Asthma MedDRA version: 9.1 Level: LLT Classification code 10003553 Term: Asthma
Conditions
Interventions
Product Name: PF-00610355
Pharmaceutical Form: Inhalation powder
Current Sponsor code: PF-00610355
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutic
Sponsors
Pfizer Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: Screening (Visit 1) Inclusion Criteria 1. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 2. Male/Female between and including the ages of 18-65 years. Females may be of either childbearing or non-child bearing potential. See section 4.4.1 for full requirements. 3. Females must be postmenopausal (=2 year), surgically sterilized or using adequate contraception (see section 4.4.1 for full requirements). All females must also have a negative urine pregnancy test. 4. Body Mass Index (BMI) of approximately 18 to 33 kg/m2 and a body weight of =50 kg (110 lbs). On a case-by-case basis (after discussion with Pfizer Clinician), subjects with a BMI 33 kg/m2 may be allowed in the study provided that BMI is proportionate to physical build, weight is stable and the subject is not morbidly obese, anorexic, bulimic or cachectic. 5. Subjects with a physician documented history or diagnosis of persistent asthma (according to GINA, 2007) definition of asthma, for at least 6 months prior to Screening Visit 1. 6. Subjects who have been maintained on a stable dose of ICS over the previous month prior to screening. 7. Subject selection is based on maintenance treatment prior to screening. The population most closely relates to the National Institute of Health Expert Panel Report 3 (NIH EPR 3) guidelines. Thus subjects are at Step 3 or 4 of treatment (or judged similar in severity to these subjects). Subjects must be maintained on one of the following treatments prior to screening: ? Low dose ICS plus LABA ? Medium dose ICS alone ? Medium dose ICS plus LABA 8. Treatment judged to be equivalent to medium dose ICS plus LABA (eg, high dose ICS alone). 9. Trough FEV1 must be 50-100% of predicted (for age, height, sex, race) on current ICS treatment after abstaining from LABA (where applicable) for a minimum of 24 hours and after abstaining from short acting bronchodilator (SABA) for a minimum of 6 hours. 10. Subjects on prior treatment of low dose ICS alone may also be recruited provided they meet the NIH EPR 3 criteria for ‘not well controlled’ (specifically: symptoms >2 days/week and night-time awakenings 1-3 times/ week and/or use of SABA >2 days/ week. These subjects must have a trough FEV1 50-80% of predicted (for age, height, sex, race) on current ICS treatment after abstaining from SABA for a minimum of 6 hours. 11. Reversibility =15% and =200 ml (within 15-45 minutes following 200 mcg salbutamol, administered with spacer) on current ICS treatment and after abstaining from LABA (where applicable) for a minimum of 24 hours and after abstaining from SABA for a minimum of 6 hours. 12. Subjects with seasonal or perennial asthma (eg, to common aeroallergens) may be included provided they are either asymptomatic (and expect to remain so throughout the study) or are willing to be maintained throughout the study using a regular dose of intranasal corticosteroids and/ or intranasal antihistamines only, and the allergy is known not to cause a worsening of asthma symptoms. 13. Judged able to switch to Asmanex Twisthaler 200 or 400 mcg per day and as needed salbutamol (SABA) for the 5 w
Exclusion criteria
Exclusion criteria: 1. Subjects who have had a severe asthma exacerbation in the 2 months prior to screening defined as follows: a short temporary increase in corticosteroid therapy (inhaled, oral or IV) in response to worsening asthma control or a decrease in the morning PEF (if known). 2. Subjects who are current smokers. Ex smokers who have given up smoking for 10 pack years (eg, 1 pack year = 20 cigarettes per day for 1 year or 5 cigarettes per day for 4 years). 3. Evidence of airways infection in the 4 weeks prior to screening. 4. The subject is diagnosed with chronic obstructive pulmonary disease (COPD) and/or other chronic lung diseases (eg, pulmonary fibrosis, bronchiectasis, pneumoconiosis, sarcoidosis, tuberculosis). 5. FEV1 4 times/ week or requirement for SABA several times/ day. (Note: eligibility based on FEV1 is wider than the NIH EPR 3 criteria as the lower limit of prebronchodilator FEV1 allowed in this study is 50%. 7. Evidence of unstable or poorly controlled asthma in the 2 weeks prior to screening, including but not limited FEV1 160 mmHg or DBP >100 mmHg), pulmonary hypertension or cerebrovascular disease (including transient ischaemic attacks). 10. ECG evidence of QTc prolongation >450 msec. 11. Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation (assessed by the investigator). 12. Hypokalaemia (below LLN for reference laboratory). 13. Liver function test abnormalities: •Alanine amino transferase >3 x upper limit of normal (ULN). •Aspartate amino transferase >3 x ULN. •Alkaline phosphatase >1.5 x ULN. •Total bilirubin >ULN. 14. Note, subjects otherwise eligible for the study but with alanine amino transferase or aspartate amino transferase levels up to 1.5x ULN may be included provided all other liver function parameters are normal. Subjects with levels >1.5x ULN < 3x ULN may be retested after approximately 1 week and included in the study if the above criteria are met. 15. Subjects with previous diagnosis of malignancy, HIV (specific screening is not required), hepatic insufficiency or severe renal insufficiency will be excluded. GFR will be calculated using plasma creatinine (determined for laboratory safety measurement at screening) according to the Cockcroft & Gault formula. Subjects with GFR<30mL/min/1.73E2 will be excluded. 16. History within the previous 6 months of an epileptic seizure, “poorly controlled” (HbAc1=10%) Type 1 or Type 2 diabetes and or acute hepatitis of any etiology.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of PF-00610355 (‘once daily’ QD doses of 100 mcg, 300 mcg and 600 mcg) in the treatment of moderate asthma following 4 weeks treatment.;Secondary Objective: To assess the safety and toleration of PF-00610355 (QD) in subjects with moderate asthma. To characterize the relationship of PF-00610355 dose (QD) to systemic pharmacodynamics (PD) (heart rate and potassium). To characterize the dose response relationship of PF-00610355 (QD) to efficacy; (forced expiratory volume (FEV1)). To assess the efficacy of PF-00610355 on quality of life (QOL), asthma symptoms, rescue medication usage, peak expiratory flow (PEF). To investigate the pharmacokinetics of PF-00610355.;Primary end point(s): Change from baseline trough (24 hours post-dose) FEV1 at week 4. | — |
Countries
Sweden
Outcome results
None listed