Gastroparesis
Conditions
Keywords
Idiopathic Gastroparesis, Diabetic Gastroparesis
Brief summary
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.
Interventions
DRUGPCS12852
PCS12852 oral tablet administered once daily
DRUGPlacebo
Placebo comparator oral tablet administered once daily
Sponsors
Processa Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Gastric Emptying Rate From Baseline as Determined by the Area Under the Curve (AUC) of the Gastric Emptying Rate | ~28 days | 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. |
| Change in Gastric Emptying Rate From Baseline Using t50 Metric for Gastric Emptying Rate | ~28 days | Time for 50% gastric emptying (t50) metric assessed by the GEBT |
| Concentrations of PCS12852 in Plasma - Cmax | Day 1 | PK parameters were estimated from concentration-time data using noncompartmental methods, as data permitted. |
| Concentrations of PCS12852 in Plasma - AUC0-last | Day 1 | PK parameters were estimated from concentration-time data using noncompartmental methods, as data permitted. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the ANMS GCSI-DD | Day 7 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PCS12852 0.1mg PCS12852 0.1mg tablet
PCS12852: PCS12852 oral tablet administered once daily | 9 |
| PCS12852 0.5mg PCS12852 0.5mg tablet
PCS12852: PCS12852 oral tablet administered once daily | 8 |
| Placebo Similar in appearance to active study drug
Placebo: Placebo comparator oral tablet administered once daily | 8 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Early Termination | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | PCS12852 0.1mg | PCS12852 0.5mg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 7 Participants | 6 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 3 Participants | 6 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 5 Participants | 2 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 7 Participants | 3 Participants | 6 Participants | 16 Participants |
| Region of Enrollment United States | 9 participants | 8 participants | 8 participants | 25 participants |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 7 Participants | 22 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Woman of Childbearing Potential | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 9 | 5 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 9 | 0 / 8 | 0 / 8 |
Outcome results
Primary
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.
Time frame: ~28 days
Population: The change from baseline to Day 28 in AUC was analyzed using an analysis of covariance (ANCOVA) model with fixed effects for treatment group and gastroparesis type (idiopathic gastroparesis \[IG\] or diabetic gastroparesis \[DG\]) and the baseline value as a continuous covariate. Only patients with a baseline and Day 28 value were included in the analysis. The parameters listed are the best comparison of the breath test as opposed to individual timepoints.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PCS12852 0.1mg | Change in Gastric Emptying Rate From Baseline as Determined by the Area Under the Curve (AUC) of the Gastric Emptying Rate | 267.12 kPCD/minutes | Standard Error 708.056 |
| PCS12852 0.5mg | Change in Gastric Emptying Rate From Baseline as Determined by the Area Under the Curve (AUC) of the Gastric Emptying Rate | 283.09 kPCD/minutes | Standard Error 871.664 |
| Placebo | Change in Gastric Emptying Rate From Baseline as Determined by the Area Under the Curve (AUC) of the Gastric Emptying Rate | 221.74 kPCD/minutes | Standard Error 738.728 |
p-value: <0.05ANCOVA
Primary
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
Time frame: ~28 days
Population: The change from baseline to Day 28 using the t50 metric was analyzed using an analysis of covariance (ANCOVA) model with fixed effects for treatment group and gastroparesis type (idiopathic gastroparesis \[IG\] or diabetic gastroparesis \[DG\]) and the baseline value as a continuous covariate. Only patients with a baseline and Day 28 value were included in the analysis. The parameters listed are the best comparison of the breath test as opposed to individual timepoints.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PCS12852 0.1mg | Change in Gastric Emptying Rate From Baseline Using t50 Metric for Gastric Emptying Rate | -4.89 Minutes | Standard Error 12.32 |
| PCS12852 0.5mg | Change in Gastric Emptying Rate From Baseline Using t50 Metric for Gastric Emptying Rate | -26.64 Minutes | Standard Error 14.971 |
| Placebo | Change in Gastric Emptying Rate From Baseline Using t50 Metric for Gastric Emptying Rate | -11.15 Minutes | Standard Error 12.365 |
p-value: <0.05ANCOVA
Primary
Concentrations of PCS12852 in Plasma - AUC0-last
PK parameters were estimated from concentration-time data using noncompartmental methods, as data permitted.
Time frame: Day 28
Population: PK parameters were not calculated for patients with 2 or fewer detectable concentrations in their PK profile.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCS12852 0.1mg | Concentrations of PCS12852 in Plasma - AUC0-last | 1.0987 h*ng/mL | Standard Deviation 1.23183 |
| PCS12852 0.5mg | Concentrations of PCS12852 in Plasma - AUC0-last | 7.4218 h*ng/mL | Standard Deviation 7.10856 |
p-value: <0.05Regression, Linear
Primary
Concentrations of PCS12852 in Plasma - AUC0-last
PK parameters were estimated from concentration-time data using noncompartmental methods, as data permitted.
Time frame: Day 1
Population: PK parameters were not calculated for patients with 2 or fewer detectable concentrations in their PK profile.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCS12852 0.1mg | Concentrations of PCS12852 in Plasma - AUC0-last | 0.6331 h*ng/mL | Standard Deviation 0.27524 |
| PCS12852 0.5mg | Concentrations of PCS12852 in Plasma - AUC0-last | 3.0612 h*ng/mL | Standard Deviation 1.58834 |
p-value: <0.05Regression, Linear
Primary
Concentrations of PCS12852 in Plasma - Cmax
PK parameters were estimated from concentration-time data using noncompartmental methods, as data permitted.
Time frame: Day 28
Population: PK parameters were not calculated for patients with 2 or fewer detectable concentrations in their PK profile.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCS12852 0.1mg | Concentrations of PCS12852 in Plasma - Cmax | 0.11984 ng/mL | Standard Deviation 0.06877 |
| PCS12852 0.5mg | Concentrations of PCS12852 in Plasma - Cmax | 0.48100 ng/mL | Standard Deviation 0.255856 |
p-value: <0.05Regression, Linear
Primary
Concentrations of PCS12852 in Plasma - Cmax
PK parameters were estimated from concentration-time data using noncompartmental methods, as data permitted.
Time frame: Day 1
Population: PK parameters were not calculated for patients with 2 or fewer detectable concentrations in their PK profile.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCS12852 0.1mg | Concentrations of PCS12852 in Plasma - Cmax | 0.12211 ng/mL | Standard Deviation 0.039216 |
| PCS12852 0.5mg | Concentrations of PCS12852 in Plasma - Cmax | 0.59986 ng/mL | Standard Deviation 0.329187 |
p-value: <0.05Regression, Linear
Secondary
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.
Time frame: Day 21
Population: Scores were not able to be calculated for some patients in the 0.5mg group due to 2 patients discontinuing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PCS12852 0.1mg | Change From Baseline in the ANMS GCSI-DD | -0.57 Units on a scale | Standard Error 0.237 |
| PCS12852 0.5mg | Change From Baseline in the ANMS GCSI-DD | -1.12 Units on a scale | Standard Error 0.29 |
| Placebo | Change From Baseline in the ANMS GCSI-DD | -0.91 Units on a scale | Standard Error 0.228 |
p-value: <0.05ANCOVA
Secondary
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.
Time frame: Day 28
Population: Scores were not able to be calculated for some patients in the 0.5mg group due to 2 patients discontinuing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PCS12852 0.1mg | Change From Baseline in the ANMS GCSI-DD | -0.61 Units on a scale | Standard Error 0.254 |
| PCS12852 0.5mg | Change From Baseline in the ANMS GCSI-DD | -1.48 Units on a scale | Standard Error 0.311 |
| Placebo | Change From Baseline in the ANMS GCSI-DD | -1.00 Units on a scale | Standard Error 0.244 |
p-value: <0.05ANCOVA
Secondary
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.
Time frame: Day 14
Population: Scores were not able to be calculated for some patients in the 0.5mg group due to 2 patients discontinuing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PCS12852 0.1mg | Change From Baseline in the ANMS GCSI-DD | -0.62 Units on a scale | Standard Error 0.218 |
| PCS12852 0.5mg | Change From Baseline in the ANMS GCSI-DD | -1.06 Units on a scale | Standard Error 0.267 |
| Placebo | Change From Baseline in the ANMS GCSI-DD | -0.82 Units on a scale | Standard Error 0.21 |
p-value: <0.05ANCOVA
Secondary
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.
Time frame: Day 7
Population: Scores were not able to be calculated for some patients in 0.5mg group due to 2 patients discontinuing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PCS12852 0.1mg | Change From Baseline in the ANMS GCSI-DD | -0.02 score on a scale | Standard Error 0.141 |
| PCS12852 0.5mg | Change From Baseline in the ANMS GCSI-DD | -0.69 score on a scale | Standard Error 0.171 |
| Placebo | Change From Baseline in the ANMS GCSI-DD | -0.58 score on a scale | Standard Error 0.138 |
p-value: <0.05ANCOVA