A clinical study to compare the safety and tolerability of two formulations of a new Systemic Sclerosis drug in Healthy Participants - Part B

Exclusion Criteria28

• Participants are excluded from the study if any of the following criteria apply:
• Any participant that has been enrolled and given IMP into Part A of the study are excluded from participating in Part B.
• Have received any Investigational medicinal product (IMP) within 30 days or 5 half-lives prior to Screening, whichever is longer.
• Have received a live attenuated vaccine within 60 days or a registered vaccine within 30 days prior to the first dose of the IMP or plans to receive such vaccines during the study.
• Have used any prescription medications within the 14 days (or 5 half-lives, whichever is longer) prior to Day 1, and/or non-prescription drugs and herbal remedies (such as St. John's Wort [Hypericum perforatum]), within the 7 days prior to Day 1, or anticipate needing to take medications during the study period. Over-the-counter multivitamins will be permitted. If needed, paracetamol (less than or equal to 2 grams/day) may be used. Any questions regarding concomitant medications should be directed to the Sponsor.
• Have a known allergy or sensitivity or contraindication to the IMP or its excipients.
• Have any clinically significant abnormality at Screening determined by medical history, vital signs, physical examination, blood chemistry, haematology, urinalysis or a 12-lead electrocardiogram (ECG), including but not limited to:
• a. Repeated measurement of systolic blood pressure 140 mmHg, diastolic blood pressure < 40 or >90 mmHg (inclusive), or pulse rate 100 bpm, pulse oximetry 1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
• c. Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin 30 mg/g at screening. Note: eGFR calculated using CKD-EPI equation.
• Have received blood products within 1 month prior to Screening.
• Have a history of thyroidectomy or thyroid disease that required medication within the past 12 months.
• Have had serious angioedema episodes within the previous 3 years or requiring angioedema medication in the previous two years.
• Have a bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with blood draws in the opinion of the investigator, contraindicate blood draws.
• Altered absorption and/or excretion of orally administered drugs e.g. Crohn’s disease, Gilbert’s syndrome, stomach or intestinal surgery etc.
• Have a history of or current clinically significant gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine, oncological, immunodeficiency, neurological, metabolic, haematological or autoimmune disorder; or a history of or current tuberculosis, epilepsy, diabetes or glaucoma as determined by the investigator.
• Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, and TB testing: a positive (not indeterminate) QuantiFERON-TB Gold test. NOTE: The QuantiFERON-TB Gold test is dependent on previous treatment(s). This test may not be suitable if previous treatment(s) produced significant immunosuppression.
• Major surgery within 3 months prior to Day 1 or planned during the study period.
• Presence of hepatitis B surface antigen or positive hepatitis C antibody or RNA test result at Screening. NOTE: participants with positive hepatitis C antibody due to prior resolved disease can be enrolled if a confirmatory negative hepatitis C RNA test result is obtained. NOTE: The RNA test is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing.
• Positive human immunodeficiency virus (HIV) antibody test.
• Have a positive alcohol breath test or urine screen for drugs of abuse at Screening or Day -1, or evidence of drug or alcohol abuse in the investigator’s opinion.
• History of drug/chemical or alcohol abuse within 6 months prior to Day -1. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol/spirits) or positive alcohol breath test at screening and Day -1.
• Use of tobacco or nicotine-containing products in excess of the equivalent of 5 cigarettes per day.
• Consumption of red wine, grapefruit, or grapefruit -related citrus fruits (e.g., Seville oranges, pomelos, fruit juices) within 7 days prior to the first dose of asengeprast.
• Are unable to provide a blood sample without undue trauma or distress.
• Have a history of or current clinically relevant social, clinical, or psychiatric condition which, in the opinion of the investigator, makes the participant unsuitable for participation in the study.
• Are pregnant, breastfeeding, or plan to become pregnant during the study period.
• Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
• Have any other medical condition or significant co-morbidities, or any finding during Screening or Day -1, in the opinion of the investigator, may interfere with the study objectives or put the participants at risk.