TU100P2T3: Effect of TU-100 in Patients Undergoing Laparoscopic Colectomy

• Sponsor: Tsumura USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02232893
• Collaborator: Cato Research (Industry)
• Enrollment: 69
• Locations: 13
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

TU-100 is a gastrointestinal drug produced from the three botanical raw materials, Asian ginseng, Zanthoxylum fruit (Japanese pepper), and ginger, based on proprietary aqueous decoction and granulation technology. The aim of this study is to assess the effect of TU-100 on post-operative quality of life during the 4 week postoperative period after straight, hand-assisted, or robot-assisted laparoscopic colectomy. Optimal efficacy parameters for subsequent outcome studies also will be explored.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Ileus	Drug: Daikenchuto (TU-100); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blinded, Placebo-Controlled Trial of TU-100 in Patients Undergoing Laparoscopic Colectomy
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: May 1, 2017
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Daikenchuto (TU-100) Daikenchuto (TU-100) 5g TID (15g/day)	Drug: Daikenchuto (TU-100); Subjects will receive 5g TID (15g/day) of TU-100. Dosage form is granule. Subject will take a daily dose divided 3 times per day for 3 days before surgery and for 28 days after surgery.
Placebo Comparator: Placebo Placebo TID	Drug: Placebo; Subjects will receive daily dose of TU-100 placebo. Dosage form is granule. Subject will take a daily dose divided 3 times per day for 3 days before surgery and for 28 days after surgery.

Outcome Measures

Primary Outcome Measures

1. Quality of Life After Surgery Based on Gastrointestinal Quality of Life Index (GIQLI) Global Score From Baseline to Visit 4. [Baseline and 15 days]

   The primary endpoint was change in The Gastrointestinal Quality of Life Index (GIQLI) global score from baseline to Visit 4 (Day 15 minus baseline). The global score could range from 0 (lowest quality of life) to 144 (highest quality of life). The effect of TU-100 on the change in GIQLI global score from baseline was assessed by using an analysis of covariance (ANCOVA) model with treatment group as a fixed effect and with baseline GIQLI global score, scheduled surgical location in the colon, and solid food before/after the first flatus as covariates.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Be at least 18 years of age

• Has a current diagnosis of colon cancer, diverticulitis, or benign colonic neoplasm

• Requires straight, hand-assisted, or robot-assisted laparoscopic colectomy

• Requires hospitalization for surgery and recovery

Exclusion Criteria:

• Has been diagnosed with rectal cancer, advanced or metastatic colon cancer, Crohn disease, ulcerative colitis, or volvulus

• Requires resection of rectal lesion

• Has received or is scheduled to receive chemotherapy during the duration of the study

• Is a pregnant or lactating female

• Has diabetic neuropathy

• Has a history or presence of diabetic gastroparesis

• Has a compromised immune system, either from treatment with corticosteroids or other immunosuppressive agent within 2 weeks of surgery or from immunosuppressive disease (e.g., human immunodeficiency virus)

• Has any other serious condition that might adversely affect suitability for participation in this study, such as liver disorder (including alanine aminotransferase or aspartate aminotransferase level greater than 2.5 times the upper limit of normal), kidney disorders, heart failure, blood disorders, or metabolic disorders

• Has a history or presence of interstitial pneumonia

• Has a history of allergic reaction to ginseng, ginger or Zanthoxylum fruit (Japanese pepper)

• Plans to receive any abdominal irradiation

• Is clinically lactose intolerant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Los Angeles Site	Los Angeles	California	United States	90048
2	Aurora Site	Aurora	Colorado	United States	80045
3	Weston Site	Weston	Florida	United States	33331
4	Atlanta Site	Atlanta	Georgia	United States	30342
5	Chicago Site	Chicago	Illinois	United States	60637
6	Metairie Site	Metairie	Louisiana	United States	70006
7	Burlington, MA Site	Burlington	Massachusetts	United States	01805
8	Coon Rapids Site	Coon Rapids	Minnesota	United States	55433
9	Minneapolis Site	Minneapolis	Minnesota	United States	55407
10	Jackson Site	Jackson	Mississippi	United States	39042
11	Cleveland Site	Cleveland	Ohio	United States	44106
12	Burlington, VT Site	Burlington	Vermont	United States	05401
13	Spokane Site	Spokane	Washington	United States	99204

Sponsors and Collaborators

• Tsumura USA
• Cato Research

Investigators

• Principal Investigator: Christine Jensen, M.D., M.P.H., Colon & Rectal Surgery Associates

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 22, 2020

More Information

Publications

None provided.

• Responsible Party: Tsumura USA
• ClinicalTrials.gov Identifier: NCT02232893
• Other Study ID Numbers: TU100P2T3
• First Posted: Sep 5, 2014
• Last Update Posted: Jun 19, 2020
• Last Verified: Jun 1, 2020

• Keywords provided by Tsumura USA: Gastrointestinal Quality of Life Index (GIQLI); Postoperative Quality of Life; Abdominal Bloating; Laparoscopic colectomy; Postoperative ileus (POI)
• Additional relevant MeSH terms: Ileus

Study Results

Participant Flow

Recruitment Details	The study was carried out at 16 sites in the United States (US).

Arm/Group Title	Daikenchuto (TU-100)	Placebo
Arm/Group Description	Daikenchuto (TU-100) 5g TID (15g/day) Daikenchuto (TU-100): Subjects will receive 5g TID (15g/day) of TU-100. Dosage form is granule. Subject will take a daily dose divided 3 times per day for 3 days before surgery and for 28 days after surgery.	Placebo TID Placebo: Subjects will receive daily dose of TU-100 placebo. Dosage form is granule. Subject will take a daily dose divided 3 times per day for 3 days before surgery and for 28 days after surgery.
Period Title: Overall Study
STARTED	35	34
Safety Population	34	32
Primary Endpoint Population	24	19
COMPLETED	31	27
NOT COMPLETED	4	7

Baseline Characteristics

Arm/Group Title	TU-100	Placebo	Total
Arm/Group Description	TU-100: 5g TID (15g/day) TU-100: Subjects will receive 5g TID (15g/day) of TU-100. Dosage form is granule. Subject will take a daily dose for 3 days before surgery and for 28 days after surgery.	Placebo TID Placebo: Subjects will receive daily dose of TU-100 placebo. Dosage form is granule. Subject will take a daily dose for 3 days before surgery and for 28 days after surgery.	Total of all reporting groups
Overall Participants	34	31	65
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.8 (9.76)	58.4 (12.4)	58.6 (11.0)
Sex: Female, Male (Count of Participants)
Female	18 52.9%	17 54.8%	35 53.8%
Male	16 47.1%	14 45.2%	30 46.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.9%	1 3.2%	3 4.6%
Not Hispanic or Latino	32 94.1%	30 96.8%	62 95.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	34 100%	31 100%	65 100%

Outcome Measures

1. Primary Outcome

Title	Quality of Life After Surgery Based on Gastrointestinal Quality of Life Index (GIQLI) Global Score From Baseline to Visit 4.
Description	The primary endpoint was change in The Gastrointestinal Quality of Life Index (GIQLI) global score from baseline to Visit 4 (Day 15 minus baseline). The global score could range from 0 (lowest quality of life) to 144 (highest quality of life). The effect of TU-100 on the change in GIQLI global score from baseline was assessed by using an analysis of covariance (ANCOVA) model with treatment group as a fixed effect and with baseline GIQLI global score, scheduled surgical location in the colon, and solid food before/after the first flatus as covariates.
Time Frame	Baseline and 15 days

Outcome Measure Data

Analysis Population Description

Among the ITT population, patients who provided GIQLI scores both at baseline and Visit 4 were analyzed.

Arm/Group Title	TU-100	Placebo
Arm/Group Description	TU-100: 5g TID (15g/day) TU-100: Subjects will receive 5g TID (15g/day) of TU-100. Dosage form is granule. Subject will take a daily dose divided 3 times per day for 3 days before surgery and 28 days after surgery.	Placebo TID Placebo: Subjects will receive daily dose of TU-100 placebo. Dosage form is granule. Subject will take a daily dose divided 3 times per day for 3 days before surgery and 28 days after surgery.
Measure Participants	24	19
Least Squares Mean (Standard Error) [score on a scale]	-17.20 (2.76)	-10.10 (2.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TU-100, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	2 months
Arm/Group Title	Daikenchuto (TU-100)		Placebo
Arm/Group Description	Daikenchuto (TU-100) 5g TID (15g/day) Daikenchuto (TU-100): Subjects will receive 5g TID (15g/day) of TU-100. Dosage form is granule. Subject will take a daily dose divided 3 times per day for 3 days before surgery and 28 days after surgery.		Placebo TID Placebo: Subjects will receive daily dose of TU-100 placebo. Dosage form is granule. Subject will take a daily dose divided 3 times per day for 3 days before surgery and 28 days after surgery.
All Cause Mortality
	Daikenchuto (TU-100)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/32 (0%)
Serious Adverse Events
	Daikenchuto (TU-100)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/34 (8.8%)		4/32 (12.5%)
Gastrointestinal disorders
Nausea	0/34 (0%)	0	1/32 (3.1%)	1
Small bowel obstruction	0/34 (0%)	0	1/32 (3.1%)	1
Infections and infestations
Post-operative Wound Infection	1/34 (2.9%)	1	0/32 (0%)	0
Injury, poisoning and procedural complications
Post-operative Ileus	2/34 (5.9%)	2	2/32 (6.3%)	2
Psychiatric disorders
Mental Status Changes	0/34 (0%)	0	1/32 (3.1%)	1
Vascular disorders
Hypertensive emergency	0/34 (0%)	0	1/32 (3.1%)	1
Other (Not Including Serious) Adverse Events
	Daikenchuto (TU-100)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/34 (85.3%)		23/32 (71.9%)
Cardiac disorders
Tachycardia	2/34 (5.9%)	2	0/32 (0%)	0
Gastrointestinal disorders
Nausea	13/34 (38.2%)	13	13/32 (40.6%)	13
Vomiting	5/34 (14.7%)	5	5/32 (15.6%)	5
Abdominal distension	4/34 (11.8%)	4	3/32 (9.4%)	3
Abdominal pain	3/34 (8.8%)	3	3/32 (9.4%)	3
Dyspepsia	3/34 (8.8%)	3	2/32 (6.3%)	2
Constipation	3/34 (8.8%)	3	1/32 (3.1%)	1
Injury, poisoning and procedural complications
Procedural pain	7/34 (20.6%)	7	5/32 (15.6%)	5
Incision site pain	2/34 (5.9%)	2	3/32 (9.4%)	3
Procedural nausea	4/34 (11.8%)	4	0/32 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms	2/34 (5.9%)	2	0/32 (0%)	0
Nervous system disorders
Headache	3/34 (8.8%)	3	3/32 (9.4%)	3
Psychiatric disorders
Anxiety	2/34 (5.9%)	2	0/32 (0%)	0
Renal and urinary disorders
Bladder Spasm	2/34 (5.9%)	2	0/32 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	2/34 (5.9%)	2	1/32 (3.1%)	1
Cough	2/34 (5.9%)	2	0/32 (0%)	0
Skin and subcutaneous tissue disorders
Pruritis	7/34 (20.6%)	7	2/32 (6.3%)	2
Vascular disorders
Hypotension	3/34 (8.8%)	3	3/32 (9.4%)	3
Hypertension	2/34 (5.9%)	2	0/32 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.