Efficacy, Tolerability and Pharmacokinetics of Subcutaneous Exendin (9-39) in Patients With Post Bariatric Hypoglycemia

NCT02771574 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 36673
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Post Bariatric Hypoglycemia

Keywords

Bariatric surgery complications; Glucose Metabolism Disorders; Exendin (9-39); GLP-1

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (5)

• Change in Composite Symptom Score as a Measure of Treatment Effect

  Baseline, Day 3

• Pharmacokinetics of Subcutaneous Avexitide: Plasma Concentration Prior to Dosing (Co)

  Day 3 (Predose)

• Pharmacokinetics of Subcutaneous Avexitide: Maximum Plasma Concentration (Cmax)

  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)

  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)

  Day 3 (Predose, and 60, 120, 150, 180, 210, 240, 270, 300, 330, 450, 720 minutes post-dose)

Study Arms (5)

Part A: Lyo avexitide 0.05 mg/kg

EXPERIMENTAL

Participants will receive lyophilized avexitide (Lyo avexitide) twice daily for 3 days

Drug: Lyo avexitide

Part A: Lyo avexitide 0.15 mg/kg

EXPERIMENTAL

Participants will receive Lyo avexitide twice daily for 3 days

Drug: Lyo avexitide

Part A: Lyo avexitide 0.35 mg/kg

EXPERIMENTAL

Participants will receive Lyo avexitide twice daily for 3 days

Drug: Lyo avexitide

Part A: Lyo avexitide 0.46 mg/kg

EXPERIMENTAL

Participants will receive Lyo avexitide twice daily for 3 days

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

Drug: Liq avexitide

Interventions

Lyo avexitide DRUG

Lyophilized avexitide (Lyo avexitide) administered subcutaneously (sc)

Also known as: Exendin (9-39)

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 avexitide DRUG

Liquid avexitide (Liq avexitide) administered subcutaneously (sc)

Also known as: Exendin (9-39)

Part B: Liq avexitide 0.38 (±0.03) mg/kg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Tracey McLaughlin: lead
• Eiger BioPharmaceuticals: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (1)

• 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.

  PMID: 32250530 RESULT

MeSH Terms

Conditions

Glucose Metabolism Disorders

Interventions

exendin (9-39)

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Cindy Lamendola
• Organization: Stanford University School of Medicine

clamendola@stanford.edu

650-723-3141

Study Officials

• Marilyn Tan, MD

  Clinical Assistant Professor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine (Endocrinology)

Study Record Dates

• First Submitted: May 6, 2016
• First Posted: May 13, 2016
• Study Start: May 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: November 13, 2020
• Results First Posted: August 14, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)