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

NCT01944683 | Completed Phase 1

• 1 other identifier: GGF2-CV-1007
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 8

Brief Summary

The study will examine midazolam pharmacokinetics following single dose administration of 3 planned dose levels of GGF2 .

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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)

Study Arms (2)

GGF2

EXPERIMENTAL

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.

Drug: GGF2; Drug: Midazolam

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo; Drug: Midazolam

Interventions

Placebo OTHER

Placebo

GGF2 DRUG

GGF2

Midazolam DRUG

GGF2; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Acorda Therapeutics: lead

Study Sites (8)

UCSD Medical Center

La Jolla, California, 92037, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Tulane University School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Duke Clinical Research Unit

Durham, North Carolina, 27710, United States

Location

New Orleans Center for Clinical Research (NOCCR)

Knoxville, Tennessee, 37920, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Sentara Cardiovascular Research Institute

Norfolk, Virginia, 23507, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Midazolam

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Andrew Eisen, MD

  Acorda Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2013
• First Posted: September 18, 2013
• Study Start: September 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: July 1, 2016
• Last Updated: July 13, 2016

Record last verified: 2016-07

Locations

US (8)