Short Bowel Syndrome
Conditions
Brief summary
The primary objective of the trial is to confirm the efficacy of glepaglutide in reducing parenteral support volume in patients with short bowel syndrome. Glepaglutide is the International Nonproprietary Name and USAN for ZP1848.
Detailed description
A Phase 3, international, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of glepaglutide subcutaneous (SC) injections in patients with short bowel syndrome (SBS).
Interventions
DRUGglepaglutide
Glucagon-Like Peptide-2 (GLP-2) analog
DRUGPlacebo
Placebo for glepaglutide
Sponsors
Zealand Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained before any trial-related activity. * Diagnosis of SBS defined as remaining small bowel in continuity of estimated less than 200 cm and considered stable with regard to PS need. No restorative surgery planned in the trial period. * Requiring PS at least 3 days per week and maintains a stable PS volume for at least 2 weeks. * In case of remnant colon: documented colonoscopy which does not give rise to any safety concerns.
Exclusion criteria
* More than 2 SBS-related or PS-related hospitalizations within 6 months prior to Screening. No SBS-related hospitalizations within 30 days prior to randomization. * Poorly controlled inflammatory bowel disease that is moderately or severely active or fistula interfering with measurements or examinations required in the trial. * Bowel obstruction. * Known radiation enteritis or significant villous atrophy. * Cardiac disease defined as: decompensated heart failure (New York Heart Association \[NYHA\] Class III-IV), unstable angina pectoris, and/or myocardial infarction within the last 6 months prior to Screening. * Clinically significant abnormal ECG. * Repeated systolic blood pressure measurements \> 180 mm Hg. * Human immunodeficiency virus positive, acute liver disease, or unstable chronic liver disease. * Any history of colon cancer. History of any other cancers unless disease-free state for at least 5 years. * Estimated creatinine clearance \< 30 mL/min. * Severe hepatic impairment. * Use of GLP-1, GLP-2, human growth hormone, somatostatin, or analogs thereof, within 3 months prior to Screening. * Use of dipeptidyl peptidase (DPP)-4 inhibitors within 3 months prior to Screening. * Unstable systemic immunosuppressive therapy within 3 months prior to Screening. * Unstable biological therapy within 6 months prior to Screening. * Females of childbearing potential, who are pregnant, breast-feeding, intend to become pregnant or are not using highly effective contraceptive methods. * Previous exposure to glepaglutide. * Current, or within 30 days prior to Screening, participation in another interventional clinical trial that includes administration of an active compound. * Any condition or disease or circumstance that in the Investigator's opinion would put the patient at any undue risk, prevent completion of the trial, or interfere with the analysis of the trial results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Weekly Parenteral Support (PS) Volume | 24 weeks | Change in weekly PS volume from baseline to Week 24. Baseline actual weekly PS volume was defined as the actual PS volume derived from a valid 7-day period prior to visit 1 (Day 1), i.e. during the stabilization phase. The actual weekly PS volume at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 was derived as the actual weekly PS volume received during the valid 7-day period prior to the visit. The source for the derivation was the PS volumes recorded by the patients in the eDiary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days Off PS | 24 weeks | Achieving 1 or more days per week off PS |
| Weaned Off PS | 24 weeks | Reduction in weekly PS volume of 100 percent (weaned off) |
| Energy Content | 24 weeks | Change in weekly energy content of PS from baseline |
| Days on PS | 24 weeks | Change in number of days on PS per week from baseline |
| Change in PS Volume Per Week | 20 and 24 weeks | Achieving reduction of at least 40 percent in PS volume from baseline to both 20 and 24 weeks |
| Clinical Response in PS Volume | 20 and 24 weeks | Clinical response, defined as at least 20% reduction in actual weekly PS volume from baseline to both Weeks 20 and 24. |
| Safety - Adverse Events | 28 weeks | Incidence and type of Adverse Events over an average of 28 weeks (24 weeks treatment + 4 weeks follow up) |
| Number of Patients With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) | 28 weeks | Number of patients with clinically significant changes in ECG will be reported. Monitored ECG parameters included heart rate (beats/min), PR interval (ms), PR interval Aggregate (ms), QRS duration aggregate (ms), QT interval aggregate (ms), QTcF interval aggregate (ms), and RR interval (ms), as well as the overall interpretation of each subject's ECG recorded as Normal, Abnormal Not Clinically Significant, or Abnormal Clinically Significant. |
| Safety - Changes in Blood Pressure From Baseline | Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 | Changes in blood pressure are reported at Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 The data collected data are of seated diastolic and systolic blood pressure (mmHg). During treatment phase visits, vital signs were collected before investigational product injection. |
| Safety - Changes in Body Temperature From Baseline | 28 weeks | Changes in body temperature are reported The body temperature (ºC or ºF) was measured according to the site's usual procedure. During treatment phase visits, vital signs were collected before investigational product injection. |
| Immunogenicity - Occurrence of Anti-drug Antibodies | 28 weeks | Occurrence of antibodies against glepaglutide The occurrence of glepaglutide-binding antibodies (ADA), M2 binding antibodies (M2 BAb), glepaglutide neutralizing antibodies (NAb) and GLP-2 cross-reacting antibodies (GLP-2 CR) was tested. |
| Patient Global Impression of Change Scale (PGIC) | 24 weeks | Patient Global Impression of Change scale (PGIC) improvement at Weeks 4, 12, 20, and 24 PGIC improvement was defined as responding Very Much Improved or Much Improved on a 7-point Likert Scale. Improvement between each glepaglutide treatment regimen compared to placebo was tested by week, using the CMH test adjusted for the stratification factor. Improvement between each glepaglutide treatment regimen versus placebo was tested using collapsed categories of Improvement, No Change, and Worsening, where Improvement is defined as a response of Very Much Improved or Much Improved or Minimally Improved, and No Change is defined as the response of No Change, and Worsening is defined as a response of Minimally Worse or Much Worse or Very Much Worse. Improvement using collapsed categories between each glepaglutide treatment regimen compared to placebo was tested by week using a Mantel-Haenszel chi-squared test for ordered categories. |
Countries
Belgium, Canada, Denmark, France, Germany, Netherlands, Poland, United Kingdom, United States
Participant flow
Recruitment details
This trial was conducted in (number of sites that randomized patients in parenthesis) Belgium (1), Denmark (2), France (2), Germany (5), the Netherlands (1), Poland (3), Canada (3), the US (7), and the UK (5).
Pre-assignment details
Patients were diagnosed with SBS and required PS at least 3 days/week. They were willing to adhere to an individual pre-defined drinking menu during 48 h measurement periods and maintain a stable weight. The drinking menu and the PS volume and content were adjusted during an optimization phase following by a stabilization phase.
Participants by arm
| Arm | Count |
|---|---|
| Glepaglutide SC Injections Twice Weekly Intervention: Glepaglutide
glepaglutide: Glucagon-Like Peptide-2 (GLP-2) analog | 35 |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly Intervention: Glepaglutide
glepaglutide: Glucagon-Like Peptide-2 (GLP-2) analog
Placebo: Placebo for glepaglutide | 35 |
| Placebo SC Injections Twice Weekly Intervention: Placebo
Placebo: Placebo for glepaglutide | 36 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | ICF withdrawal | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Glepaglutide SC Injections Twice Weekly | Total | Placebo SC Injections Twice Weekly | Glepaglutide SC Injections Once Weekly and Placebo Once Weekly |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 25 Participants | 6 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 81 Participants | 30 Participants | 28 Participants |
| Age, Continuous | 56.9 years STANDARD_DEVIATION 13.4 | 55.0 years STANDARD_DEVIATION 12.4 | 55.0 years STANDARD_DEVIATION 11.8 | 54.0 years STANDARD_DEVIATION 12 |
| BMI | 23.57 kg/m^2 STANDARD_DEVIATION 3.35 | 23.28 kg/m^2 STANDARD_DEVIATION 3.37 | 23.54 kg/m^2 STANDARD_DEVIATION 3.57 | 22.72 kg/m^2 STANDARD_DEVIATION 3.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 95 Participants | 32 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 10 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 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 | 5 Participants | 13 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) White | 28 Participants | 89 Participants | 30 Participants | 31 Participants |
| Region of Enrollment Belgium | 3 participants | 10 participants | 3 participants | 4 participants |
| Region of Enrollment Canada | 1 participants | 4 participants | 3 participants | 0 participants |
| Region of Enrollment Denmark | 5 participants | 8 participants | 1 participants | 2 participants |
| Region of Enrollment France | 5 participants | 9 participants | 3 participants | 1 participants |
| Region of Enrollment Germany | 3 participants | 12 participants | 5 participants | 4 participants |
| Region of Enrollment Netherlands | 2 participants | 4 participants | 2 participants | 0 participants |
| Region of Enrollment Poland | 8 participants | 27 participants | 12 participants | 7 participants |
| Region of Enrollment United Kingdom | 4 participants | 9 participants | 1 participants | 4 participants |
| Region of Enrollment United States | 4 participants | 23 participants | 6 participants | 13 participants |
| Sex: Female, Male Female | 19 Participants | 57 Participants | 20 Participants | 18 Participants |
| Sex: Female, Male Male | 16 Participants | 49 Participants | 16 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 | 0 / 36 |
| other Total, other adverse events | 30 / 35 | 31 / 35 | 25 / 36 |
| serious Total, serious adverse events | 9 / 35 | 10 / 35 | 7 / 36 |
Outcome results
Primary
Change in Weekly Parenteral Support (PS) Volume
Change in weekly PS volume from baseline to Week 24. Baseline actual weekly PS volume was defined as the actual PS volume derived from a valid 7-day period prior to visit 1 (Day 1), i.e. during the stabilization phase. The actual weekly PS volume at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 was derived as the actual weekly PS volume received during the valid 7-day period prior to the visit. The source for the derivation was the PS volumes recorded by the patients in the eDiary.
Time frame: 24 weeks
Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of trial drug (glepaglutide or placebo). All efficacy analyses were based on the FAS. Patients were included in the analyses as randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Change in Weekly Parenteral Support (PS) Volume | -5.13 L/week |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Change in Weekly Parenteral Support (PS) Volume | -3.76 L/week |
| Placebo SC Injections Twice Weekly | Change in Weekly Parenteral Support (PS) Volume | -2.85 L/week |
p-value: 0.003995% CI: [-3.83, -0.73]Mixed Models Analysis
p-value: 0.2795% CI: [-2.52, 0.71]Mixed Models Analysis
Secondary
Change in PS Volume Per Week
Achieving reduction of at least 40 percent in PS volume from baseline to both 20 and 24 weeks
Time frame: 20 and 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Change in PS Volume Per Week | 15 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Change in PS Volume Per Week | 10 Participants |
| Placebo SC Injections Twice Weekly | Change in PS Volume Per Week | 8 Participants |
Secondary
Clinical Response in PS Volume
Clinical response, defined as at least 20% reduction in actual weekly PS volume from baseline to both Weeks 20 and 24.
Time frame: 20 and 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Clinical Response in PS Volume | 23 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Clinical Response in PS Volume | 16 Participants |
| Placebo SC Injections Twice Weekly | Clinical Response in PS Volume | 14 Participants |
p-value: 0.625595% CI: [-16.2, 27.1]Cochran-Mantel-Haenszel
p-value: 0.024395% CI: [4.3, 48.9]Cochran-Mantel-Haenszel
Secondary
Clinical Response in PS Volume
Reduction of at least 20 percent in PS volume from baseline to both 12 and 24 weeks.
Time frame: 12 and 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Clinical Response in PS Volume | 19 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Clinical Response in PS Volume | 15 Participants |
| Placebo SC Injections Twice Weekly | Clinical Response in PS Volume | 13 Participants |
Secondary
Days Off PS
Achieving 1 or more days per week off PS
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Days Off PS | 18 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Days Off PS | 12 Participants |
| Placebo SC Injections Twice Weekly | Days Off PS | 7 Participants |
p-value: 0.004395% CI: [11.4, 51.9]Cochran-Mantel-Haenszel
p-value: 0.167595% CI: [-5.4, 32]Cochran-Mantel-Haenszel
Secondary
Days on PS
Change in number of days on PS per week from baseline
Time frame: 24 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Days on PS | -1.00 days/week |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Days on PS | 0.00 days/week |
| Placebo SC Injections Twice Weekly | Days on PS | 0.00 days/week |
Secondary
Energy Content
Change in weekly energy content of PS from baseline
Time frame: 24 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Energy Content | -7360.6 kJ/week |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Energy Content | -3085.9 kJ/week |
| Placebo SC Injections Twice Weekly | Energy Content | -734.2 kJ/week |
Secondary
Immunogenicity - Occurrence of Anti-drug Antibodies
Occurrence of antibodies against glepaglutide The occurrence of glepaglutide-binding antibodies (ADA), M2 binding antibodies (M2 BAb), glepaglutide neutralizing antibodies (NAb) and GLP-2 cross-reacting antibodies (GLP-2 CR) was tested.
Time frame: 28 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Immunogenicity - Occurrence of Anti-drug Antibodies | M2 BAb (Treatment-induced) | 28 Participants |
| Glepaglutide SC Injections Twice Weekly | Immunogenicity - Occurrence of Anti-drug Antibodies | ADA (Treatment-induced) | 30 Participants |
| Glepaglutide SC Injections Twice Weekly | Immunogenicity - Occurrence of Anti-drug Antibodies | NAb M2 (Treatment-induced) | 10 Participants |
| Glepaglutide SC Injections Twice Weekly | Immunogenicity - Occurrence of Anti-drug Antibodies | GLP-2 CR (Treatment-induced) | 6 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Immunogenicity - Occurrence of Anti-drug Antibodies | GLP-2 CR (Treatment-induced) | 11 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Immunogenicity - Occurrence of Anti-drug Antibodies | NAb M2 (Treatment-induced) | 14 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Immunogenicity - Occurrence of Anti-drug Antibodies | ADA (Treatment-induced) | 31 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Immunogenicity - Occurrence of Anti-drug Antibodies | M2 BAb (Treatment-induced) | 29 Participants |
| Placebo SC Injections Twice Weekly | Immunogenicity - Occurrence of Anti-drug Antibodies | ADA (Treatment-induced) | 0 Participants |
| Placebo SC Injections Twice Weekly | Immunogenicity - Occurrence of Anti-drug Antibodies | M2 BAb (Treatment-induced) | 0 Participants |
| Placebo SC Injections Twice Weekly | Immunogenicity - Occurrence of Anti-drug Antibodies | NAb M2 (Treatment-induced) | 0 Participants |
| Placebo SC Injections Twice Weekly | Immunogenicity - Occurrence of Anti-drug Antibodies | GLP-2 CR (Treatment-induced) | 0 Participants |
Secondary
Number of Patients With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG)
Number of patients with clinically significant changes in ECG will be reported. Monitored ECG parameters included heart rate (beats/min), PR interval (ms), PR interval Aggregate (ms), QRS duration aggregate (ms), QT interval aggregate (ms), QTcF interval aggregate (ms), and RR interval (ms), as well as the overall interpretation of each subject's ECG recorded as Normal, Abnormal Not Clinically Significant, or Abnormal Clinically Significant.
Time frame: 28 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Number of Patients With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) | 0 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Number of Patients With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) | 0 Participants |
| Placebo SC Injections Twice Weekly | Number of Patients With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) | 0 Participants |
Secondary
Patient Global Impression of Change Scale (PGIC)
Patient Global Impression of Change scale (PGIC) improvement at Weeks 4, 12, 20, and 24 PGIC improvement was defined as responding Very Much Improved or Much Improved on a 7-point Likert Scale. Improvement between each glepaglutide treatment regimen compared to placebo was tested by week, using the CMH test adjusted for the stratification factor. Improvement between each glepaglutide treatment regimen versus placebo was tested using collapsed categories of Improvement, No Change, and Worsening, where Improvement is defined as a response of Very Much Improved or Much Improved or Minimally Improved, and No Change is defined as the response of No Change, and Worsening is defined as a response of Minimally Worse or Much Worse or Very Much Worse. Improvement using collapsed categories between each glepaglutide treatment regimen compared to placebo was tested by week using a Mantel-Haenszel chi-squared test for ordered categories.
Time frame: 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Patient Global Impression of Change Scale (PGIC) | PGIC improved | 22 participants |
| Glepaglutide SC Injections Twice Weekly | Patient Global Impression of Change Scale (PGIC) | PGIC much/very much improved | 17 participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Patient Global Impression of Change Scale (PGIC) | PGIC improved | 27 participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Patient Global Impression of Change Scale (PGIC) | PGIC much/very much improved | 11 participants |
| Placebo SC Injections Twice Weekly | Patient Global Impression of Change Scale (PGIC) | PGIC improved | 13 participants |
| Placebo SC Injections Twice Weekly | Patient Global Impression of Change Scale (PGIC) | PGIC much/very much improved | 2 participants |
Secondary
Safety - Adverse Events
Incidence and type of Adverse Events over an average of 28 weeks (24 weeks treatment + 4 weeks follow up)
Time frame: 28 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | AE Severity: Mild | 28 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | Serious adverse events | 9 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | AE Severity: Severe | 10 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | AE Severity: Moderate | 15 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | All AEs | 33 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | Relationship: Related | 27 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | Relationship: Unlikely related | 18 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | Relationship: Not related | 26 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | AEs leading to trial withdrarwal | 2 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | AEs with action taken drug withdrawn | 2 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | AEs with action taken drug interrupted | 3 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | Outcome: Recovered/resolved | 32 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | Outcome: Recovering/resolving | 7 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | Outcome: Recovered/resolved with sequelae | 1 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | Outcome: Not recovered/not resolved | 17 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | Outcome: Fatal | 0 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | Outcome: Unknown | 1 Participants |
| Glepaglutide SC Injections Twice Weekly | Safety - Adverse Events | Outcome: MIssing | 0 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | Outcome: MIssing | 0 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | All AEs | 33 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | AEs with action taken drug withdrawn | 1 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | Outcome: Recovering/resolving | 9 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | Serious adverse events | 10 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | Outcome: Not recovered/not resolved | 14 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | Outcome: Fatal | 0 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | AE Severity: Severe | 5 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | AEs with action taken drug interrupted | 0 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | Outcome: Unknown | 0 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | AE Severity: Moderate | 18 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | AEs leading to trial withdrarwal | 0 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | Outcome: Recovered/resolved with sequelae | 1 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | AE Severity: Mild | 32 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | Relationship: Not related | 26 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | Outcome: Recovered/resolved | 30 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | Relationship: Related | 26 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Adverse Events | Relationship: Unlikely related | 16 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | Relationship: Related | 14 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | Relationship: Unlikely related | 9 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | Relationship: Not related | 23 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | Outcome: Not recovered/not resolved | 9 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | AEs leading to trial withdrarwal | 0 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | Outcome: MIssing | 0 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | AEs with action taken drug withdrawn | 0 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | AEs with action taken drug interrupted | 3 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | Outcome: Fatal | 0 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | Outcome: Recovered/resolved | 25 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | All AEs | 27 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | Serious adverse events | 7 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | Outcome: Recovering/resolving | 5 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | AE Severity: Severe | 2 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | AE Severity: Moderate | 14 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | AE Severity: Mild | 24 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | Outcome: Recovered/resolved with sequelae | 0 Participants |
| Placebo SC Injections Twice Weekly | Safety - Adverse Events | Outcome: Unknown | 0 Participants |
Secondary
Safety - Changes in Blood Pressure From Baseline
Changes in blood pressure are reported at Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24 The data collected data are of seated diastolic and systolic blood pressure (mmHg). During treatment phase visits, vital signs were collected before investigational product injection.
Time frame: Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24
Population: At certain visits those data are missing for some patients.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 16 Systolic blood pressure | 0.1 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 4 Systolic blood pressure | -1.7 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 4 Diastolic blood pressure | 0.0 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 20 Systolic blood pressure | 1.3 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 2 Systolic blood pressure | 1.0 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 2 Diastolic blood pressure | 2.5 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 24 Systolic blood pressure | -1.0 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 12 Diastolic blood pressure | -2.8 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 1 Diastolic blood pressure | 0.4 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 8 Systolic blood pressure | 0.3 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 24 Diastolic blood pressure | 2.2 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 1 Systolic blood pressure | -2.8 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 12 Systolic blood pressure | -4.4 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 20 Diastolic blood pressure | 2.1 mmHg |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 8 Diastolic blood pressure | -0.5 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 8 Diastolic blood pressure | 1.9 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 1 Systolic blood pressure | 0.3 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 2 Systolic blood pressure | -0.1 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 4 Systolic blood pressure | -0.2 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 8 Systolic blood pressure | -1.5 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 12 Systolic blood pressure | 3.3 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 16 Systolic blood pressure | 0.4 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 20 Systolic blood pressure | 1.2 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 24 Systolic blood pressure | -1.1 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 1 Diastolic blood pressure | 0.5 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 2 Diastolic blood pressure | -0.7 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 4 Diastolic blood pressure | -0.2 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 12 Diastolic blood pressure | 2.0 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 20 Diastolic blood pressure | -0.7 mmHg |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Blood Pressure From Baseline | Week 24 Diastolic blood pressure | 0.0 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 16 Systolic blood pressure | -1.1 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 20 Diastolic blood pressure | 0.4 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 4 Diastolic blood pressure | -1.5 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 12 Systolic blood pressure | -0.4 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 8 Systolic blood pressure | -2.5 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 8 Diastolic blood pressure | -0.6 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 4 Systolic blood pressure | -0.3 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 1 Systolic blood pressure | -4.5 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 12 Diastolic blood pressure | 0.9 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 24 Systolic blood pressure | -5.9 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 2 Systolic blood pressure | -2.7 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 1 Diastolic blood pressure | -2.0 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 20 Systolic blood pressure | -1.0 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 24 Diastolic blood pressure | -0.9 mmHg |
| Placebo SC Injections Twice Weekly | Safety - Changes in Blood Pressure From Baseline | Week 2 Diastolic blood pressure | -1.7 mmHg |
Secondary
Safety - Changes in Body Temperature From Baseline
Changes in body temperature are reported The body temperature (ºC or ºF) was measured according to the site's usual procedure. During treatment phase visits, vital signs were collected before investigational product injection.
Time frame: 28 weeks
Population: At certain visits those data are missing for some patients.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 1 | 0.0 degree C |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 24 | -0.0 degree C |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 8 | 0.0 degree C |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 2 | 0.1 degree C |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 20 | 0.1 degree C |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 4 | -0.1 degree C |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 12 | -0.0 degree C |
| Glepaglutide SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 16 | -0.0 degree C |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Body Temperature From Baseline | Week 16 | -0.0 degree C |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Body Temperature From Baseline | Week 20 | 0.0 degree C |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Body Temperature From Baseline | Week 24 | 0.1 degree C |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Body Temperature From Baseline | Week 8 | 0.1 degree C |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Body Temperature From Baseline | Week 1 | -0.0 degree C |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Body Temperature From Baseline | Week 2 | -0.0 degree C |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Body Temperature From Baseline | Week 4 | -0.0 degree C |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Safety - Changes in Body Temperature From Baseline | Week 12 | -0.0 degree C |
| Placebo SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 4 | 0.1 degree C |
| Placebo SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 1 | 0.1 degree C |
| Placebo SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 8 | -0.1 degree C |
| Placebo SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 24 | 0.1 degree C |
| Placebo SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 16 | 0.0 degree C |
| Placebo SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 12 | 0.1 degree C |
| Placebo SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 2 | 0.0 degree C |
| Placebo SC Injections Twice Weekly | Safety - Changes in Body Temperature From Baseline | Week 20 | 0.1 degree C |
Secondary
Weaned Off PS
Reduction in weekly PS volume of 100 percent (weaned off)
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glepaglutide SC Injections Twice Weekly | Weaned Off PS | 5 Participants |
| Glepaglutide SC Injections Once Weekly and Placebo Once Weekly | Weaned Off PS | 4 Participants |
| Placebo SC Injections Twice Weekly | Weaned Off PS | 0 Participants |
p-value: 0.01695% CI: [2.5, 25.6]Cochran-Mantel-Haenszel
p-value: 0.042495% CI: [0.7, 21.6]Cochran-Mantel-Haenszel