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

NCT01132703 | Completed Phase 1

• 1 other identifier: RPI 101
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Traumatic Brain Injury; Stroke

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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

Study Arms (4)

Matching Placebo

PLACEBO COMPARATOR

Matching placebo (glyburide excipients without active) is administered as a bolus followed by continuous infusion for 72 hours.

Drug: Placebo

Glyburide for Injection: Dose 1

EXPERIMENTAL

Glyburide is administered as a bolus followed by a infusion for 72 hours

Drug: Glyburide for Injection

Glyburide for Injection: Dose 2

EXPERIMENTAL

Glyburide is administered as a bolus followed by a infusion for 72 hours

Drug: Glyburide for Injection

Glyburide for Injection: Dose 3

EXPERIMENTAL

Glyburide is administered as a bolus followed by a infusion for 72 hours.

Drug: Glyburide for Injection

Interventions

Glyburide for Injection DRUG

Administered as specified in the Treatment Arm.

Also known as: RP-1127, glibenclamide, glybenclamide

Glyburide for Injection: Dose 1; Glyburide for Injection: Dose 2; Glyburide for Injection: Dose 3

Placebo DRUG

Administered as specified in the Treatment Arm.

Matching Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Clinically significant history of hypoglycemia as assessed by the investigator.
• History of seizure disorder, even if currently not receiving anticonvulsant medications.
• History of adverse reaction to glyburide, other sulfonylurea class of anti-diabetic medications, or other sulfa drugs.
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency as determined by G6PD enzyme testing at screening.
• 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.
• 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).
• 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.
• Received another investigational drug within 30 days prior to randomization.
• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (1)

Jasper Clinic

Kalamazoo, Michigan, 49007, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Stroke

Interventions

Glyburide; Injections

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonylurea Compounds; Urea; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2010
• First Posted: May 28, 2010
• Study Start: January 7, 2010
• Primary Completion: May 7, 2010
• Study Completion: May 7, 2010
• Last Updated: June 21, 2021

Record last verified: 2021-06

Locations

US (1)