Drug Interaction Study on Linaprazan Glurate Capsules, Clarithromycin Tablets, Amoxicillin Capsules, and Bismuth Potassium Citrate Capsules
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Jiangsu Sinorda Biomedicine Co., Ltd
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Steady state maximum concentration (Cmax,ss)
Overview
Brief Summary
This study is a drug-drug interaction (DDI) investigation involving Linaprazan Glurate capsules and a combination of clarithromycin tablets, amoxicillin capsules, and bismuth potassium citrate capsules. The study plan is divided into two parts: one involving Hp-negative healthy subjects and the other involving Hp-positive subjects.
Detailed Description
The first part of the study is designed as a single-center, randomized, open-label, four-period, four-sequence crossover trial to evaluate the changes in pharmacokinetic (PK) profiles of Linaprazan Glurate capsules when co-administered with clarithromycin tablets and amoxicillin capsules compared to their individual administration, as well as the safety and tolerability of the combination therapy in Hp-negative healthy adult Chinese subjects.
The second part of the study is designed as a single-center, randomized, open-label, parallel-group, positive-controlled trial to compare the differences in systemic exposure of bismuth potassium citrate capsules between the Linaprazan Glurate capsule-based quadruple therapy (combined with clarithromycin tablets, amoxicillin capsules, and bismuth potassium citrate capsules) and the esomeprazole magnesium enteric-coated tablet-based quadruple therapy (combined with clarithromycin tablets, amoxicillin capsules, and bismuth potassium citrate capsules), to evaluate the pharmacodynamic effects on intragastric pH, to assess the safety and tolerability of the Linaprazan Glurate capsule-based quadruple therapy, and to preliminarily explore its efficacy in eradicating Helicobacter pylori (Hp) in Hp-positive subjects.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age range: 18 to 55 years old (including 18 and 55);
- •Male weight ≥50.0 kg, female weight ≥45.0 kg; Body Mass Index (BMI) between 19.0 and 26.0 kg/m²(including critical value); BMI=weight/height2 (m2)
- •Part 1 Study and Part 2 Study:
- •Part 1: Subjects must be Helicobacter pylori-negative at screening; Part 2: Subjects must be Helicobacter pylori-positive at screening;
- •From signing informed consent until 3 months after study completion, subjects must: Implement appropriate and effective contraception to prevent pregnancy (applies to subject or partner); Refrain from sperm donation or egg donation plans;
- •Subjects must fully comprehend the trial content, voluntarily participate in the trial, Provide written informed consent;
Exclusion Criteria
- •Subjects known as Hypersensitivity History: Known allergy to: Linaprazan Glurate capsules, Esomeprazole (Part 2 only), Penicillin, Macrolide antibiotics, Any component of bismuth potassium citrate;History of severe immediate hypersensitivity to: Other macrolide antibiotics, β-lactam agents (e.g., cephalosporins, carbapenems, monobactams),Multiple drug hypersensitivity (e.g., allergic reactions to ≥2 medications/foods);
- •Clinically Significant Abnormalities at Screening: Abnormalities deemed clinically significant by investigators based on: Medical history review, Vital signs, Physical examination, 12-lead ECG, Laboratory tests: Complete blood count (CBC), Blood chemistry, Urinalysis, Coagulation tests ;
- •Subjects with Penicillin sodium skin test positivity during screening;
- •Subjects with use of any investigational product within 3 months prior to screening;
- •Subjects with use of potassium-competitive acid blockers (P-CABs) within 3 months prior to screening;
- •Subjects with use within 30 days prior to screening of Prescription drugs, Over-the-counter ,OTC) medications, Herbal medicines, Dietary supplements;
- •Subjects with history of diseases in the following systems (also investigator-determined as ineligible): Central nervous system, Cardiovascular system, Respiratory system, Digestive system, Endocrine system, Immune system, Neurological/Psychiatric systems, Hematologic/Lymphatic systems, Musculoskeletal system;
- •Gastrointestinal/Surgical History: History of gastrointestinal diseases or surgeries including:Gastric surgery (except pyloromyotomy for infantile pyloric stenosis), Cholecystectomy, Vagotomy, Bowel resection, Any surgery potentially affecting GI motility, pH, or absorption, Conditions impacting drug ADME: Dysphagia, Vomiting, Severe diarrhea;
- •Cardiac Abnormalities: Clinically significant ECG abnormality history, Family history of Long QT Syndrome (grandparents, parents, siblings), Screening QTcF prolongation: 450 msec in males, 470 msec in females;
- •Subjects with major surgery within 3 months prior to screening,and planned surgery during trial participation;
Arms & Interventions
Linaprazan Glurate Capsules 50mg BID, consecutive 7-day dosing per period
Glurate Capsules Capsules 50mg, BID, consecutive 7-day dosing per period in Part 1.
Intervention: Linaprazan Glurate Capsules (Drug)
Linaprazan Glurate Capsules 50mg BID, consecutive 7-day dosing per period
Glurate Capsules Capsules 50mg, BID, consecutive 7-day dosing per period in Part 1.
Intervention: Amoxicillin Capsules (Drug)
Linaprazan Glurate Capsules 50mg BID, consecutive 7-day dosing per period
Glurate Capsules Capsules 50mg, BID, consecutive 7-day dosing per period in Part 1.
Intervention: Clarithromycin tablets (Drug)
Linaprazan Glurate Capsules 50mg BID, consecutive 14-day dosing
Linaprazan Glurate Capsules 50mg BID, consecutive 14-day dosing in part 2.
Intervention: Linaprazan Glurate Capsules (Drug)
Linaprazan Glurate Capsules 50mg BID, consecutive 14-day dosing
Linaprazan Glurate Capsules 50mg BID, consecutive 14-day dosing in part 2.
Intervention: Bismuth Potassium Citrate Capsules (Drug)
Linaprazan Glurate Capsules 50mg BID, consecutive 14-day dosing
Linaprazan Glurate Capsules 50mg BID, consecutive 14-day dosing in part 2.
Intervention: Amoxicillin Capsules (Drug)
Linaprazan Glurate Capsules 50mg BID, consecutive 14-day dosing
Linaprazan Glurate Capsules 50mg BID, consecutive 14-day dosing in part 2.
Intervention: Clarithromycin tablets (Drug)
Esomeprazole Magnesium Enteric-coated Tablets 20mg BID, consecutive 14-day dosing.
Esomeprazole Magnesium Enteric-coated Tablets 20mg, BID in Part 2.
Intervention: Bismuth Potassium Citrate Capsules (Drug)
Esomeprazole Magnesium Enteric-coated Tablets 20mg BID, consecutive 14-day dosing.
Esomeprazole Magnesium Enteric-coated Tablets 20mg, BID in Part 2.
Intervention: Amoxicillin Capsules (Drug)
Esomeprazole Magnesium Enteric-coated Tablets 20mg BID, consecutive 14-day dosing.
Esomeprazole Magnesium Enteric-coated Tablets 20mg, BID in Part 2.
Intervention: Clarithromycin tablets (Drug)
Esomeprazole Magnesium Enteric-coated Tablets 20mg BID, consecutive 14-day dosing.
Esomeprazole Magnesium Enteric-coated Tablets 20mg, BID in Part 2.
Intervention: Esomeprazole Magnesium Enteric-coated Tablets (Drug)
Outcomes
Primary Outcomes
Steady state maximum concentration (Cmax,ss)
Time Frame: 7 days
Cmax,ss of of Linaprazan Glurate and its active metabolite(s), clarithromycin and its active metabolite(s), and amoxicillin in Part 1 study.
AUC0-τ,ss(The area under the drug-time curve within the dosing interval after reaching the steady state)
Time Frame: 7 days
AUC0-τ,ss of Linaprazan Glurate and its active metabolite(s), clarithromycin and its active metabolite(s), and amoxicillin in Part 1 study.
Cav,ss (Average steady-state blood drug concentration)
Time Frame: 7 days
Cav,ss of Linaprazan Glurate and its active metabolite(s), clarithromycin and its active metabolite(s), and amoxicillin in Part 1 study.
Tmax,ss (Steady-state peak time)
Time Frame: 7 days
Tmax,ss of Linaprazan Glurate and its active metabolite(s), clarithromycin and its active metabolite(s), and amoxicillin in Part 1 study.
CLss/F(Steady-state apparent clearance rate)
Time Frame: 7 days
CLss/F of Linaprazan Glurate and its active metabolite(s), clarithromycin and its active metabolite(s), and amoxicillin in Part 1 study.
t1/2z(Terminal elimination half-life)
Time Frame: 7, 14 days
t1/2z of Linaprazan Glurate and its active metabolite(s), clarithromycin and its active metabolite(s), and amoxicillin in Part 1 study; and t1/2z of Pharmacokinetic Parameters of Bismuth in Part 2 study.
Vz/F (Apparent volume of distribution in the terminal elimination phase)
Time Frame: 7, 14 days
Vz/F of Linaprazan Glurate and its active metabolite(s), clarithromycin and its active metabolite(s), and amoxicillin in Part 1 study; and Vz/F of Pharmacokinetic Parameters of Bismuth in Part 2 study.
λz (Terminal elimination rate constant)
Time Frame: 7, 14 days
λz of Linaprazan Glurate and its active metabolite(s), clarithromycin and its active metabolite(s), and amoxicillin in Part 1 study; and λz of Pharmacokinetic Parameters of Bismuth in Part 2 study.
MRT(mean residence time)
Time Frame: 7 days
MRT of Linaprazan Glurate and its active metabolite(s), clarithromycin and its active metabolite(s), and amoxicillin in Part 1 study.
Cmax(Maximum observed plasma drug concentration)
Time Frame: 14 days
Cmax of Pharmacokinetic Parameters of Bismuth in Part 2 study.
AUC0-τ (The area under the drug-time curve within the dosing interval)
Time Frame: 14 days
AUC0-τ of Pharmacokinetic Parameters of Bismuth in Part 2 study.
Tmax (Time to reach maximum plasma concentration)
Time Frame: 14 days
Tmax of Pharmacokinetic Parameters of Bismuth in Part 2 study.
CL/F (apparent clearance)
Time Frame: 14 days
CL/F of Pharmacokinetic Parameters of Bismuth in Part 2 study.
Ae0-τ (Amount of drug excreted in urine over the dosing interval)
Time Frame: 14 days
Ae0-τ of Pharmacokinetic Parameters of Bismuth in Part 2 study.
fe (Amount of drug excreted in urine over the dosing interval)
Time Frame: 14 days
fe of Pharmacokinetic Parameters of Bismuth in Part 2 study.
CLR (renal clearance)
Time Frame: 14 days
CLR of Pharmacokinetic Parameters of Bismuth in Part 2 study.
Secondary Outcomes
- The percentage of time over a 24-hour period that intragastric pH ≥ 4 and pH ≥ 6(1, 14 days)
- Proportion of subjects with successful Helicobacter pylori (Hp) eradication(1, 14 days)
- Number of subjests With Adverse Events(up to 56 days)
- Number of subjests With Clinically Notable Electrocardiogram (ECG) Values(up to 56 days)