Clinical trial NCT03544229: A Study to Evaluate the Efficacy and Safety of TAK-906 in Adult Participants With Symptomatic Idiopathic or Diabetic Gastroparesis
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2b Study to Evaluate the Efficacy and Safety of Twice-Daily Oral Administration of a Peripherally Acting Dopamine Receptor D2/D3 Antagonist, TAK-906 for the Treatment of Adult Subjects With Symptomatic Idiopathic or Diabetic Gastroparesis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Gastroparesis
Idiopathic Gastroparesis
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-06-01
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and safety of treatment with 2 dose levels of TAK-906 in adult participants with gastroparesis compared with placebo during 12 weeks of treatment.

Detailed description: The drug being tested in this study is called TAK-906. TAK-906 is being tested to treat people who have symptomatic idiopathic or diabetic gastroparesis.

The study will enroll approximately 205 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups (in 1:1:1:1 ratio) which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

* TAK-906 Maleate 5 mg (After implementation of Amendment 8, participants will not be further randomized to this arm)
* TAK-906 Maleate 25 mg
* TAK-906 Maleate 50 mg Placebo (dummy inactive pill) - this is a capsule that looks like the study drug but has no active ingredient

Prior to Amendment 8, participants were randomized to receive TAK-906 5 mg. After implementation of Amendment 8, participants will not be further randomized to this dose arm. All participants will be asked to take one capsule twice daily, at approximately the same time each day throughout the study.

This multi-center trial will be conducted worldwide. The overall study duration is approximately 17 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone 30 days after receiving their last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. Should have experienced symptoms of gastroparesis (e.g., postprandial fullness, nausea, vomiting, upper abdominal pain, and early satiety for at least 3 months before screening as assessed by a physician.
2. Must have confirmed delayed gastric emptying by meeting 1 of the following criteria:

   1. Confirmed by an accepted diagnostic testing method (Gastric Emptying Breath Test \[GEBT\], scintigraphy, or wireless motility capsule) that is documented in the participant's medical records prior to screening; OR
   2. Participants without previous confirmation of delayed gastric emptying prior to screening will undergo a GEBT after they have stopped taking prohibited medications.
3. Must have an average composite ANMS GCSI-DD symptom score ≥2 during the 7 days before randomization. The predominant symptom experienced by participants must not be abdominal pain.
4. 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 (e.g. motion sickness, glaucoma, menstrual cycles, migraine headache).
5. Has a body mass index (BMI) of ≥18 to ≤40 kg/m\^2 inclusive.
6. Participant with diabetes mellitus must have glycosylated hemoglobin (HbA1c) ≤11% at screening and before randomization.
7. Absence of gastric outlet obstruction confirmed by upper GI, computed tomography or endoscopy.

Exclusion Criteria:

1. Known secondary causes of gastroparesis including but not limited to Parkinson disease, cancer, viral illness, or connective tissue diseases.
2. Predominant gastroparetic symptom is epigastric pain, diffuse abdominal pain, or pain associated with bowel movement.
3. Is taking medications that affect gastric emptying including opioids, glucagon-like peptide-1 analogs (e.g., exenatide, liraglutide), amylin analogs (e.g., pramlintide), and cannabinoids.
4. 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.
5. History of intra-pyloric botulinum toxin injection within 3 months of Screening or currently has functioning implantable electric stimulator.
6. Nasogastric, percutaneous endoscopic gastrostomy, or percutaneous endoscopic jejunostomy feeding tube or inpatient hospitalization for gastroparesis within 2 weeks before the Screening Visit.
7. Required parenteral nutrition for treatment of gastroparesis within 2 months before the Screening Visit.
8. Previous diagnosis of gastric bezoar (the presence of retained liquid, bile, or small amounts of poorly organized food residue is permitted).
9. Poor control of diabetes within 30 days prior to randomization, including diabetic ketoacidosis, hypoglycemia requiring medical intervention, admission for control of diabetes or diabetic complications.
10. Elevated serum prolactin (\>upper limit of normal \[ULN\]) at Screening.
11. Has concurrent hypogonadism, current clinically significant menstrual abnormalities, such as amenorrhea or oligomenorrhea, or other clinical features of hyperprolactinemia such as galactorrhea or gynecomastia.
12. Has acute or chronic liver disease meeting any of the criteria described below:

    * Has an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin \>2.0 times the ULN.
    * Has pre-existing liver cirrhosis that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe; total score 10 to 15 points) (see Appendix B).
    * Has acute or chronic hepatitis B or C virus infection, manifesting as one of the following at screening:
    * Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). NOTE: if a participants tests negative for HBsAg, but positive for HBcAb, the participant would be eligible if the Investigator has documentation of other test results showing that the participant does not have active hepatitis B infection.
    * Participants with positive hepatitis C antibody (HCV IgG) and quantitative HCV polymerase chain reaction (PCR). HCV PCR is performed only if HCV IgG is positive.
13. Has renal impairment, defined as a lower limit of (estimated glomerular filtration rate \[eGFR\]) \<30 mL/min at screening visit.
14. Has active neoplastic disease or history of neoplastic disease within 5 years of screening visit (except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix that has been definitively treated with standard of care approaches).
15. Uncontrolled or poorly controlled medical or psychiatric comorbidities which might affect their ability to participate in the study.
16. Has known COVID-19 infection, or suspected COVID-19 infection (as assessed by the investigator).
17. Signs/symptoms or history of extrapyramidal system disease and other clinically relevant CNS or neuropsychiatric disease including but not limited to tardive dyskinesia, neuroleptic malignant syndrome, acute dystonia, parkinsonian like symptoms, severe mental depression, and history of suicide attempt.

Primary outcomes:
measure: Change From Baseline in the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary (ANMS GCSI-DD) Composite Score at Week 12 of the Treatment Period
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Percentage of Participants With at Least 50% Reduction From Baseline in ANMS GCSI-DD Composite Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the ANMS GCSI-DD Nausea Symptom Score at Week 12 of the Treatment Period
timeFrame: Baseline and Week 12
measure: Change From Baseline in the ANMS GCSI-DD Early Satiety Symptom Score at Week 12 of the Treatment Period
timeFrame: Baseline and Week 12
measure: Change From Baseline in the ANMS GCSI-DD Postprandial Fullness Symptom Score at Week 12 of the Treatment Period
timeFrame: Baseline and Week 12
measure: Change From Baseline in the ANMS GCSI-DD Upper Abdominal Pain Symptom Score at Week 12 of the Treatment Period
timeFrame: Baseline and Week 12
measure: Change From Baseline in the ANMS GCSI-DD Recorded Vomiting Frequency at Week 12 of the Treatment Period
timeFrame: Baseline and Week 12
measure: Change From Baseline in the ANMS GCSI-DD Overall Severity of Gastroparesis Symptoms Score at Week 12 of the Treatment Period
timeFrame: Baseline and Week 12
measure: Change From Baseline in the ANMS GCI-DD Bloating Severity Scale Score at Week 12 of the Treatment Period
timeFrame: Baseline and Week 12
measure: Change From Baseline in the ANMS GCSI-DD Total Score at Week 12 of the Treatment Period
timeFrame: Baseline and Week 12
measure: Percentage of Symptomatic Weeks
timeFrame: Up to 12 weeks
measure: Change From Baseline in the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) Total Score at Week 12 of the Treatment Period
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialists of the Southeast
state: Alabama
city: Tucson
country: United States
facility: Del Sol Research Management
state: Arizona
city: Tucson
country: United States
facility: Del Sol Research Management
state: Arizona
city: Chula Vista
country: United States
facility: GW Research
state: California
city: Corona
country: United States
facility: Trial Connections - New Hope Research Development
state: California
city: Garden Grove
country: United States
facility: Paragon Rx Clinical - Garden Grove
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute Inc.
state: California
city: Northridge
country: United States
facility: California Medical Research Associates
state: California
city: Orange
country: United States
facility: ISS - Conquest Clinical Research
state: California
city: San Diego
country: United States
facility: Precision Research Institute
state: California
city: Bristol
country: United States
facility: Connecticut Clinical Research Foundation
state: Connecticut
city: Clearwater
country: United States
facility: ISS - Innovative Research of West Florida
state: Florida
city: Hialeah
country: United States
facility: Elias Research Associates - Direct Helpers Research Center - Hialeah
state: Florida
city: Hialeah
country: United States
facility: International Research Associates
state: Florida
city: Hialeah
country: United States
facility: Palmetto Research
state: Florida
city: Homestead
country: United States
facility: Homestead Associates in Research
state: Florida
city: Inverness
country: United States
facility: Gastroenterology Associates - Crystal River
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: Baptist Diabetes Associates Research
state: Florida
city: Miami
country: United States
facility: PharmaSouth Research
state: Florida
city: Miami
country: United States
facility: Miami Dade Medical Research Institute
state: Florida
city: Miami
country: United States
facility: Anchor Medical Research
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute - New Port Richey
state: Florida
city: Port Orange
country: United States
facility: Advanced Medical Research Center
state: Florida
city: Athens
country: United States
facility: Summit Clinical Research
state: Georgia
city: Atlanta
country: United States
facility: Digestive Healthcare of Georgia - Atlanta
state: Georgia
city: Oak Lawn
country: United States
facility: DM Clinical Research - Southwest Gastroenterology - Oak Lawn
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Crestview Hills
country: United States
facility: Tri-State Gastroenterology Associates
state: Kentucky
city: Columbia
country: United States
facility: Gastro Center of Maryland
state: Maryland
city: Boston
country: United States
facility: MGH Digestive Healthcare
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: West Roxbury
country: United States
facility: Veterans Affairs Medical Center - West Roxbury
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan
state: Michigan
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan
state: Michigan
city: Flowood
country: United States
facility: Gastrointestinal Associates and Endoscopy Center
state: Mississippi
city: Missoula
country: United States
facility: Montana Medical Research
state: Montana
city: Albuquerque
country: United States
facility: Lovelace Scientific Resources - Albuquerque
state: New Mexico
city: Brooklyn
country: United States
facility: NY Scientific
state: New York
city: Great Neck
country: United States
facility: Long Island Gastrointestinal Research Group
state: New York
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Concord
country: United States
facility: Chevy Chase Clinical Research
state: North Carolina
city: Fayetteville
country: United States
facility: Fayetteville Gastroenterology Associates
state: North Carolina
city: Greenville
country: United States
facility: Carolina Digestive Diseases
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Salisbury
country: United States
facility: PMG Research of Salisbury
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: Gastroenterology Associates of the Piedmont
state: North Carolina
city: Cincinnati
country: United States
facility: Consultants for Clinical Research
state: Ohio
city: Dayton
country: United States
facility: Providence Health Partners - Center for Clinical Research
state: Ohio
city: Stillwater
country: United States
facility: Elite Research - Lynn Institute of Stillwater
state: Oklahoma
city: Tulsa
country: United States
facility: Options Health Research
state: Oklahoma
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Wyomissing
country: United States
facility: Digestive Disease Associates - Wyomissin
state: Pennsylvania
city: Chattanooga
country: United States
facility: ClinSearch
state: Tennessee
city: Jackson
country: United States
facility: Clinical Research Solutions - Jackson
state: Tennessee
city: Knoxville
country: United States
facility: New Phase Research and Development
state: Tennessee
city: Nashville
country: United States
facility: Quality Medical Research
state: Tennessee
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center - El Paso
state: Texas
city: Houston
country: United States
facility: Spring Gastroenterology Associates - Houston
state: Texas
city: Houston
country: United States
facility: Biopharma Informatic Houston 1
state: Texas
city: Houston
country: United States
facility: Biopharma Informatic Houston 2
state: Texas
city: McAllen
country: United States
facility: Rio Grande Gastroenterology
state: Texas
city: San Antonio
country: United States
facility: Clinical Associates in Research Therapeutics of America
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Chesapeake
country: United States
facility: Gastroenterology Associates of Tidewater
state: Virginia
city: Edegem
country: Belgium
facility: Universiteit Antwerpen
state: Antwerpen
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
state: Flemish Brabant
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis Sint-Lucas
state: West-vlaanderen
city: Kortrijk
country: Belgium
facility: AZ Groeninge Campus Kennedylaan
state: West-vlaanderen
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Bruxelles
country: Belgium
facility: Hopital Erasme
city: Gent
country: Belgium
facility: Universiteit Gent
city: Kasugai-shi
country: Japan
facility: Tokai Memorial Hospital
state: Aichi
city: Nagoya City
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Nagoya-shi
country: Japan
facility: Meitetsu Hospital
state: Aichi
city: Nagoya
country: Japan
facility: Chubu-Rosai Hospital
state: Aichi
city: Abiko
country: Japan
facility: Tokatsu Tsujinaka Hospital
state: Chiba
city: Matsuyama
country: Japan
facility: Matsuyama Shimin Hospital
state: Ehime
city: Fukuoka-shi
country: Japan
facility: Hatakeyama Clinic
state: Fukuoka
city: Kasuya-gun
country: Japan
facility: Oishi Clinic
state: Fukuoka
city: Koriyama City
country: Japan
facility: Igarashi Internal Medicine Surgery Clinic
state: Fukushima
city: Gifu-city
country: Japan
facility: Asahi University Hospital
state: Gifu
city: Bibai
country: Japan
facility: Nakamura Digestive Organ Internal Medicine Clinic
state: Hokkaido
city: Sapporo-Shi
country: Japan
facility: Akakura GI Clinic
state: Hokkairdo
city: Nishinomiya
country: Japan
facility: Hyogo Prefectural Nishinomiya Hospital
state: Hyogo
city: Nishinomiya
country: Japan
facility: Hyogo College of Medicine Hospital
state: Hyogo
city: Takarazuka-shi
country: Japan
facility: Takarazuka City Hospital
state: Hyogo
city: Hitachi
country: Japan
facility: Hitachi, Ltd. Hitachinaka General Hospital
state: Ibaraki
city: Mito-shi
country: Japan
facility: Minami Akatsuka Clinic
state: Ibaraki
city: Tsuchiura City
country: Japan
facility: Tsuchiura Beryl Clinic
state: Ibaraki
city: Yokohama-city
country: Japan
facility: Medical Corporation Shintoukai Yokohama Minoru Clinic
state: Kanagawa
city: Takatsuki-shi
country: Japan
facility: Takatsuki Red Cross Hospital
state: Osaka
city: Kumagaya
country: Japan
facility: Medical Corporation Kumagaya General Hospital
state: Saitama
city: Tokorozawa
country: Japan
facility: Wakasa Clinic
state: Saitama
city: Yaizu
country: Japan
facility: Community Hospital Koga Hospital
state: Shizuoka
city: Setagaya-Ku
country: Japan
facility: Shimokitazawa Tomo Clinic
state: Tokyo
city: Kumamoto
country: Japan
facility: Morinaga Ueno Clinic
city: Kyoto
country: Japan
facility: Ijinkai Takeda General Hospital
city: Okayama
country: Japan
facility: Okayama Saiseikai General Hospital
city: Saitama
country: Japan
facility: Medical Corporation Kamata Clinic
city: Yamagata
country: Japan
facility: Gastroenterology and Internal Medicine, Oizumi Medical Clinic
city: Bydgoszcz
country: Poland
facility: VITAMED Galaj i Cichomski spolka jawna
state: Kujawsko-pomorskie
city: Grudziadz
country: Poland
facility: Centrum Medyczne Clw-Med Aneta Cichomska i Joanna uka-Wendrowska sp.j.
state: Kujawsko-pomorskie
city: Warszawa
country: Poland
facility: Bodyclinic
state: Mazowieckie
city: Chojnice
country: Poland
facility: Centrum Medyczne Lukamed Joanna Luka
state: Pomorskie
city: Kielce
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej - Witamed Poradnia Diabetolo
state: Swietokrzyskie
city: Sopot
country: Poland
facility: Endoskopia
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Yamaguchi T, Kudou K, Okamoto H, Chen C, Whiting R, Sekino H. Evaluating the Safety, Tolerability, and Disposition of Trazpiroben, a D2 /D3 Receptor Antagonist: Phase I Single- and Multiple-Ascending Dose Studies in Healthy Japanese Participants. Clin Pharmacol Drug Dev. 2022 Jun;11(6):695-706. doi: 10.1002/cpdd.1057. Epub 2021 Dec 29.