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

Tracking Information

• First Submitted Date: April 14, 2010
• First Posted Date: May 28, 2010
• Last Update Posted Date: June 21, 2021
• Actual Study Start Date: January 7, 2010
• Actual Primary Completion Date: May 7, 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 16, 2021)

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

Original Primary Outcome Measures (submitted: May 26, 2010)

Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 28 Days ]

In particular, events of hypoglycemia and EKG changes will be studied

Current Secondary Outcome Measures (submitted: June 16, 2021)

• Pharmacokinetic (PK) Parameter of Glyburide: Clearance (CL) [ Time Frame: Day 1 (baseline) and at multiple time points up to Day 5 ]
• PK Parameter of Glyburide: Volume of Distribution (Vz) [ Time Frame: Day 1 (baseline) and at multiple time points up to Day 5 ]
• PK Parameter of Glyburide: Elimination Rate Constant (λz) [ Time Frame: Day 1 (baseline) and at multiple time points up to Day 5 ]
• PK Parameter of Glyburide: Half-Life (t1/2) [ Time Frame: Day 1 (baseline) and at multiple time points up to Day 5 ]
• PK Parameter of Glyburide: Predicted Steady-State Concentration (Css) [ Time Frame: Day 1 (baseline) and at multiple time points up to Day 5 ]
• 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 ]
• 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 ]
• PD Parameter of Glyburide: Change from Baseline in Serum Insulin [ Time Frame: Day 1 (baseline) and at multiple time points up to Day 5 ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety Study of RP-1127 (Glyburide for Injection) in Healthy Volunteers
• 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
• 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.
• Detailed Description: This study was previously posted by Remedy Pharmaceuticals, Inc. and has since been acquired by Biogen.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Traumatic Brain Injury
• Stroke

Intervention

• Drug: Glyburide for Injection
  Administered as specified in the Treatment Arm.
  Other Names:

  • RP-1127
  • glibenclamide
  • glybenclamide
• Drug: Placebo
  Administered as specified in the Treatment Arm.

Study Arms

• Placebo Comparator: Matching Placebo
  Matching placebo (glyburide excipients without active) is administered as a bolus followed by continuous infusion for 72 hours.
  Intervention: Drug: Placebo
• Experimental: Glyburide for Injection: Dose 1
  Glyburide is administered as a bolus followed by a infusion for 72 hours
  Intervention: Drug: Glyburide for Injection
• Experimental: Glyburide for Injection: Dose 2
  Glyburide is administered as a bolus followed by a infusion for 72 hours
  Intervention: Drug: Glyburide for Injection
• Experimental: Glyburide for Injection: Dose 3
  Glyburide is administered as a bolus followed by a infusion for 72 hours.
  Intervention: Drug: Glyburide for Injection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 3, 2014): 34
• Original Estimated Enrollment (submitted: May 26, 2010): 30
• Actual Study Completion Date: May 7, 2010
• Actual Primary Completion Date: May 7, 2010 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01132703
• Other Study ID Numbers: RPI 101
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Biogen
• Original Responsible Party: CEO, Remedy Pharmaceuticals, Inc.
• Current Study Sponsor: Biogen
• Original Study Sponsor: Remedy Pharmaceuticals, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Biogen
• Verification Date: June 2021