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)

NCT ID: NCT03268941

Last Updated: 2021-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-26
• Study Completion Date: 2018-03-09

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.

Conditions

Diabetes Mellitus and Gastroparesis, Idiopathic Gastroparesis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Part 1: Placebo

TAK-906 placebo-matching (4x0 mg), capsule, orally, twice daily (BID) on Days 1-8 and once on Day 9 under fasted conditions.

Group Type: PLACEBO_COMPARATOR

TAK-906 Maleate Placebo

Intervention Type: DRUG

TAK-906 placebo-matching Capsules

Part 1: TAK 906 Maleate 5 mg

TAK-906 maleate 1x5 mg, capsule, orally, BID and TAK-906 maleate placebo-matching (3x0 mg), capsules, orally, BID on Days 1-8, followed by TAK-906 maleate 1x5 mg, capsule, orally once on Day 9 under fasted conditions.

Group Type: EXPERIMENTAL

TAK-906 Maleate

Intervention Type: DRUG

TAK-906 Maleate Capsules

Part 1: TAK 906 Maleate 25 mg

TAK-906 maleate 1x25 mg, capsule, orally, BID and TAK-906 maleate placebo-matching (3x0 mg), capsules, orally, BID on Days 1-8 followed by TAK-906 maleate 1x25 mg, capsule, orally, once on Day 9 under fasted conditions.

Group Type: EXPERIMENTAL

TAK-906 Maleate

Intervention Type: DRUG

TAK-906 Maleate Capsules

Part 1: TAK 906 Maleate 100 mg

TAK-906 maleate 100 mg (4x25 mg), capsules, orally, BID on Days 1-8 and once a day on Day 9 under fasted conditions.

Group Type: EXPERIMENTAL

TAK-906 Maleate

Intervention Type: DRUG

TAK-906 Maleate Capsules

Part 2: TAK-906 Maleate 25 mg Fed Condition

TAK-906 maleate 1x25 mg, capsule, orally, once on Day 1 of Period 1 under fed conditions (high fat breakfast), followed by a minimum 7- day washout.

Group Type: EXPERIMENTAL

TAK-906 Maleate

Intervention Type: DRUG

TAK-906 Maleate Capsules

Part 2: TAK-906 Maleate 25 mg Fasted Condition

TAK-906 maleate 1x25 mg, capsule, orally, once on Day 1 of Period 2 under fasted conditions.

Group Type: EXPERIMENTAL

TAK-906 Maleate

Intervention Type: DRUG

TAK-906 Maleate Capsules

Part 2: Metoclopramide 10 mg

Metaclopramide 10 mg, tablet, orally, once, 1 hour prior to breakfast on Day 1 in Part 2.

Group Type: ACTIVE_COMPARATOR

Metaclopramide

Intervention Type: DRUG

Metaclopramide Tablets

Interventions

TAK-906 Maleate

TAK-906 Maleate Capsules

Intervention Type: DRUG

Metaclopramide

Metaclopramide Tablets

Intervention Type: DRUG

TAK-906 Maleate Placebo

TAK-906 placebo-matching Capsules

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

9171 West Thunderbird Road

Peoria, Arizona, United States

850 North Kolb Road

Tucson, Arizona, 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

125 Clairemont Avenue

Decatur, Georgia, United States

616 South Washington Street

Bastrop, Louisiana, United States

6035 Shallowford Road

Chattanooga, Tennessee, United States

26 Stonecreek Circle

Jackson, Tennessee, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34148244 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

U1111-1196-9143

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-906-1002

Identifier Type: -

Identifier Source: org_study_id