| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Postprandial Distress Syndrome |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10064536 |
| E.1.2 | Term | Functional dyspepsia |
|
| 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 |
| To assess the efficacy of 3 dosing regimens of ATI-7505 compared to placebo in patients with PDS by comparing at the end of Day 42 the percentage of patients in each treatment group who have adequate relief of PDS symptoms on at least 50% of the tratment days. |
|
| E.2.2 | Secondary objectives of the trial |
| - To determine the safety and tolerability of ATI-7505 in patients with PDS; - To determine the time to recurrence of the 2 primary PDS symptoms measured during the 42-day primary efficacy period; and - To determine the effect of ATI-7505 treatment on health-related quality of life (QOL) indices in patients with PDS. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| At screening: Patients are eligible to participate in the study if they: a. are willing and able to provide written informed consent; b. are male or female between 18 and 75 years of age, inclusive, at Screening; c. were diagnosed with PDS at least 6 months prior to screening, OR had onset of 2 or more PDS symptoms at least 6 months prior to screening; d. have experienced early satiety or bothersome postprandial fullness repeatedly during the 3 months prior to screening along with one or more of the following symptoms for PDS: early satiety, bothersome postprandial fullness, upper abdominal bloating or distention, postprandial nausea, excessive belching; e. had a normal upper GI endoscopy within the past year (ie, no evidence of erosions or other mucosal abnormalities). g. if female, are: postmenopausal (at least 1 year without spontaneous menses), or surgically sterile (tubal ligation or hysterectomy), or using highly effective (ICH 1997) contraception (eg, oral, intramuscular, transdermal, or implanted hormonal contraception [at least 3 months prior to enrollment], sexual partner with non-reversed vasectomy [with azoospermia in 2 tests], 2 independent barrier methods [ie, a combination of 2 of the following methods: condom, diaphragm, or properly applied spermicide], or intra-uterine device). Women who are using contraception will be required to have a pregnancy test (urine) at the Screening, Baseline, Day 29, and Day 58 visits; h. have had no significant changes in diet in the 2 months prior to screening and are not planning such changes for the duration of the study; i. if taking proton pump inhibitors (PPIs), oral contraceptives, and/or selective serotonin reuptake inhibitors (SSRIs), have been on a stable dose for at least 3 months. At randomization: Patients are eligible for randomization to a treatment group in the study if they: a. have no more than 2 PDS symptom-free days per week during the 2-week run-in period; b. have an average PDS-symptom score for either primary symptom (early satiety or bothersome postprandial fullness) of greater than mild severity (>2 on the 1-5 Likert scale) for the 2-week run-in period; c. have no more than 1 day per week with an EPS-symptom score of greater than moderate severity (>3 on the 1-5 Likert scale) during the 2-week run-in period; d. have an average EPS score of, at most, mild severity (≤2 on the 1-5 Likert scale) for each week of the 2-week run-in period; e. have no more than 3 days per week with heartburn during the 2-week run-in period; f. have been at least 70% compliant during the 2-week run-in period with electronic patient reported outcome (ePRO) e-diary entries (at least 10 out of 14 e-diary entries); and g. have not missed more than 3 consecutive days of e-diary entries. |
|
| E.4 | Principal exclusion criteria |
| Patients will be excluded from admission to the 2-week run-in period or randomization to a treatment group if they have/are: a. a body mass index (BMI) >32; b. current peptic ulcer disease (PUD); c. heartburn that occurs >3 times per week; d. current Helicobacter pylori (H pylori) infection confirmed by stool sample testing or breath testing, or H pylori eradication therapy within the 6 months prior to screening; e. a total Patient Health Questionnaire 15-item Somatic Symptom Severity Scale (PHQ-15) score >17 f. presence or suspected presence of unstable coronary artery disease, organic gastrointestinal disease, or collagen vascular disease within the 6 months prior to screening; g. any alarm symptoms including uninvestigated anemia, rectal bleeding, weight loss, or unresolved fever within the 6 months prior to screening; h. taking prohibited medications specified in Section 3.3 within 30 days prior to screening or planning to take prohibited medications at any time during the study; i. at screening, a QT interval corrected for heart rate using Bazett’s correction formula (QTcB) >440 msec as determined by the Investigator. The ECG core laboratory will also determine the QTcB and the QT interval corrected for heart rate using Fridericia’s correction formula (QTcF). If either QTcB or QTcF reported by the ECG core laboratory exceeds 440 msec, the patient will not be randomized; j. at the Baseline visit, a QTcB >440 msec as determined by the Investigator; k. a clinically significant abnormal 12-lead ECG (eg, with evidence of acute or recent myocardial infarction or ischemia, rhythm disturbance, or conduction abnormality other than first degree AV block); l. a family history of sudden death at age <40 years; m. a personal or family history of long QT syndrome; n. evidence of current or recent alcohol or drug abuse within the 6 months prior to screening; o. participating in another drug or medical device study or use of any investigational drug within 30 days before dosing or planning to use prior to study completion; p. a serum potassium, magnesium, or calcium value outside the laboratory reference range at screening or baseline; q. a serum aspartate transaminase (AST), alanine transaminase (ALT), or gamma glutamyl transferase (GGT) ≥3 times the upper limit of the normal laboratory reference range at screening or baseline, or a bilirubin value ≥2 times the upper limit of the normal laboratory reference range at screening; r. diabetes mellitus requiring insulin therapy or oral hypoglycemic agents; s. a hemoglobin A1c (Hgb A1c) >7% at screening; t. any laboratory value outside the laboratory reference range at screening or baseline that are considered to be clinically significant by the Investigator; u. a positive pregnancy test or are nursing or planning a pregnancy during screening, run-in, active treatment, or the follow-up period; or v. a history or presence, upon clinical evaluation, of any illness or condition that might impact the safety of study drug administration or evaluability of drug effect based on the Investigator’s discretion. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint will be the responder rate for each treatment group through Day 42. Responder rate is defined as the percentage of patients who have adequate symptom relief at least 50% (≥50%) of the treatment days during the 42-day primary efficacy period based on daily patient responses via telephone electronic diary (eDiary) to the question, “In the past 24 hours, have you had adequate relief of either or both of these 2 meal-related symptoms: uncomfortable fullness after a meal or the inability to finish a meal?” In this study an adaptive interim efficacy analysis (Bauer and Kohne 1994, Posch et al 2005) will be utilized when 25% and 50% of the planned patients have completed at least 6 weeks of study drug treatment. These analyses will be conducted by an external independent statistician. One of the 4 possible courses of action resulting from the interim analyses is changing the primary efficacy endpoint to the mean score change from baseline over time for the 2 primary PDS symptoms (fullness and early satiety) measured during the 42-day primary efficacy period. If, after an interim analysis, the primary endpoint is changed to the mean change from baseline evaluation, then only patients randomized after the change in the primary endpoint who took at least 1 dose of the study medication will be included in the new primary analysis. |
|
| 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 | Yes |
| 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 | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| - same IMP used at different dosage |
|
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
|
| The study is considered terminated upon completion of all patient treatments and evaluations. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
Print
