Clinical trial NCT01132703: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Traumatic Brain Injury
Stroke
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2010-05-28
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants with Adverse Events and Serious Adverse Events
timeFrame: Up to Day 28
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameter of Glyburide: Clearance (CL)
timeFrame: Day 1 (baseline) and at multiple time points up to Day 5
measure: PK Parameter of Glyburide: Volume of Distribution (Vz)
timeFrame: Day 1 (baseline) and at multiple time points up to Day 5
measure: PK Parameter of Glyburide: Elimination Rate Constant (λz)
timeFrame: Day 1 (baseline) and at multiple time points up to Day 5
measure: PK Parameter of Glyburide: Half-Life (t1/2)
timeFrame: Day 1 (baseline) and at multiple time points up to Day 5
measure: PK Parameter of Glyburide: Predicted Steady-State Concentration (Css)
timeFrame: Day 1 (baseline) and at multiple time points up to Day 5
measure: PK Paramater of Metabolites (M1 and M2): Maximum Plasma Concentrations (Cmax)
timeFrame: Day 1 (baseline) and at multiple time points up to Day 5
measure: Pharmacodynamic (PD) Parameter of Glyburide: Change from Baseline in Blood Glucose
timeFrame: Day 1 (baseline) and at multiple time points up to Day 5
measure: PD Parameter of Glyburide: Change from Baseline in Serum Insulin
timeFrame: Day 1 (baseline) and at multiple time points up to Day 5
Other outcomes:
Locations:
city: Kalamazoo
country: United States
facility: Jasper Clinic
state: Michigan
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: