A first-in-man clinical trial to evaluate the safety and drug levels of single doses of inhaled GRC 17536 in healthy adult volunteers and multiple doses in mild asthmatics; and to evaluate safety and efficacy of inhaled GRC 17536 in mild asthmatics.
- Conditions
- Respiratory conditions such as mild asthma.MedDRA version: 15.1Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2012-002567-99-GB
- Lead Sponsor
- Glenmark Pharmaceuticals SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Part 1 (SAD): Healthy subjects
1. Subjects who are able and willing to give written informed consent;
2. Male subjects aged 18 to 50 years inclusive;
3. Weight =50 kg;
4. Body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive;
5. Healthy as determined by pre-study medical history, physical examination, and 12-lead ECG;
6. Non-smokers or ex-smokers for at least 12 months with less than a 10-pack per year history;
7. Clinical laboratory tests within the reference ranges or clinically acceptable to the Investigator;
8. Negative screens for drugs of abuse and alcohol (urine) at screening and admission. Subjects must test negative for the following: amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, ethanol, opiates and cotinine;
9. Medical history must be verified by either a personal physician or medical practitioner as appropriate
10. Male subjects should agree not to not donate sperm for 3 months post last dose; and
11. Female partners (of child bearing potential) of male subjects should use 2 methods of highly effective contraception for 3 months post last dose.
Parts 2 (MAD) and 3 (Allergen challenge):
1. Subjects who are able and willing to give written informed consent
2. Male and non-childbearing female subjects aged 18 to 65 years inclusive;
3. Weight =50 kg;
4. Body mass index (BMI) between 18.0 and 32.0 kg/m2 inclusive
5. Female subjects should be of non-child bearing potential, either surgically sterile or post menopausal for 2 years prior to screening, as confirmed by follicle stimulating hormone (FSH) and luteinizing hormone (LH);
6. Male subjects should agree to not donate sperm from first dose until 3 months post last dose
7. Two methods of highly effective contraception should be used if the female partner of a male subject is of child bearing potential (Section 9.4.1)
8. Steroid-naïve subjects with mild asthma for at least 6 months that satisfy the Global Initiative for Asthma (GINA) (6) definition of asthma, but otherwise healthy;
9. Non-smokers or ex-smokers for at least 12 months with less than a 10 pack year history;
10. Not taking any concomitant anti-asthma (except short-acting inhaled ß2-agonists or anti-allergy medication (except antihistamines) for at least 6 weeks prior to screening visit and willing to continue throughout the study period;
11. Pre-bronchodilator FEV1 of >70% of the predicted normal value for age, height and sex at screening and prior to first dose administration;
12. Positive methacholine with a provocative concentration of methacholine resulting in a 20% fall in FEV1 (PC20 methacholine) of equal to or less than 8 mg/mL at screening (Part 3 only);
13. Documented allergy to at least one common allergen (house dust mite, pollen allergens or cat dander) as confirmed by a skin prick test wheal =3 mm in diameter). Historical data (up to 1 year) may be used (Part 3 only);
14. Early asthmatic response (EAR) (FEV1 fall of = 20%, 0 to 60 minutes after allergen challenge) and LAR (FEV1 fall of =15% 3 to 8 hours after challenge) (Part 3 only); and.
15. Able to provide an acceptable a sputum sample which is suitable for analysis (Part 3 only).
To be randomised on Day 1 in Part 3, subjects must have:
Compliance with withholding of disallowed concomitant medication.
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 84
F.1.3 Elderly (>=65 years) no
Part 1 (SAD): Healthy subjects
1. Subjects with evidence or history of clinically significant haematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease;
2. Subjects with a supine systolic blood pressure (SBP) =160 mmHg and/or a supine diastolic blood pressure (DBP) =100 mmHg;
3. History of alcohol abuse or drug addiction as seen on positive screen on drugs of abuse or positive alcohol test;
4. Positive screen on hepatitis B surface antigen (HBsAg), antibodies to the hepatitis C virus (HCV) or antibodies to the human immunodeficiency virus (HIV) 1/2;
5. 12-lead ECG demonstrating QTcF >450 ms at screening;
6. Abnormal liver function tests;
7. Current diagnosis of active epilepsy or any active seizure disorder;
8. Subjects who have a significant infection or known inflammatory process on screening or admission;
9. Subjects who have acute gastrointestinal symptoms at the time of screening or admission;
10. Subjects who have an acute infection such as influenza at the time of screening or admission;
11. Subjects who have received any investigational drug (including GRC 17536) in any clinical trial within 3 months, or who are on extended follow-up;
12. Subjects who do not agree to use medically acceptable methods of contraception;
13. Strong or moderate inhibitors or inducers of CYP3A4;
14. Herbal medication/supplements, St John’s Wort and grapefruit juice for 14 days prior to screening;
Parts 2 (MAD) and 3 (Allergen challenge):
1. Subjects with evidence or history of clinically significant haematological, renal, endocrine, pulmonary (excluding mild asthma), gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
2. Worsening of asthma in the 4 weeks preceding the screening visit (requiring daily use of nebulised ß2-agonists or any use of long acting ß agonists (LABA), or requiring in-patient hospitalisation for asthma control, or requiring emergency room treatment, or requiring systemic corticosteroids for asthma control) or respiratory infection in the 4 weeks preceding the screening visit or during the admission period 1;
3. Use of any immunotherapy within 3 months prior to screening;
4. Use of nasal or inhaled corticosteroids, intraophthalmic corticosteroids, nasal, inhaled, or intraophthalmic cromolyn sodium or nedocromil, leukotriene receptor antagonists and 5-lipoxygenase inhibitors within 6 weeks prior to screening;
5. Patient on LABA and long-acting anti cholinergics;
6. History of life-threatening asthma,
7. Symptomatic with allergic rhinitis (eg, hay fever), requiring treatment, at screening or predicted to have symptomatic allergic rhinitis (eg, hay fever) during the time of study, requiring treatment;
8. History of serious adverse reaction, severe hypersensitivity or allergy to any drug or in any other circumstance (e.g. anaphylaxis);
9. Clinically significant abnormalities in physical examination and/or in laboratory test results (including haematology and chemistry panels, urinalysis) as assessed by the Investigator;
10. Subjects who have received any investigational drug (including GRC 17536) in any clinical trial within 3 months, or who are on extended follow-up;
11. Current diagnosis of active epilepsy or any active seizure disorder requiring chronic therapy with anti-epileptic drug(s);
12. Strong or moderate inhibitors or inducers of CYP3A4
13. Herbal medication/supplements
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method