Ensayos clínicos

Inclusion Criteria:

• In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
• The subject or, when applicable, the subject’s legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization before the initiation of any study procedures.
• The subject should have 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.
• The subject should have confirmed delayed gastric emptying at screening.
• The subject must have an average composite ANMS GCSI-DD symptom score ≥ 2 during the 7 days before randomization. The predominant symptom experienced by subjects must not be abdominal pain.
• The subject 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).
• The subject is an adult man or woman aged 18 to 85 years, inclusive, at the screening visit.
• The subject has a BMI of ≥ 19 to ≤ 40 kg/m^2 inclusive.
• Absence of gastric outlet obstruction confirmed by upper GI, computed tomography or endoscopy.
• A male subject who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use barrier method of contraception (eg, condom with or without spermicide) from signing of informed consent throughout the duration of the study and for 95 days after last dose. The female partner of childbearing potential of the male subject should also use a highly effective method of contraception during this period.   A female subject of childbearing potential* who is sexually active with a nonsterilized male partner agrees to use a highly effective method of contraception from signing of informed consent throughout the duration of the study and for 35 days after the last dose.

Special Inclusion for Subjects with Diabetes Mellitus

• A subject with diabetes mellitus must have HbA1c ≤11% before the randomization visit.

During Screening Period

• The subject has shown compliance with the completion of the Daily Symptom Diary, defined as ≥80% diary completions for a minimum of 14 days during the symptom assessment period.

Exclusion Criteria:

• The subject has received any investigational compound within 30 days or 5 half-lives, whichever is longer, before screening.
• The subject’s predominant symptom is epigastric pain, diffuse abdominal pain, or pain associated with bowel movement.
• The subject has received TAK-906 in a previous clinical study or as a therapeutic agent.
• The subject is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
• The subject has, in the judgment of the investigator, clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes at screening.
• The subject takes or is required to take excluded medications.
• If female, the subject is pregnant, lactating, breastfeeding, or has breastfed within 6 months or is intending to become pregnant before participating in this study, during the study, and within 35 days after last dose of the study drug; or intending to donate ova during such time period.
• If male, the subject intends to donate sperm during the course of this study or for 95 days thereafter.
• The subject has known secondary causes of gastroparesis including but not limited to Parkinson disease, cancer, viral illness, or connective tissue diseases.
• The subject has a 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.
• The subject has a presence of thyroid dysfunction not controlled by treatment.
• The subject has a known or history of inflammatory bowel disease.
• The subject has current chronic diarrhea (defined as > 3 loose bowel movements daily for at least 2 weeks).
• The subject has a history of intrapyloric botulinum toxin injection within 3 months of screening or currently has functioning implantable gastric electric stimulator.
• The subject has had a nasogastric, percutaneous endoscopic gastrostomy, or percutaneous endoscopic jejunostomy feeding tube or inpatient hospitalization for gastroparesis within 2 weeks before the screening visit.
• The subject has had required parenteral nutrition for treatment of gastroparesis within 2 months before the screening visit.
• The subject has a previous diagnosis of gastric bezoar (the presence of retained liquid, bile, or small amounts of poorly organized food residue is permitted).
• The subject has a clinically significant known disorder of small intestinal absorption (e.g., refractory celiac disease), exocrine pancreatic function (e.g., chronic pancreatitis), liver (e.g., cirrhosis or severe cholestasis), and pulmonary function (e.g., severe chronic obstructive pulmonary disease or O2 requirements).
• The subject has a history of alcohol or drug abuse or dependence within the last year before screening or a positive drug test result at screening.
• The subject is a chronic smoker who is unable or unwilling to abstain from smoking during the 3 visits during which the GEBT will be performed.
• The subject has experienced 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.
• The subject has a history of anorexia nervosa, binge eating or bulimia within 5 years of screening.
• The subject has a history of acute myocardial infarction or unstable angina within 12 months before study entry.
• The subject has a severe cardiovascular autonomic neuropathy.
• The subject has any clinically important abnormalities in rate, rhythm, conduction, or morphology of resting ECG.
• The subject has prolonged QTcF interval (≥ 450 msec) or risk factors of QT interval prolongation, for example, clinically relevant electrolyte imbalance and family history of QT interval prolongation.
• The subject uses a cardiac medical device such as pacemakers and defibrillators (bladder stimulators, spinal stimulators, medication infusion devices, insulin pumps, continuous glucose monitors are permitted).
• The subject has a lifestyle in which drowsiness may risk personal or public safety.
• The subject has an elevated serum prolactin (>upper limit of normal [ULN]) at screening Visit 2. A high prolactin level at the screening visit that is considered to be due to stress of venipuncture, chest wall stimulation, or other physiological causes may be retested after a few days and if normal, the subject may be enrolled in the study.
• The subject has concurrent hypogonadism, current clinically significant menstrual abnormalities such as amenorrhea or oligomenorrhea related to hyperprolactinemia, or other clinical features of hyperprolactinemia such as galactorrhea or gynecomastia.
• The subject has any signs/symptoms or history of extrapyramidal system disease and other clinically relevant CNS or neuropsychiatric disease including but not limited to tardive dyskinesia, neuroleptic malignant syndrome, acute dystonia, parkinsonian like symptoms, severe mental depression, and history of suicide attempt.
• The subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin > 2.0 times the ULN.
• The subject has pre-existing hepatic disease that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe; total score 10 to 15 points).
• The subject has a history of any psychiatric disorder or cognitive impairment that would interfere with participation in the study.
• The subject has a known liver disease or is positive for hepatitis B or C. For hepatitis B/C, the subject has 1 of the following at screening:
  • Chronic hepatitis B virus infection: positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody; or
  • Chronic hepatitis C virus (HCV) infection: positive for HCV antibody that is confirmed with a positive HCV RNA viral load test (those treated and cured for HCV infection are allowed).
• The subject has any identified congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, HIV infection, organ transplantation).
• The subject has renal impairment, defined as a lower limit of (eGFR) < 30 mL/min at screening visit.
• The subject 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).
• The subject has poor venous access or inability to tolerate venipuncture.
• The subject has hypersensitivity to Spirulina, egg, milk, or wheat allergens.
• The subject has a history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator contraindicates their participation.
• The subject has any other significant, uncontrolled organic or systemic medical condition or social circumstance that, in the investigator’s opinion, would mean it was not appropriate for the subject to participate in this clinical study.