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)

NCT03268941 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: TAK-906-1002U1111-1196-9143
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 9

Brief Summary

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

Conditions

Diabetes Mellitus and Gastroparesis, Idiopathic Gastroparesis

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (4)

• 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)

• 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)

• 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)

• 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 Outcomes (8)

• 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

  Day 1 predose (Baseline), 1 hour and at multiple timepoints (Up to 8 hours) postdose

• 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

  Baseline and Day 7

• 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

  Baseline and Day 1 of Part 1

• Percent Change From Baseline in Gastric Emptying (GE) Time as Measured by the SmartPill on Day 7 for Part 1

  Baseline and Day 7

• AUCτ: 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

Study Arms (7)

Part 1: Placebo

PLACEBO COMPARATOR

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

Drug: TAK-906 Maleate Placebo

Part 1: TAK 906 Maleate 5 mg

EXPERIMENTAL

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.

Drug: TAK-906 Maleate

Part 1: TAK 906 Maleate 25 mg

EXPERIMENTAL

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.

Drug: TAK-906 Maleate

Part 1: TAK 906 Maleate 100 mg

EXPERIMENTAL

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

Drug: TAK-906 Maleate

Part 2: TAK-906 Maleate 25 mg Fed Condition

EXPERIMENTAL

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.

Drug: TAK-906 Maleate

Part 2: TAK-906 Maleate 25 mg Fasted Condition

EXPERIMENTAL

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

Drug: TAK-906 Maleate

Part 2: Metoclopramide 10 mg

ACTIVE COMPARATOR

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

Drug: Metaclopramide

Interventions

TAK-906 Maleate DRUG

TAK-906 Maleate Capsules

Part 1: TAK 906 Maleate 100 mg; Part 1: TAK 906 Maleate 25 mg; Part 1: TAK 906 Maleate 5 mg; Part 2: TAK-906 Maleate 25 mg Fasted Condition; Part 2: TAK-906 Maleate 25 mg Fed Condition

Metaclopramide DRUG

Metaclopramide Tablets

Part 2: Metoclopramide 10 mg

TAK-906 Maleate Placebo DRUG

TAK-906 placebo-matching Capsules

Part 1: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible for participation in this trial, the participant must:
• Has a documented diagnosis of diabetes mellitus gastroparesis (DG) or idiopathic gastroparesis (IG).
• 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.
• 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.
• 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.
• 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.
• 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.
• Has haemoglobin A1c (HBA1c) less than (\<) 10 percent (%) (for diabetes mellitus only).

You may not qualify if:

• The participant must be excluded from participating in the trial if the participant:
• Has acute severe gastroenteritis and pronounced dehydration in the past 48 hours prior to Screening, gastric pacemaker, chronic parenteral feeding or persistent severe vomiting.
• Has a known disturbance of small intestinal absorption, exocrine pancreatic function, liver metabolism, and pulmonary function.
• Has a history of anorexia nervosa or bulimia.
• Previous history of bezoars (the presence of retained liquid, bile, or small amounts of poorly organized food residue is permitted).
• Difficulty swallowing solid food or pills.
• Prior surgery involving the luminal gastrointestinal (GI) tract (cholecystectomy, appendectomy, and hysterectomy are permitted if performed greater than (\>) 3 months prior to SmartPill test).
• Any abdominal or pelvic surgery within the past 3 months.
• Known or history of inflammatory bowel disease.
• Has active diverticulitis, diverticular stricture, and other intestinal strictures.
• Has had diabetic ketoacidosis (within the prior 4 weeks).

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (9)

9171 West Thunderbird Road

Peoria, Arizona, 85381, United States

Location

850 North Kolb Road

Tucson, Arizona, 85710, United States

Location

11219 Financial Centre Parkway

Little Rock, Arkansas, 72211, United States

Location

13055 Southwest 42nd Street

Miami, Florida, 33175, United States

Location

8200 Southwest 117th Avenue

Miami, Florida, 33183, United States

Location

125 Clairemont Avenue

Decatur, Georgia, 30030, United States

Location

616 South Washington Street

Bastrop, Louisiana, 71220, United States

Location

6035 Shallowford Road

Chattanooga, Tennessee, 37421, United States

Location

26 Stonecreek Circle

Jackson, Tennessee, 38305, United States

Location

Related Publications (1)

• 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.

  PMID: 34148244 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Gastroparesis

Interventions

Metoclopramide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenyl Ethers; Phenols

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The study has two parts: Part 1 (double-blind) and Part 2 (open-label).
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2017
• First Posted: August 31, 2017
• Study Start: September 26, 2017
• Primary Completion: March 9, 2018
• Study Completion: March 9, 2018
• Last Updated: January 6, 2021
• Results First Posted: July 23, 2019

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (9)