A Double-Blind Pharmacokinetic Interaction Study Evaluating the Effect of a Single IV Infusion of GGF2 or Placebo on Midazolam Pharmacokinetics in Patients With Heart Failure
- Registration Number
- NCT01944683
- Lead Sponsor
- Acorda Therapeutics
- Brief Summary
The study will examine midazolam pharmacokinetics following single dose administration of 3 planned dose levels of GGF2 .
- Detailed Description
This drug-drug interaction (DDI) study evaluates the potential effect of intravenously administered GGF2 on the elimination kinetics of midazolam.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 22
- If female, must be at least 2 years post-menopausal or have bilateral oophorectomy, hysterectomy or documented sterility
- If male, must have documented sterility (by verbal report or previous vasectomy), or if non-sterile, must agree to use barrier contraception for the entire duration of the trial and until 3 months after the last dose of investigational product. Must also agree not to donate sperm during the study and up to 3 months after the last dose of investigational product
- Stable coronary disease without unstable angina or acute coronary syndrome in the last 6 months
- All cardiac medications, specifically beta-blockers, renin-angiotensin system inhibitors, aldosterone antagonists, hydralazine and nitrates are at a stable dose (at least 4 weeks) prior to Day 1
- Any previous exposure to GGF2 or other neuregulins
- Initiation or change of a prescription medication within the 2 weeks prior to Day 1, and/or concomitant medication regimen is expected to change during the course of the study
- Known allergic reaction to midazolam, or any of the components of midazolam syrup (including cherry flavoring), or components of GGF2 diluent
- Known specific hepatic disease; total bilirubin >2 mg/dL, AST > 100 IU
- History of hepatic impairment (hepatitis B and C)
- Type I Diabetes
- Documented stroke or transient ischemic attack (TIA) within 2 months of study enrollment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Patients will be randomized to receive GGF2 or Placebo and on study day 3 administered a single IV infusion. Each patient will receive 5 oral doses of Midazolam syrup on study day 1 and days 4 through 7 respectively. GGF2 Midazolam Patients will be randomized to receive GGF2 or Placebo and on study day 3 administered a single IV infusion. Each patient will receive 5 oral doses of Midazolam syrup on study day 1 and days 4 through 7 respectively. Placebo Midazolam Patients will be randomized to receive GGF2 or Placebo and on study day 3 administered a single IV infusion. Each patient will receive 5 oral doses of Midazolam syrup on study day 1 and days 4 through 7 respectively. GGF2 GGF2 Patients will be randomized to receive GGF2 or Placebo and on study day 3 administered a single IV infusion. Each patient will receive 5 oral doses of Midazolam syrup on study day 1 and days 4 through 7 respectively.
- Primary Outcome Measures
Name Time Method Safety and tolerability of GGF2 IV infusion in patients with heart failure assessed by review of Treatment Emergent Adverse Events (TEAE) 90 days (± 3 days) Pharmacokinetic (PK) parameter Area Under the Curve (AUC) of a single dose of midazolam when administered prior to and following a single IV infusion of GGF2 or Placebo Day 1 to Day 7
- Secondary Outcome Measures
Name Time Method Change from baseline of 2D-Echocardiogram (2D-ECHO) or ECHO with contrast Visit 1 (day-14 to day-1) and visits 2-5 (day 8 through day 90 ± 3 days) Change from baseline of the Six-Minute Walk Test (6MWT) Visit 1 (day-14 to day-1) and visits 3-5 (day 14 through day 90 ± 3 days) Change from baseline of metabolic testing measuring maximum capacity of body to transport and use oxygen during incremental exercise (VCO2 and VO2 max) Visit 1 (day-14 to day-1) and visits 3-5 (day 14 through day 90 ± 3 days) Change from baseline of the M.D. Anderson Symptom Inventory (MDASI) score Visit 1 (day-14 to day-1) and visits 3-5 (day 14 through day 90 ± 3 days) MDASI is a questionnaire asking patients about the severity of their heart disease symptoms and impact of the symptoms on daily functioning during the past 24 hours.
Scale ranges from 0 (sympton has not been present) to 10 (the symptom was as bad as you can imagine it could be).
Trial Locations
- Locations (8)
Orange County Research Center
🇺🇸Tustin, California, United States
Tulane University School of Medicine
🇺🇸New Orleans, Louisiana, United States
Sentara Cardiovascular Research Institute
🇺🇸Norfolk, Virginia, United States
UCSD Medical Center
🇺🇸La Jolla, California, United States
Duke Clinical Research Unit
🇺🇸Durham, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
New Orleans Center for Clinical Research (NOCCR)
🇺🇸Knoxville, Tennessee, United States
Jacksonville Center for Clinical Research
🇺🇸Jacksonville, Florida, United States