Post Bariatric HypoglycemiaPhase 2NCT02771574
Efficacy, Tolerability and Pharmacokinetics of Subcutaneous Exendin (9-39) in Patients With Post Bariatric Hypoglycemia
A Phase 2 study testing Lyo avexitide and Liq avexitide in people with Post Bariatric Hypoglycemia, run by Tracey McLaughlin at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Post Bariatric Hypoglycemia
- What is being tested?
- Lyo avexitide and Liq avexitide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- May 2016to Jun 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Post-bariatric surgery more than 6 months prior to signing the informed consent
- Reported history of Whipple's triad: the occurrence of hypoglycemic symptoms associated with a capillary blood glucose of ≤55 mg/dL, and resolution with glucose or carbohydrate administration.
- Symptomatic hypoglycemia during the baseline/screening oral glucose tolerance test (OGTT), as defined by the presence of plasma glucose ≤55 mg/dL with concomitant autonomic and/or neuroglycopenic symptoms.
Who cannot join
- Patients currently using sulfonylureas or other medications that may interfere with glucose metabolism within 5 half-lives of drug.
- Participation in any clinical investigation within 4 weeks prior to dosing
- History of or current insulinoma
- Active infection or significant acute illness within 2 weeks prior to dosing
- Female patients who are pregnant or lactating
- Women of childbearing potential and not utilizing effective contraceptive methods
- Inadequate end organ function
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: A Phase 2 Multi-Ascending Dose Trial to Assess the Efficacy, Tolerability and Pharmacokinetic Profile of Exendin (9-39) in Patients With Post-bariatric Hyperinsulinemic Hypoglycemia
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.
Read the detailed description
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).
- Conditions
- Post Bariatric Hypoglycemia
- Being tested
- Lyo avexitide, Liq avexitide
- Keywords
- Bariatric surgery complications, Glucose Metabolism Disorders, Exendin (9-39), GLP-1
- Medical subject headings
- Glucose Metabolism Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lyo avexitideDrug
Also called Exendin (9-39)
Lyophilized avexitide (Lyo avexitide) administered subcutaneously (sc)
Liq avexitideDrug
Also called Exendin (9-39)
Liquid avexitide (Liq avexitide) administered subcutaneously (sc)
| Study group | Role | What they receive |
|---|---|---|
| Part A: Lyo avexitide 0.05 mg/kg | Experimental | Participants will receive lyophilized avexitide (Lyo avexitide) twice daily for 3 days Receives: Drug: Lyo avexitide |
| Part A: Lyo avexitide 0.15 mg/kg | Experimental | Participants will receive Lyo avexitide twice daily for 3 days Receives: Drug: Lyo avexitide |
| Part A: Lyo avexitide 0.35 mg/kg | Experimental | Participants will receive Lyo avexitide twice daily for 3 days Receives: Drug: Lyo avexitide |
| Part A: Lyo avexitide 0.46 mg/kg | Experimental | Participants will receive Lyo avexitide twice daily for 3 days Receives: Drug: Lyo avexitide |
| Part B: Liq avexitide 0.38 (±0.03) mg/kg | Experimental | Participants will receive liquid avexitide (Liq avexitide) twice daily for 3 days Receives: Drug: Liq avexitide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nadir Glucose
Nadir glucose at baseline and at Day 3 of treatment during oral glucose tolerance test (OGTT).
Measured: Day 3 (time zero then every 30 minutes until 180 minutes or gylcemic rescue was required)
Secondary outcomes (5)
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.
Measured: 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.
Measured: Day 3 (Predose)
Pharmacokinetics of Subcutaneous Avexitide: Maximum Plasma Concentration (Cmax)
Pharmacokinetics of subcutaneous avexitide were assessed on Day 3 of twice daily dosing.
Measured: 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.
Measured: 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.
Measured: Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2016 (estimated)
- Study startMay 2016
- Primary completionJun 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post Bariatric HypoglycemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tracey McLaughlin
- Sponsor type
- University, hospital or other
- Collaborators
- Eiger BioPharmaceuticals
- Responsible party
- Sponsor-investigator, Tracey McLaughlin, Stanford University
- Investigators
- Marilyn Tan, MD, Principal investigator, Clinical Assistant Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02771574
- Sponsor's protocol ID
- 36673
- Status last verified
- Oct 2020
- First submitted
- 6 May 2016
- Last updated
- 13 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32250530
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Multi-Ascending Dose Trial to Assess the Efficacy, Tolerability and Pharmacokinetic Profile of Exendin (9-39) in Patients With Post-bariatric Hyperinsulinemic Hypoglycemia
- ClinicalTrials.gov ID
- NCT02771574
- Acronym / sponsor ID
- 36673
- Conditions
- Post Bariatric Hypoglycemia
- Keywords
- Bariatric surgery complications, Glucose Metabolism Disorders, Exendin (9-39), GLP-1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Tracey McLaughlinUniversity, hospital or other
- Collaborators
- Eiger BioPharmaceuticals
- Study start
- May 2016
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 13 May 2016 (estimated)
- Results
- Posted 14 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, care provider)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part A: Lyo avexitide 0.05 mg/kg | Experimental | Drug: Lyo avexitideParticipants will receive lyophilized avexitide (Lyo avexitide) twice daily for 3 days |
| Part A: Lyo avexitide 0.15 mg/kg | Experimental | Drug: Lyo avexitideParticipants will receive Lyo avexitide twice daily for 3 days |
| Part A: Lyo avexitide 0.35 mg/kg | Experimental | Drug: Lyo avexitideParticipants will receive Lyo avexitide twice daily for 3 days |
| Part A: Lyo avexitide 0.46 mg/kg | Experimental | Drug: Lyo avexitideParticipants will receive Lyo avexitide twice daily for 3 days |
| Part B: Liq avexitide 0.38 (±0.03) mg/kg | Experimental | Drug: Liq avexitideParticipants will receive liquid avexitide (Liq avexitide) twice daily for 3 days |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Post-bariatric surgery more than 6 months prior to signing the informed consent
- Reported history of Whipple's triad: the occurrence of hypoglycemic symptoms associated with a capillary blood glucose of ≤55 mg/dL, and resolution with glucose or carbohydrate administration.
- Symptomatic hypoglycemia during the baseline/screening oral glucose tolerance test (OGTT), as defined by the presence of plasma glucose ≤55 mg/dL with concomitant autonomic and/or neuroglycopenic symptoms.
Key exclusion criteria (7 listed)
- Patients currently using sulfonylureas or other medications that may interfere with glucose metabolism within 5 half-lives of drug.
- Participation in any clinical investigation within 4 weeks prior to dosing
- History of or current insulinoma
- Active infection or significant acute illness within 2 weeks prior to dosing
- Female patients who are pregnant or lactating
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lyo avexitideAlso: Exendin (9-39)Lyophilized avexitide (Lyo avexitide) administered subcutaneously (sc) | Drug | Part A: Lyo avexitide 0.05 mg/kg, Part A: Lyo avexitide 0.15 mg/kg, Part A: Lyo avexitide 0.35 mg/kg, Part A: Lyo avexitide 0.46 mg/kg |
| Liq avexitideAlso: Exendin (9-39)Liquid avexitide (Liq avexitide) administered subcutaneously (sc) | Drug | Part B: Liq avexitide 0.38 (±0.03) mg/kg |
Primary outcome
Nadir Glucose
Time frame: Day 3 (time zero then every 30 minutes until 180 minutes or gylcemic rescue was required)
Nadir glucose at baseline and at Day 3 of treatment during oral glucose tolerance test (OGTT).
5 secondary outcomes
Change in Composite Symptom Score as a Measure of Treatment Effect
Time frame: Baseline, Day 3
Pharmacokinetics of Subcutaneous Avexitide: Plasma Concentration Prior to Dosing (Co)
Time frame: Day 3 (Predose)
Pharmacokinetics of Subcutaneous Avexitide: Maximum Plasma Concentration (Cmax)
Time frame: 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)
Time frame: 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)
Time frame: Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 32250530Tan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marilyn Tan, MD principal investigator
Clinical Assistant Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lyo avexitide and Liq avexitide in people with Post Bariatric Hypoglycemia, run by Tracey McLaughlin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Nadir Glucose (time frame: Day 3 (time zero then every 30 minutes until 180 minutes or gylcemic rescue was required)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02771574, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2020.