Trial Outcomes & Findings for Short Bowel Syndrome and Teduglutide Versus Placebo (NCT NCT02099084)

Results Overview

The time for half of the ingested solids or liquids to leave the stomach.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

8 participants

Primary outcome timeframe

approximately 2 hours after radiolabeled meal is ingested

Results posted on

2016-02-22

Participant Flow

Subjects were recruited from the Mayo Clinic Home Parenteral Nutrition program in Rochester, Minnesota.

Participant milestones

Participant milestones
Measure	Teduglutide First, Then Placebo Teduglutide 0.05 mg/kg/d administered subcutaneously for 7 days, followed by a 14-day washout period, and placebo administered subcutaneously for 7 days.	Placebo First, Then Teduglutide Placebo administered subcutaneously for 7 days, followed by a 14-day washout period, and Teduglutide 0.05 mg/kg/d administered subcutaneously for 7 days.
First Intervention STARTED	4	4
First Intervention COMPLETED	4	4
First Intervention NOT COMPLETED	0	0
Washout Period of 14 Days STARTED	4	4
Washout Period of 14 Days COMPLETED	4	4
Washout Period of 14 Days NOT COMPLETED	0	0
Second Intervention STARTED	4	4
Second Intervention COMPLETED	4	4
Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Short Bowel Syndrome and Teduglutide Versus Placebo

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entire Study Population n=8 Participants Includes groups randomized to receive placebo first and Teduglutide first.
Age, Continuous	54 years STANDARD_DEVIATION 13 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants

PRIMARY outcome

Timeframe: approximately 2 hours after radiolabeled meal is ingested

The time for half of the ingested solids or liquids to leave the stomach.

Outcome measures

Outcome measures
Measure	Teduglutide n=8 Participants Teduglutide 0.05 mg/kg/d administered subcutaneously for 7 days in either first intervention period or second intervention period	Placebo n=8 Participants Placebo administered subcutaneously daily for 7 days in either first intervention period or second intervention period
Gastric Emptying Half-Time (T1/2)	113 minutes Standard Deviation 16	106 minutes Standard Deviation 20

PRIMARY outcome

Timeframe: baseline, approximately 6 hours after ingestion of radiolabeled meal

Given the variable extent of the residual length of the small intestine and colon, the proportion emptied from the body at 6 hours was assessed as an overall estimate of the whole gut transit. The 6-hour values for intra-abdominal counts were then compared with the 100% reference values of counts (at time zero, which is immediately after ingestion of the radiolabeled meal) to determine the percentage of isotope retained in the abdomen. 100% minus the percentage of retained isotope reflected the amount emptied from the GI tract.

Outcome measures

Outcome measures
Measure	Teduglutide n=8 Participants Teduglutide 0.05 mg/kg/d administered subcutaneously for 7 days in either first intervention period or second intervention period	Placebo n=8 Participants Placebo administered subcutaneously daily for 7 days in either first intervention period or second intervention period
Overall Gut Transit	53.4 Percentage of isotope emptied Standard Deviation 15	62.4 Percentage of isotope emptied Standard Deviation 15.2

SECONDARY outcome

Timeframe: baseline, approximately 2 hours and 8 hours after ingestion of radiolabeled meal

Permeability is measured through differential excretion of urine saccharides. A sugar solution (200 mg of mannitol and 1 g lactulose in 30 mL of water) was administered with the radiolabeled test meal at visits 1 and 2. Urine was collected during 0-2 and 2-8 hours. A baseline urine sample was also collected prior to ingestion of the sugars. Chemical analysis was preformed with high-speed liquid chromatography tandem mass spectrometry.

Outcome measures

Outcome measures
Measure	Teduglutide n=8 Participants Teduglutide 0.05 mg/kg/d administered subcutaneously for 7 days in either first intervention period or second intervention period	Placebo n=8 Participants Placebo administered subcutaneously daily for 7 days in either first intervention period or second intervention period
Change in Small Intestinal and Colonic Permeability as Measured by Urinary Excretion of Mannitol 0 - 2 hours	16.2 mg Standard Error 3.6	11.3 mg Standard Error 2.2
Change in Small Intestinal and Colonic Permeability as Measured by Urinary Excretion of Mannitol 0 - 8 hours	48.8 mg Standard Error 8.9	32.7 mg Standard Error 5.9

SECONDARY outcome

Timeframe: baseline, approximately 2 hours after ingestion of radiolabeled meal

Permeability is measured through differential excretion of urine saccharides. A sugar solution (200 mg of mannitol and 1 g lactulose in 30 mL of water) was administered with the radiolabeled test meal at visits 1 and 2. Urine was collected during 0-2 and 2-8 hours. A baseline urine sample was also collected prior to ingestion of the sugars. Chemical analysis was preformed with high-speed liquid chromatography tandem mass spectrometry.

Outcome measures

Outcome measures
Measure	Teduglutide n=8 Participants Teduglutide 0.05 mg/kg/d administered subcutaneously for 7 days in either first intervention period or second intervention period	Placebo n=8 Participants Placebo administered subcutaneously daily for 7 days in either first intervention period or second intervention period
Change in Small Intestinal and Colonic Permeability as Measured by Urinary Excretion of Lactulose at 2 Hours	0.42 mg Standard Deviation 0.14	0.38 mg Standard Deviation 0.14

SECONDARY outcome

Timeframe: baseline, approximately 2 hours after ingestion of radiolabeled meal

Permeability is measured through differential excretion of urine saccharides. A sugar solution (200 mg of mannitol and 1 g lactulose in 30 mL of water) was administered with the radiolabeled test meal at visits 1 and 2. Urine was collected during 0-2 and 2-8 hours. A baseline urine sample was also collected prior to ingestion of the sugars. Chemical analysis was preformed with high-speed liquid chromatography tandem mass spectrometry.

Outcome measures

Outcome measures
Measure	Teduglutide n=8 Participants Teduglutide 0.05 mg/kg/d administered subcutaneously for 7 days in either first intervention period or second intervention period	Placebo n=8 Participants Placebo administered subcutaneously daily for 7 days in either first intervention period or second intervention period
Change in Small Intestinal and Colonic Permeability as Measured by Lactulose/Mannitol Ratio at 2 Hours	0.024 ratio Standard Deviation 0.005	0.021 ratio Standard Deviation 0.005

OTHER_PRE_SPECIFIED outcome

Timeframe: approximately 8 hours after ingestion of radiolabeled meal

After an overnight fast, subjects received a single dose of placebo or Teduglutide 1 hour before breakfast, then consumed a radiolabeled meal. After 8 hours a stool collection was taken.

Outcome measures

Outcome measures
Measure	Teduglutide n=8 Participants Teduglutide 0.05 mg/kg/d administered subcutaneously for 7 days in either first intervention period or second intervention period	Placebo n=8 Participants Placebo administered subcutaneously daily for 7 days in either first intervention period or second intervention period
Stool Weight at 8 Hours	77 g Standard Deviation 18	106 g Standard Deviation 43

OTHER_PRE_SPECIFIED outcome

Timeframe: Start of the ingestion of the radiolabeled meal until 8 hours after the meal

After an overnight fast, subjects received a single dose of placebo or Teduglutide 1 hour before breakfast, then consumed a radiolabeled meal. Urine was collected twice: from the start of the ingestion of the meal to 2 hours, and 2-8 hours. The total volume of urine collected was the sum of these two collections.

Outcome measures

Outcome measures
Measure	Teduglutide n=8 Participants Teduglutide 0.05 mg/kg/d administered subcutaneously for 7 days in either first intervention period or second intervention period	Placebo n=8 Participants Placebo administered subcutaneously daily for 7 days in either first intervention period or second intervention period
Urine Volume at 8 Hours	408.9 mL Standard Deviation 52.2	365.7 mL Standard Deviation 57.3

Adverse Events

Teduglutide

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Teduglutide n=8 participants at risk Teduglutide 0.05 mg/kg/d administered subcutaneously for 7 days in either first intervention period or second intervention period	Placebo n=8 participants at risk Placebo administered subcutaneously daily for 7 days in either first intervention period or second intervention period
Gastrointestinal disorders Moderate abdominal discomfort	0.00% 0/8 • Adverse event data were collected for approximately 21 days. Adverse events were recorded in the daily stool diary. Participants were contacted on day 2 and day 5 of each phase of the study medications. Participants also met with study staff on visits 1-3.	12.5% 1/8 • Number of events 2 • Adverse event data were collected for approximately 21 days. Adverse events were recorded in the daily stool diary. Participants were contacted on day 2 and day 5 of each phase of the study medications. Participants also met with study staff on visits 1-3.
General disorders Headache	12.5% 1/8 • Number of events 1 • Adverse event data were collected for approximately 21 days. Adverse events were recorded in the daily stool diary. Participants were contacted on day 2 and day 5 of each phase of the study medications. Participants also met with study staff on visits 1-3.	0.00% 0/8 • Adverse event data were collected for approximately 21 days. Adverse events were recorded in the daily stool diary. Participants were contacted on day 2 and day 5 of each phase of the study medications. Participants also met with study staff on visits 1-3.
Gastrointestinal disorders Nausea	12.5% 1/8 • Number of events 1 • Adverse event data were collected for approximately 21 days. Adverse events were recorded in the daily stool diary. Participants were contacted on day 2 and day 5 of each phase of the study medications. Participants also met with study staff on visits 1-3.	0.00% 0/8 • Adverse event data were collected for approximately 21 days. Adverse events were recorded in the daily stool diary. Participants were contacted on day 2 and day 5 of each phase of the study medications. Participants also met with study staff on visits 1-3.
Gastrointestinal disorders Increase in size of stoma	25.0% 2/8 • Number of events 2 • Adverse event data were collected for approximately 21 days. Adverse events were recorded in the daily stool diary. Participants were contacted on day 2 and day 5 of each phase of the study medications. Participants also met with study staff on visits 1-3.	0.00% 0/8 • Adverse event data were collected for approximately 21 days. Adverse events were recorded in the daily stool diary. Participants were contacted on day 2 and day 5 of each phase of the study medications. Participants also met with study staff on visits 1-3.

Additional Information

Dr. Michael Camilleri

Mayo Clinic

Phone: 507-284-6218

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place