E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Gastroparesis is a motility (movement) disorder of the stomach associated with slow or delayed emptying after meals. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018043 |
E.1.2 | Term | Gastroparesis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051153 |
E.1.2 | Term | Diabetic gastroparesis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021227 |
E.1.2 | Term | Idiopathic gastroparesis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 treatment with 2 dose levels of TAK-906 in adult subjects with gastroparesis compared with placebo during 12 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of TAK-906 doses compared with placebo during 12 weeks of treatment
Additional Objectives:
• To evaluate the PK of TAK-906 in subjects with gastroparesis,
• To evaluate the effect of TAK-906 on quality of life compared with placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject eligibility is determined according to the following criteria before entry into the study:
• Adult men and women aged 18 to 85 years, inclusive, and with body mass index ≥19 to ≤40 kg/m2 inclusive.
• Subjects should have symptoms of gastroparesis (eg, postprandial fullness, nausea, vomiting, upper abdominal pain, and early satiety) for at least 3 months before screening as assessed by a physician.
• Subjects 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.
• Subjects 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 (eg, motion sickness, glaucoma, menstrual cycles, migraine headache).
• Subjects must have confirmed delayed gastric emptying using an accepted diagnostic testing method that is documented in the subject's medical records prior to screening, OR that is confirmed by the GEBT performed at Visit 2. Delayed gastric emptying is defined as time to gastric half emptying (t1/2) ≥79 minutes (80th percentile).
• Absence of gastric outlet obstruction confirmed by upper gastrointestinal (GI), computed tomography, or endoscopy.
Special Inclusion for Subjects with Diabetes Mellitus
• Subjects must have glycosylated hemoglobin (HbA1c) ≤11% before the randomization visit. |
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E.4 | Principal exclusion criteria |
Any subject who meets any of the following criteria will not qualify for entry into the study:
• Known secondary causes of gastroparesis including but not limited to Parkinson disease, cancer, viral illness, or connective tissue diseases.
• Predominant gastroparetic symptom is epigastric pain, diffuse abdominal pain, or pain associated with bowel movement.
• Is taking medications that affect gastric emptying including opioids, glucagon-like peptide-1 analogs (eg,exenatide, liraglutide), amylin analogs (eg, pramlintide), and cannabinoids.
• 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.
• History of intrapyloric botulinum toxin injection within 3 months of screening or currently has a functioning implantable gastric electric stimulator.
• Nasogastric, percutaneous endoscopic gastrostomy, or percutaneous endoscopic jejunostomy feeding tube or inpatient hospitalization for gastroparesis within 2 weeks before the screening visit.
• Required parenteral nutrition for treatment of gastroparesis within 2 months before the screening visit.
• Previous diagnosis of gastric bezoar (the presence of retained liquid, bile, or small amounts of poorly organized food residue is permitted).
• Poor control of diabetes within 30 days before study entry, including diabetic ketoacidosis, hypoglycemia requiring medical intervention, admission for control of diabetes or diabetic complications.
• Elevated serum prolactin (>upper limit of normal [ULN]) at screening. 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 subjects may be enrolled in the study.
• Medical history of hypogonadism, current clinically significant menstrual abnormalities, or other clinical features of hyperprolactinemia will be excluded.
• The subject has acute or chronic liver disease meeting any of the criteria described below:
– The subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin >2.0 times the ULN.
– The subject 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) (see Appendix B).
– The subject 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 subject tests negative for HBsAg, but positive for HBcAb, the subject would be eligible if the Investigator has documentation of other test results showing that the subject does not have active hepatitis B infection.
- Subjects with positive hepatitis C antibody (HCV IgG) and quantitative HCV polymerase chain reaction (PCR). HCV PCR is performed only if HCV IgG is positive.
• Any signs/symptoms or history of extrapyramidal system disease and other clinically relevant central nervous system or neuropsychiatric disease including but not limited to tardive dyskinesia, neuroleptic malignant syndrome, acute dystonia, parkinsonian like symptoms, severe depression and history of suicide attempt.
• The subject has known COVID-19 infection, or suspected COVID-19 infection (as assessed by the investigator). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to Week 12 of the treatment period in the ANMS GCSI-DD composite score (nausea,
early satiety, upper abdominal pain, and postprandial fullness). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Proportion of subjects with at least 50% reduction from baseline in ANMS GCSI-DD composite score at Week 12.
• Change from baseline to Week 12 of the treatment period in the ANMS GCSI-DD nausea symptom score.
• Change from baseline to Week 12 of the treatment period in the ANMS GCSI-DD early satiety symptom score.
• Change from baseline to Week 12 of the treatment period in the ANMS GCSI-DD postprandial fullness symptom score.
• Change from baseline to Week 12 of the treatment period in the ANMS GCSI-DD upper abdominal pain symptom score.
• Change from baseline to Week 12 of the treatment period in the ANMS GCSI-DD recorded vomiting frequency.
• Change from baseline to Week 12 of the treatment period in the ANMS GCSI-DD overall severity of
gastroparesis symptoms score.
• Change from baseline to Week 12 of the treatment period in the bloating severity scale score.
• Change from baseline to Week 12 of the treatment period in the ANMS GCSI-DD total score (nausea, early satiety, upper abdominal pain, postprandial fullness, bloating, and vomiting).
• Proportion of symptomatic weeks (weeks with symptoms assessed as >mild [average ANMS GCSI-DD composite score ≥2]) during 12 weeks of treatment.
• Change from baseline to Week 12 of the treatment period in the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) total score. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | No |
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 |
Japan |
United States |
Belgium |
Poland |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |