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

This drug-drug interaction (DDI) study evaluates the potential effect of intravenously
administered GGF2 on the elimination kinetics of midazolam.

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