28 Day Repeat Dose in Cystic Fibrosis Patients

NCT00903201 | Completed Phase 2 Results DMC

• 1 other identifier: 110399
• Study Type: interventional
• Target: 146
• Locations: 5 countries
• Sites: 33

Brief Summary

The purpose of this study is to determine whether the safety, tolerability and pharmacodynamics of SB656933 in patients that have cystic fibrosis

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  Day 1 to Day 42

Secondary Outcomes (12)

• Number of Participants With Pseudomonas Aeruginosa and Staphylococcus Aureus Count in Sputum

  Day 1 and Day 28

• Induced Sputum Neutrophil Number

  Day 28

• Induced Sputum Neutrophil Percentage

  Day 28

• Induced Sputum Inflammatory Markers-Myeloperoxidase and Neutrophil Elastase

  Day 28

• Serum and Plasma Markers of Inflammation- Clara Cell Secretory Protein (CC-16) and CXCL8 (Interleukin-8 [IL-8])

  Day 14 and Day 28

Study Arms (3)

Treatment A

EXPERIMENTAL

20 mg of SB656933

Drug: SB656933

Treatment B

EXPERIMENTAL

50 mg of SB656933

Drug: SB656933

Placebo

EXPERIMENTAL

Placebo

Drug: Placebo

Interventions

SB656933 DRUG

20 mg

Treatment A

Placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (33)

GSK Investigational Site

Birmingham, Alabama, 35233, United States

Location

GSK Investigational Site

Tucson, Arizona, 85724, United States

Location

GSK Investigational Site

Palo Alto, California, 94304, United States

Location

GSK Investigational Site

Denver, Colorado, 80206, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30322, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Worcester, Massachusetts, 01655, United States

Location

GSK Investigational Site

Albany, New York, 12208, United States

Location

GSK Investigational Site

Akron, Ohio, 44308, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45229, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44106, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15213, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Colchester, Vermont, 05446, United States

Location

GSK Investigational Site

Madison, Wisconsin, 53792-9988, United States

Location

GSK Investigational Site

Milwaukee, Wisconsin, 53226, United States

Location

GSK Investigational Site

Toronto, Ontario, M5B 1W8, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2W 1T8, Canada

Location

GSK Investigational Site

Lille, 59037, France

Location

GSK Investigational Site

Montpellier, 34295, France

Location

GSK Investigational Site

Paris, 75679, France

Location

GSK Investigational Site

Pessac, 33604, France

Location

GSK Investigational Site

Reims, 51092, France

Location

GSK Investigational Site

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60590, Germany

Location

GSK Investigational Site

Bochum, North Rhine-Westphalia, 44791, Germany

Location

GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

GSK Investigational Site

Berlin, 13353, Germany

Location

GSK Investigational Site

Hamburg, 22763, Germany

Location

GSK Investigational Site

Haifa, 31096, Israel

Location

GSK Investigational Site

Jerusalem, 91240, Israel

Location

GSK Investigational Site

Petah Tikva, 49202, Israel

Location

Related Publications (1)

• 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.

  PMID: 22995323 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

SB 656933

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2009
• First Posted: May 18, 2009
• Study Start: September 28, 2009
• Primary Completion: December 29, 2010
• Study Completion: December 29, 2010
• Last Updated: November 17, 2017
• Results First Posted: November 17, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

US (17); CA (2); IL (3); DE (6); FR (5)