Helicobacter Pylori
Conditions
Keywords
Drug Therapy
Brief summary
Helicobacter Pylori (H Pylori) is a bug found in the digestive system. It can cause soreness and redness in the stomach (gastritis). It can also cause ulcers in the stomach and other parts of the digestive system. Vonoprazan is a medicine to treat people with H Pylori. It is taken together with other medicines to fight infections caused by H Pylori. The main aim of this study is to learn if vonoprazan changes how the other medicines are processed by the body. It will be compared with another medicine called esomeprazole. Other aims are to check for side effects from the study medicines. At the first visit, the study doctor will check who can take part. Participants who take part will be picked for 1 of 2 treatments by chance. * Vonoprazan taken with bismuth, clarithromycin, and amoxicillin * Esomeprazole taken with bismuth, clarithromycin, and amoxicillin Both treatments will last for 14 days. Participants will stay in the clinic throughout their treatment. After treatment, the clinic staff will telephone the participants 2 days later for a check-up. The participants will visit the clinic 4 weeks later for a final check-up.
Detailed description
This is a study in healthy participants with Helicobacter pylori (HP positive) to evaluate the safety, tolerability and PK of a quadruple therapy with bismuth, clarithromycin, amoxicillin, and vonoprazan versus quadruple therapy with bismuth, clarithromycin, amoxicillin, and esomeprazole. The treatment phase consists of quadruple therapy twice daily (BID) with bismuth potassium citrate (600 mg), clarithromycin (500 mg), amoxicillin (1000 mg), and vonoprazan (20 mg) (Group B) or quadruple therapy BID with bismuth potassium citrate (600 mg), clarithromycin (500 mg), amoxicillin (1000 mg), and esomeprazole (20 mg) (Group A) from Days 1 to 14. Participants will be discharged on Day 15 after all procedures have been performed. This single-center will be conducted in China. Participants will remain confined to the study site from check-in (Day -1) through Day 15 and will followed up through call on Day 17 and return on Day 42 for a follow-up assessment.
Interventions
DRUGClarithromycin
Clarithromycin tablets.
DRUGAmoxicillin
Amoxicillin capsules.
DRUGBismuth potassium citrate
Bismuth potassium citrate tablets.
DRUGEsomeprazole
Esomeprazole tablets.
DRUGVonoprazan
Vonoprazan tablets.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. HP positive participants. 2. Weighs at least 50 kilogram (kg) and has a body mass index between greater than (\>) 18 and less than equal to (\<=) 30 kilogram per square meter (kg/m\^2), inclusive, at screening and Day -1 (check-in). 3. Is willing to abstain from strenuous exercise from 72 hours before first dose (Day 1) until the Follow-up call on Day 17.
Exclusion criteria
1. Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1). 2. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as regular consumption of 21 units or more units per week) at any time prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study (up to Day 17). 3. Has history of gastroesophageal reflux disease (GERD), symptomatic GERD, erosive esophagitis, duodenal ulcer, gastric ulcer, Barrett's esophagus, or Zollinger-Ellison syndrome, or has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs. 4. Has undergone therapeutic upper gastrointestinal endoscopic therapy (example, endoscopic hemostasis or excision including biopsy) within 30 days prior to Screening. 5. Has undergone major surgical procedures within the past 1 month or are scheduled to undergo surgical procedures that may affect gastric acid secretion (example, abdominal surgery, vagotomy, or craniotomy). 6. Has a history of cancer, except basal cell carcinoma or Stage 1 squamous cell carcinoma of the skin that has been in remission for at least 5 years prior to Day 1. 7. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen at Screening. 8. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 6 weeks prior to Check-in. Cotinine test is positive at Screening or Check-in. 9. Has poor peripheral venous access. 10. Has donated or lost 450 milliliter (mL) or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 90 days prior to Day 1. 11. Has abnormal Screening or Check-in laboratory values that suggest a clinically significant underlying disease or subject with the following laboratory abnormalities: alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin \> the upper limit of normal (ULN). 12. Has reduced renal function assessed by having an estimated glomerular filtration rate \<90 milliliter per min per 1.73 square meter (mL/min/1.73 m\^2) (as estimated by Chronic Kidney Disease-Epidemology Collaboration) at Screening or Check-in.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax: Maximum Observed Plasma Concentration for Bismuth | Day 14: 0 to 12 hours after the morning dose |
| AUCτ: Area Under the Plasma Concentration-time Curve During a Dosing Interval τ for Bismuth | Day 14: 0 to 12 hours after the morning dose |
| Aeτ: Total Amount of Bismuth Excreted in Urine During a Dosing Interval τ for Bismuth | Day 14: 0 to 12 hours after the morning dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experience at Least One Treatment-Emergent Adverse Event (TEAE) | From the first dose of study drug up to Day 17 | An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an AE with an onset that occurs after receiving study drug. |
| Percentage of Participants Who Discontinued Study Drug Due to a Treatment-Emergent Adverse Event (TEAE) | From the first dose of study drug up to Day 17 | — |
Countries
China
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in China from 06 April 2021 to 05 November 2021.
Pre-assignment details
Helicobacter pylori (H pylori) positive participants were enrolled and randomized to one of the two treatment groups to either receive quadruple therapy with bismuth, clarithromycin, amoxicillin, and vonoprazan versus quadruple therapy with bismuth, clarithromycin, amoxicillin, and esomeprazole.
Participants by arm
| Arm | Count |
|---|---|
| Clarithromycin + Amoxicillin + Bismuth + Vonoprazan Clarithromycin 500 mg, tablets, orally, BID, along with amoxicillin 1000 mg, capsules, orally, BID, bismuth potassium citrate 600 mg, capsules, orally, BID, and vonoprazan 20 mg, tablets, orally, BID on Days 1 to 14. | 22 |
| Clarithromycin + Amoxicillin + Bismuth + Esomeprazole Clarithromycin 500 mg, tablets, orally, BID, along with amoxicillin 1000 mg, capsules, orally, BID, bismuth potassium citrate 600 mg, capsules, orally, BID, and esomeprazole 20 mg, tablets, orally, BID on Days 1 to 14. | 22 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Liver Function Test Abnormalities | 2 | 4 |
| Overall Study | Pretreatment Event/Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Clarithromycin + Amoxicillin + Bismuth + Vonoprazan | Clarithromycin + Amoxicillin + Bismuth + Esomeprazole | Total |
|---|---|---|---|
| Age, Continuous | 34.5 years STANDARD_DEVIATION 9.6 | 31.6 years STANDARD_DEVIATION 9.59 | 33.1 years STANDARD_DEVIATION 9.6 |
| Body Mass Index (BMI) | 22.4 kg/m^2 STANDARD_DEVIATION 2.07 | 23.1 kg/m^2 STANDARD_DEVIATION 3.09 | 22.7 kg/m^2 STANDARD_DEVIATION 2.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 22 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 167.2 cm STANDARD_DEVIATION 6.58 | 165.6 cm STANDARD_DEVIATION 7.17 | 166.4 cm STANDARD_DEVIATION 6.85 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 22 Participants | 44 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 22 Participants | 22 Participants | 44 Participants |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 17 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 27 Participants |
| Weight | 62.8 kg STANDARD_DEVIATION 9.23 | 63.2 kg STANDARD_DEVIATION 8.23 | 63.0 kg STANDARD_DEVIATION 8.64 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 21 / 22 | 21 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Aeτ: Total Amount of Bismuth Excreted in Urine During a Dosing Interval τ for Bismuth
Time frame: Day 14: 0 to 12 hours after the morning dose
Population: PK Analysis Set included participants who received the study drug (bismuth, vonoprazan or esomeprazole, clarithromycin, amoxicillin) and had at least 1 measurable plasma drug concentration after start of dosing without protocol violations or events with potential to affect the PK concentrations and who had completed minimum protocol procedures.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clarithromycin + Amoxicillin + Bismuth + Vonoprazan | Aeτ: Total Amount of Bismuth Excreted in Urine During a Dosing Interval τ for Bismuth | 1026 micrograms (μg) | Standard Deviation 546 |
| Clarithromycin + Amoxicillin + Bismuth + Esomeprazole | Aeτ: Total Amount of Bismuth Excreted in Urine During a Dosing Interval τ for Bismuth | 1037 micrograms (μg) | Standard Deviation 562.5 |
Primary
AUCτ: Area Under the Plasma Concentration-time Curve During a Dosing Interval τ for Bismuth
Time frame: Day 14: 0 to 12 hours after the morning dose
Population: PK Analysis set included participants who received the study drug (bismuth, vonoprazan or esomeprazole, clarithromycin, amoxicillin) and had at least 1 measurable plasma drug concentration after start of dosing without protocol violations or events with potential to affect the PK concentrations and who had completed minimum protocol procedures.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Clarithromycin + Amoxicillin + Bismuth + Vonoprazan | AUCτ: Area Under the Plasma Concentration-time Curve During a Dosing Interval τ for Bismuth | 146 hour*nanogram/milliliter (h*ng/mL) |
| Clarithromycin + Amoxicillin + Bismuth + Esomeprazole | AUCτ: Area Under the Plasma Concentration-time Curve During a Dosing Interval τ for Bismuth | 137 hour*nanogram/milliliter (h*ng/mL) |
90% CI: [0.82, 1.4]
Primary
Cmax: Maximum Observed Plasma Concentration for Bismuth
Time frame: Day 14: 0 to 12 hours after the morning dose
Population: Pharmacokinetic (PK) Analysis Set included participants who received the study drug (bismuth, vonoprazan or esomeprazole, clarithromycin, amoxicillin) and had at least 1 measurable plasma drug concentration after start of dosing without protocol violations or events with potential to affect the PK concentrations and who had completed minimum protocol procedures.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Clarithromycin + Amoxicillin + Bismuth + Vonoprazan | Cmax: Maximum Observed Plasma Concentration for Bismuth | 42.8 nanogram per milliliter (ng/mL) |
| Clarithromycin + Amoxicillin + Bismuth + Esomeprazole | Cmax: Maximum Observed Plasma Concentration for Bismuth | 32.9 nanogram per milliliter (ng/mL) |
90% CI: [0.94, 1.81]
Secondary
Percentage of Participants Who Discontinued Study Drug Due to a Treatment-Emergent Adverse Event (TEAE)
Time frame: From the first dose of study drug up to Day 17
Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clarithromycin + Amoxicillin + Bismuth + Vonoprazan | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-Emergent Adverse Event (TEAE) | 9.1 percentage of participants |
| Clarithromycin + Amoxicillin + Bismuth + Esomeprazole | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-Emergent Adverse Event (TEAE) | 22.7 percentage of participants |
Secondary
Percentage of Participants Who Experience at Least One Treatment-Emergent Adverse Event (TEAE)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an AE with an onset that occurs after receiving study drug.
Time frame: From the first dose of study drug up to Day 17
Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clarithromycin + Amoxicillin + Bismuth + Vonoprazan | Percentage of Participants Who Experience at Least One Treatment-Emergent Adverse Event (TEAE) | 95.5 percentage of participants |
| Clarithromycin + Amoxicillin + Bismuth + Esomeprazole | Percentage of Participants Who Experience at Least One Treatment-Emergent Adverse Event (TEAE) | 95.5 percentage of participants |