Enhanced Recovery After Surgery
Conditions
Brief summary
This multicenter, randomized, double-blinded, placebo-controlled study will evaluate the effect of TU-100 on resolution of postoperative ileus (POI) in subjects undergoing open or laparoscopic bowel resection (BR).
Detailed description
Subjects will be screened up to 28 days before their planned surgery and will be randomized 1:1:1 (TU-100 15 g/day: TU-100 7.5 g/day: placebo) on postoperative Day 1 before the first dose of study medication. After randomization, subjects will receive a total daily dose of TU-100 15g, TU-100 7.5 g, or matching placebo (3 times per day (TID)) until hospital discharge or ≤ 10 days (whichever is earlier). All subjects will be treated with study medication as adjunct to an enhanced recovery (ERAS) pathway for gastrointestinal (GI) recovery.
Interventions
DRUGTU-100
Treatment with investigational product
DRUGPlacebo
Treatment with placebo product
Sponsors
Tsumura USA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Investigators, study staff, sponsor designees, and subjects will be blinded to randomized study treatment for the duration of the study. The pharmacist or designee performing the preparation and administration will also be blinded.
Intervention model description
Randomized, Double-Blind, Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female ≥ 18 years of age 2. Women of childbearing potential (WOCBP) or men whose sexual partners are WOCBP; must be able and willing to use at least 1 highly effective method of contraception during the study and for 30 days after the last dose of study drug 3. American Society of Anesthesiologists Physical Status Score of 1 to 3 4. Scheduled for an elective BR via open or laparoscopic approach 5. Ability to understand the study procedures, have agreed to participate in the study program, and have voluntarily provided informed consent
Exclusion criteria
1. Scheduled for a BR that is not listed in this protocol 2. Requires any additional resections beyond the intestine (eg, hepatectomy, distal pancreatectomy, pancreaticoduodenectomy, gastric resection, uterine resection), or concomitant surgeries (with the exception of biopsies) 3. Requires the formation of a stoma (ileostomy or colostomy) 4. History of surgeries, illness, or behavior (eg, depression, psychosis) that in the opinion of the investigator might confound the study results or pose additional risk in administering the study procedures 5. Have a functional colostomy or ileostomy 6. Diagnosed with advanced or metastatic colon cancer (Stage IV by tumor, node, and metastasis classification) 7. Positive coronavirus disease 2019 (COVID-19) test 8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including human immunodeficiency virus (HIV)), diabetes, symptomatic congestive heart failure and ejection fraction \< 35%, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with protocol requirements 9. Chronic pain syndrome unrelated to the planned surgery requiring consistent management with analgesics and/or other non-pharmacologic modalities 10. Myocardial infarction within 3 months 11. Corrected QT interval \> 500 msec 12. Diabetic gastroparesis 13. Compromised immune system, either from treatment with corticosteroids or other immunosuppressive agent within 2 weeks of surgery or from immunosuppressive disease (HIV) 14. Pregnant (identified by a positive serum pregnancy test) or lactating, or are not postmenopausal (no menses for at least 1 year) and are of childbearing potential and not using an accepted method of birth control (surgical sterilization, intrauterine contraceptive device, oral contraceptive, diaphragm, or condom in combination with contraceptive cream, jelly, or foam or abstinence) 15. Participated in another investigational drug/biologic or medical device study within 30 days of surgery or will be enrolled in another investigational drug or medical device study, or any study in which active subject participation is required outside routine hospital data collection during the course of the study 16. Illicit drug use or alcohol abuse based on medical history, or currently engaged in illicit drug use or alcohol abuse 17. Uses of supplemental ginger, ginseng, or Zanthoxylum fruit within 72 hours before randomization 18. Has a history of allergic reactions to ginseng, ginger, Zanthoxylum fruit, or lactose 19. Has clinical symptoms of lactose intolerance after ingesting milk or milk-containing products (abdominal pain, flatulence, diarrhea) 20. Unwilling or unable to comply with procedures described in this protocol or is otherwise unacceptable for enrollment in the opinion of the investigator 21. Has a history of previous surgeries, illness (interstitial pneumonia), or behavior (depression, psychosis) that, in the opinion of the investigator, might confound the study results or pose additional risk in administering the study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Gastrointestinal Recovery (GIR) | From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier) | Time to achieve recovery of GI motility as measured by a composite endpoint representing upper AND lower GI recovery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GIR Outcome Related to Length of Hospitalization (Mean) | From surgery to hospital discharge | Mean number of days that the subject stayed in the hospital calculated based on calendar day of discharge order written |
| GIR Outcome Related to Length of Hospitalization (Median) | From surgery to hospital discharge | Median number of days that the subject stayed in the hospital calculated based on calendar day of discharge order written |
| Percentage of GIR Responders | From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier) | Percentage of subjects who achieve GIR (GIR responders) by day |
| POI-related Morbidity | From the day after surgery to discharge follow-up visit (30 days (+ 15 days) after hospital discharge) | Primary POI that is not secondary to surgical complication, such as anastomotic leak, abscess formation, or sepsis that requires readmission within 7 days of discharge, or need for postoperative nasal gastric tube insertion to manage symptoms of POI (vomiting/retching, abdominal distension) |
| Number of Participants With Adverse Events | From baseline to discharge follow-up visit (30 days (+ 15 days) after hospital discharge) | Number of patients with adverse events (AEs) observed following administration of TU-100. |
| Time to GIR Responses | From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier) | Time to achieve first toleration of solid diet AND first bowel movement (Time to GI-2), time to first toleration of clear liquids, and time to absence of distension and presence of bowel sounds and flatus |
| Time to Discharge | From surgery to hospital discharge | Time at which the subject is considered ready for discharge by the investigator based solely on GI recovery (Time to ready for discharge), and time at which the investigator writes discharge order for the subject (Time to discharge order written) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subject-Reported Occurrence of Abdominal Bloating | From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier) | Subjects will record the occurrence of abdominal bloating in their eDiaries on all postoperative in-hospital days. |
| Subject-Reported Bothersomeness of Abdominal Bloating | From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier) | Subjects who answered that they felt bloated will record bothersomeness of abdominal bloating in their eDiaries on all postoperative in-hospital days. Bothersomeness is measured on a scale of 0-10 with 10 being the most bothersome. |
| Subject-Reported Occurrence of Nausea | From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier) | Subjects will record the occurrence of nausea in their eDiaries on all postoperative in-hospital days. |
| Subject-Reported Bothersomeness of Nausea | From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier) | Subjects who answered that they felt nauseous will record bothersomeness of nausea in their eDiaries on all postoperative in-hospital days. Bothersomeness is measured on a scale of 0-10 with 10 being the most bothersome. |
Countries
United States
Participant flow
Recruitment details
The study was carried out at 36 sites in the United States (US).
Participants by arm
| Arm | Count |
|---|---|
| TU-100 15 g/Day Subjects will receive a total daily dose of TU-100 5 g TID until hospital discharge or ≤ 10 days (whichever is earlier).
TU-100: Treatment with investigational product | 132 |
| TU-100 7.5 g/Day Subjects will receive a total daily dose of TU-100 2.5 g TID until hospital discharge or ≤ 10 days (whichever is earlier).
TU-100: Treatment with investigational product | 130 |
| Placebo Subjects will receive placebo TID until hospital discharge or ≤ 10 days (whichever is earlier).
Placebo: Treatment with placebo product | 130 |
| Total | 392 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Did Not Receive the Study Drug | 2 | 4 | 4 |
| Overall Study | Lost to Follow-up | 3 | 3 | 2 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 1 |
| Overall Study | Subject Refusal of Study Procedures or Unable to Take the Study Drug | 2 | 5 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 6 | 4 |
Baseline characteristics
| Characteristic | TU-100 15 g/Day | TU-100 7.5 g/Day | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 13.14 | 58.3 years STANDARD_DEVIATION 13.07 | 58.5 years STANDARD_DEVIATION 12.09 | 58.2 years STANDARD_DEVIATION 12.75 |
| BMI | 28.43 kg/m2 STANDARD_DEVIATION 6.242 | 29.46 kg/m2 STANDARD_DEVIATION 5.788 | 28.97 kg/m2 STANDARD_DEVIATION 5.649 | 28.95 kg/m2 STANDARD_DEVIATION 5.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 9 Participants | 13 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 125 Participants | 121 Participants | 116 Participants | 362 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 1 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 6 Participants | 10 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 7 Participants | 15 Participants |
| Race (NIH/OMB) White | 109 Participants | 118 Participants | 110 Participants | 337 Participants |
| Sex: Female, Male Female | 68 Participants | 69 Participants | 72 Participants | 209 Participants |
| Sex: Female, Male Male | 64 Participants | 61 Participants | 58 Participants | 183 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 132 | 0 / 130 | 0 / 130 |
| other Total, other adverse events | 29 / 132 | 39 / 130 | 39 / 130 |
| serious Total, serious adverse events | 19 / 132 | 14 / 130 | 9 / 130 |
Outcome results
Primary
Time to Gastrointestinal Recovery (GIR)
Time to achieve recovery of GI motility as measured by a composite endpoint representing upper AND lower GI recovery
Time frame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
Population: Analysis population includes subjects in the Full Analysis Set in each treatment group who receive at least 1 dose of study medication, who underwent an elective bowel resection surgery as specified in the protocol, and who provided at least 1 post-surgery assessment of the primary endpoint (TGIR) during the treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TU-100 15 g/Day | Time to Gastrointestinal Recovery (GIR) | 32.6 hours |
| TU-100 7.5 g/Day | Time to Gastrointestinal Recovery (GIR) | 30.8 hours |
| Placebo | Time to Gastrointestinal Recovery (GIR) | 33.4 hours |
p-value: 0.76790% CI: [0.74, 1.12]Chi-squared
p-value: 0.10790% CI: [0.95, 1.44]Chi-squared
Secondary
GIR Outcome Related to Length of Hospitalization (Mean)
Mean number of days that the subject stayed in the hospital calculated based on calendar day of discharge order written
Time frame: From surgery to hospital discharge
Population: Analysis population includes subjects in the Full Analysis Set in each treatment group who receive at least 1 dose of study medication, who underwent an elective bowel resection surgery as specified in the protocol, and who provided at least 1 post-surgery assessment of the primary endpoint (TGIR) during the treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TU-100 15 g/Day | GIR Outcome Related to Length of Hospitalization (Mean) | 3.3 days | Standard Deviation 3.07 |
| TU-100 7.5 g/Day | GIR Outcome Related to Length of Hospitalization (Mean) | 2.7 days | Standard Deviation 1.3 |
| Placebo | GIR Outcome Related to Length of Hospitalization (Mean) | 3.3 days | Standard Deviation 3 |
p-value: 0.923t-test, 2 sided
p-value: 0.039t-test, 2 sided
Secondary
GIR Outcome Related to Length of Hospitalization (Median)
Median number of days that the subject stayed in the hospital calculated based on calendar day of discharge order written
Time frame: From surgery to hospital discharge
Population: Analysis population includes subjects in the Full Analysis Set in each treatment group who receive at least 1 dose of study medication, who underwent an elective bowel resection surgery as specified in the protocol, and who provided at least 1 post-surgery assessment of the primary endpoint (TGIR) during the treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TU-100 15 g/Day | GIR Outcome Related to Length of Hospitalization (Median) | 3 days |
| TU-100 7.5 g/Day | GIR Outcome Related to Length of Hospitalization (Median) | 2 days |
| Placebo | GIR Outcome Related to Length of Hospitalization (Median) | 3 days |
Secondary
Number of Participants With Adverse Events
Number of patients with adverse events (AEs) observed following administration of TU-100.
Time frame: From baseline to discharge follow-up visit (30 days (+ 15 days) after hospital discharge)
Population: Analysis population includes all randomized subjects who were administered at least one dose of study treatment (safety analysis set). More details on patient incidence of adverse events (AEs) observed following administration of TU-100 is entered in AE section.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TU-100 15 g/Day | Number of Participants With Adverse Events | 78 Participants |
| TU-100 7.5 g/Day | Number of Participants With Adverse Events | 73 Participants |
| Placebo | Number of Participants With Adverse Events | 81 Participants |
Secondary
Percentage of GIR Responders
Percentage of subjects who achieve GIR (GIR responders) by day
Time frame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
Population: Analysis population includes subjects in the Full Analysis population in each treatment group who receive at least 1 dose of study medication, who underwent an elective BR surgery as specified in the protocol, and who provided at least 1 post-surgery assessment of the primary endpoint (TGIR) during the treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TU-100 15 g/Day | Percentage of GIR Responders | Day 1 | 20.5 percentage of subjects |
| TU-100 15 g/Day | Percentage of GIR Responders | Day 2 | 47.0 percentage of subjects |
| TU-100 15 g/Day | Percentage of GIR Responders | Day 3 | 18.2 percentage of subjects |
| TU-100 15 g/Day | Percentage of GIR Responders | Day 4 | 3.8 percentage of subjects |
| TU-100 7.5 g/Day | Percentage of GIR Responders | Day 4 | 1.6 percentage of subjects |
| TU-100 7.5 g/Day | Percentage of GIR Responders | Day 1 | 22.7 percentage of subjects |
| TU-100 7.5 g/Day | Percentage of GIR Responders | Day 3 | 14.1 percentage of subjects |
| TU-100 7.5 g/Day | Percentage of GIR Responders | Day 2 | 55.5 percentage of subjects |
| Placebo | Percentage of GIR Responders | Day 4 | 6.2 percentage of subjects |
| Placebo | Percentage of GIR Responders | Day 2 | 42.3 percentage of subjects |
| Placebo | Percentage of GIR Responders | Day 3 | 20.8 percentage of subjects |
| Placebo | Percentage of GIR Responders | Day 1 | 24.6 percentage of subjects |
Comparison: For Day 1p-value: 0.43495% CI: [0.44, 1.42]Regression, Logistic
Comparison: For Day 1p-value: 0.7195% CI: [0.51, 1.59]Regression, Logistic
Comparison: For Day 2p-value: 0.4195% CI: [0.75, 2.02]Chi-squared
Comparison: For Day 2p-value: 0.03795% CI: [1.03, 2.81]Regression, Logistic
Comparison: For Day 3p-value: 0.57995% CI: [0.46, 1.55]Regression, Logistic
Comparison: For Day 3p-value: 0.16795% CI: [0.33, 1.21]Regression, Logistic
Comparison: For Day 4p-value: 0.495% CI: [0.21, 1.86]Regression, Logistic
Comparison: For Day 4p-value: 0.08395% CI: [0.07, 1.18]Regression, Logistic
Secondary
POI-related Morbidity
Primary POI that is not secondary to surgical complication, such as anastomotic leak, abscess formation, or sepsis that requires readmission within 7 days of discharge, or need for postoperative nasal gastric tube insertion to manage symptoms of POI (vomiting/retching, abdominal distension)
Time frame: From the day after surgery to discharge follow-up visit (30 days (+ 15 days) after hospital discharge)
Population: Analysis population includes subjects in the Full Analysis population in each treatment group who receive at least 1 dose of study medication, who underwent an elective BR surgery as specified in the protocol, and who provided at least 1 post-surgery assessment of the primary endpoint (TGIR) during the treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TU-100 15 g/Day | POI-related Morbidity | 7 Participants |
| TU-100 7.5 g/Day | POI-related Morbidity | 5 Participants |
| Placebo | POI-related Morbidity | 5 Participants |
p-value: 0.62195% CI: [0.43, 4.14]Regression, Logistic
p-value: 0.96295% CI: [0.31, 3.46]Regression, Logistic
Secondary
Time to Discharge
Time at which the subject is considered ready for discharge by the investigator based solely on GI recovery (Time to ready for discharge), and time at which the investigator writes discharge order for the subject (Time to discharge order written)
Time frame: From surgery to hospital discharge
Population: Analysis population includes subjects in the Full Analysis Set in each treatment group who receive at least 1 dose of study medication, who underwent an elective bowel resection surgery as specified in the protocol, and who provided at least 1 post-surgery assessment of the primary endpoint (TGIR) during the treatment period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TU-100 15 g/Day | Time to Discharge | Time to ready for discharge | 56.1 hours |
| TU-100 15 g/Day | Time to Discharge | Time to discharge order written | 64.3 hours |
| TU-100 7.5 g/Day | Time to Discharge | Time to ready for discharge | 52.2 hours |
| TU-100 7.5 g/Day | Time to Discharge | Time to discharge order written | 58.1 hours |
| Placebo | Time to Discharge | Time to ready for discharge | 66.1 hours |
| Placebo | Time to Discharge | Time to discharge order written | 66.6 hours |
Comparison: For Time to ready for dischargep-value: 0.48990% CI: [0.81, 1.24]Chi-squared
Comparison: For Time to ready for dischargep-value: 0.13890% CI: [0.93, 1.42]Chi-squared
Comparison: For Time to discharge order writtenp-value: 0.47390% CI: [0.82, 1.24]Chi-squared
Comparison: For Time to discharge order writtenp-value: 0.04590% CI: [1.01, 1.53]Chi-squared
Secondary
Time to GIR Responses
Time to achieve first toleration of solid diet AND first bowel movement (Time to GI-2), time to first toleration of clear liquids, and time to absence of distension and presence of bowel sounds and flatus
Time frame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
Population: Analysis population includes subjects in the Full Analysis Set in each treatment group who receive at least 1 dose of study medication, who underwent an elective bowel resection surgery as specified in the protocol, and who provided at least 1 post-surgery assessment of the primary endpoint (TGIR) during the treatment period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TU-100 15 g/Day | Time to GIR Responses | Median Time to first toleration of clear liquids | 24.0 hours |
| TU-100 15 g/Day | Time to GIR Responses | Median Time to GI-2 | 49.4 hours |
| TU-100 15 g/Day | Time to GIR Responses | Median Time to absence of distension and presence of bowel sounds and flatus | 38.2 hours |
| TU-100 7.5 g/Day | Time to GIR Responses | Median Time to first toleration of clear liquids | 22.5 hours |
| TU-100 7.5 g/Day | Time to GIR Responses | Median Time to GI-2 | 45.2 hours |
| TU-100 7.5 g/Day | Time to GIR Responses | Median Time to absence of distension and presence of bowel sounds and flatus | 40.1 hours |
| Placebo | Time to GIR Responses | Median Time to GI-2 | 47.2 hours |
| Placebo | Time to GIR Responses | Median Time to absence of distension and presence of bowel sounds and flatus | 41.2 hours |
| Placebo | Time to GIR Responses | Median Time to first toleration of clear liquids | 23.3 hours |
Comparison: For Time to GI-2p-value: 0.7890% CI: [0.71, 1.13]Chi-squared
Comparison: For Time to GI-2p-value: 0.3390% CI: [0.84, 1.34]Chi-squared
Comparison: For Time to first toleration of clear liquidsp-value: 0.78890% CI: [0.73, 1.11]Chi-squared
Comparison: For Time to first toleration of clear liquidsp-value: 0.05590% CI: [0.99, 1.51]Chi-squared
Comparison: For Time to absence of distension and presence of bowel sounds and flatusp-value: 0.30690% CI: [0.86, 1.32]Chi-squared
Comparison: For Time to absence of distension and presence of bowel sounds and flatusp-value: 0.24390% CI: [0.88, 1.35]Chi-squared
Other Pre-specified
Subject-Reported Bothersomeness of Abdominal Bloating
Subjects who answered that they felt bloated will record bothersomeness of abdominal bloating in their eDiaries on all postoperative in-hospital days. Bothersomeness is measured on a scale of 0-10 with 10 being the most bothersome.
Time frame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
Population: Analysis population includes subjects in the Full Analysis population in each treatment group who receive at least 1 dose of study medication, who underwent an elective BR surgery as specified in the protocol, and who answered that they felt nausea on the day in the questionnaire through the eDiaries. Data is collected during hospital stays, and no longer collected once the subjects are discharged. Number Analyzed for each day represents number of subject with data for the day.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| TU-100 15 g/Day | Subject-Reported Bothersomeness of Abdominal Bloating | Day 2 | 5.6 score of bloating bothersomeness | Standard Error 0.44 |
| TU-100 15 g/Day | Subject-Reported Bothersomeness of Abdominal Bloating | Day 1 | 5.2 score of bloating bothersomeness | Standard Error 0.34 |
| TU-100 15 g/Day | Subject-Reported Bothersomeness of Abdominal Bloating | Day 3 | 5.6 score of bloating bothersomeness | Standard Error 0.62 |
| TU-100 7.5 g/Day | Subject-Reported Bothersomeness of Abdominal Bloating | Day 2 | 4.4 score of bloating bothersomeness | Standard Error 0.43 |
| TU-100 7.5 g/Day | Subject-Reported Bothersomeness of Abdominal Bloating | Day 1 | 4.2 score of bloating bothersomeness | Standard Error 0.33 |
| TU-100 7.5 g/Day | Subject-Reported Bothersomeness of Abdominal Bloating | Day 3 | 4.3 score of bloating bothersomeness | Standard Error 0.64 |
| Placebo | Subject-Reported Bothersomeness of Abdominal Bloating | Day 1 | 5.2 score of bloating bothersomeness | Standard Error 0.33 |
| Placebo | Subject-Reported Bothersomeness of Abdominal Bloating | Day 3 | 5.0 score of bloating bothersomeness | Standard Error 0.51 |
| Placebo | Subject-Reported Bothersomeness of Abdominal Bloating | Day 2 | 4.6 score of bloating bothersomeness | Standard Error 0.36 |
Comparison: For Day 1, LS mean difference between placebo and TU-100 15 g/day. Mixed Model Repeated Measures approach was used to assess the bothersomeness of Abdominal Bloating as the dependent variable and treatment group, surgical approach and treatment group by visit as covariates. An unstructured covariance structure is used to model the within-subject errors, shared across treatments.p-value: 0.91995% CI: [-0.9, 0.8]Mixed Models Analysis
Comparison: For Day 1, LS mean difference between placebo and TU-100 7.5 g/day. Mixed Model Repeated Measures approach was used to assess the bothersomeness of Abdominal Bloating as the dependent variable and treatment group, surgical approach and treatment group by visit as covariates. An unstructured covariance structure is used to model the within-subject errors, shared across treatments.p-value: 0.01695% CI: [-1.8, -0.2]Mixed Models Analysis
Comparison: For Day 2, LS mean difference between placebo and TU-100 15 g/day. Mixed Model Repeated Measures approach was used to assess the bothersomeness of Abdominal Bloating as the dependent variable and treatment group, surgical approach and treatment group by visit as covariates. An unstructured covariance structure is used to model the within-subject errors, shared across treatments.p-value: 0.06495% CI: [-0.1, 2]Mixed Models Analysis
Comparison: For Day 2, LS mean difference between placebo and TU-100 7.5 g/day. Mixed Model Repeated Measures approach was used to assess the bothersomeness of Abdominal Bloating as the dependent variable and treatment group, surgical approach and treatment group by visit as covariates. An unstructured covariance structure is used to model the within-subject errors, shared across treatments.p-value: 0.68395% CI: [-1.3, 0.8]Mixed Models Analysis
Comparison: For Day 3, LS mean difference between placebo and TU-100 15 g/day. Mixed Model Repeated Measures approach was used to assess the bothersomeness of Abdominal Bloating as the dependent variable and treatment group, surgical approach and treatment group by visit as covariates. An unstructured covariance structure is used to model the within-subject errors, shared across treatments.p-value: 0.46295% CI: [-1, 2.1]Mixed Models Analysis
Comparison: For Day 3, LS mean difference between placebo and TU-100 7.5 g/day. Mixed Model Repeated Measures approach was used to assess the bothersomeness of Abdominal Bloating as the dependent variable and treatment group, surgical approach and treatment group by visit as covariates. An unstructured covariance structure is used to model the within-subject errors, shared across treatments.p-value: 0.34395% CI: [-2.3, 0.8]Mixed Models Analysis
Other Pre-specified
Subject-Reported Bothersomeness of Nausea
Subjects who answered that they felt nauseous will record bothersomeness of nausea in their eDiaries on all postoperative in-hospital days. Bothersomeness is measured on a scale of 0-10 with 10 being the most bothersome.
Time frame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
Population: Analysis population includes subjects in the Full Analysis population in each treatment group who receive at least 1 dose of study medication, who underwent an elective BR surgery as specified in the protocol, and who answered that they felt nausea on the day in the questionnaire through the eDiaries. Data is collected during hospital stays, and no longer collected once the subjects are discharged. Number Analyzed for each day represents number of subject with data for the day.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| TU-100 15 g/Day | Subject-Reported Bothersomeness of Nausea | Day 2 | 6.0 score of nausea bothersomeness | Standard Error 0.53 |
| TU-100 15 g/Day | Subject-Reported Bothersomeness of Nausea | Day 1 | 5.5 score of nausea bothersomeness | Standard Error 0.46 |
| TU-100 15 g/Day | Subject-Reported Bothersomeness of Nausea | Day 3 | 6.7 score of nausea bothersomeness | Standard Error 0.78 |
| TU-100 7.5 g/Day | Subject-Reported Bothersomeness of Nausea | Day 2 | 4.7 score of nausea bothersomeness | Standard Error 0.66 |
| TU-100 7.5 g/Day | Subject-Reported Bothersomeness of Nausea | Day 1 | 6.0 score of nausea bothersomeness | Standard Error 0.47 |
| TU-100 7.5 g/Day | Subject-Reported Bothersomeness of Nausea | Day 3 | 5.5 score of nausea bothersomeness | Standard Error 0.86 |
| Placebo | Subject-Reported Bothersomeness of Nausea | Day 1 | 6.1 score of nausea bothersomeness | Standard Error 0.48 |
| Placebo | Subject-Reported Bothersomeness of Nausea | Day 3 | 6.5 score of nausea bothersomeness | Standard Error 0.79 |
| Placebo | Subject-Reported Bothersomeness of Nausea | Day 2 | 5.8 score of nausea bothersomeness | Standard Error 0.54 |
Comparison: For Day 1, least square (LS) mean difference between placebo and TU-100 15 g/day. Mixed Model Repeated Measures approach was used to assess the bothersomeness of Nausea as the dependent variable and treatment group, surgical approach and treatment group by visit as covariates. An unstructured covariance structure is used to model the within-subject errors, shared across treatments.p-value: 0.35995% CI: [-1.8, 0.6]Mixed Models Analysis
Comparison: For Day 1, LS mean difference between placebo and TU-100 7.5 g/day. Mixed Model Repeated Measures approach was used to assess the bothersomeness of Nausea as the dependent variable and treatment group, surgical approach and treatment group by visit as covariates. An unstructured covariance structure is used to model the within-subject errors, shared across treatments.p-value: 0.90795% CI: [-1.3, 1.2]Mixed Models Analysis
Comparison: For Day 2, LS mean difference between placebo and TU-100 15 g/day. Mixed Model Repeated Measures approach was used to assess the bothersomeness of Nausea as the dependent variable and treatment group, surgical approach and treatment group by visit as covariates. An unstructured covariance structure is used to model the within-subject errors, shared across treatments.p-value: 0.85695% CI: [-1.3, 1.6]Mixed Models Analysis
Comparison: For Day 2, LS mean difference between placebo and TU-100 7.5 g/day. Mixed Model Repeated Measures approach was used to assess the bothersomeness of Nausea as the dependent variable and treatment group, surgical approach and treatment group by visit as covariates. An unstructured covariance structure is used to model the within-subject errors, shared across treatments.p-value: 0.1895% CI: [-2.7, 0.5]Mixed Models Analysis
Comparison: For Day 3, LS mean difference between placebo and TU-100 15 g/day. Mixed Model Repeated Measures approach was used to assess the bothersomeness of Nausea as the dependent variable and treatment group, surgical approach and treatment group by visit as covariates. An unstructured covariance structure is used to model the within-subject errors, shared across treatments.p-value: 0.81495% CI: [-1.9, 2.4]Mixed Models Analysis
Comparison: For Day 3, LS mean difference between placebo and TU-100 7.5 g/day. Mixed Model Repeated Measures approach was used to assess the bothersomeness of Nausea as the dependent variable and treatment group, surgical approach and treatment group by visit as covariates. An unstructured covariance structure is used to model the within-subject errors, shared across treatments.p-value: 0.40995% CI: [-3.2, 1.3]Mixed Models Analysis
Other Pre-specified
Subject-Reported Occurrence of Abdominal Bloating
Subjects will record the occurrence of abdominal bloating in their eDiaries on all postoperative in-hospital days.
Time frame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
Population: Analysis population includes subjects in the Full Analysis population in each treatment group who receive at least 1 dose of study medication, who underwent an elective BR surgery as specified in the protocol, and who answered to the questionnaire through the eDiaries. The questionnaire is only answered during hospital stays, and data is no longer collected once the subjects are discharged. Number Analyzed for each day represents number of subject answered the questionnaire for the day.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TU-100 15 g/Day | Subject-Reported Occurrence of Abdominal Bloating | Day 1 | 61 Participants |
| TU-100 15 g/Day | Subject-Reported Occurrence of Abdominal Bloating | Day 2 | 30 Participants |
| TU-100 15 g/Day | Subject-Reported Occurrence of Abdominal Bloating | Day 3 | 14 Participants |
| TU-100 15 g/Day | Subject-Reported Occurrence of Abdominal Bloating | Day 4 | 6 Participants |
| TU-100 7.5 g/Day | Subject-Reported Occurrence of Abdominal Bloating | Day 4 | 7 Participants |
| TU-100 7.5 g/Day | Subject-Reported Occurrence of Abdominal Bloating | Day 1 | 67 Participants |
| TU-100 7.5 g/Day | Subject-Reported Occurrence of Abdominal Bloating | Day 3 | 13 Participants |
| TU-100 7.5 g/Day | Subject-Reported Occurrence of Abdominal Bloating | Day 2 | 30 Participants |
| Placebo | Subject-Reported Occurrence of Abdominal Bloating | Day 4 | 11 Participants |
| Placebo | Subject-Reported Occurrence of Abdominal Bloating | Day 2 | 49 Participants |
| Placebo | Subject-Reported Occurrence of Abdominal Bloating | Day 3 | 21 Participants |
| Placebo | Subject-Reported Occurrence of Abdominal Bloating | Day 1 | 66 Participants |
Comparison: For Day 1p-value: 0.4395% CI: [0.46, 1.4]Regression, Logistic
Comparison: For Day 1p-value: 0.73995% CI: [0.62, 1.96]Regression, Logistic
Comparison: For Day 2p-value: 0.1395% CI: [0.25, 1.2]Regression, Logistic
Comparison: For Day 2p-value: 0.09995% CI: [0.24, 1.13]Regression, Logistic
Comparison: For Day 3p-value: 0.68695% CI: [0.23, 2.63]Regression, Logistic
Comparison: For Day 3p-value: 0.64495% CI: [0.22, 2.56]Regression, Logistic
Comparison: For Day 4p-value: 0.49895% CI: [0.09, 3.18]Regression, Logistic
Comparison: For Day 4p-value: 0.795% CI: [0.12, 4.05]Regression, Logistic
Other Pre-specified
Subject-Reported Occurrence of Nausea
Subjects will record the occurrence of nausea in their eDiaries on all postoperative in-hospital days.
Time frame: From the day after surgery (Day 1) until hospital discharge or Day 10 (whichever is earlier)
Population: Analysis population includes subjects in the Full Analysis population in each treatment group who receive at least 1 dose of study medication, who underwent an elective BR surgery as specified in the protocol, and who answered to the questionnaire through the eDiaries. The questionnaire is only answered during hospital stays, and data is no longer collected once the subjects are discharged. Number Analyzed for each day represents number of subject answered the questionnaire for the day.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TU-100 15 g/Day | Subject-Reported Occurrence of Nausea | Day 1 | 39 Participants |
| TU-100 15 g/Day | Subject-Reported Occurrence of Nausea | Day 3 | 10 Participants |
| TU-100 15 g/Day | Subject-Reported Occurrence of Nausea | Day 4 | 3 Participants |
| TU-100 15 g/Day | Subject-Reported Occurrence of Nausea | Day 2 | 26 Participants |
| TU-100 7.5 g/Day | Subject-Reported Occurrence of Nausea | Day 1 | 37 Participants |
| TU-100 7.5 g/Day | Subject-Reported Occurrence of Nausea | Day 2 | 16 Participants |
| TU-100 7.5 g/Day | Subject-Reported Occurrence of Nausea | Day 3 | 9 Participants |
| TU-100 7.5 g/Day | Subject-Reported Occurrence of Nausea | Day 4 | 6 Participants |
| Placebo | Subject-Reported Occurrence of Nausea | Day 3 | 11 Participants |
| Placebo | Subject-Reported Occurrence of Nausea | Day 1 | 35 Participants |
| Placebo | Subject-Reported Occurrence of Nausea | Day 2 | 25 Participants |
| Placebo | Subject-Reported Occurrence of Nausea | Day 4 | 6 Participants |
Comparison: For Day 1p-value: 0.60495% CI: [0.66, 2.05]Regression, Logistic
Comparison: For Day 1p-value: 0.69395% CI: [0.63, 1.99]Regression, Logistic
Comparison: For Day 2p-value: 0.12295% CI: [0.85, 3.78]Regression, Logistic
Comparison: For Day 2p-value: 0.51895% CI: [0.36, 1.67]Regression, Logistic
Comparison: For Day 3p-value: 0.52895% CI: [0.46, 4.53]Regression, Logistic
Comparison: For Day 3p-value: 0.68995% CI: [0.4, 4.07]Regression, Logistic
Comparison: For Day 4p-value: 0.65395% CI: [0.12, 3.7]Regression, Logistic
Comparison: For Day 4p-value: 0.45295% CI: [0.37, 9.25]Regression, Logistic