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 various 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 pharmacokinetics of TAK-906 in subjects with gastroparesis
To evaluate the effect of TAK-906 on quality of life compared with placebo.
To evaluate the potential relationship between changes in C-reactive protein (CRP), glucose-dependent
insulinotropic peptide (GIP), peptide tyrosine tyrosine (PYY), clinical symptoms and motility response
To evaluate the effect of TAK-906 on GEBT. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 at Screening: delayed gastric emptying by GEBT,defined as time to gastric half emptying (t1/2) ≥79 minutes (80th percentile).
Absence of gastric outlet obstruction confirmed by upper GI, CT, 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 |
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.
Signs/symptoms of extrapyramidal system disease and other clinically relevant central nervous system or neuropsychiatric disease included but not limited to tardive dyskinesia, neuroleptic malignant syndrome, acute dystonia, parkinsonian like symptoms and severe depression. |
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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 | 4 |
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 | 7 |
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 |
Belgium |
Italy |
Japan |
Poland |
United States |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |