FF/VI vs FP, Ph 4, Asthma, excercise

Phase 1

Conditions: Adolescent and Adult Subjects with Asthma andExercise-Induced Bronchoconstriction
MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2017-001516-11-Outside-EU/EEA

Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: A

Sex: All

Target Recruitment: 66

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria
apply:
1. Informed consent: Subjects must give their signed and dated written informed consent to participate prior to commencing any study related activities.
2. Age Range: 12 to 50 years of age, inclusive, at Visit 1 (Screening).
3. Diagnosis: A diagnosis of asthma, as defined by the National Institutes of Health [NIH, 2007], for at least 12 weeks prior to Visit 1.
4. Asthma Severity: Subjects must have a pre-bronchodilator FEV1 of =70% of the predicted normal value. Predicted values will be based upon Global Lung Function Initiative (GLI) [Quanjer, 2012] equations for spirometry reference values.
5. Evidence of EIB: Subjects must answer Yes” to at least 2 of the following 3 questions reflecting on the previous 12 months:
- Are you short of breath during exercise or other physical exertion?
- Do you wheeze after exercise or other physical exertion?
- Do you cough after exercise or other physical exertion?
6. Concurrent Anti-Asthma Therapy: Subjects must be taking low- to moderate dose inhaled steroids for 12 weeks prior to Visit 1 in order to participate with no change in dose for the 4 weeks prior to Visit 1. Example dosages considered appropriate for study participation are outlined in the SRM.
7. Gender: Subjects may be male or an eligible female.
A female is eligible to enter and participate in the study if she is of:
Non-child bearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile).
Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, > 45 years, in the absence of hormone replacement therapy.
OR
Child bearing potential, has a negative pregnancy test at screening, and agrees to acceptable contraceptive methods approved in their local country, when used consistently and correctly (i.e., in accordance with the approved product label and the instructions of the physician for the duration of the study – screening to follow-up contact). See Appendix 5.
8. Albuterol/salbutamol Use: All subjects must be able to replace their current short-acting beta2-agonist (SABA) with albuterol/salbutamol, to be used only on an as-needed basis for the duration of the study. Each subject must be judged capable of withholding albuterol/salbutamol for at least 6 hours prior to performing spirometric evaluations.
9. Physical Capacity: Each subject must be physically able to perform the exercise challenges on a treadmill when bronchodilators have been withheld.
Are the trial subjects under 18? yes
Number of subjects for this age range: 17
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 57
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria
apply:
1. Intermittent Asthma, Seasonal Asthma, or Exercise-Induced
Bronchoconstriction Only: Subjects with only intermittent or seasonal asthma or only exercise-induced asthma are excluded from participation in this study.
2. History of Life-threatening Asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 10 years.
3. Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 12 weeks of Visit 1 or that resulted in an overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.
4. Symptomatic Allergic Rhinitis: Subjects with symptomatic allergic rhinitis at Visit 1 may be treated for up to four weeks with intranasal corticosteroids followed by a repeat screening visit to determine eligibility prior to entry into the study. Subjects that continue to be symptomatic after up to four weeks of treatment will be excluded.
5. 12-Lead Electrocardiogram (ECG): A subject is not eligible if he/she has an abnormal, clinically significant ECG as determined by the investigator at the Screening Visit.
6. Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
7. Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of Visit 1 and led to a change in asthma management or, in the opinion of the investigator, is expected to affect the subject’s asthma status or the subject’s ability to participate in the study.
8. Concurrent Respiratory Disease: A subject must not have current evidence of:
a. Atelectasis
b. Bronchopulmonary dysplasia
c. Chronic bronchitis
d. Chronic obstructive pulmonary disease (current or past diagnosis including asthma/COPD overlap)
e. Pneumonia
f. Pneumothorax
g. Interstitial lung disease
h. Or any evidence of concurrent respiratory disease other than asthma
9. Other Concurrent Diseases/Abnormalities: A subject must not have any clinically significant, uncontrolled condition, or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
The list of additional excluded conditions/diseases includes, but is not limited to, the following: (Table 1 Page 33 of the protocol)
10. Investigational Medications: A subject must not have used any investigational drug within 30 days prior to Visit 1 or within five half-lives (t½) of the prior investigational study, whichever is longer of the two periods.
11. Allergies:
a) Drug Allergy: Any adverse reaction including immediate or delayed
hypersensitivity to any beta2-agonist, sympathomimetic drug, or any
intranasal, inhaled, or systemic corticosteroid therapy, or excipients used with FF/VI 100/25 or FP 250 (i.e., drug, lactose or magnesium stearate).
b) Milk Protein Allergy: History of severe milk protein allergy.
c) Latex Allergy: History of allergy or sensitivity to latex that in the opinion of the investigator contraindicates the subject’s participation in the study.
12. Concomitant Medication: Administration of prescription or non-prescriptio