
- has clinically significant weight loss( ≥5% after a previously stable period).
- has recent change in pancreatic enzyme requirements in the past 2 months.
Show all 26Show fewer
- Recent viral infection (within 4 weeks of dosing), with or without steroid or antibiotic treatment. Presumed viral infection will be determined according to the judgment of the Investigator and no specific testing for virus will be required.
- Subjects unable to produce a technically acceptable sputum sample.
- Clinically significant hepatic impairment
- Evidence of cirrhosis
- Patients with elevated INR that is due to suspected vitamin K deficiency may be enrolled at the discretion of the Investigator and after consultation with the GSK medical monitor
- Blood pressure persistently >155/95 mmHg at screening.
- Positive HIV, Hepatitis B surface antigen or Hepatitis C antibody at screening.
- History of regular alcohol consumption averaging >7 drinks/week for women or >14 drinks/week for men. One drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits) within 6 months of screening.
- Urinary cotinine levels indicative of smoking.
- Use of oral or parenteral corticosteroids within 4 weeks of screening; regular use (>3 x/wk) of high dose NSAIDS (e.g. >1.6g ibuprofen/day on a regular basis), within 4 weeks of screening.
- Colonization with Burkholderia cepacia
- Subjects currently being treated for mycobacterial infection
- Subjects with presumed active Allergic Bronchopulmonary Aspergillosis (ABPA)
- Subjects who have newly started therapy with azithromycin within the past 3 months.
- In the judgment of the investigator, clinically significant hemoptysis (> 30 cc per episode) within the last 6 months
- Donation of blood in excess of 500 mL within a 56-day period prior to dosing
- Participation in a trial with any drug within 30 days or 5 half-lives (whichever is longer), or participation in a trial with a new chemical entity within 2 months prior to first dose of current study medication, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study procedures or compromise subject safety.
- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, and cannabinoids. Subjects who use benzodiazepines or other anxiolytic on a regular basis can be included at the discretion of the investigator and in consultation with the GSK medical monitor
- Patients may not be on an inhaled antibiotic during the study (i.e. must be an "off-TOBI" month; cessation of TOBI or other inhaled antibiotics commences from one week prior to dosing until final PK draw). Patients on maintenance therapy with hypertonic saline solution or inhaled DNase may continue these therapies.
- Unwillingness or inability to follow the procedures outlined in the protocol.
Trial locations and contacts
33 sites in 5 countries.
33 sites in 5 countries
United States17 sites
GSK Investigational Site
Akron, Ohio, 44308
GSK Investigational Site
Albany, New York, 12208
GSK Investigational Site
Atlanta, Georgia, 30322
GSK Investigational Site
Birmingham, Alabama, 35233
GSK Investigational Site
Chicago, Illinois, 60637
GSK Investigational Site
Cincinnati, Ohio, 45229
GSK Investigational Site
Cleveland, Ohio, 44106
GSK Investigational Site
Colchester, Vermont, 05446
GSK Investigational Site
Denver, Colorado, 80206
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
Madison, Wisconsin, 53792-9988
GSK Investigational Site
Milwaukee, Wisconsin, 53226
GSK Investigational Site
Palo Alto, California, 94304
GSK Investigational Site
Philadelphia, Pennsylvania, 19104
GSK Investigational Site
Pittsburgh, Pennsylvania, 15213
GSK Investigational Site
Tucson, Arizona, 85724
GSK Investigational Site
Worcester, Massachusetts, 01655
Germany6 sites
GSK Investigational Site
Berlin, 13353
GSK Investigational Site
Bochum, North Rhine-Westphalia, 44791
GSK Investigational Site
Essen, North Rhine-Westphalia, 45122
GSK Investigational Site
Frankfurt am Main, Hesse, 60590
GSK Investigational Site
Hamburg, 22763
GSK Investigational Site
Tübingen, Baden-Wurttemberg, 72076
France5 sites
GSK Investigational Site
Lille, 59037
GSK Investigational Site
Montpellier, 34295
GSK Investigational Site
Paris, 75679
GSK Investigational Site
Pessac, 33604
GSK Investigational Site
Reims, 51092
Israel3 sites
GSK Investigational Site
Haifa, 31096
GSK Investigational Site
Jerusalem, 91240
GSK Investigational Site
Petah Tikva, 49202
Canada2 sites
GSK Investigational Site
Montreal, Quebec, H2W 1T8
GSK Investigational Site
Toronto, Ontario, M5B 1W8
About this study
Official title: A Randomized, Double Blind, Parallel Group, Placebo Controlled 28 Day Study to Investigate the Safety, Tolerability and Pharmacodynamics of SB-656933 in Patients With Cystic Fibrosis.
The purpose of this study is to determine whether the safety, tolerability and pharmacodynamics of SB656933 in patients that have cystic fibrosis
Read the detailed description
This proof of mechanism study aims to evaluate the safety, tolerability and pharmacodynamics of SB-656933 following 28 days of daily administration of 20 and 50 mg SB-656933 in patients with CF compared to placebo. The primary endpoints of the study will be the effect of SB-656933 on safety and tolerability (adverse events, vital signs, clinical laboratory assessments, 12-lead electrocardiograms, and urinalysis) following 28 days of dosing. Secondary endpoints will include levels of neutrophil elastase in induced sputum and other sputum markers of inflammation (e.g. myeloperoxidase, total protein), induced sputum cells (i.e. total sputum neutrophil counts, percent sputum neutrophils) and sputum microbiology. Other assessments will include lung function measurements (spirometry); serum and plasma markers of inflammation (e.g. fibrinogen, CC-16, CRP, MMP8, MMP9, SP-D, and CXCL-8), quality of life questionnaire, and population pharmacokinetics parameters of SB-656933
- Conditions
- Cystic Fibrosis
- Being tested
- SB656933, Placebo
- Keywords
- cystic fibrosis
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SB656933Drug
20 mg
SB656933Drug
50mg
PlaceboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Experimental | 20 mg of SB656933 Receives: Drug: SB656933 |
| Treatment B | Experimental | 50 mg of SB656933 Receives: Drug: SB656933 |
| Placebo | Experimental | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Measured: Up to Follow-up (up to 42 days)
Number of Participants With Vital Signs of Potential Clinical Importance
Vital signs included heart rate, systolic and diastolic blood pressure and body temperature. Prior to vital signs all participants rested for at least five minutes in the seated, semi-supine, or supine position. The choice of position was kept constant for the duration of the study. Any results falling outside the normal range were repeated at the discretion of the Investigator. Potential clinical concern range for systolic blood pressure: <85 and >160 millimeter of mercury (mmHg), for diastolic: <45 and >100 mmHg and heart rate: <40 and >110 beats per minute. Number of participants with vital signs of potential clinical importance are presented.
Measured: Up to Follow-up (up to 42 days)
Number of Participants With Hematology Abnormalities of Potential Clinical Importance
Hematology parameters were reviewed prior to participants receiving first dose of study medication. The potential clinical concern range for hematology parameters were: Red blood cell (RBC) count (low: < 3.72 * 10^12/Liters (L) and high: > 6.313 * 10^12/L), lymphocytes (low: < 0.8 gigacells/L), hematocrit (low: > 0.075 ratio change from Baseline and high: > 0.54 ratio), mean cell hemoglobin (MCH) (low: < 23.8 picograms (pg) and high: > 39.6 pg), mean cell volume (MCV) (low: <73 femtoliters (FL) and high: >110 FL), platelet count (low: < 100 gigacells/L and high: > 550 gigacells/L), white blood cell (WBC) count (low: < 3 gigacells/L and high: > 20 gigacells/L) and eosinophils (high: > 1 gigacells/L). Only those parameters for which at least one value of potential clinical concern was reported are summarized. Number of participants with hematology abnormalities of potential clinical importance are presented.
Measured: Up to Follow-up (up to 42 days)
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance
The potential clinical concern range for clinical chemistry parameters were: glucose (low: < 2.8 millimole [mmol]/L and high: > 9.4 mmol/L), creatine kinase (high: > 3 * upper limit of normal units [ULN]/L), phosphorous, inorganic (low: < 0.8 mmol/L and high: > 1.6 mmol/L), total bilirubin (high: ≥ 1.5 * ULN micromole [μmol]/L), uric acid (low: < 41.636 μmol/L and high: > 582.904 μmol/L), alkaline phosphatase (ALP) (high: ≥ 2 * ULN international units [IU/L]/L), gamma glutamyl transpeptidase (GGT) (high: ≥ 110 IU/L), carbon dioxide content (low: < 18 mmol/L and high: > 32 mmol/L), direct bilirubin (high: > 1.5 * ULN μmol/L), potassium (low: < 3.0 mmol/L and high: > 5.5 mmol/L) and aspartate aminotransferase (AST) (high: ≥ 3* ULN IU/L). Only those parameters for which at least one value of potential clinical concern was reported are summarized. Number of participants with clinical chemistry abnormalities of potential clinical importance.
Measured: Up to Follow-up (up to 42 days)
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Prior to ECG recordings, all participants rested for at least 5 minutes in the seated, semi-supine, or supine position. The choice of position was kept constant for the duration of the study. Participants avoided hot and cold food for at least 30 minutes prior to an ECG measurement. Any results falling outside normal range were repeated at the discretion of the Investigator. ECG Baseline values taken within 2.5 hours prior to first dose were calculated using the mean value of triplicate pre-dose readings. Triplicate readings were taken at least five minutes apart. Participants agreed to abstain from hot and cold drinks and food prior to an ECG measurement. ECG machine calculated heart rate and measured PR, QRS, QT, and QT corrected by Bazett's formula (QTcB), QT corrected by Fridericia's formula (QTcF) intervals. Number of participants with abnormal (not clinically significant [NCS] and clinically significant [CS]) electrocardiogram (ECG) findings are presented.
Measured: Up to Follow-up (up to 42 days)
Number of Participants With Cystic Fibrosis (CF) Exacerbation
CF is one of the most common, lethal, autosomal recessive disease characterized by airway obstruction, bronchiectasis and infection, and exocrine pancreatic insufficiency. Number of participants with CF exacerbation are presented.
Measured: Day 1 to Day 42
Secondary outcomes (12)
Number of Participants With Pseudomonas Aeruginosa and Staphylococcus Aureus Count in Sputum
Bacterial colony count of both Pseudomonas aeruginosa and Staphylococcus aureus in sputum were performed. Participants were graded as no bacteria in sputum, 1+, 2+, 3+ and 4+, which indicated proportional concentration of Pseudomonas aeruginosa and Staphylococcus aureus in sputum, where no bacteria indicated there was no bacteria in sputum, 1+ indicated slightly positive and 4+ indicated highly positive. Higher grades (4+) indicated worst outcomes (highly infected sputum). Number of participants with Pseudomonas aeruginosa and staphylococcus aureus count in sputum are presented.
Measured: Day 1 and Day 28
Induced Sputum Neutrophil Number
Sputum samples were taken after bronchodilation and number of neutrophils in induced sputum were reported.
Measured: Day 28
Induced Sputum Neutrophil Percentage
Sputum samples were taken after bronchodilation and percentage of neutrophils in induced sputum are presented.
Measured: Day 28
Induced Sputum Inflammatory Markers-Myeloperoxidase and Neutrophil Elastase
Sputum samples were taken after bronchodilation. Mean induced sputum inflammatory markers namely Myeloperoxidase and neutrophil elastase are presented.
Measured: Day 28
Serum and Plasma Markers of Inflammation- Clara Cell Secretory Protein (CC-16) and CXCL8 (Interleukin-8 [IL-8])
Blood samples intended for CC-16 and CXCL8 were collected in 5.0 milliliter (mL) serum separator goldtopped blood collection tubes, then immediately mixed by gentle inversion 10 times. The samples were permitted to coagulate for 30 to 60 minutes before centrifugation at 1600 g for 15 minutes. Two 0.75 mL aliquots of serum supernatant were transferred separately into two Sarstedt tubes and frozen at -70 degree Celsius (°C). Plasma samples intended for CC-16 and CXCL8 were centrally analyzed using a commercial test kit based on enzyme-linked immunosorbent assay (ELISA) method.
Measured: Day 14 and Day 28
Serum and Plasma Markers of Inflammation- C-reactive Protein (CRP)
Blood samples intended for C-Reactive Protein (CRP) analysis were collected in 4.0 mL plain red-topped blood collection tubes. The samples were permitted to coagulate for 30 to 60 minutes before centrifugation at 1600 gram (g) for 15 minutes. A 1 mL volume of serum supernatant was transferred via pipette into a Nunc tube and stored at room temperature. Central analysis of CRP in serum samples was measured via fixed time nephelometry on the Behring Nephelometer II.
Measured: Day 14 and Day 28
Serum and Plasma Markers of Inflammation- Fibrinogen
Blood samples intended for fibrinogen analysis were collected in 4.5 mL 3.2 % sodium citrate blue-topped blood collection tubes, then immediately mixed by gentle inversion eight to ten times. Each sample was centrifuged at 1600 g for 15 minutes. A 1 mL volume of plasma supernatant was transferred via pipette into a Nunc tube, frozen at -20°C. Central analysis of fibrinogen in plasma samples was completed via photometric clot detection with automatic sample preparation.
Measured: Day 14 and Day 28
Serum and Plasma Markers of Inflammation- Matrix Metalloproteinase-8 (MMP8), Matrix Metalloproteinase-9 (MMP9) and Surfactant Protein D (SP-D)
Blood samples intended for MMP-8 and MMP-9 analyses were collected in 4.0 mL lithium heparin greentopped collection tubes, then immediately mixed by gentle inversion five times. The samples were centrifuged at 1800 g for 15 minutes within 30 minutes of collection. A 2 mL volume of supernatant was transferred into a Sarstedt tube and subsequently centrifuged at 10000 g for 10 minutes at 2 to 8°C for complete platelet removal. A 1 mL volume of plasma supernatant was transferred into a Sarstedt tube and frozen at -70°C. Blood samples intended for SP-D were collected in 5.0 mL serum separator goldtopped blood collection tubes, then immediately mixed by gentle inversion 10 times. The samples were permitted to coagulate for 30 to 60 minutes before centrifugation at 1600 g for 15 minutes. Two 0.75 mL aliquots of serum supernatant were transferred separately into two Sarstedt tubes and frozen at -70°C. Plasma samples were centrally analyzed using a commercial test kit based on ELISA method.
Measured: Day 14 and Day 28
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC)
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Measured: Baseline (Day 1) to Day 14 and Day 28
Area Under the Plasma Drug Concentration (AUC) Versus Time Curve: AUC From Time Zero (Pre-dose) to Four Hours Post Dose (AUC[0-4]) and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t])
Blood samples were taken via an indwelling cannula (or by direct venepuncture), collected into a 3.0 mL Ethylenediaminetetraacetic acid (EDTA) lavender-topped collection tube, immediately mixed by gentle inversion ten times, then placed on water ice. The samples were centrifuged at 1600 g for 15 minutes at 4°C for 10 minutes. Supernatant plasma was transferred to a 1.8 mL Nunc tube and frozen at -20°C.
Measured: Day 1: pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose and Day 28: pre-dose, 1 and 4 hours
Maximum Observed Plasma Drug Concentration (Cmax)
Blood samples were taken via an indwelling cannula (or by direct venepuncture), collected into a 3.0 mL EDTA lavender-topped collection tube, immediately mixed by gentle inversion ten times, then placed on water ice. The samples were centrifuged at 1600 g for 15 minutes at 4°C for 10 minutes. Supernatant plasma was transferred to a 1.8 mL Nunc tube and frozen at -20°C.
Measured: Day 1: pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose and Day 28: pre-dose, 1 and 4 hours
Time to Maximum Observed Plasma Drug Concentration (Tmax)
Blood samples were taken via an indwelling cannula (or by direct venepuncture), collected into a 3.0 mL EDTA lavender-topped collection tube, immediately mixed by gentle inversion ten times, then placed on water ice. The samples were centrifuged at 1600 g for 15 minutes at 4°C for 10 minutes. Supernatant plasma was transferred to a 1.8 mL Nunc tube and frozen at -20°C.
Measured: Day 1: pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose and Day 28: pre-dose, 1 and 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2009 (estimated)
- Study start28 Sep 2009
- Primary completion29 Dec 2010
- Study completion29 Dec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 146 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00903201
- Sponsor's protocol ID
- 110399
- Status last verified
- Aug 2017
- First submitted
- 14 May 2009
- Last updated
- 17 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Moss RB, Mistry SJ, Konstan MW, Pilewski JM, Kerem E, Tal-Singer R, Lazaar AL; CF2110399 Investigators. Safety and early treatment effects of the CXCR2 antagonist SB-656933 in patients with cystic fibrosis. J Cyst Fibros. 2013 May;12(3):241-8. doi: 10.1016/j.jcf.2012.08.016. Epub 2012 Sep 17.
PubMed 22995323
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Parallel Group, Placebo Controlled 28 Day Study to Investigate the Safety, Tolerability and Pharmacodynamics of SB-656933 in Patients With Cystic Fibrosis.
- ClinicalTrials.gov ID
- NCT00903201
- Acronym / sponsor ID
- 110399
- Conditions
- Cystic Fibrosis
- Keywords
- cystic fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 146 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 28 Sep 2009 (actual)
- Primary completion
- 29 Dec 2010 (actual)
- Study completion
- 29 Dec 2010 (actual)
- First posted
- 18 May 2009 (estimated)
- Results
- Posted 17 Nov 2017
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 determine whether the safety, tolerability and pharmacodynamics of SB656933 in patients that have cystic fibrosis
Detailed description
This proof of mechanism study aims to evaluate the safety, tolerability and pharmacodynamics of SB-656933 following 28 days of daily administration of 20 and 50 mg SB-656933 in patients with CF compared to placebo. The primary endpoints of the study will be the effect of SB-656933 on safety and tolerability (adverse events, vital signs, clinical laboratory assessments, 12-lead electrocardiograms, and urinalysis) following 28 days of dosing. Secondary endpoints will include levels of neutrophil elastase in induced sputum and other sputum markers of inflammation (e.g. myeloperoxidase, total protein), induced sputum cells (i.e. total sputum neutrophil counts, percent sputum neutrophils) and sputum microbiology. Other assessments will include lung function measurements (spirometry); serum and plasma markers of inflammation (e.g. fibrinogen, CC-16, CRP, MMP8, MMP9, SP-D, and CXCL-8), quality of life questionnaire, and population pharmacokinetics parameters of SB-656933
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Experimental | Drug: SB65693320 mg of SB656933 |
| Treatment B | Experimental | Drug: SB65693350 mg of SB656933 |
| Placebo | Experimental | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Diagnosis of CF based on the following: sweat chloride > 60 mEq/L and/or genotype with 2 identifiable mutations consistent with CF; (ΔF508 homozygote, or ΔF508 heterozygote with a second allele known to cause the disease, or two alleles known to cause a class I, II, or III mutation) and one or more clinical features consistent with CF.
- Male and female subjects aged ≥18 years of age
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory].
- Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until one week after the last dose.
Key exclusion criteria (26 listed)
- Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination, or ECG, that is not associated with cystic fibrosis.
- Neutrophil count <1.5x109 /L
- In the judgment of the PI, the patient:
- suffers from clinically unstable pancreatic function
- has clinically significant weight loss( ≥5% after a previously stable period).
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 |
|---|---|---|
| SB65693320 mg | Drug | Treatment A |
| SB65693350mg | Drug | Treatment B |
| Placeboplacebo | Drug | Placebo |
Primary outcome
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Time frame: Up to Follow-up (up to 42 days)
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Number of Participants With Vital Signs of Potential Clinical Importance
Time frame: Up to Follow-up (up to 42 days)
Vital signs included heart rate, systolic and diastolic blood pressure and body temperature. Prior to vital signs all participants rested for at least five minutes in the seated, semi-supine, or supine position. The choice of position was kept constant for the duration of the study. Any results falling outside the normal range were repeated at the discretion of the Investigator. Potential clinical concern range for systolic blood pressure: <85 and >160 millimeter of mercury (mmHg), for diastolic: <45 and >100 mmHg and heart rate: <40 and >110 beats per minute. Number of participants with vital signs of potential clinical importance are presented.
Number of Participants With Hematology Abnormalities of Potential Clinical Importance
Time frame: Up to Follow-up (up to 42 days)
Hematology parameters were reviewed prior to participants receiving first dose of study medication. The potential clinical concern range for hematology parameters were: Red blood cell (RBC) count (low: < 3.72 * 10^12/Liters (L) and high: > 6.313 * 10^12/L), lymphocytes (low: < 0.8 gigacells/L), hematocrit (low: > 0.075 ratio change from Baseline and high: > 0.54 ratio), mean cell hemoglobin (MCH) (low: < 23.8 picograms (pg) and high: > 39.6 pg), mean cell volume (MCV) (low: <73 femtoliters (FL) and high: >110 FL), platelet count (low: < 100 gigacells/L and high: > 550 gigacells/L), white blood cell (WBC) count (low: < 3 gigacells/L and high: > 20 gigacells/L) and eosinophils (high: > 1 gigacells/L). Only those parameters for which at least one value of potential clinical concern was reported are summarized. Number of participants with hematology abnormalities of potential clinical importance are presented.
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance
Time frame: Up to Follow-up (up to 42 days)
The potential clinical concern range for clinical chemistry parameters were: glucose (low: < 2.8 millimole [mmol]/L and high: > 9.4 mmol/L), creatine kinase (high: > 3 * upper limit of normal units [ULN]/L), phosphorous, inorganic (low: < 0.8 mmol/L and high: > 1.6 mmol/L), total bilirubin (high: ≥ 1.5 * ULN micromole [μmol]/L), uric acid (low: < 41.636 μmol/L and high: > 582.904 μmol/L), alkaline phosphatase (ALP) (high: ≥ 2 * ULN international units [IU/L]/L), gamma glutamyl transpeptidase (GGT) (high: ≥ 110 IU/L), carbon dioxide content (low: < 18 mmol/L and high: > 32 mmol/L), direct bilirubin (high: > 1.5 * ULN μmol/L), potassium (low: < 3.0 mmol/L and high: > 5.5 mmol/L) and aspartate aminotransferase (AST) (high: ≥ 3* ULN IU/L). Only those parameters for which at least one value of potential clinical concern was reported are summarized. Number of participants with clinical chemistry abnormalities of potential clinical importance.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame: Up to Follow-up (up to 42 days)
Prior to ECG recordings, all participants rested for at least 5 minutes in the seated, semi-supine, or supine position. The choice of position was kept constant for the duration of the study. Participants avoided hot and cold food for at least 30 minutes prior to an ECG measurement. Any results falling outside normal range were repeated at the discretion of the Investigator. ECG Baseline values taken within 2.5 hours prior to first dose were calculated using the mean value of triplicate pre-dose readings. Triplicate readings were taken at least five minutes apart. Participants agreed to abstain from hot and cold drinks and food prior to an ECG measurement. ECG machine calculated heart rate and measured PR, QRS, QT, and QT corrected by Bazett's formula (QTcB), QT corrected by Fridericia's formula (QTcF) intervals. Number of participants with abnormal (not clinically significant [NCS] and clinically significant [CS]) electrocardiogram (ECG) findings are presented.
Number of Participants With Cystic Fibrosis (CF) Exacerbation
Time frame: Day 1 to Day 42
CF is one of the most common, lethal, autosomal recessive disease characterized by airway obstruction, bronchiectasis and infection, and exocrine pancreatic insufficiency. Number of participants with CF exacerbation are presented.
12 secondary outcomes
Number of Participants With Pseudomonas Aeruginosa and Staphylococcus Aureus Count in Sputum
Time frame: Day 1 and Day 28
Induced Sputum Neutrophil Number
Time frame: Day 28
Induced Sputum Neutrophil Percentage
Time frame: Day 28
Induced Sputum Inflammatory Markers-Myeloperoxidase and Neutrophil Elastase
Time frame: Day 28
Serum and Plasma Markers of Inflammation- Clara Cell Secretory Protein (CC-16) and CXCL8 (Interleukin-8 [IL-8])
Time frame: Day 14 and Day 28
Serum and Plasma Markers of Inflammation- C-reactive Protein (CRP)
Time frame: Day 14 and Day 28
Serum and Plasma Markers of Inflammation- Fibrinogen
Time frame: Day 14 and Day 28
Serum and Plasma Markers of Inflammation- Matrix Metalloproteinase-8 (MMP8), Matrix Metalloproteinase-9 (MMP9) and Surfactant Protein D (SP-D)
Time frame: Day 14 and Day 28
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC)
Time frame: Baseline (Day 1) to Day 14 and Day 28
Area Under the Plasma Drug Concentration (AUC) Versus Time Curve: AUC From Time Zero (Pre-dose) to Four Hours Post Dose (AUC[0-4]) and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-t])
Time frame: Day 1: pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose and Day 28: pre-dose, 1 and 4 hours
Maximum Observed Plasma Drug Concentration (Cmax)
Time frame: Day 1: pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose and Day 28: pre-dose, 1 and 4 hours
Time to Maximum Observed Plasma Drug Concentration (Tmax)
Time frame: Day 1: pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose and Day 28: pre-dose, 1 and 4 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22995323Moss RB, Mistry SJ, Konstan MW, Pilewski JM, Kerem E, Tal-Singer R, Lazaar AL; CF2110399 Investigators. Safety and early treatment effects of the CXCR2 antagonist SB-656933 in patients with cystic fibrosis. J Cyst Fibros. 2013 May;12(3):241-8. doi: 10.1016/j.jcf.2012.08.016. Epub 2012 Sep 17.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
33 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SB656933 in people with Cystic Fibrosis, run by GlaxoSmithKline at 33 sites in 5 countries.
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 17 inclusion and 26 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: finished, as of the sponsor's last update on 17 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United States, Germany, France, Israel, Canada. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) (time frame: Up to Follow-up (up to 42 days)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00903201, which also lists 1 linked publication.
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 17 Nov 2017.