Clinical trial NCT01944683: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Failure
Lead sponsor: Acorda Therapeutics
Sponsor class: INDUSTRY
First posted: 2013-09-18
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and tolerability of GGF2 IV infusion in patients with heart failure assessed by review of Treatment Emergent Adverse Events (TEAE)
timeFrame: 90 days (± 3 days)
measure: 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
timeFrame: Day 1 to Day 7
Secondary outcomes:
measure: Change from baseline of 2D-Echocardiogram (2D-ECHO) or ECHO with contrast
timeFrame: Visit 1 (day-14 to day-1) and visits 2-5 (day 8 through day 90 ± 3 days)
measure: Change from baseline of the Six-Minute Walk Test (6MWT)
timeFrame: Visit 1 (day-14 to day-1) and visits 3-5 (day 14 through day 90 ± 3 days)
measure: Change from baseline of metabolic testing measuring maximum capacity of body to transport and use oxygen during incremental exercise (VCO2 and VO2 max)
timeFrame: Visit 1 (day-14 to day-1) and visits 3-5 (day 14 through day 90 ± 3 days)
measure: Change from baseline of the M.D. Anderson Symptom Inventory (MDASI) score
timeFrame: Visit 1 (day-14 to day-1) and visits 3-5 (day 14 through day 90 ± 3 days)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Medical Center
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: Durham
country: United States
facility: Duke Clinical Research Unit
state: North Carolina
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research (NOCCR)
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Norfolk
country: United States
facility: Sentara Cardiovascular Research Institute
state: Virginia
Study officials:
affiliation: Acorda Therapeutics
name: Andrew Eisen, MD
role: STUDY_DIRECTOR
References: