Randomized, Double-Blind Study on Clinical Outcomes, Tolerability, and Safety of Oral Pantoprazole in Pediatric Patients with Healed Erosive Esophagitis
- Trial ID
- 2023-508770-28-00
- Protocol
- B1791094
- Sponsor
- Pfizer Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to explore the maintenance of healing of **erosive esophagitis** in pediatric participants aged 1 to 11 years and 12 to 17 years. This is clinically relevant as maintaining the healing of erosive esophagitis is crucial in preventing complications such as strictures and Barrett's esophagus, which can significantly impact the quality of life and long-term health outcomes in pediatric patients.
Secondary objectives include:
- To explore the safety and tolerability of oral **pantoprazole**.
Participants
The clinical trial involves a total of **108 participants** diagnosed with **erosive esophagitis**, focusing on the maintenance of healing in pediatric subjects. The study population includes both male and female participants aged 1 to 17 years, with a minimum body weight of 7 kg. Participants were selected based on the presence of a documented erosive lesion with an LA Grade of A to D, confirmed by an initial diagnostic EGD performed no more than 12 weeks prior to study entry. The trial includes individuals who have either not completed or have completed at least 8 weeks of healing therapy with a proton pump inhibitor (PPI). Participants must be capable of providing informed consent or assent and demonstrate willingness and ability to comply with study requirements, including completing an eDiary and adhering to scheduled visits and treatment plans. The trial population encompasses both genders and includes vulnerable populations, with no specific lifestyle considerations such as diet or physical activity mentioned. The sponsor has not provided additional information regarding the general health status of the participants.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the clinical outcomes, tolerability, and safety of two doses of oral **pantoprazole** in pediatric participants aged 1 to 17 years who require maintenance therapy for healed **erosive esophagitis**. The trial is expected to last until December 2027, with recruitment starting in December 2023. Participants will be involved in the study for a maximum of 24 weeks, during which they will receive either pantoprazole or a placebo. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and safety, and an end-of-study visit to assess the primary endpoint of endoscopically confirmed maintenance of healing of erosive esophagitis at Week 24.
Participants must have a documented erosive lesion with an LA Grade of A to D prior to starting proton pump inhibitor (PPI) treatment. The inclusion criteria require participants to have undergone an esophagogastroduodenoscopy (EGD) to confirm the presence of an erosive esophagitis lesion. If the lesion is confirmed, participants will be enrolled and randomized into the maintenance phase of the study. The trial will assess safety and tolerability through physical examinations, adverse event monitoring, clinical laboratory measurements, blood pressure, and pulse rate. Participants may be terminated early from the study if they do not meet the inclusion criteria, if they experience significant adverse events, or if they withdraw consent.
Treatment
The clinical trial involves the administration of **pantoprazole sodium sesquihydrate** in various dosages to evaluate its efficacy in maintaining the healing of erosive esophagitis in pediatric participants. The experimental medication, pantoprazole, is provided in capsule form and is manufactured by Pfizer Inc. The active substance, pantoprazole sodium sesquihydrate, is of chemical origin. The trial includes four different dosages of pantoprazole: 5 mg, 10 mg, 20 mg, and 40 mg. Each dosage is administered orally once daily, with a maximum treatment period of 24 weeks. The dosing schedule is designed to ensure participant compliance, and adherence is monitored throughout the study.
In addition to the experimental medication, a **placebo** is utilized as a comparator treatment. The placebo is designed to match the pantoprazole sodium 40 mg, 20 mg, 10 mg, and 5 mg delayed-release granules in HPMC capsules. The placebo is administered in the same manner as the active drug, ensuring the study remains double-blind. The use of a placebo allows for the assessment of pantoprazole's true efficacy and safety profile by providing a baseline for comparison. Participant compliance with the placebo regimen is also monitored to maintain the integrity of the trial results.
Efficacy
Efficacy in this clinical trial will be assessed primarily through the **endoscopically confirmed maintenance of healing of erosive esophagitis** at Week 24. This endpoint will be evaluated to determine the effectiveness of oral pantoprazole in maintaining the healing of erosive esophagitis in pediatric participants aged 1 to 11 years and 12 to 17 years. The assessment will involve endoscopic procedures to confirm the healing status of the esophagitis lesions. The trial is designed to explore the maintenance of healing in participants who have previously undergone healing therapy for erosive esophagitis.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants must have a documented erosive lesion with an LA Grade of A to D prior to starting PPI treatment: a. A participant who enters the study before the diagnostic EGD has been performed must have recorded a CSS ≥16 on the GASP-Q or a CSS ≥8 on the GSQ-YC as appropriate, at Screening, in order to enter the study. Once enrolled, this participant will undergo an initial EGD to confirm the presence of EE. Note: If an EE lesion is confirmed by the initial diagnostic EGD, the participant can be enrolled in the study. If no EE lesion is confirmed by the initial endoscopy, the participant will be terminated from the study. b. The following criteria apply to a participant who undergoes screening for the study after a diagnostic EGD has already confirmed the presence of an EE lesion: - The initial diagnostic EGD must have been performed no more than 12 weeks prior to study entry; - The EGD report must be available and must indicate the presence of anEE lesion; - If the participant has already started PPI treatment to heal the lesion before entering the study, but has not completed at least 8 weeks of healing therapy, the participant must continue treatment with the same PPI for a total of up to 8 weeks, after which follow-up EGD will be performed at the end of Week 8 to confirm healing of the lesion; - If the participant began healing treatment with a PPI other than pantoprazole prior to study enrollment, that PPI must be approved for the treatment of erosive esophagitis in pediatric participants and the dose being taken must be according to the local prescribing information; - If the participant began healing treatment with pantoprazole prior to study enrollment, the dose of pantoprazole being taken must be consistent with the dosing scheme for the Healing Phase of the protocol. c. The following criteria apply to a participant who undergoes screening for the study after a diagnostic EGD has already confirmed the presence of an EE lesion and after they have completed at least 8 weeks of healing therapy with a PPI: - The initial diagnostic EGD must have been performed no more than 12 weeks prior to study entry; - The EGD report must be available and must indicate the presence of an EE lesion, including photographic evidence of the lesion; - The participant will enter the study at the end of Week 8 and will undergo follow-up EGD to confirm lesion healing, if that has not already been done, prior to being randomized into the Maintenance Phase of the study.
- Capable of giving signed informed consent/assent, which includes compliance with the requirements and restrictions listed in the ICD and in the protocol.
- Willingness and ability of the participant or parent/legal guardian to complete the eDiary including the GASPQ or GSQ-YC, PGIS or P-RGIS, study intervention log, and rescue medicine log, throughout the study.
- Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures, including the use of the eDiary.
- Male and female participants aged 1 to 17 years.
- Minimum body weight 7 kg
- Females of childbearing or non-childbearing potential may be enrolled in the study: To be considered a female of non-childbearing potential, the participant must meet at least 1 of the following criteria: - Premenarchal: The investigator (or other appropriate staff) must discuss the participant's premenarchal status with the participant and parent/legal guardian at office visits and during telephone contacts, as participants who achieve menarche during the study would no longer be considered "female participants of non-childbearing potential" and must comply with the protocol requirements applicable to women of childbearing potential.
Exclusion Criteria
- Previous administration of an investigational drug or vaccine within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Note: local regulations or other factors may require more than 30 days.
- Children that may be at high risk from procedural sedation should be carefully evaluated. Participants with a history of complications during prior procedural sedation (eg, for upper endoscopy) should be excluded. Participants graded as ASA Classification System I or II only should be included (See Section 8.1.3.8 of the protocol).
- History or presence of upper gastrointestinal anatomic or motor disorders, including the following: • Esophageal strictures, webs, diverticula, or other gastroduodenal pathology seen on EGD. • Gastrointestinal strictures of any kind. • Esophageal or gastric motor disorders (eg, scleroderma). • Barrett's esophagus. • Peptic ulcer disease, erosive gastritis and/or erosive duodenitis. • Eosinophilic esophagitis by histology (eosinophils per high powered field). • Gastrointestinal malabsorption. • H. pylori infection within the past 6 months. • Cystic Fibrosis
- Family history of malignant hyperthermia
- Known hypersensitivity to any PPI, including pantoprazole or to any substituted benzimidazole or to any of the excipients.
- Any disorder requiring chronic (daily) use of warfarin, heparin, other anticoagulants, methotrexate, atazanavir or nelfinavir, clopidogrel, or potent inhibitors or inducers of CYP2C19 (eg, phenytoin, sulfamethoxazole, valproic acid, carbamazepine, and griseofulvin).
- Serum creatine kinase levels >3 x upper limit of normal.
- Known history of human immunodeficiency virus or clinical manifestations of acquired immune deficiency syndrome.
- Active malignancy of any type, or history of a malignancy. Participants with a history of malignancies that have been surgically removed or eradicated by irradiation or chemotherapy and who have no evidence of recurrence for at least 5 years before Screening are acceptable.
- Diagnosed as having or has received treatment for esophageal, gastric, pyloric channel, or duodenal ulceration within 30 days before the Screening visit.
- ALT or BUN >2.0 ULN or estimated creatinine >1.5 X ULN for age or any other laboratory abnormality considered by the Investigator to be clinically significant within 14 days before the Baseline Visit (Day 1).
- Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or study intervention administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
- Has, in the Investigator's opinion, a serious chronic condition (eg, diabetes, epilepsy), which is either not stable or not well controlled and may interfere with the conduct of the study.
- Has any condition possibly affecting drug absorption (eg, gastrectomy).
- Frequent, repeated use of oral or parenteral glucocorticoids (eg, prednisone, prednisolone, dexamethasone). Steroid inhalers and topical steroids may be used.
- Pregnant female participants; breastfeeding female participants.
- Is unwilling or unable to comply with the Lifestyle Considerations section (Section 5.3) described in the protocol.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 01 Dec 2023 | 3 |
 Slovakia | Not Recruiting | 01 Dec 2023 | 15 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
The placebo for the pantoprazole sodium 40 mg, 20 mg, 10 mg and 5 mg delayed release granules in HPMC capsules | Placebo | N/A | — | — | — | N/A |
PANTOPRAZOLE | Test | CAPSULE | ORAL | 20 | 24 | PRD10867217 |
PANTOPRAZOLE | Test | CAPSULE | ORAL USE | 40 | 24 | PRD10867228 |
PANTOPRAZOLE | Test | CAPSULE | ORAL USE | 5 | 24 | PRD10867130 |
PANTOPRAZOLE | Test | CAPSULE | ORAL USE | 10 | 24 | PRD10867189 |