| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| erosive esophagitis due to GERD Los Angeles grade C or D and patients with grades A or B who partially responded to PPI patients with grades A or B who partially responded to PPI |
|
| E.1.1.1 | Medical condition in easily understood language |
| erosive esophagitis due to GERD |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10063657 |
| E.1.2 | Term | Erosive esophagitis |
| E.1.2 | System Organ Class | 100000004856 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of the study is to support dose selection for X842, through assessment of healing of erosive esophagitis due to GERD after 4 weeks of treatment. |
|
| E.2.2 | Secondary objectives of the trial |
- Evaluate the safety and tolerability of the four dose levels of X842 and lansoprazole, where lansoprazole will serve as the active comparator.
- Evaluate the reflux related symptom pattern during the initial 4 weeks treatment with four dose levels of X842 and with lansoprazole, and the symptom pattern during the subsequent additional 4 weeks (Weeks 5-8) open-label treatment with lansoprazole 30 mg QD
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Written informed consent must be obtained before any study related assessment is performed.
2. Male or female patient aged 18-75 years inclusive at the time of obtaining the informed consent .
3. Body mass index (BMI) ≥ 18 and ≤ 40 kg/m2 at screening
4. Gastro-esophageal reflux disease with endoscopically confirmed esophagitis:
• LA grade C or D ≤7 days before randomization (with or without historical PPI treatment)
or
• LA grade A or B ≤7 days before randomization
and
history of treatment with standard healing course of PPI* for minimum of 8 weeks prior to screening and ≤7 days of non-treatment during this
period**.
and
at least partial symptom response during the minimum of 8 weeks of PPI treatment.
Note: partial symptom response is defined as a clear symptom improvement (heartburn or regurgitation) after start of the PPI treatment course. To qualify, the patient's response must be YES to the Investigator´s standardized question to the patient: Did you feel a clear symptom improvement in heartburn or regurgitation after you started the PPI treatment course?
* All PPIs EXCEPT lansoprazole
** Non-treatment days are counted from end day of PPI therapy until
endoscopy demonstrating erosive esophagitis due to GERD."
5. Willing and able to comply with all aspects of the protocol (including PK sampling, capsule swallowing, diary completion, etc.) |
|
| E.4 | Principal exclusion criteria |
1. Female pts of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using one of the following adequate methods of contraception during dosing and for at least 7 days after the last dose of study medication:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
•Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks before taking the first dose of study treatment. In case of oophorectomy alone, only when the reproductive status of the patient has been confirmed by follow-up hormone level assessment
•Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that pt.
•Placement of a non-hormonal IUD
•Double barrier methods of contraception: condom in combination with occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/vaginal suppository
Note: Patients who are already on hormonal contraceptives prior to study enrollment must agree to:
• replace hormonal contraception with double barrier method or
• use double barrier contraception method in addition to the hormonal contraceptives
2.Female pts of non-childbearing potential not requiring a contraceptive method, are defined as
• Pre-menopausal females with a documented tubal ligation or hysterectomy; or
• Post-menopausal females defined as at least 12 months of amenorrhea (without an alternative medical cause) and confirmed with simultaneous serum follicle stimulation hormone (FSH), consistent with post-menopausal status according to central laboratory ranges.
Patients who do not meet one of these two criteria above will be considered being of childbearing potential, and are excluded unless using one of the adequate contraceptive methods defined in Exclusion Criterion #1.
3.Male pts with a partner of childbearing potential, unless they are willing to use condoms in combination with a second method of adequate contraception (e.g. double barrier method), and they agree not to father a child during dosing and for at least 7 days after the last dose of study medication. Each male pt will be considered as potent unless surgically sterilized (at least 6 months prior to screening).
4.Presence of esophageal ulcer, stricture, Barrett´s esophagus or suspected esophagitis secondary to infection, inflammatory disease, ingestion of erosive chemicals or history of any surgical or medical condition which might significantly alter the GERD status or the absorption, distribution, metabolism or excretion of drugs. The Investigator is to be guided by evidence of any of the following: history of major gastrointestinal surgery such as gastrectomy, gastroenterostomy, bowel resection or transjugular intrahepatic portosystemic shunt (TIPS)
5.Known severe atrophic gastritis
6.Any planned major surgery within the duration of the study
7.Any clinically significant laboratory parameter outside reference value that, in the opinion of the Investigator, may suggest a new or insufficiently understood disease, may present an unreasonable risk to the patient as a result of his/her participation in the study, or may interfere with study assessments.
Any of these screening laboratory tests results are exclusionary:
•Serum ALT or AST > 1.5 × the upper limit of normal (ULN) for the central laboratory conducting the test
•Serum Total Bilirubin > 1.5 × ULN for the central laboratory conducting the test
•Serum Creatinine > 1.5 × ULN for the central laboratory conducting the test
•Estimated glomerular filtration rate ≤ 59 mL/min (calculated using the Modification of Diet in Renal Disease equation)
8.After 10 min supine rest at the time of screening, any vital signs values outside the following ranges:
•Systolic BP >160 mmHg or < 90 mmHg
•Diastolic BP >100 mmHg or < 60 mmHg
•Heart rate <40 or >95 beats per min
9.History of long QTc syndrome (e.g. QTc ≥450 ms for males and ≥470 ms for females)
10.Cardiac arrhythmias or any clinically significant abnormalities in the resting 12-lead ECG at the time of screening, as judged by the Investigator
11.Administration of another new chemical entity or has participated in any other clinical study that included drug treatment with less than 1 month between administration of last dose and first dose of IMP in this study.
12.Positive screen for drugs of abuse at screening
13.Current or history of alcohol, drug abuse and/or use of anabolic steroids within 2 years prior to screening
14.Women who are pregnant or breast feeding.
15.Pts who have previously participated (completed or withdrawn) in this study CX842A2201
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Healing of erosive esophagitis due to GERD based on endoscopic assessment after 4 weeks of double-blind treatment |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Physical examination, weight, body mass index (BMI), vital signs, electrocardiogram (ECG) recordings, safety laboratory measurements (hematology/clinical chemistry/urinalysis), adverse event (AE), treatment emergent adverse event (TEAE), adverse event of special interest (AESI), serious adverse event (SAE) reporting, concomitant medication(s).
- Percentage of heartburn-free 24-hour days during the Weeks 1-8 (Visits 2-9) based on eDiary (RESQ-eDiary)
- Investigator assessment of symptom at Weeks 1-8 (Visits 2-9)
- Reflux related symptoms as measured by change from baseline in QOLRAD score assessed after 1, 2, 4 and 8 weeks of treatment
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Georgia |
| Serbia |
| Ukraine |
| United States |
| Czechia |
| Hungary |
| Poland |
| Bulgaria |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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