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

• ClinicalTrials.gov Identifier: NCT01132703
• Recruitment Status: Completed
• First Posted: May 28, 2010
• Last Update Posted: June 21, 2021
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Traumatic Brain Injury; Stroke	Drug: Glyburide for Injection; Drug: Placebo	Phase 1

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 7, 2010
• Actual Primary Completion Date: May 7, 2010
• Actual Study Completion Date: May 7, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Adverse Events and Serious Adverse Events [ Time Frame: Up to Day 28 ]
   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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Michigan

Jasper Clinic

Kalamazoo, Michigan, United States, 49007

Sponsors and Collaborators

Biogen

Investigators

• Study Director: Medical Director; Biogen

More Information

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT01132703
• Other Study ID Numbers: RPI 101
• First Posted: May 28, 2010
• Last Update Posted: June 21, 2021
• Last Verified: June 2021

Additional relevant MeSH terms:

Brain Injuries; Brain Injuries, Traumatic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Glyburide; Hypoglycemic Agents; Physiological Effects of Drugs