Trial Outcomes & Findings for Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Teduglutide in Japanese Subjects With PN-dependent Short Bowel Syndrome (SBS) (NCT NCT02340819)
NCT ID: NCT02340819
Last Updated: 2021-06-09
Results Overview
Absolute change from baseline in weekly PS volume at Week 24 was reported.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
11 participants
Primary outcome timeframe
Baseline (stage 2), Week 24
Results posted on
2021-06-09
Participant Flow
The study was conducted at five centers in Japan between 18 December 2014 (first participant first visit) and 12 November 2018 (last participant last visit).
Screened participants underwent a maximum 8 week parenteral support (PS) optimization period and 4 to 8 week stabilization period (stage 1) followed by 24 weeks treatment period (stage 2), and a long-term extension period were all participants received same treatment of stage 2 in stage 3 and stage 4. Total study duration was up to 47 months.
Participant milestones
| Measure |
Teduglutide
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Overall Study
STARTED
|
11
|
|
Overall Study
Started Stage 2
|
11
|
|
Overall Study
Completed Stage 2
|
9
|
|
Overall Study
Started Stage 3
|
8
|
|
Overall Study
Completed Stage 3
|
7
|
|
Overall Study
Started Stage 4
|
7
|
|
Overall Study
Completed Stage 4
|
7
|
|
Overall Study
COMPLETED
|
7
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Teduglutide
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
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|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Discontinued with other reason
|
1
|
Baseline Characteristics
Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Teduglutide in Japanese Subjects With PN-dependent Short Bowel Syndrome (SBS)
Baseline characteristics by cohort
| Measure |
Teduglutide
n=11 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
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|---|---|
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Age, Continuous
|
40.9 Years
STANDARD_DEVIATION 12.41 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (stage 2), Week 24Population: Intent-to-treat (ITT) population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Absolute change from baseline in weekly PS volume at Week 24 was reported.
Outcome measures
| Measure |
Teduglutide
n=9 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
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|---|---|
|
Stage 2: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24
|
-4.92 Liter per week (L/week)
Standard Deviation 4.749
|
PRIMARY outcome
Timeframe: Baseline (stage 2), Week 24Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Percent change from baseline in weekly PS volume at Week 24 was reported.
Outcome measures
| Measure |
Teduglutide
n=9 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Stage 2: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24
|
-30.07 Percent change in PS volume
Standard Deviation 25.892
|
PRIMARY outcome
Timeframe: End of Stage 2 (up to Week 24)Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2.
Response was defined as the achievement of at least a 20% reduction from baseline (Visit 2) in weekly PS volume at Week 20 and again at Week 24.
Outcome measures
| Measure |
Teduglutide
n=11 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
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Stage 2: Percentage of Participants Who Demonstrate Response to Teduglutide at End of Stage 2
PS Response: Yes
|
45.5 Percentage of Participants
|
|
Stage 2: Percentage of Participants Who Demonstrate Response to Teduglutide at End of Stage 2
PS Response: No
|
54.5 Percentage of Participants
|
PRIMARY outcome
Timeframe: Baseline (stage 2), Week 24Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Absolute change from baseline in number of days per Week of PS usage at Week 24 was reported.
Outcome measures
| Measure |
Teduglutide
n=9 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
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|---|---|
|
Stage 2: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at Week 24
|
-1.0 Days per week (days/week)
Standard Deviation 1.80
|
PRIMARY outcome
Timeframe: Baseline (stage 2), Week 24Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Plasma citrulline was measured as an assessment of enterocyte mass. Absolute change from baseline in plasma citrulline levels at Week 24 was reported.
Outcome measures
| Measure |
Teduglutide
n=9 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Stage 2: Absolute Change From Baseline in Plasma Citrulline Levels at Week 24
|
15.0 Micromoles per liter
Standard Deviation 17.37
|
PRIMARY outcome
Timeframe: Baseline (stage 2), Week 24Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Plasma citrulline was measured as an assessment of enterocyte mass. Percent change from baseline in plasma citrulline at Week 24 was reported.
Outcome measures
| Measure |
Teduglutide
n=9 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Stage 2: Percent Change From Baseline in Plasma Citrulline Levels at Week 24
|
86.9 Percent change
Standard Deviation 112.33
|
PRIMARY outcome
Timeframe: Week 24Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2.
Enteral autonomy was defined as no prescribed PS and no use of PS recorded in the participant diary at the end of stage 2. Number of participants who achieved enteral autonomy at Week 24 was reported.
Outcome measures
| Measure |
Teduglutide
n=11 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
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|---|---|
|
Stage 2: Number of Participants Who Achieved Enteral Autonomy at Week 24
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline (stage 3), Extension Month 24Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Absolute change from baseline in weekly PS volume at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.
Outcome measures
| Measure |
Teduglutide
n=7 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
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|---|---|
|
Stage 3: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at Extension Month 24
|
-8.33 L/week
Standard Deviation 5.940
|
PRIMARY outcome
Timeframe: Baseline (stage 3), Extension Month 24Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Percent change from baseline in weekly PS volume at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.
Outcome measures
| Measure |
Teduglutide
n=7 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
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|---|---|
|
Stage 3: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at Extension Month 24
|
-53.53 Percent change in PS volume
Standard Deviation 33.866
|
PRIMARY outcome
Timeframe: Baseline (stage 3), Extension Month 24Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Absolute change from baseline in number of days per Week of PS usage at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.
Outcome measures
| Measure |
Teduglutide
n=7 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Stage 3: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at Extension Month 24
|
-2.1 days/week
Standard Deviation 3.34
|
PRIMARY outcome
Timeframe: Baseline (stage 3), Extension Month 24Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Plasma citrulline was measured as an assessment of enterocyte mass. Absolute change from baseline in plasma citrulline levels at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.
Outcome measures
| Measure |
Teduglutide
n=7 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
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|---|---|
|
Stage 3: Absolute Change From Baseline in Plasma Citrulline Levels at Extension Month 24
|
28.3 Micromoles per liter
Standard Deviation 24.05
|
PRIMARY outcome
Timeframe: Baseline (stage 3), Extension Month 24Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Plasma citrulline was measured as an assessment of enterocyte mass. Percent change from baseline in plasma citrulline at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.
Outcome measures
| Measure |
Teduglutide
n=7 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Stage 3: Percent Change From Baseline in Plasma Citrulline Levels at Extension Month 24
|
135.0 Percent change
Standard Deviation 84.17
|
PRIMARY outcome
Timeframe: Baseline (stage 4), End of Treatment (up to 47 months)Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2.
Absolute change from baseline in weekly PS volume at end of treatment was reported.
Outcome measures
| Measure |
Teduglutide
n=11 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
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|---|---|
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Stage 4: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment
|
-5.08 L/week
Standard Deviation 6.404
|
PRIMARY outcome
Timeframe: Baseline (stage 4), End of Treatment (up to 47 months)Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2.
Percent change from baseline in weekly PS volume at end of treatment was reported.
Outcome measures
| Measure |
Teduglutide
n=11 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
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|---|---|
|
Stage 4: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment
|
-34.12 Percent change in PS volume
Standard Deviation 38.877
|
PRIMARY outcome
Timeframe: Baseline (stage 4), End of Treatment (up to 47 months)Population: ITT population consists of all participants who were enrolled and eligible to enter Stage 2.
Absolute change from baseline in number of days per week of PS usage at end of treatment was reported.
Outcome measures
| Measure |
Teduglutide
n=11 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Stage 4: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at End of Treatment
|
-1.4 days/week
Standard Deviation 2.80
|
PRIMARY outcome
Timeframe: Baseline (stage 4), End of Treatment (up to 47 months)Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2.
Plasma citrulline was measured as an assessment of enterocyte mass. Absolute change from baseline in plasma citrulline levels at end of treatment was reported.
Outcome measures
| Measure |
Teduglutide
n=11 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Stage 4: Absolute Change From Baseline in Plasma Citrulline Levels at End of Treatment
|
19.3 Micromoles per liter
Standard Deviation 19.96
|
PRIMARY outcome
Timeframe: Baseline (stage 4), End of Treatment (up to 47 months)Population: ITT population consisted of all participants who were enrolled and eligible to enter Stage 2.
Plasma citrulline was measured as an assessment of enterocyte mass. Percent change in plasma citrulline from baseline at end of treatment was reported.
Outcome measures
| Measure |
Teduglutide
n=11 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Stage 4: Percent Change From Baseline in Plasma Citrulline Levels at End of Treatment
|
110.3 Percent change
Standard Deviation 98.13
|
SECONDARY outcome
Timeframe: Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosePopulation: Pharmacokinetic (PK) analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data were considered sufficient and interpretable.
Area under the concentration-time curve from time zero to infinity of teduglutide in plasma were evaluated.
Outcome measures
| Measure |
Teduglutide
n=8 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-Inf) of Teduglutide in Plasma
|
204 Nanogram*hour per milliliter (ng*h/mL)
Standard Deviation 51.1
|
SECONDARY outcome
Timeframe: Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosePopulation: PK analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data were considered sufficient and interpretable.
Area under the concentration-time curve from time zero to the last time point of teduglutide in plasma were evaluated.
Outcome measures
| Measure |
Teduglutide
n=8 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Area Under the Concentration-Time Curve From Time Zero to the Last Time Point (AUC0-t) of Teduglutide in Plasma
|
201 ng*h/mL
Standard Deviation 51.6
|
SECONDARY outcome
Timeframe: Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosePopulation: PK analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data were considered sufficient and interpretable.
Maximum concentration of teduglutide in plasma were evaluated.
Outcome measures
| Measure |
Teduglutide
n=8 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Maximum Concentration (Cmax) of Teduglutide in Plasma
|
49.7 Nanogram per milliliter (ng/mL)
Standard Deviation 19.7
|
SECONDARY outcome
Timeframe: Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosePopulation: PK analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data were considered sufficient and interpretable.
Time to reach maximum observed drug concentration of teduglutide in plasma was evaluated.
Outcome measures
| Measure |
Teduglutide
n=8 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Time to Reach Maximum Observed Drug Concentration (Tmax) of Teduglutide in Plasma
|
2.49 hour
Interval 1.17 to 4.0
|
SECONDARY outcome
Timeframe: Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosePopulation: PK analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data were considered sufficient and interpretable.
Terminal half-life of teduglutide in plasma were evaluated.
Outcome measures
| Measure |
Teduglutide
n=8 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Terminal Half-Life (t1/2) of Teduglutide in Plasma
|
1.06 hour
Interval 0.62 to 2.63
|
SECONDARY outcome
Timeframe: Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosePopulation: PK analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data are considered sufficient and interpretable.
Apparent clearance of teduglutide in plasma were evaluated.
Outcome measures
| Measure |
Teduglutide
n=8 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Apparent Clearance (CL/F) of Teduglutide in Plasma
|
14.5 liter per hour (L/h)
Standard Deviation 4.09
|
SECONDARY outcome
Timeframe: Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosePopulation: PK analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data were considered sufficient and interpretable.
Apparent volume of distribution of teduglutide in plasma were evaluated.
Outcome measures
| Measure |
Teduglutide
n=8 Participants
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Apparent Volume of Distribution (Vz/F) of Teduglutide in Plasma
|
27.8 liter
Standard Deviation 22.5
|
Adverse Events
Teduglutide
Serious events: 7 serious events
Other events: 11 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Teduglutide
n=11 participants at risk
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Vascular disorders
Thrombophlebitis
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Enteritis
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Enterocolitis
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Intestinal obstruction
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Device occlusion
|
9.1%
1/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Pyrexia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Arthritis bacterial
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Catheter site infection
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Device related infection
|
63.6%
7/11 • Number of events 19 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Sepsis
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Streptococcal infection
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Renal and urinary disorders
Renal failure acute
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Hepatobiliary disorders
Acute hepatic failure
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Metabolism and nutrition disorders
Dehydration
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
Other adverse events
| Measure |
Teduglutide
n=11 participants at risk
Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
|
|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
27.3%
3/11 • Number of events 3 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Abdominal pain
|
36.4%
4/11 • Number of events 5 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Abdominal tenderness
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Cheilitis
|
9.1%
1/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Constipation
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Dental caries
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
27.3%
3/11 • Number of events 3 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Dyspepsia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Enterocolitis
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Epigastric discomfort
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Eructation
|
9.1%
1/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Blood and lymphatic system disorders
Anaemia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
36.4%
4/11 • Number of events 4 • From start of study treatment up to end of the study (up to 47 months)
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Musculoskeletal and connective tissue disorders
Polyarthritis
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Musculoskeletal and connective tissue disorders
Temporomandibular joint syndrome
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian adenoma
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Vascular disorders
Vascular pain
|
18.2%
2/11 • Number of events 3 • From start of study treatment up to end of the study (up to 47 months)
|
|
Endocrine disorders
Thyroid cyst
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Eye disorders
Asthenopia
|
9.1%
1/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Eye disorders
Dry eye
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Eye disorders
Eye oedema
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Eye disorders
Vision blurred
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Eye disorders
Vitreous opacities
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Gingival pain
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Nausea
|
27.3%
3/11 • Number of events 7 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Pancreatic duct dilatation
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Pancreatitis
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Proctalgia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Stomatitis
|
27.3%
3/11 • Number of events 3 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Toothache
|
9.1%
1/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Gastrointestinal disorders
Vomiting
|
27.3%
3/11 • Number of events 3 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Catheter site inflammation
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Catheter site pain
|
18.2%
2/11 • Number of events 3 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Chest pain
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Device occlusion
|
27.3%
3/11 • Number of events 4 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Fatigue
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Hypothermia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Injection site reaction
|
18.2%
2/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Injury associated with device
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Malaise
|
9.1%
1/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Oedema
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Puncture site pain
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Pyrexia
|
45.5%
5/11 • Number of events 7 • From start of study treatment up to end of the study (up to 47 months)
|
|
General disorders
Thirst
|
9.1%
1/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Cardiac disorders
Cardiac failure acute
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Immune system disorders
Hypersensitivity
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Anal abscess
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Balanitis candida
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Catheter site infection
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Cellulitis
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Device related infection
|
18.2%
2/11 • Number of events 3 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Gingivitis
|
9.1%
1/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Influenza
|
18.2%
2/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Nasopharyngitis
|
45.5%
5/11 • Number of events 15 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Oral candidiasis
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Oral herpes
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Respiratory tract infection
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Infections and infestations
Trichophytosis
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Injury, poisoning and procedural complications
Procedural pain
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Injury, poisoning and procedural complications
Stoma site reaction
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Investigations
Blood alkaline phosphatase increased
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Investigations
Blood creatinine increased
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Investigations
C-reactive protein increased
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Investigations
Carcinoembryonic antigen increased
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Investigations
Intestinal transit time increased
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Investigations
Lipase increased
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Investigations
Liver function test abnormal
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Investigations
Oxygen saturation decreased
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Investigations
Platelet count decreased
|
9.1%
1/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Investigations
Urine output decreased
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Renal and urinary disorders
Haematuria
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Renal and urinary disorders
Renal cyst
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Renal and urinary disorders
Urinary incontinence
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Hepatobiliary disorders
Hyperplastic cholecystopathy
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Metabolism and nutrition disorders
Dehydration
|
18.2%
2/11 • Number of events 3 • From start of study treatment up to end of the study (up to 47 months)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Metabolism and nutrition disorders
Hypozincaemia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Metabolism and nutrition disorders
Malnutrition
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Nervous system disorders
Amnesia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Nervous system disorders
Dizziness
|
9.1%
1/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Nervous system disorders
Dyslalia
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Nervous system disorders
Headache
|
54.5%
6/11 • Number of events 10 • From start of study treatment up to end of the study (up to 47 months)
|
|
Nervous system disorders
Presyncope
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Nervous system disorders
Somnolence
|
18.2%
2/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Psychiatric disorders
Anxiety disorder
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Psychiatric disorders
Depression
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Psychiatric disorders
Insomnia
|
18.2%
2/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
18.2%
2/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
18.2%
2/11 • Number of events 3 • From start of study treatment up to end of the study (up to 47 months)
|
|
Skin and subcutaneous tissue disorders
Acne
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Skin and subcutaneous tissue disorders
Dermal cyst
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
18.2%
2/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Skin and subcutaneous tissue disorders
Erythema
|
9.1%
1/11 • Number of events 1 • From start of study treatment up to end of the study (up to 47 months)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
18.2%
2/11 • Number of events 2 • From start of study treatment up to end of the study (up to 47 months)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER