A Phase I, Single-center, Open-label, Fixed Sequence Study in Chinese Healthy Male Adults to Evaluate the Effect of Omeprazole on the Pharmacokinetics of AB-106
Overview
- Phase
- Phase 1
- Intervention
- Multiple administration of omeprazole Single administration of AB-106
- Conditions
- Pharmacokinetic Study
- Sponsor
- Nuvation Bio Inc.
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Cmax
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a single-center, open-label, fixed sequence phase I clinical study. To evaluate the effect of continuous administration of omeprazole magnesium enteric coated tablets on PK after single dose AB-106 capsule administration in Chinese healthy male subjects. This study includes a screening period (1-28 days before administration), treatment period (34 days), and follow-up period ( after the last dose completed 7 ± 3 days). The treatment period of this study was divided into two periods, and the subjects were divided into two groups, 12 subjects in the first group and 10 subjects in the second group. The treatment method and research process of each group of subjects are the same. After the first group of subjects completes the second cycle and is evaluated by the investigator and sponsor, the second group of subjects can start administration. If there are no more than 4 subjects in the first group who have vomiting gastrointestinal reaction (vomiting occurs within 8 hours after each cycle of administration) after completing the two cycles of administration of AB-106 400 mg, they can be added to the second group of subjects, and the number of added subjects shall not exceed the number of subjects who have vomiting gastrointestinal reaction. If more than 4 subjects have gastrointestinal reaction of vomiting, the investigator and sponsor will make a comprehensive evaluation, and can reduce the dosage of AB-106 to 200 mg, and 22 subjects will be included in the trial at one time or supplemented in the second group to complete the 400 mg dose group
Investigators
Eligibility Criteria
Inclusion Criteria
- •Chinese male healthy subjects (health refers to the state without clinically relevant abnormalities confirmed by medical history, physical examination, vital signs, 12 lead ECG and clinical laboratory examination).
- •The age at the time of signing the informed consent was between 18 and 55 years old (including the threshold).
- •When screening, the body weight was more than 50 kg, and the body mass index (BMI) was between 19 and 26 kg/m2 (including the cut-off value).
- •Subjects voluntarily signed the Informed Consent Form (ICF).
- •Subjects can communicate well with researchers and complete the study according to the protocol.
- •Male subjects with fertility agree that they and their sexual partners must take effective contraceptive measures during the study period and within 90 days after the last dose, and agree not to donate sperm during this period.
Exclusion Criteria
- •Evidence or medical history (including drug allergy) of hematology, kidney, endocrine, lung, gastrointestinal, cardiovascular, liver, spirit, nerve or allergic diseases with clinical significance according to the judgment of the investigator.
- •According to the judgment of the researcher, abnormal laboratory tests with clinical significance (blood routine test, blood biochemical test \[fasting\], urine routine test, blood coagulation function test).
- •Systolic blood pressure\<90 mmHg or ≥ 140 mmHg, diastolic blood pressure\<50 mmHg or ≥ 90 mmHg, and the abnormality judged by the investigator is clinically significant.
- •People with eye diseases or people with a history of eye diseases who are considered by the investigator to increase the risk of the subject through eye examination.
- •12 lead ECG showed QTcF\>450 ms (msec) or QRS interval\>120 msec.
- •Fever history within 5 days before administration.
- •People with positive detection of hepatitis B virus surface antigen (HBs Ag), hepatitis C virus antibody (HCV Ab), human immunodeficiency virus (HIV) antibody, or Treponema pallidum (TP) antibody.
- •The food or drug known to be used 28 days before screening is a powerful inhibitor of cytochrome P450 3A4 enzyme (CYP3A4); Known for use 28 days before screening Its drug is CYP3A4 potent inducer; The drug used 28 days before screening and during the study was CYP3A4 substrate with a narrow therapeutic window.
- •The food or drug known to be used 28 days before screening is the substrate of P-gp
- •Take Chinese herbal supplements within 28 days before screening; Take any clinical study drug within 3 months or 5 half lives (whichever is longer) before screening; Prescription drugs or over-the-counter drugs and dietary supplements were used within 14 days or 5 half lives (whichever is longer) before screening. As an exception, acetaminophen/paracetamol can be used in a dose of 1 g/day.
Arms & Interventions
Omeprazole combined with AB-106 group
Intervention: Multiple administration of omeprazole Single administration of AB-106
Outcomes
Primary Outcomes
Cmax
Time Frame: Day 1 to day15 for both treatment cycle one and cycle two, the total duration is 30 days
plasma drug peak concentration
AUClast
Time Frame: Day 1 to day15 for both treatment cycle one and cycle two, the total duration is 30 days
area under the plasma drug concentration time curve from 0 to the last measurable drug concentration time point
AUCinf
Time Frame: Day 1 to day15 for both treatment cycle one and cycle two, the total duration is 30 days
Area under the plasma drug concentration time curve from 0 to infinity (if it can be calculated reliably)
Secondary Outcomes
- Vz/F(Day 1 to day15 for both treatment cycle one and cycle two, the total duration is 30 days)
- Number of adverse events as assessed by CTCAE 5.0(Screening period (1-28 days before treatment), treatment period (34 days) and follow-up period (7 ± 3 days after the last visit). The total duration is about 69 days.)
- t1/2(Day 1 to day15 for both treatment cycle one and cycle two, the total duration is 30 days)
- CL/F(Day 1 to day15 for both treatment cycle one and cycle two, the total duration is 30 days)
- Tmax(Day 1 to day15 for both treatment cycle one and cycle two, the total duration is 30 days)
- λ z(Day 1 to day15 for both treatment cycle one and cycle two, the total duration is 30 days)