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

Diabetic Gastroparesis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03544229
• Other study ID #: TAK-906-2002
• Secondary ID: 2018-001275-21U1
• Status: Completed
• Phase: Phase 2
• Start date: October 14, 2018
• Est. completion date: July 15, 2021

Study information

• Verified date: October 2022
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 242
• Est. completion date: July 15, 2021
• Est. primary completion date: June 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetic Gastroparesis
• Gastroparesis
• Idiopathic Gastroparesis

Intervention

Drug:
• TAK-906 Maleate
TAK-906 maleate capsules.
• Placebo
TAK-906 maleate placebo-matching capsules.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Japan,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Baseline and Week 12
Secondary	Percentage of Participants With at Least 50% Reduction From Baseline in ANMS GCSI-DD Composite Score at 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.	Baseline and Week 12
Secondary	Change From Baseline in the ANMS GCSI-DD Nausea Symptom Score at Week 12 of the Treatment Period	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.	Baseline and Week 12
Secondary	Change From Baseline in the ANMS GCSI-DD Early Satiety Symptom Score at Week 12 of the Treatment Period	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.	Baseline and Week 12
Secondary	Change From Baseline in the ANMS GCSI-DD Postprandial Fullness Symptom Score at Week 12 of the Treatment Period	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.	Baseline and Week 12
Secondary	Change From Baseline in the ANMS GCSI-DD Upper Abdominal Pain Symptom Score at Week 12 of the Treatment Period	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.	Baseline and Week 12
Secondary	Change From Baseline in the ANMS GCSI-DD Recorded Vomiting Frequency at Week 12 of the Treatment Period	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.	Baseline and Week 12
Secondary	Change From Baseline in the ANMS GCSI-DD Overall Severity of Gastroparesis Symptoms Score at Week 12 of the Treatment Period	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.	Baseline and Week 12
Secondary	Change From Baseline in the ANMS GCI-DD Bloating Severity Scale Score at Week 12 of the Treatment Period	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.	Baseline and Week 12
Secondary	Change From Baseline in the ANMS GCSI-DD Total Score at Week 12 of the Treatment Period	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.	Baseline and Week 12
Secondary	Percentage of Symptomatic 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.	Up to 12 weeks
Secondary	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	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.	Baseline and Week 12

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