Phase 1b Study of Pharmacokinetic Interaction, Evaluating the Effect of a Single IV Infusion of GGF2 or Placebo on Midazolam Pharmacokinetics in Patients With Heart Failure
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Acorda Therapeutics
- Enrollment
- 22
- Locations
- 8
- Primary Endpoint
- Safety and tolerability of GGF2 IV infusion in patients with heart failure assessed by review of Treatment Emergent Adverse Events (TEAE)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: GGF2 (Drug)
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.
Intervention: Midazolam (Drug)
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.
Intervention: Placebo (Other)
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.
Intervention: Midazolam (Drug)
Outcomes
Primary Outcomes
Safety and tolerability of GGF2 IV infusion in patients with heart failure assessed by review of Treatment Emergent Adverse Events (TEAE)
Time Frame: 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
Time Frame: Day 1 to Day 7
Secondary Outcomes
- 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))