Cystic fibrosis MedDRA version: 12.1 Level: LLT Classification code 10011763 Term: Cystic fibrosis lung
Conditions
Interventions
Product Name: SB-656933 Tablets
Product Code: SB-656933-AAA
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: SB-656933-AAA
Concentration unit: mg milligram(s)
Concentration type: equal
Co
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of CF based on the following: sweat chloride > 60 mEq/L and/or genotype with 2 identifiable mutations consistent with CF; and one or more clinical features consistent with CF. 2. Male and female subjects aged =18 years of age 3. 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; - child-bearing potential and agrees to use one of the contraception methods listed in the protocol 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. 4. 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. 5. 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. 6. Able to perform lung function tests reliably. 7. FEV1 >40% and 15% over the past 12 months. 9. Clinically colonized by a bacterial organism commonly seen in cystic fibrosis other than Burkholderia cepacia 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. 10. To be eligible, female patients must have a negative pregnancy test (urine or serum) and not be nursing at screening or prior to dosing. 11. Subjects must have a QTcB or QTcF 2.0 xULN (isolated bilirubin >2.0xULN is acceptable if bilirubin is fractionated and direct bilirubin =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination, or ECG, that is not associated with cystic fibrosis. • Neutrophil count 155/95 mmHg at screening. 7. Positive HIV, Hepatitis B surface antigen or Hepatitis C antibody at screening. 8. History of regular alcohol consumption averaging >7 drinks/week for women or >14 drinks/week for men. 9. Urinary cotinine levels indicative of smoking. 10. Use of oral or parenteral corticosteroids within 4 weeks of screening. 11. Colonization with Burkholderia cepacia 12. Subjects currently being treated for mycobacterial infection 13. Subjects with presumed active Allergic Bronchopulmonary Aspergillosis (ABPA) 14. Subjects who have newly started therapy with azithromycin within the past 3 months. 15. In the judgment of the investigator, clinically significant hemoptysis (> 30 cc per episode) within the last 6 months 16. Donation of blood in excess of 500 mL within a 56-day period prior to dosing 17. 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. 18. The subject has a positive pre-study drug/alcohol screen. 19. Patients may not be on an inhaled antibiotic during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of 28 days repeat dosing with SB-656933 in subjects with cystic fibrosis;Secondary Objective: To evaluate the effects of 28 days of treatment with SB-656933 in patients with Cystic Fibrosis compared with placebo on: • Sputum microbiology • Sputum neutrophils • Sputum markers of inflammation • Pulmonary function assessed by spirometry • Systemic markers of inflammation in serum • Daily Respiratory Symptom Diary for Cystic Fibrosis (Self Reported Version) • Repeat dose pharmacokinetics of SB-656933 in cystic fibrosis patients ;Primary end point(s): Safety and tolerability of SB-656933 in subjects with cystic fibrosis, including, adverse events, vital signs, clinical laboratory assessments (hematology, chemistry, urinalysis, and VB-1), electrocardiographic (ECG) parameters, and exacerbation of CF (including withdrawals, time to exacerbations and/or new antibiotic prescription). | — |
Countries
Germany
Outcome results
None listed