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| Name | Class |
|---|---|
| Eiger BioPharmaceuticals | INDUSTRY |
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This study is designed to evaluate the efficacy, safety and pharmacokinetics of subcutaneous exendin (9-39) in subjects with post-bariatric hypoglycemia. Development of this subcutaneous formulation of exendin (9-39) would represent a targeted therapeutic approach for this rare disease with unmet clinical need.
Post-Bariatric Hypoglycemia (PBH) is a rare, but increasingly reported disease occurring after bariatric surgery, characterized by severe hypoglycemic episodes accompanied by symptoms of hypoglycemia. At the moment, no medical therapies have been developed for this disorder, but the clinical need is great. The major contributory factor is thought to be an exaggerated secretion of glucagon-like peptide-1 (GLP-1) due to altered nutrient transit after bariatric surgery. GLP-1 is an incretin hormone secreted primarily by the distal ileum that contributes to postprandial glucose regulation. Exendin (9-39) is a specific GLP-1 receptor antagonist, that when given via continuous IV infusion, has been shown to effectively prevent postprandial hypoglycemia and reduce symptoms of hypoglycemia in patients with PBH. This study is designed to assess the efficacy, safety and pharmacokinetic profile of a novel subcutaneous formulation of exendin (9-39).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: Lyo avexitide 0.05 mg/kg | Experimental | Participants will receive lyophilized avexitide (Lyo avexitide) twice daily for 3 days |
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| Part A: Lyo avexitide 0.15 mg/kg | Experimental | Participants will receive Lyo avexitide twice daily for 3 days |
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| Part A: Lyo avexitide 0.35 mg/kg | Experimental | Participants will receive Lyo avexitide twice daily for 3 days |
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| Part A: Lyo avexitide 0.46 mg/kg | Experimental | Participants will receive Lyo avexitide twice daily for 3 days |
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| Part B: Liq avexitide 0.38 (±0.03) mg/kg | Experimental | Participants will receive liquid avexitide (Liq avexitide) twice daily for 3 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lyo avexitide | Drug | Lyophilized avexitide (Lyo avexitide) administered subcutaneously (sc) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Nadir Glucose | Nadir glucose at baseline and at Day 3 of treatment during oral glucose tolerance test (OGTT). | Day 3 (time zero then every 30 minutes until 180 minutes or gylcemic rescue was required) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Composite Symptom Score as a Measure of Treatment Effect | Symptoms of hypoglycemia were assessed using the Edinburgh Hypoglycemia Symptom Scale that measures the intensity of 13 commonly experienced hypoglycemic symptoms, each severity graded on a 6-point Likert scale (0 = not present, 5 = severe). Scores are summed for a composite score ranging from 0 to 65, with higher scores corresponding to more severe hypoglycemia symptoms. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marilyn Tan, MD | Clinical Assistant Professor | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University School of Medicine | Stanford | California | 94305 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32250530 | Result | Tan M, Lamendola C, Luong R, McLaughlin T, Craig C. Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9-39) for treatment of post-bariatric hypoglycaemia. Diabetes Obes Metab. 2020 Aug;22(8):1406-1416. doi: 10.1111/dom.14048. Epub 2020 May 4. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: Lyo Avexitide 0.5 mg/kg | Lyophilized avexitide (Lyo avexitide) administered subcutaneously (sc) twice daily for 3 days |
| FG001 | Part A: Lyo Avexitide 0.15 mg/kg | Lyo avexitide administered sc twice daily for 3 days |
| FG002 | Part A: Lyo Avexitide 0.35 mg/kg | Lyo avexitide administered sc twice daily for 3 days |
| FG003 | Part A: Lyo Avexitide 0.46 mg/kg | Lyo avexitide administered sc twice daily for 3 days |
| FG004 | Part B: Liq Avexitide 0.38 (±0.03) mg/kg | Liquid avexitide (Liq avexitide) administered sc twice daily for 3 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Lyo Avexitide Dose Level 1 (3 Days) |
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| Lyo Avexitide Dose Level 2 (3 Days) |
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| Lyo Avexitide Dose Level 3 (3 Days) |
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| Lyo Avexitide Dose Level 4 (3 Days) |
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| Liq Avexitide (3 Days) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A: Lyo Avexitide 0.05 mg/kg | Lyo avexitide administered sc twice daily for 3 days |
| BG001 | Part A: Lyo Avexitide 0.15 mg/kg | Lyo avexitide administered sc twice daily for 3 days |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Nadir Glucose | Nadir glucose at baseline and at Day 3 of treatment during oral glucose tolerance test (OGTT). | Posted | Mean | Standard Deviation | mg/dL | Day 3 (time zero then every 30 minutes until 180 minutes or gylcemic rescue was required) |
|
Three (3) days per treatment period
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A: Lyo Avexitide 0.05 mg/kg | Lyo avexitide administered sc twice daily for 3 days |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Cindy Lamendola | Stanford University School of Medicine | 650-723-3141 | clamendola@stanford.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 20, 2020 | Jul 20, 2020 | SAP_001.pdf |
| Prot | Yes | No | No | Study Protocol | May 6, 2016 | Aug 19, 2020 | Prot_002.pdf |
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| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| ID | Term |
|---|---|
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C083773 | exendin (9-39) |
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| Liq avexitide | Drug | Liquid avexitide (Liq avexitide) administered subcutaneously (sc) |
|
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| Baseline, Day 3 |
| Pharmacokinetics of Subcutaneous Avexitide: Plasma Concentration Prior to Dosing (Co) | Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing. | Day 3 (Predose) |
| Pharmacokinetics of Subcutaneous Avexitide: Maximum Plasma Concentration (Cmax) | Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing. | Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose) |
| Pharmacokinetics of Subcutaneous Avexitide: Time of Maximum Plasma Concentration (Tmax) | Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing. | Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose) |
| Pharmacokinetics of Subcutaneous Avexitide: Area Under the Plasma Concentration Versus Time Curve (AUC) | Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing. | Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose) |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| BG002 | Part A: Lyo Avexitide 0.35 mg/kg | Lyo avexitide administered sc twice daily for 3 days |
| BG003 | Part A: Lyo Avexitide 0.46 mg/kg | Lyo avexitide administered sc twice daily for 3 days |
| BG004 | Part B: Liq Avexitide 0.38 mg/kg | Liq avexitide administered sc twice daily for 3 days |
| BG005 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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Lyo avexitide administered sc twice daily for 3 days
| OG003 | Part A: Lyo Avexitide 0.46 mg/kg | Lyo avexitide administered sc twice daily for 3 days |
| OG004 | Part A: Lyo Avexitide 0.35 mg/kg and 0.46 mg/kg Groups | Lyo avexitide administered sc twice daily for 3 days This reporting group is a pooled analysis of data from the Part A: Lyo avexitide 0.35 mg/kg and 0.46 mg/kg groups. |
| OG005 | Part B: Liq Avexitide 0.38 (±0.03) mg/kg | Liq avexitide administered sc twice daily for 3 days |
|
|
| Secondary | Change in Composite Symptom Score as a Measure of Treatment Effect | Symptoms of hypoglycemia were assessed using the Edinburgh Hypoglycemia Symptom Scale that measures the intensity of 13 commonly experienced hypoglycemic symptoms, each severity graded on a 6-point Likert scale (0 = not present, 5 = severe). Scores are summed for a composite score ranging from 0 to 65, with higher scores corresponding to more severe hypoglycemia symptoms. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Day 3 |
|
|
|
| Secondary | Pharmacokinetics of Subcutaneous Avexitide: Plasma Concentration Prior to Dosing (Co) | Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing. | Posted | Mean | Standard Deviation | ng/mL | Day 3 (Predose) |
|
|
|
| Secondary | Pharmacokinetics of Subcutaneous Avexitide: Maximum Plasma Concentration (Cmax) | Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing. | Posted | Mean | Standard Deviation | ng/mL | Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose) |
|
|
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| Secondary | Pharmacokinetics of Subcutaneous Avexitide: Time of Maximum Plasma Concentration (Tmax) | Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing. | Posted | Mean | Standard Deviation | minutes | Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose) |
|
|
|
| Secondary | Pharmacokinetics of Subcutaneous Avexitide: Area Under the Plasma Concentration Versus Time Curve (AUC) | Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing. | Posted | Mean | Standard Deviation | ng/mL*min | Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose) |
|
|
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| 0 |
| 3 |
| 0 |
| 3 |
| 1 |
| 3 |
| EG001 | Part A: Lyo Avexitide 0.15 mg/kg | Lyo avexitide administered sc twice daily for 3 days | 0 | 5 | 0 | 5 | 0 | 5 |
| EG002 | Part A: Lyo Avexitide 0.35 mg/kg | Lyo avexitide administered sc twice daily for 3 days | 0 | 3 | 0 | 3 | 2 | 3 |
| EG003 | Part A: Lyo Avexitide 0.46 mg/kg | Lyo avexitide administered sc twice daily for 3 days | 0 | 3 | 0 | 3 | 2 | 3 |
| EG004 | Part B: Liq Avexitide 0.38 (±0.03) mg/kg | Liq avexitide administered sc twice daily for 3 days | 0 | 5 | 0 | 5 | 0 | 5 |
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Day 3 |
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