Diabetic Gastroparesis, Idiopathic Gastroparesis
Conditions
Interventions
investigational material(s)
Generic name etc : TAK-906 Maleate 5 mg, 25 mg, or 50 mg
INN of investigational material : -
Therapeutic category code : 239 Other agents affecting digestive organs
Dosage
Sponsors
Takeda Pharmaceutical Company Limited
Millennium Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Should have experienced symptoms of gastroparesis (e.g., postprandial fullness, nausea, vomiting, upper abdominal pain, and early satiety for at least 3 months before screening as assessed by a physician. 2. .Must have confirmed delayed gastric emptying by meeting 1 of the following criteria: a) Confirmed by an accepted diagnostic testing method (Gastric Emptying Breath Test [GEBT], scintigraphy, or wireless motility capsule) that is documented in the participant's medical records prior to screening; OR b) Participants without previous confirmation of delayed gastric emptying prior to screening will undergo a GEBT after they have stopped taking prohibited medications. 3. Must have an average composite ANMS GCSI-DD symptom score >=2 during the 7 days before randomization. The predominant symptom experienced by participants must not be abdominal pain. 4. Must experience nausea: nausea subscale (of ANMS GCSI-DD) symptom score >=2 at least 4 of 7 days or an average nausea subscale symptom score >=2 during the 7 days before randomization. Nausea symptoms must not be attributable to a central disorder (e.g. motion sickness, glaucoma, menstrual cycles, migraine headache). 5. Has a body mass index (BMI) of >=18 to <=40 kg/m^2 inclusive 6. Participant with diabetes mellitus must have glycosylated hemoglobin (HbA1c) <=11% at screening and before randomization. 7. Absence of gastric outlet obstruction confirmed by upper GI, computed tomography or endoscopy.
Exclusion criteria
Exclusion criteria: 1. Known secondary causes of gastroparesis including but not limited to Parkinson disease, cancer, viral illness, or connective tissue diseases. 2. Predominant gastroparetic symptom is epigastric pain, diffuse abdominal pain, or pain associated with bowel movement. 3. Is taking medications that affect gastric emptying including opioids, glucagon-like peptide-1 analogs (e.g., exenatide, liraglutide), amylin analogs (e.g., pramlintide), and cannabinoids. 4. Prior history of gastric surgery, including but not limited to gastrectomy, gastric bypass, gastric banding, bariatric surgery, pyloroplasty, vagotomy, or fundoplication, which has manipulated the natural anatomy of the stomach. 5. History of intra-pyloric botulinum toxin injection within 3 months of Screening or currently has functioning implantable electric stimulator. 6. Nasogastric, percutaneous endoscopic gastrostomy, or percutaneous endoscopic jejunostomy feeding tube or inpatient hospitalization for gastroparesis within 2 weeks before the Screening Visit. 7. Required parenteral nutrition for treatment of gastroparesis within 2 months before the Screening Visit. 8. Previous diagnosis of gastric bezoar (the presence of retained liquid, bile, or small amounts of poorly organized food residue is permitted). 9. Poor control of diabetes within 30 days prior to randomization, including diabetic ketoacidosis, hypoglycemia requiring medical intervention, admission for control of diabetes or diabetic complications 10. Elevated serum prolactin (>upper limit of normal [ULN]) at Screening. 11. Has concurrent hypogonadism, current clinically significant menstrual abnormalities, such as amenorrhea or oligomenorrhea, or other clinical features of hyperprolactinemia such as galactorrhea or gynecomastia. 12. Has acute or chronic liver disease meeting any of the criteria described below: - Has an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin >2.0 times the ULN. - Has pre-existing liver cirrhosis that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe; total score 10 to 15 points). - Has acute or chronic hepatitis B or C virus infection, manifesting as one of the following at screening: - Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). NOTE: if a participants tests negative for HBsAg, but positive for HBcAb, the participant would be eligible if the Investigator has documentation of other test results showing that the participant does not have active hepatitis B infection. - Participants with positive hepatitis C antibody (HCV IgG) and quantitative HCV polymerase chain reaction (PCR). HCV PCR is performed only if HCV IgG is positive. 13. Has renal impairment, defined as a lower limit of (estimated glomerular filtration rate [eGFR]) <30 mL/min at screening visit. 14. Has active neoplastic disease or history of neoplastic disease within 5 years of screening visit (except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix that has been definitively treated with standard of care approaches). 15. Uncontrolled or poorly controlled medical or psychiatric comorbidities which might affect their ability to participate in the study. 16. Has known COVID-19 infection, or suspected COVID-19 infection (as assessed by the investigator). 17. Signs/symptoms or history of extrapyramidal system disease and other clinically relevant CNS or neuropsychiatric disease including but
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Change From Baseline in American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary (ANMS GCSI-DD) Composite Score at Week 12 of the Treatment Period Timeframe; Baseline and Week 12 ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD composite score includes score of nausea, early satiety, upper abdominal pain, and postprandial fullness. The severity scores of these symptoms range from 0 (none) to 4 (very severe). The daily composite score was calculated by summing the scores on the 4 symptom items (nausea, early satiety, postprandial fullness, and upper abdominal pain) and then dividing by 4, that was the number of items within the composite score. Thus, the maximum daily composite score was (4 symptoms x maximum score 4 divided by 4) = 16/4 = 4. The ANMS GCSI-DD daily composite score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicated improvement. Mixed-effects Model for Repeated Measures (MMRM) was used for the analysis | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Percentage of Participants with At Least 50% Reduction From Baseline in ANMS GCSI-DD Composite Score at Week 12 Timeframe; Baseline and Week 12 ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis . The ANMS GCSI-DD composite score includes score of nausea, early satiety, upper abdominal pain and postprandial fullness. The severity scores of these symptoms range from 0 (none) to 4 (very severe). The daily composite score was calculated by summing the scores on the 4 symptom items (nausea, early satiety, postprandial fullness, and upper abdominal pain) and then dividing by 4, that was the number of items within the composite score. Thus, the maximum daily composite score was (4 symptoms x maximum score 4 divided by 4) = 16/4 = 4. The ANMS GCSI-DD daily composite score ranged from 0 to 4 with higher scores reflecting greater symptom severity efficacy Change from Baseline in the ANMS GCSI-DD Nausea Symptom Score at Week 12 of the Treatment Period Timeframe; Baseline and Week 12 ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD nausea symptom score ranges from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. MMRM was used for analysis. efficacy Change from Baseline in the ANMS GCSI-DD Early Satiety Symptom Score at Week 12 of the Treatment Period Timeframe; Baseline and Week 12 ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses early satiety on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD early satiety symptom score ranges from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from Baseline indicates impr | — |
Countries
Japan, Japan, Other (Refer to the section, "Other".)
Outcome results
None listed