Safety Study of RP-1127 (Glyburide for Injection) in Healthy Volunteers

A Phase I Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of Escalating Doses of RP-1127 (Glyburide for Injection) in Healthy Male and Female Volunteers

The primary objective of this study is to evaluate the safety and tolerability of different dose levels of glyburide for injection, administered as a bolus dose followed by a 3-day continuous infusion. The secondary objectives are to assess the pharmacokinetics (PK) of glyburide and blood glucose and serum insulin pharmacodynamic (PD) responses to glyburide.

Study Overview

• Status: Completed
• Conditions: Stroke; Traumatic Brain Injury
• Intervention / Treatment: Drug: Placebo; Drug: Glyburide for Injection

Detailed Description

This study was previously posted by Remedy Pharmaceuticals, Inc. and has since been acquired by Biogen.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Jasper Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. A healthy male or a healthy nonpregnant, nonlactating female.
2. Capable of understanding and complying with the protocol and has signed the informed consent form before the Screening procedures begin.
3. Have a body mass index of between 18.0 and 30.0 kg/m², inclusive.
4. A clinically normal physical examination, 12-lead electrocardiogram (ECG), screening laboratory studies and urinalysis.
5. A negative urine or saliva test for selected substances of abuse and cotinine.

Exclusion Criteria:

1. Clinically significant history of hypoglycemia as assessed by the investigator.
2. History of seizure disorder, even if currently not receiving anticonvulsant medications.
3. History of adverse reaction to glyburide, other sulfonylurea class of anti-diabetic medications, or other sulfa drugs.
4. Glucose-6-phosphate dehydrogenase (G6PD) deficiency as determined by G6PD enzyme testing at screening.
5. Be an active smoker or user of other forms of tobacco. Former smokers or tobacco users must have refrained from smoking or using other forms of tobacco for at least 6 months prior to dosing on Study Day 1.
6. A history or clinical manifestations of significant metabolic (including diabetes mellitus, hypercholesterolemia, or dyslipidemia), hematologic, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urologic, immunologic, or psychiatric disorders (a history of mild depression, currently not receiving therapy, is acceptable).
7. Use any prescription medication within 14 days prior to randomization, or nonprescription drugs within 7 days. Exceptions may be made by the medical monitor on a case-by-case basis.
8. Received another investigational drug within 30 days prior to randomization.
9. A positive hepatitis virus test (Hepatitis B virus surface antigen or hepatitis C virus antibody) or a positive human immunodeficiency virus (HIV) antibody test at screening. If the HIV test is positive, the subject will be informed privately and referred for additional counseling.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Matching Placebo; Matching placebo (glyburide excipients without active) is administered as a bolus followed by continuous infusion for 72 hours.	Drug: Placebo; Administered as specified in the Treatment Arm.
Experimental: Glyburide for Injection: Dose 1; Glyburide is administered as a bolus followed by a infusion for 72 hours	Drug: Glyburide for Injection; Administered as specified in the Treatment Arm.; Other Names: RP-1127; glibenclamide; glybenclamide
Experimental: Glyburide for Injection: Dose 2; Glyburide is administered as a bolus followed by a infusion for 72 hours	Drug: Glyburide for Injection; Administered as specified in the Treatment Arm.; Other Names: RP-1127; glibenclamide; glybenclamide
Experimental: Glyburide for Injection: Dose 3; Glyburide is administered as a bolus followed by a infusion for 72 hours.	Drug: Glyburide for Injection; Administered as specified in the Treatment Arm.; Other Names: RP-1127; glibenclamide; glybenclamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events and Serious Adverse Events	An adverse event (AE) is defined as any untoward medical occurence such as a sign, symptom, and/or laboratory finding that is concurrent with the use of a drug in humans. A serious adverse event is any AE that is fatal, life-threatening, requires or prolongs hospital stay, results in persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event	Up to Day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic (PK) Parameter of Glyburide: Clearance (CL)	Day 1 (baseline) and at multiple time points up to Day 5
PK Parameter of Glyburide: Volume of Distribution (Vz)	Day 1 (baseline) and at multiple time points up to Day 5
PK Parameter of Glyburide: Elimination Rate Constant (λz)	Day 1 (baseline) and at multiple time points up to Day 5
PK Parameter of Glyburide: Half-Life (t1/2)	Day 1 (baseline) and at multiple time points up to Day 5
PK Parameter of Glyburide: Predicted Steady-State Concentration (Css)	Day 1 (baseline) and at multiple time points up to Day 5
PK Paramater of Metabolites (M1 and M2): Maximum Plasma Concentrations (Cmax)	Day 1 (baseline) and at multiple time points up to Day 5
Pharmacodynamic (PD) Parameter of Glyburide: Change from Baseline in Blood Glucose	Day 1 (baseline) and at multiple time points up to Day 5
PD Parameter of Glyburide: Change from Baseline in Serum Insulin	Day 1 (baseline) and at multiple time points up to Day 5

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2010
• Primary Completion (Actual): May 7, 2010
• Study Completion (Actual): May 7, 2010

Study Registration Dates

• First Submitted: April 14, 2010
• First Submitted That Met QC Criteria: May 26, 2010
• First Posted (Estimate): May 28, 2010

Study Record Updates

• Last Update Posted (Actual): June 21, 2021
• Last Update Submitted That Met QC Criteria: June 16, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Hypoglycemic Agents; Physiological Effects of Drugs; Glyburide
• Other Study ID Numbers: RPI 101