Safety, PK and Efficacy of PCS12852 on Gastric Emptying Rate in Patients With Moderate to Severe Gastroparesis

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled study that will compare the effect of 2 different dosage regimens of PCS12852 on gastric emptying time to placebo in both idiopathic gastroparesis (IG) and diabetic gastroparesis (DG) patients.

Official Title
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A Phase 2A, Placebo-controlled, Randomized, Dose Response Study of the Safety, Pharmacokinetics and Efficacy of PCS12852 on Gastric Emptying Rate Assessed by 13C Spirulina GEBT in Patients With Moderate to Severe Gastroparesis

Conditions
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Gastroparesis

Intervention / Treatment
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* Drug: PCS12852
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has documented diagnosis of moderate to severe DG or IG according to the ANMS GCSI-DD score during the Screening period (score of >2 on average of the screening days). Moderate to severe delay in gastric emptying rate as measured by the GEBT at Screening defined as GE half-time (t1/2) ≥ the 80th percentile of normative data as determined by Cairn Diagnostics. Male or female patients 18 to 80 years of age, inclusive, at baseline. Has continuous moderate to severe symptoms for gastroparesis (that is, chronic postprandial fullness, abdominal pain, postprandial nausea, vomiting, loss of appetite and/or early satiety) as assessed by the investigator for at least the past 3 months. Has hemoglobin A1c (BbA1c) < 11%. Has Body Mass Index range between 18-40. Women of childbearing potential must use one of the following acceptable methods of contraception throughout the study (1 month prior to Screening through 1 month after last dose of study medication): oral contraceptive medication, IUD, hormonal implants, injectable contraceptive methods, double-barrier methods, or tubal ligation. Male patients must be willing to use acceptable contraceptive measures such as vasectomy or double-barrier method and refrain from sexual activity with any female who is pregnant or lactating. Female partners of study participants are asked to use acceptable methods of contraception. Exclusion Criteria: Has acute, severe gastroenteritis and pronounced dehydration in the past 48 hours prior to Screening, chronic parenteral feeding or persistent severe vomiting. Has known hypersensitivity to Spirulina, egg, milk products or wheat allergens. Has a known disturbance of small intestinal absorption, exocrine pancreatic function, liver metabolism or pulmonary function. Has a history of anorexia nervosa or bulimia. Previous history of bezoars (the presence of retained liquid, bile, or small amounts of poorly organized food residue is permitted). Prior surgery involving any gastrointestinal surgery, including the luminal gastrointestinal (GI) tract (cholecystectomy and appendectomy are permitted if performed >3 months prior to baseline GEBT). Any abdominal or pelvic surgery within the past 3 months. Known history of the following GI conditions: inflammatory bowel disease; irritable bowel syndrome with diarrhea; or any other active disorder that could explain symptoms in the opinion of the investigator. Has active diverticulitis, diverticular stricture, and other intestinal strictures. Currently taking Glucagon-like peptide-1 (GLP-1) agonists, e.g. exenatide, liraglutide, semaglutide or dulaglutide, or pramlintide. Has severe psychiatric illness (including suicidal tendencies or ideation) or neurological illness. Use of narcotics/opioids, drugs used to treat gastroparesis within 3 days of the Screening GEBT test. Clinically significant cardiac disease including but not limited to unstable angina, acute myocardial infarction within 6 months of baseline, and arrhythmia requiring therapy. Patient has QTc interval ≥ 480 milliseconds on Screening ECG. History of cerebral hemorrhage, cerebrovascular accident, transient ischemic attack, gastrointestinal bleeding, or retinal hemorrhage within 6 months of baseline. Patient has active or history of neoplastic disease (except for adequately treated non-invasive basal cell and/or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) within the past 5 years prior to baseline. Presence of clinically significant medical condition(s) including but not limited to: renal, hepatic, cardiovascular, hematological, gastrointestinal, endocrine, pulmonary, neurological, psychiatric, substance abuse, and or any other clinically significant disease or disorder, which in the opinion of the investigator, may put the patient at risk due to participation in the study, influence the results of the study, and/or affect the patient's ability to complete the study. History of or current diagnosis of active tuberculosis (TB); undergoing treatment for latent TB infection (LTBI); untreated LTBI (as determined by documented results within 3 months of the Screening Visit of a positive TB skin test with purified protein derivative with induration ≥ 5 mm, a positive QuantiFERON TB test or positive or borderline T-SPOT [Elispot] test); or positive TB test at Screening. Patients with documented completion of appropriate LTBI treatment would not be excluded and are not required to be tested. Currently taking known P-gp and BCRP inhibitors or inducers and gastric acid reducing agents. E.g., proton pump inhibitors or H2 receptor antagonists. Other inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PCS12852 0.1mg<br>PCS12852 0.1mg tablet | Drug: PCS12852<br>* PCS12852 oral tablet administered once daily<br>|
| Experimental: PCS12852 0.5mg<br>PCS12852 0.5mg tablet | Drug: PCS12852<br>* PCS12852 oral tablet administered once daily<br>|
| Placebo Comparator: Placebo<br>Similar in appearance to active study drug | Drug: Placebo<br>* Placebo comparator oral tablet administered once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gastric Emptying Rate From Baseline as Determined by the Area Under the Curve (AUC) of the Gastric Emptying Rate | Change from baseline in gastric emptying rate was determined by the AUC by Gastric Emptying Breath Test (GEBT) at Day 28 after administration of PCS12852 or placebo. |  28 days | 
| Change in Gastric Emptying Rate From Baseline Using t50 Metric for Gastric Emptying Rate | Time for 50% gastric emptying (t50) metric assessed by the GEBT |  28 days | 
| Concentrations of PCS12852 in Plasma - Cmax | PK parameters were estimated from concentration-time data using noncompartmental methods, as data permitted. | Day 1 | 
| Concentrations of PCS12852 in Plasma - AUC0-last | PK parameters were estimated from concentration-time data using noncompartmental methods, as data permitted. | Day 1 | 
| Concentrations of PCS12852 in Plasma - AUC0-last | PK parameters were estimated from concentration-time data using noncompartmental methods, as data permitted. | Day 28 | 
| Concentrations of PCS12852 in Plasma - Cmax | PK parameters were estimated from concentration-time data using noncompartmental methods, as data permitted. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the ANMS GCSI-DD | Change from baseline in the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary (ANMS GCSI-DD). Scores range from 0-4 for the gastroparesis-related symptoms (nausea, early satiety, postprandial fullness, upper abdominal pain, and vomiting), with 4 meaning a worse outcome. | Day 7 | 
| Change From Baseline in the ANMS GCSI-DD | Change from baseline in the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary. Scores range from 0-4 for the gastroparesis-related symptoms (nausea, early satiety, postprandial fullness, upper abdominal pain, and vomiting), with 4 meaning a worse outcome. | Day 14 | 
| Change From Baseline in the ANMS GCSI-DD | Change from baseline in the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary. Scores range from 0-4 for the gastroparesis-related symptoms (nausea, early satiety, postprandial fullness, upper abdominal pain, and vomiting), with 4 meaning a worse outcome. | Day 21 | 
| Change From Baseline in the ANMS GCSI-DD | Change from baseline in the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary. Scores range from 0-4 for the gastroparesis-related symptoms (nausea, early satiety, postprandial fullness, upper abdominal pain, and vomiting), with 4 meaning a worse outcome. | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idiopathic Gastroparesis, Diabetic Gastroparesis