Clinical trial NCT03268941: A Study to Evaluate the Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) for TAK-906 in Participants With Diabetes Mellitus and Gastroparesis (DG) or With Idiopathic Gastroparesis (IG)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus and Gastroparesis, Idiopathic Gastroparesis
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-08-31
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this study is to evaluate the safety, PK and PD of TAK-906 in participants with Gastroparesis (GP).

Detailed description: The drug being tested in this study is called TAK-906 maleate. TAK-906 maleate is being tested to treat people who have DG or IG. This study will assess the safety, tolerability, PK/PD and food effect of TAK-906 and will determine the effect of TAK-906 on gastric emptying (GE).

The study enrolled a total of 51 participants. This study will be conducted in two parts: Part 1 and Part 2. Part 1 will consist of 48 participants enrolled in 3 active treatment groups and 1 placebo group. Participants in Part 1 will be randomly assigned (by chance, like flipping a coin) to one of the 3 active treatment groups or 1 placebo group-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* TAK 906 maleate 5 mg
* TAK 906 maleate 25 mg
* TAK 906 maleate 100 mg
* Placebo

All participants who will complete Part 1 of the study will be eligible for enrollment in Part 2. Part 2 consisted of 21 participants who completed Part 1 and were assigned to the 2 open-label treatment groups as follow:

* TAK-906 maleate 25 mg Fed + TAK-906 maleate 25 mg Fasted: crossover design, with a minimum 7-day washout in doses of each period.
* Metoclopramide 10 mg

This multi-center trial will be conducted the United States. The overall time to participate in this study is approximately 8 weeks. Participants will make a final visit to the clinic 10-14 days after receiving their last dose of study drug for a follow-up assessment.

Eligibility criteria: 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).

Primary outcomes:
measure: Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From Baseline to 14 days after the last dose of study drug (Up to approximately 39 days)
measure: Number of Participants With Markedly Abnormal Laboratory Parameters Values
timeFrame: From Baseline to 14 days after the last dose of study drug in Part 1 (Up to approximately 23 days)
measure: Number of Participants With Markedly Abnormal Vital Signs
timeFrame: From Baseline to 14 days after the last dose of study drug (Up to approximately 39 days)
measure: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values
timeFrame: From Baseline to 14 days after the last dose of study drug (Up to approximately 39 days)
Secondary outcomes:
measure: 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
timeFrame: Day 1 predose (Baseline), 1 hour and at multiple timepoints (Up to 8 hours) postdose
measure: 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
timeFrame: Baseline and Day 7
measure: 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
timeFrame: Baseline and Day 1 of Part 1
measure: Percent Change From Baseline in Gastric Emptying (GE) Time as Measured by the SmartPill on Day 7 for Part 1
timeFrame: Baseline and Day 7
measure: AUCτ: Area Under the Plasma Concentration-time Curve From 0 to Time (T) Over the Dosing Interval for TAK-906 in Part 1
timeFrame: 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
measure: Cmax: Maximum Observed Plasma Concentration for TAK 906 in Part 1
timeFrame: 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
measure: Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1
timeFrame: Part 1: Predose on Days 2, 3, 4, 5, 6, 7, 8 and 9
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 in Part 1
timeFrame: 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
Other outcomes:
Locations:
city: Peoria
country: United States
facility: 9171 West Thunderbird Road
state: Arizona
city: Tucson
country: United States
facility: 850 North Kolb Road
state: Arizona
city: Little Rock
country: United States
facility: 11219 Financial Centre Parkway
state: Arkansas
city: Miami
country: United States
facility: 13055 Southwest 42nd Street
state: Florida
city: Miami
country: United States
facility: 8200 Southwest 117th Avenue
state: Florida
city: Decatur
country: United States
facility: 125 Clairemont Avenue
state: Georgia
city: Bastrop
country: United States
facility: 616 South Washington Street
state: Louisiana
city: Chattanooga
country: United States
facility: 6035 Shallowford Road
state: Tennessee
city: Jackson
country: United States
facility: 26 Stonecreek Circle
state: Tennessee
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Kuo B, Scimia C, Dukes G, Zhang W, Gupta S, Chen C, Chuang E, Camilleri M. Randomised clinical trial: safety, pharmacokinetics and pharmacodynamics of trazpiroben (TAK-906), a dopamine D2 /D3 receptor antagonist, in patients with gastroparesis. Aliment Pharmacol Ther. 2021 Aug;54(3):267-280. doi: 10.1111/apt.16451. Epub 2021 Jun 20.