Diabetes Mellitus and Gastroparesis, Idiopathic Gastroparesis Clinical Trial
Official title:
A 2-Part, Randomized, Double Blind and Open-Label, Placebo and Active-Comparator Controlled Trial to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics for TAK-906 in Subjects With Diabetes Mellitus and Gastroparesis or With Idiopathic Gastroparesis
| Verified date | December 2020 |
| Source | Takeda |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this study is to evaluate the safety, PK and PD of TAK-906 in participants with Gastroparesis (GP).
| Status | Completed |
| Enrollment | 51 |
| Est. completion date | March 9, 2018 |
| Est. primary completion date | March 9, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 75 Years |
| Eligibility | Inclusion Criteria In order to be eligible for participation in this trial, the participant must: 1. Has a documented diagnosis of diabetes mellitus gastroparesis (DG) or idiopathic gastroparesis (IG). 2. Has a body mass index (BMI) greater than or equal to (>=) 18 and less than or equal to (<=) 40 kilogram per square meter (kg/m^2) at the Screening Visit. 3. Be a non-smoker who has not used tobacco or nicotine-containing products (example, nicotine patch) for at least 6 months prior to trial drug administration of the initial dose of trial drug/invasive procedure. 4. Has symptoms for gastroparesis (GP) (that is, chronic postprandial fullness, abdominal pain, postprandial nausea, vomiting, loss of appetite and/or early satiety) the past 3 months. 5. Has documented slow gastric emptying (GE), with delayed GE by 13C-Spirulina gastric emptying breath test (GEBT) at Screening defined as >=80th percentile. Note: If a participant has had a documented scintigraphy or GEBT within the last 12 months that confirms the diagnosis of delayed GE, a screening GEBT would not be required. 6. Has nausea subscale (of American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary [ANMS-GCSI-DD]) symptom score >=2 at least 3 of 7 days during Screening. 7. Has haemoglobin A1c (HBA1c) less than (<) 10 percent (%) (for diabetes mellitus only). Exclusion Criteria The participant must be excluded from participating in the trial if the participant: 1. Has acute severe gastroenteritis and pronounced dehydration in the past 48 hours prior to Screening, gastric pacemaker, chronic parenteral feeding or persistent severe vomiting. 2. Has a known disturbance of small intestinal absorption, exocrine pancreatic function, liver metabolism, and pulmonary function. 3. Has a history of anorexia nervosa or bulimia. 4. Previous history of bezoars (the presence of retained liquid, bile, or small amounts of poorly organized food residue is permitted). 5. Difficulty swallowing solid food or pills. 6. Prior surgery involving the luminal gastrointestinal (GI) tract (cholecystectomy, appendectomy, and hysterectomy are permitted if performed greater than (>) 3 months prior to SmartPill test). 7. Any abdominal or pelvic surgery within the past 3 months. 8. Known or history of inflammatory bowel disease. 9. Has active diverticulitis, diverticular stricture, and other intestinal strictures. 10. Had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter [mL]) within 4 weeks prior to the pretrial (screening) visit milligram per deciliter (mg/dL) (14.99 millimole per liter [mmol/L]) during any visit up to and including the randomization visit (Period 1 Day 1 predose). Note: If the participant meets this exclusion criterion and the investigator believes that the value is not consistent with the participant's current self-monitoring blood glucose values, the participant should not be excluded at this time. The visit can be repeated within 5 to 7 days. 11. Has had diabetic ketoacidosis (within the prior 4 weeks). |
| Country | Name | City | State |
|---|---|---|---|
| United States | 616 South Washington Street | Bastrop | Louisiana |
| United States | 6035 Shallowford Road | Chattanooga | Tennessee |
| United States | 125 Clairemont Avenue | Decatur | Georgia |
| United States | 26 Stonecreek Circle | Jackson | Tennessee |
| United States | 11219 Financial Centre Parkway | Little Rock | Arkansas |
| United States | 13055 Southwest 42nd Street | Miami | Florida |
| United States | 8200 Southwest 117th Avenue | Miami | Florida |
| United States | 9171 West Thunderbird Road | Peoria | Arizona |
| United States | 850 North Kolb Road | Tucson | Arizona |
| Lead Sponsor | Collaborator |
|---|---|
| Millennium Pharmaceuticals, Inc. |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A SAE is an AE resulting in any of the following outcomes or deemed significant for any following reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. | From Baseline to 14 days after the last dose of study drug (Up to approximately 39 days) | |
| Primary | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Clinical Laboratory parameters included tests for chemistry, hematology and urinalysis. Markedly abnormal values during treatment period were categorized as:alanine aminotransferase (ALT)>3.0 U/L*upper limit of normal(ULN),albumin<25 g/L*lower limit of normal(LLN),alkaline phosphatase >3.0 U/L*ULN,aspartate aminotransferase >3.0 U/L*ULN,bilirubin >2 umol/L*ULN,blood urea nitrogen(BUN) >10.7 mmol/L,calcium <1.75 mmol/L, >2.88 mmol/L,chloride <75 mmol/L, >126 mmol/L,creatinine >177umol/L,gamma glutamyl transferase (GGT) >3 U/L*ULN,glucose <2.8 mmol/L, >19.4 mmol/L,phosphate <0.52 mmol/L, >2.10 mmol/L,potassium<3 mmol/L, >6 mmol/L,sodium <130 mmol/L, >150 mmol/L,hematocrit (%) <0.8*LLN, >1.2*ULN,hemoglobin <0.8 g/L*LLN, >1.2 g/L*ULN,leukocytes <0.5 (10^9/L)*LLN, >1.5 (10^9/L)*ULN,erythrocytes<0.8 (10^12/L)*LLN, >1.2(10^12/L)*ULN,platelets <75(10^9/L), >600(10^9/L). Participants with at least 1 markedly abnormal laboratory parameter value is reported. | From Baseline to 14 days after the last dose of study drug in Part 1 (Up to approximately 23 days) | |
| Primary | Number of Participants With Markedly Abnormal Vital Signs | Vital signs included body temperature, diastolic and systolic blood pressure (mmHg), and heart rate (beats per minute [bpm]). Heart rate<50 bpm and systolic blood pressure <85 mmHg were considered markedly abnormal. | From Baseline to 14 days after the last dose of study drug (Up to approximately 39 days) | |
| Primary | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | The 12-lead electrocardiogram (ECG) values outside the range Heart Rate <50 (beats/min), PR Interval =120 (msec), PR Interval =200 (msec), QRS Duration =120 (msec), QT Interval =460 (msec) were considered markedly abnormal. | From Baseline to 14 days after the last dose of study drug (Up to approximately 39 days) | |
| Secondary | Change From Baseline in Serum Prolactin Concentration on Day 1 at Tmax, Time of First Occurrence of Maximum Serum Concentration (Cmax) for TAK-906 Maleate for Part 1 | Change in serum prolactin on Day 1 at the Tmax, time of first occurrence of maximum serum concentration (Cmax) relative to Baseline was calculated as a ratio of maximum serum prolactin concentration on Day 1 to serum prolactin concentration at Baseline. | Day 1 predose (Baseline), 1 hour and at multiple timepoints (Up to 8 hours) postdose | |
| Secondary | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time as Measured by the 13C Spirulina GEBT Following Multiple Dose Administration of TAK-906 Maleate on Day 7 for Part 1 | The GEBT is a nonradioactive, noninvasive, orally administered test for measuring the rate of solid phase gastric emptying (GE) in adults. The GEBT measures how fast solid food moves from the stomach to the small intestine during the digestive process and aids in the diagnosis of delayed stomach emptying (GP). GE half-emptying time is the time in minutes (min) for half of the ingested solids to leave the stomach. This value was measured by the 13C spirulina GEBT. | Baseline and Day 7 | |
| Secondary | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time Following Single Dose Administration of TAK-906 Maleate as Measured by the 13C Spirulina GEBT on Day 1 | The GEBT is a nonradioactive, noninvasive, orally administered test for measuring the rate of solid phase gastric emptying (GE) in adults. The GEBT measures how fast solid food moves from the stomach to the small intestine during the digestive process and aids in the diagnosis of delayed stomach emptying (GP). GE half-emptying time is the time in minutes (min) for half of the ingested solids to leave the stomach. This value was measured by the 13C spirulina GEBT. | Baseline and Day 1 of Part 1 | |
| Secondary | Percent Change From Baseline in Gastric Emptying (GE) Time as Measured by the SmartPill on Day 7 for Part 1 | SmartPill is an ingestible capsule that measures pressure, potential of hydrogen (pH) and temperature as it travels through the gastrointestinal (GI) tract to assess GE and GI motility. SmartPill eliminates radiation exposure and is the only motility test that provides a complete transit profile of the GI tract. | Baseline and Day 7 | |
| Secondary | AUCt: Area Under the Plasma Concentration-time Curve From 0 to Time (T) Over the Dosing Interval for TAK-906 in Part 1 | Part 1: Day 1 predose and at multiple timepoints, (Up to 8 hours) postdose and Day 7 predose and at multiple timepoints (Up to 48 hours) postdose | ||
| Secondary | Cmax: Maximum Observed Plasma Concentration for TAK 906 in Part 1 | Part 1: Day 1 predose and at multiple timepoints, (Up to 8 hours) postdose and Day 7 predose and at multiple timepoints (Up to 48 hours) postdose | ||
| Secondary | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Part 1: Predose on Days 2, 3, 4, 5, 6, 7, 8 and 9 | ||
| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 in Part 1 | Part 1: Day 1 predose and at multiple timepoints, (Up to 8 hours) postdose and Day 7 predose and at multiple timepoints (Up to 48 hours) postdose |