A Study to Evaluate the Efficacy and Safety of TAK-906 in Adult Participants With Symptomatic Idiopathic or Diabetic Gastroparesis

Phase 2

Completed

Conditions: Idiopathic Gastroparesis
Diabetic Gastroparesis

Interventions: Drug: TAK-906 Maleate
Drug: Placebo

Registration Number: NCT03544229

Lead Sponsor: Millennium Pharmaceuticals, Inc.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 242

Inclusion Criteria

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.
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.
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.
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).
Has a body mass index (BMI) of ≥18 to ≤40 kg/m^2 inclusive.
Participant with diabetes mellitus must have glycosylated hemoglobin (HbA1c) ≤11% at screening and before randomization.
Absence of gastric outlet obstruction confirmed by upper GI, computed tomography or endoscopy.

Exclusion Criteria

Known secondary causes of gastroparesis including but not limited to Parkinson disease, cancer, viral illness, or connective tissue diseases.
Predominant gastroparetic symptom is epigastric pain, diffuse abdominal pain, or pain associated with bowel movement.
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.
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.
History of intra-pyloric botulinum toxin injection within 3 months of Screening or currently has functioning implantable electric stimulator.
Nasogastric, percutaneous endoscopic gastrostomy, or percutaneous endoscopic jejunostomy feeding tube or inpatient hospitalization for gastroparesis within 2 weeks before the Screening Visit.
Required parenteral nutrition for treatment of gastroparesis within 2 months before the Screening Visit.
Previous diagnosis of gastric bezoar (the presence of retained liquid, bile, or small amounts of poorly organized food residue is permitted).
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.
Elevated serum prolactin (>upper limit of normal [ULN]) at Screening.
Has concurrent hypogonadism, current clinically significant menstrual abnormalities, such as amenorrhea or oligomenorrhea, or other clinical features of hyperprolactinemia such as galactorrhea or gynecomastia.
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.
Has renal impairment, defined as a lower limit of (estimated glomerular filtration rate [eGFR]) <30 mL/min at screening visit.
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).
Uncontrolled or poorly controlled medical or psychiatric comorbidities which might affect their ability to participate in the study.
Has known COVID-19 infection, or suspected COVID-19 infection (as assessed by the investigator).
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TAK-906 Maleate 5 mg	TAK-906 Maleate	TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.
TAK-906 Maleate 25 mg	TAK-906 Maleate	TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.
Placebo	Placebo	TAK-906 maleate placebo-matching capsules, orally, twice daily (BID) for up to 12 weeks.
TAK-906 Maleate 50 mg	TAK-906 Maleate	TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.

Primary Outcome Measures

Name	Time	Method
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	Baseline and Week 12	ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD composite score included score of nausea, early satiety, upper abdominal pain, and postprandial fullness. The severity scores of these symptoms range from 0 (none) to 4 (very severe). The daily composite score was calculated by summing the scores on the 4 symptom items (nausea, early satiety, postprandial fullness, and upper abdominal pain) and then dividing by 4, that is the number of items within the composite score. Thus, the maximum daily composite score was (4 symptoms × maximum score 4 divided by 4) = 16/4 = 4. The ANMS GCSI-DD daily composite score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. Mixed-effects Model for Repeated Measures (MMRM) was used for the analysis.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the ANMS GCSI-DD Early Satiety Symptom Score at Week 12 of the Treatment Period	Baseline and Week 12	ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea, early satiety, postprandial fullness, and upper abdominal pain on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD early satiety symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from Baseline indicated improvement. MMRM was used for the analysis.
Change From Baseline in the ANMS GCSI-DD Nausea Symptom Score at Week 12 of the Treatment Period	Baseline and Week 12	ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea, early satiety, postprandial fullness, and upper abdominal pain on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD nausea symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. MMRM was used for analysis.
Change From Baseline in the ANMS GCI-DD Bloating Severity Scale Score at Week 12 of the Treatment Period	Baseline and Week 12	The bloating severity scale was scored from 0 to 4 (where 0 = no symptom and 4 = severe symptom). The daily total score can range from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. MMRM was used for analysis.
Change From Baseline in the ANMS GCSI-DD Total Score at Week 12 of the Treatment Period	Baseline and Week 12	Daily total score was calculated by summing scores on each of the 5 symptom items in ANMS GCSI-DD (nausea, early satiety, postprandial fullness, upper abdominal pain and vomiting) plus the bloating severity item and then dividing by 6. When calculating total score, vomiting frequency was scored from 0 to 4 (where 0=no vomiting and 4=four or more episodes of vomiting). The daily total score can range from 0 to 4 with higher scores reflecting greater symptom severity. MMRM was used for analyses.
Change From Baseline in the ANMS GCSI-DD Overall Severity of Gastroparesis Symptoms Score at Week 12 of the Treatment Period	Baseline and Week 12	The overall severity of gastroparesis symptoms is the participant report of the overall severity rating of their symptoms as entered daily in the ANMS GCSI-DD and at time of visit. Severity was rated on a 0 (none) to 4 (very severe) scale. Higher score values indicated more severe symptoms. MMRM was used for the analysis.
Percentage of Symptomatic Weeks	Up to 12 weeks	Symptomatic weeks are weeks with average composite symptom score assessed as \>mild \[ANMS GCSI-DD score ≥2\] during 12 weeks of treatment. Analysis of variance (ANOVA) was used for the analysis.
Percentage of Participants With at Least 50% Reduction From Baseline in ANMS GCSI-DD Composite Score at Week 12	Baseline and Week 12	ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis . The ANMS GCSI-DD composite score included score of nausea, early satiety, upper abdominal pain and postprandial fullness. The severity scores of these symptoms range from 0 (none) to 4 (very severe). The daily composite score was calculated by summing the scores on the 4 symptom items (nausea, early satiety, postprandial fullness, and upper abdominal pain) and then dividing by 4, that is the number of items within the composite score. Thus, the maximum daily composite score was (4 symptoms × maximum score 4 divided by 4) = 16/4 = 4. The ANMS GCSI-DD daily composite score ranged from 0 to 4 with higher scores reflecting greater symptom severity.
Change From Baseline in the ANMS GCSI-DD Postprandial Fullness Symptom Score at Week 12 of the Treatment Period	Baseline and Week 12	ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea, early satiety, postprandial fullness, and upper abdominal pain on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD postprandial fullness symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. MMRM was used for the analysis.
Change From Baseline in the ANMS GCSI-DD Upper Abdominal Pain Symptom Score at Week 12 of the Treatment Period	Baseline and Week 12	ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea, early satiety, postprandial fullness, and upper abdominal pain on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD upper abdominal pain symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. MMRM was used for the analysis.
Change From Baseline in the ANMS GCSI-DD Recorded Vomiting Frequency at Week 12 of the Treatment Period	Baseline and Week 12	Vomiting frequency was collected as the number of times a participant vomited in a 24-hour period i.e., vomiting episodes using the ANMS GCSI-DD. The daily score was averaged over 7 days. Higher scores indicate more severe symptoms. MMRM was used for the analysis.
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	Baseline and Week 12	The PAGI-SYM total score is defined as the mean of 6 PAGI-SYM subscale scores from 20 items. A 6-point Likert response scale, ranging from 0 (none) to 5 (very severe), is used to measure symptom severity in participants with upper GI disorders. The negative change from baseline indicates improvement. MMRM was used for analysis.

Trial Locations

Locations (108): Spring Gastroenterology Associates - Houston
🇺🇸
Houston, Texas, United States
Biopharma Informatic Houston 2
🇺🇸
Houston, Texas, United States
Baptist Diabetes Associates Research
🇺🇸
Miami, Florida, United States
Precision Research Institute
🇺🇸
San Diego, California, United States
Consultants for Clinical Research
🇺🇸
Cincinnati, Ohio, United States
Clinical Associates in Research Therapeutics of America
🇺🇸
San Antonio, Texas, United States
Sun Research Institute
🇺🇸
San Antonio, Texas, United States
Hyogo Prefectural Nishinomiya Hospital
🇯🇵
Nishinomiya, Hyogo, Japan
Takatsuki Red Cross Hospital
🇯🇵
Takatsuki-shi, Osaka, Japan
Quality Medical Research
🇺🇸
Nashville, Tennessee, United States
Hyogo College of Medicine Hospital
🇯🇵
Nishinomiya, Hyogo, Japan
Hopital Erasme
🇧🇪
Bruxelles, Belgium
Meitetsu Hospital
🇯🇵
Nagoya-shi, Aichi, Japan
Matsuyama Shimin Hospital
🇯🇵
Matsuyama, Ehime, Japan
Montana Medical Research
🇺🇸
Missoula, Montana, United States
Minami Akatsuka Clinic
🇯🇵
Mito-shi, Ibaraki, Japan
Del Sol Research Management
🇺🇸
Tucson, Arizona, United States
VITAMED Galaj i Cichomski spolka jawna
🇵🇱
Bydgoszcz, Kujawsko-pomorskie, Poland
Centrum Medyczne Clw-Med Aneta Cichomska i Joanna uka-Wendrowska sp.j.
🇵🇱
Grudziadz, Kujawsko-pomorskie, Poland
GW Research
🇺🇸
Chula Vista, California, United States
Trial Connections - New Hope Research Development
🇺🇸
Corona, California, United States
ISS - Innovative Research of West Florida
🇺🇸
Clearwater, Florida, United States
Paragon Rx Clinical - Garden Grove
🇺🇸
Garden Grove, California, United States
California Medical Research Associates
🇺🇸
Northridge, California, United States
Connecticut Clinical Research Foundation
🇺🇸
Bristol, Connecticut, United States
Torrance Clinical Research Institute Inc.
🇺🇸
Lomita, California, United States
ISS - Conquest Clinical Research
🇺🇸
Orange, California, United States
International Research Associates
🇺🇸
Hialeah, Florida, United States
Elias Research Associates - Direct Helpers Research Center - Hialeah
🇺🇸
Hialeah, Florida, United States
Palmetto Research
🇺🇸
Hialeah, Florida, United States
Homestead Associates in Research
🇺🇸
Homestead, Florida, United States
PharmaSouth Research
🇺🇸
Miami, Florida, United States
Mayo Clinic
🇺🇸
Jacksonville, Florida, United States
Miami Dade Medical Research Institute
🇺🇸
Miami, Florida, United States
Advanced Medical Research Center
🇺🇸
Port Orange, Florida, United States
Summit Clinical Research
🇺🇸
Athens, Georgia, United States
DM Clinical Research - Southwest Gastroenterology - Oak Lawn
🇺🇸
Oak Lawn, Illinois, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
MGH Digestive Healthcare
🇺🇸
Boston, Massachusetts, United States
NY Scientific
🇺🇸
Brooklyn, New York, United States
Gastrointestinal Associates and Endoscopy Center
🇺🇸
Flowood, Mississippi, United States
Atrium Health
🇺🇸
Charlotte, North Carolina, United States
Long Island Gastrointestinal Research Group
🇺🇸
Great Neck, New York, United States
Clinical Research Institute of Michigan
🇺🇸
Chesterfield, Michigan, United States
Chevy Chase Clinical Research
🇺🇸
Concord, North Carolina, United States
Carolina Digestive Diseases
🇺🇸
Greenville, North Carolina, United States
Wake Research Associates
🇺🇸
Raleigh, North Carolina, United States
Trial Management Associates
🇺🇸
Wilmington, North Carolina, United States
Providence Health Partners - Center for Clinical Research
🇺🇸
Dayton, Ohio, United States
Elite Research - Lynn Institute of Stillwater
🇺🇸
Stillwater, Oklahoma, United States
Options Health Research
🇺🇸
Tulsa, Oklahoma, United States
Temple University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
ClinSearch
🇺🇸
Chattanooga, Tennessee, United States
Clinical Research Solutions - Jackson
🇺🇸
Jackson, Tennessee, United States
New Phase Research and Development
🇺🇸
Knoxville, Tennessee, United States
Texas Tech University Health Sciences Center - El Paso
🇺🇸
El Paso, Texas, United States
Rio Grande Gastroenterology
🇺🇸
McAllen, Texas, United States
Universiteit Antwerpen
🇧🇪
Edegem, Antwerpen, Belgium
Gastroenterology Associates of Tidewater
🇺🇸
Chesapeake, Virginia, United States
Universitair Ziekenhuis Leuven
🇧🇪
Leuven, Flemish Brabant, Belgium
Algemeen Ziekenhuis Sint-Lucas
🇧🇪
Brugge, West-vlaanderen, Belgium
AZ Groeninge Campus Kennedylaan
🇧🇪
Kortrijk, West-vlaanderen, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪
Brussels, Belgium
Universiteit Gent
🇧🇪
Gent, Belgium
Tokai Memorial Hospital
🇯🇵
Kasugai-shi, Aichi, Japan
Hatakeyama Clinic
🇯🇵
Fukuoka-shi, Fukuoka, Japan
Asahi University Hospital
🇯🇵
Gifu-city, Gifu, Japan
Akakura GI Clinic
🇯🇵
Sapporo-Shi, Hokkairdo, Japan
Nakamura Digestive Organ Internal Medicine Clinic
🇯🇵
Bibai, Hokkaido, Japan
Hitachi, Ltd. Hitachinaka General Hospital
🇯🇵
Hitachi, Ibaraki, Japan
Medical Corporation Shintoukai Yokohama Minoru Clinic
🇯🇵
Yokohama-city, Kanagawa, Japan
Tsuchiura Beryl Clinic
🇯🇵
Tsuchiura City, Ibaraki, Japan
Wakasa Clinic
🇯🇵
Tokorozawa, Saitama, Japan
Community Hospital Koga Hospital
🇯🇵
Yaizu, Shizuoka, Japan
Ijinkai Takeda General Hospital
🇯🇵
Kyoto, Japan
Morinaga Ueno Clinic
🇯🇵
Kumamoto, Japan
Okayama Saiseikai General Hospital
🇯🇵
Okayama, Japan
Shimokitazawa Tomo Clinic
🇯🇵
Setagaya-Ku, Tokyo, Japan
Medical Corporation Kamata Clinic
🇯🇵
Saitama, Japan
Gastroenterology and Internal Medicine, Oizumi Medical Clinic
🇯🇵
Yamagata, Japan
Bodyclinic
🇵🇱
Warszawa, Mazowieckie, Poland
Centrum Medyczne Lukamed Joanna Luka
🇵🇱
Chojnice, Pomorskie, Poland
Endoskopia
🇵🇱
Sopot, Poland
Niepubliczny Zaklad Opieki Zdrowotnej - Witamed Poradnia Diabetolo
🇵🇱
Kielce, Swietokrzyskie, Poland
Digestive Disease Associates - Wyomissin
🇺🇸
Wyomissing, Pennsylvania, United States
Digestive Health Specialists of the Southeast
🇺🇸
Dothan, Alabama, United States
Gastroenterology Associates - Crystal River
🇺🇸
Inverness, Florida, United States
Advanced Research Institute - New Port Richey
🇺🇸
New Port Richey, Florida, United States
Anchor Medical Research
🇺🇸
Miami, Florida, United States
Digestive Healthcare of Georgia - Atlanta
🇺🇸
Atlanta, Georgia, United States
Tri-State Gastroenterology Associates
🇺🇸
Crestview Hills, Kentucky, United States
Gastroenterology Associates of Western Michigan
🇺🇸
Wyoming, Michigan, United States
Gastro Center of Maryland
🇺🇸
Columbia, Maryland, United States
Veterans Affairs Medical Center - West Roxbury
🇺🇸
West Roxbury, Massachusetts, United States
Fayetteville Gastroenterology Associates
🇺🇸
Fayetteville, North Carolina, United States
PMG Research of Salisbury
🇺🇸
Salisbury, North Carolina, United States
Biopharma Informatic Houston 1
🇺🇸
Houston, Texas, United States
Nagoya City University Hospital
🇯🇵
Nagoya City, Aichi, Japan
Tokatsu Tsujinaka Hospital
🇯🇵
Abiko, Chiba, Japan
Chubu-Rosai Hospital
🇯🇵
Nagoya, Aichi, Japan
Oishi Clinic
🇯🇵
Kasuya-gun, Fukuoka, Japan
Igarashi Internal Medicine Surgery Clinic
🇯🇵
Koriyama City, Fukushima, Japan
Medical Corporation Kumagaya General Hospital
🇯🇵
Kumagaya, Saitama, Japan
Takarazuka City Hospital
🇯🇵
Takarazuka-shi, Hyogo, Japan
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Gastroenterology Associates of the Piedmont
🇺🇸
Winston-Salem, North Carolina, United States
Lovelace Scientific Resources - Albuquerque
🇺🇸
Albuquerque, New Mexico, United States
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States