A study to look at different types and doses of medications called inhaled corticosteroids (ICS), and compare how they effect the lungs. ICS drugs are a common treatment for asthma and have an anti-inflammatory effect in the airways of the lungs.

Phase 1

• Conditions: Asthma; 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: EUCTR2016-003002-14-GB
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-12-07
• Study Completion: 2018-12-20
• Last Update Posted: 20 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

1. Age of subject: 18 to 65 years of age inclusive, at the time of signing the informed consent.
2. Asthma: Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit.
3. Severity of disease:
a) Pre-bronchodilator FEV1 = 65% of predicted at screening.
b) The pre-dose baseline FEV1 should not have changed significantly in the opinion of the investigator from the screening baseline value and should be = 65% predicted for the subject to continue.
c) Documented sensitivity to AMP with a provocative concentration of AMP resulting in a fall of =20% FEV1 with a PC20 AMP =80 mg/mL at the screening visit.
4. Current Therapy:
• Short-Acting Beta2-Agonists (SABA): prescribed SABA for at least 12 weeks prior to screening, if needed.
• Subjects receiving low-dose ICS as defined in Appendix 5 may take part after a 4 week ICS washout prior to AMP challenge. The subject’s asthma symptoms must remain stable during this 4-week period as assessed at screening visit 2. Stable asthma is defined as:
• No more than 2 consecutive days where =12 inhalations/day of salbutamol were used.
• No severe asthma exacerbations requiring use of systemic corticosteroids (tablets, suspension, or injection) or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids.
• No clinical asthma worsening which in the opinion of the investigator requires additional asthma treatment other than study medication or salbutamol.
• Subjects taking LABA, LAMA, leukotriene receptor antagonist (LTRA) therapy within 3 months prior to the start of the study are not eligible.
• Subjects taking biological therapies within 6 months prior to start of the study are not eligible.
5. Bodyweight and Body Mass Index (BMI): Bodyweight = 50 kg and BMI within the range 18.0-35.0 kg/m2 (inclusive).
6. Gender: Male and female.
Females:
A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (HCG) test), not lactating, and at least one of the following conditions applies prior to randomization:
a. Non-reproductive potential defined as:
• Pre-menopausal females with one of the following:
• Documented tubal ligation.
• Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion.
• Hysterectomy.
• Documented Bilateral Oophorectomy.
• Postmenopausal defined as 12 months of spontaneous amenorrhea, in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
b. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential from 30 days prior to the first dose of study medication and until at least five terminal half-lives after the last dose of study medication (Appendix 4).
The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
7.

Exclusion Criteria

1. A history of life-threatening asthma. NOTE: Life-threatening asthma is defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 5 years.
2. Other significant pulmonary diseases to include (but not limited to): severe pneumonia within 6 months of the screening visit, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, tuberculosis or other respiratory abnormalities other than asthma.
3. Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear within 4 weeks of screening that:
• 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.
4. Oropharyngeal examination: A subject will not be eligible if he/she has clinical visual evidence of oral candidiasis at screening.
5. Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 12 weeks of screening or that resulted in overnight hospitalization requiring additional treatment for asthma within 6 months prior to randomization.
6. Use of prohibited medications:
Any other medications including, anti-depressant drugs, and anti-asthma drugs (other than short acting inhaled ß-agonists supplied as rescue medication, oral contraceptives not listed in Appendix 4, non-steroidal anti-inflammatory drugs, stable doses of anti-histamines, and paracetamol) for 1 week prior to screening and throughout the course of the study. Anti-histamines should be withheld 4 days prior to AMP challenge.
• Subjects must also be able to abstain from short acting inhaled ß-agonists, for 8 hours prior to spirometry.
7. Subjects undergoing de-sensitization therapy.
8. Tobacco Use: Current smokers who smoke > 20 cigarettes per week or the equivalent unit dose of other tobacco products or e-cigarettes, or smokers with a smoking history of =10 pack years.
9. History of regular alcohol consumption exceeding 21 units/week for men and 14 units/week for females (1 unit= 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of spirits) within 6 months of screening.
10. All subjects who are currently or in the last month have worked night-shifts are excluded from the study.
11. Previous Participation: Exposure to more than four new chemical entities within 12 months prior to the first dosing day or received an investigational product within 30 days of study start, or 5 half-lives of study drug if that is longer.
12. Other concurrent Diseases/Abnormalities: A subject has 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 study results if the condition/disease exacerbated during the study. (e.g. stroke or myocardial infarction within 3 months, uncontrolled hypertension, congestive heart failure, uncontrolled diabetes mellitus.)
13. Evidence of cancer or history of cancer in the past 5 years other than adequately treated basal or squamous cell carcinoma of the skin or adequately treated in situ carcinoma of the cervix.
14. Pregnancy and Lactating Females:
• Pregnant females as determined by positive urine HCG test at screening or by positive urine HCG te

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified