A Phase 1 Open-label, Non-randomized, Single Ascending Dose Escalation Study To Evaluate The Pharmacokinetics, Safety, And Tolerability Of A Ralinepag Extended Release (XR) Tablet Formulation In Healthy Chinese Subjects

ES102102

A Phase 1 Open-label, Non-randomized, Single Ascending Dose Escalation Study To Evaluate The Pharmacokinetics, Safety, And Tolerability Of A Ralinepag Extended Release (XR) Tablet Formulation In Healthy Chinese Subjects.

2020-10-09

2020-11-09

2020-11-09

Completed

Early phase I

15

Inclusion Criteria: * 1. Healthy subjects aged 18 to 45 years at the time of signing the informed consent form (ICF). 2. Body mass index of 19.0 to 25.0 kg/m2. 3. In good general health, free from clinically significant medical or psychiatric illness or disease (as determined by medical/surgical history, physical examination, weight, 12-lead ECG and clinical laboratory tests). 4. HIV, Syphilitics, Hepatitis B and Hepatitis C negative at the screening evaluation. 5. Adequate venous access in the left or right arm to allow for collection of a number of blood samples 6. Provides written informed consent. 7. Willing to comply with all study procedures and requirements. 8. Subjects of reproductive potential must agree to use an approved method of contraception from Day -1 until 30 days after study discharge: 1. Barrier method (e.g., condom) plus an approved method of highly effective contraception or 2. Female/male partner is surgically sterile. Exclusion Criteria: * 1. History or presence of malignancy, with the exception of adequately treated localized skin cancer (basal cell or squamous cell carcinoma), which is allowed. 2. History or presence of any clinically significant psychiatric condition (including depression or prior suicidal behaviour). 3. Evidence of clinically relevant medical illness, cardiovascular, hematological, gastrointestinal, hepatic, renal, rheumatologic, endocrine, pulmonary, neurologic, psychiatric or skin disorder (excluding skin cancer as described in Exclusion Criterion 1) or history of hypertension or heart disease including any abnormal laboratory results deemed clinically significant by the study investigator at screening. 4. History of dysphagia. 5. Clinically significant surgical procedure or traumatic injury within 3 months of screening. 6. History of epilepsy (other than febrile seizures during childhood). 7. Clinically significant infection within 28 days of start of dosing. 8. Currently suffers from clinically significant systemic allergic disease or has a history of significant drug allergies including a history of anaphylactic reaction (particularly reactions to general anesthetic agents); allergic reaction due to any drug which led to significant morbidity. 9. History or presence of cardiac arrhythmia or congenital long QT syndrome. 10. QTcF \>450 msec, PR \>220 msec and QRS \>120 msec on screening ECG (ECG may be repeated after consultation with the Medical Monitor). 11. Use of tobacco or nicotine containing products in the previous 6 months prior to dosing or use of a nicotine patch within 14 days prior to screening. 12. Regular alcohol consumption \> 2 units/day (1 unit = 300 mL of beer or 45 mL of alcohol 40% or 150mL of wine) or alcohol consumption within 48 hours of start of dosing. 13. Positive urine drug or alcohol breathalyzer test prior to study entry or history of alcohol or drug abuse in the last 12 months. 14. Use of any prescription medication within 14 days prior to screening. 15. Use of any over the counter (OTC) medication, herbal or hormone supplements, or diet aids within 14 days prior to screening 16. Participation in any other investigational trial in which the last dose of study drug occurred within 30 days or 5 half-lives (whichever is longer) before Check-in for Inpatient Period (Day -1) 17. Donation of blood from 30 days before Check-in for Inpatient Period (Day -1) or of plasma from 2 weeks before Check-in for Inpatient Period (Day -1) 18. Receipt of blood products within 2 months before Check-in for Inpatient Period (Day -1) 19. Abnormal supine BP (defined as either systolic BP \> 140 millimetres (mm) Hg or \< 90 mmHg or diastolic BP \> 90 mmHg or \< 50 mmHg) or abnormal pulse rate (\> 100 beats per minute \[bpm\] or \< 50 bpm), confirmed by at least 1 repeat measurement 20. Abnormal orthostatic BP at Screening or CPC Check-in on Day -1 (defined as confirmed drop in SBP \> 20 mmHg or drop in DBP \> 10 mmHg with standing). The assessment may be repeated once to assure adequate hydration. 21. Women who are pregnant, lactating or breast-feeding. 22. Known hypersensitivity to any of the excipients of Ralinepag. 23. Any inappropriate condition to participate in the study considered by investigator.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'The study is planned to enroll 15 subjects with open-label, fixed sequence, non-randomized to take a single dose of ralinepag at 3 separate dose intervals. Ralinepag will be administered at doses of 50, 100 and 150 mcg single oral each time. Subjects will receive Regimen A (single dose of ralinepag 50 mcg) in the morning of Day 1 and pharmacokinetic assessments will be conducted pre-dose and over the 96 hours post-dose. There will be a washout period of 7 days between each IMP administration. Regimens B and C (single dose of ralinepag 100 mcg and ralinepag 150 mcg) will be administered following an overnight fast on Day 8 and 15, respectively, with 96 hours of pharmacokinetic assessments as performed with Regimen A. A Follow-up phone call will take place 10±1 days post-last dose to ensure the ongoing well-being of the subjects.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 15, 'type': 'ACTUAL'}}

2024-02-01