Clinical trial NCT04859452: A Study to Evaluate the DDI of DBPR108 With Metformin,Glibenclamide,Valsartan, or Simvastatin in Healthy Subjects
Official title: A Four-part, Single-center, Open-label, Phase I Clinical Study to Evaluate the Drug-Drug Pharmacokinetic Interaction Between DBPR108 at Steady-state and Metformin Hydrochloride/Glibenclamide/Valsartan/ Simvastatin in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-04-26
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a four-part, single-center, open-label, single-sequence crossover phase I clinical study to characterize the Drug-Drug Interaction (DDI) potential of DBPR108 at steady-state with Metformin hydrochloride, Glibenclamide, Valsartan, or Simvastatin in Healthy Subjects. This study also aims to evaluate the safety and tolerability of DBPR108 in the presence of Metformin hydrochloride, Glibenclamide, Valsartan, or Simvastatin.

Detailed description: DBPR108 is a potent dipeptidylpeptidase-4 inhibitor. This study will be run in four parts to characterize the Drug-Drug Interaction (DDI) potential of DBPR108 with the expected concomitant drugs (Metformin hydrochloride, Glibenclamide, Valsartan, Simvastatin) in Healthy Subjects. Each part of this study consists of a screening period (Day -14 to Day -1), a baseline period (Day -1), a treatment period (Day 1 to Day 9), and a follow-up visit on Day 15. Approximately 14 subjects will be enrolled in each part of this study.

Eligibility criteria: Inclusion Criteria:

* Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions；
* 18 years to 45 years (inclusive), male or female；
* Male subjects weight ≥50 kg and female subjects weight ≥45 kg. Body mass index (BMI) : 18-30 kg/m2 (inclusive) (BMI= weight (kg)/height 2 (m2))；
* Subjects (including partners) are willing to use effective contraceptives from screening to the 6 months after the last dose administration；
* Be judged to be in good health by the investigator, based on the physical examination, vital sign examination, 12-lead electrocardiogram (ECG) examination and laboratory examination；

Exclusion Criteria:

* Subjects who have a history of allergic conditions (such as asthma, urticaria), or have a history of allergy to two or more drugs or food, or may be allergic to the test drug and the related compounds;
* Have a history of severe diseases, such as cardiovascular, respiratory, liver, gastrointestinal, endocrine, hematologic, mental/nervous systems diseases within 1 year prior to screening；
* Subjects who have previously undergone surgery that may affect drug absorption, distribution, metabolism, or excretion (e.g., subtotal gastrectomy), or who have a scheduled surgical plan during the study period;
* Use of any prescription drug, over-the-counter drug, or herbal medicine within 2 weeks prior to screening;
* Drug abuse, or positive urine drug screen at screening；
* Smoking more than 5 cigarettes per day within 3 months prior to screening；
* Average alcohol intake is more than 28g alcohol (male) or 14g (female) per week (14g ≈ 497mL beer, or 44mL spirits with low alcohol content, or 145mL wine) within the 3 months prior to screening, or taking any alcohol within 48 hours before dosing, or a positive ethanol breath test at screening；
* Consumption of grapefruit juice, Methylxanthine-rich food or beverage (such as coffee, tea, cola, chocolate, energy drinks) within 48 hours before the administration, or have strenuous exercise, or have other factors affecting drug absorption, distribution, metabolism, excretion, etc；
* Participation in another clinical trial within 3 months before screening；
* Blood donation (or blood loss) ≥400 mL, or receiving whole blood transfusions or erythrocyte suspension transfusions within 3 months prior to the screening；
* The patients who have undergone comprehensive inspection with any significant clinical significant in physical examination (vital signs, physical examination), routine laboratory examination (blood routine, blood biochemical examination, urine routine), chest X-ray (anteroposterior), abdominal B (liver, bile, pancreas, spleen and kidney) and other examinations, as judged by the investigator;
* Have a positive test result of hepatitis B surface antigen, hepatitis C antibody, anti-human immunodeficiency virus antibody or anti-Treponema pallidum specific antibody;
* A pregnant/lactating woman, or has a positive pregnancy test at screening or during the trial.；
* Not suitable for this study as judged by the investigator；

Primary outcomes:
measure: The pharmacokinetic parameters of Metformin, Glibenclamide, Valsartan, Simvastatin, Simvastatin acid and DBPR108
timeFrame: Day 1 to Day 9
measure: The pharmacokinetic parameters of Metformin, Glibenclamide, Valsartan, Simvastatin, Simvastatin acid and DBPR108
timeFrame: Day 1 to Day 9
Secondary outcomes:
measure: The pharmacokinetic parameters
timeFrame: Day 1 to Day 9
measure: The pharmacokinetic parameters
timeFrame: Day 1 to Day 9
measure: The pharmacokinetic parameters
timeFrame: Day 1 to Day 9
measure: The pharmacokinetic parameters
timeFrame: Day 1 to Day 9
measure: The number of volunteers with adverse events as a measure of safety and tolerability
timeFrame: Day 1 to Day 15
Other outcomes:
Locations:
city: Suzhou
country: China
facility: First Affiliated Hospital of Soochow University
Study officials:
References: