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

• Register: EUCTR
• Last refreshed on: 1 April 2013
• Main ID: EUCTR2010-018738-27-DE
• Date of registration: 16/03/2010
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Limited
• Public 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
• Scientific 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
• Date of first enrolment: 02/06/2010
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-018738-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion 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 <110% predicted.
8. Excluding periods of exacerbation, FEV1 has not decreased by >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 < 450 msec at screening as determined by the investigators review.
12. 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%).
13. Male subjects must agree to use one of the contraception methods listed in th eprotocol. This criterion must be followed from the time of the first dose of study medication until one week after the last dose.
14. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
15. The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 <1.5x109 /L
2. 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 evidence of uncontrolled hyperglycemia or recent hypoglycemia
• has recent change in pancreatic enzyme requirements in the past 2 months.
3. 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.
4. Subjects unable to produce a technically acceptable sputum sample.
5. 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
6. Blood pressure persistently >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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystic fibrosis
MedDRA version: 12.1 Level: LLT Classification code 10011763 Term: Cystic fibrosis lung

Intervention(s)

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
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

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
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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).

Main Objective: To assess the safety and tolerability of 28 days repeat dosing with SB-656933 in subjects with cystic fibrosis

Secondary ID(s)

CF2110399