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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

Primary Purpose

Heart Failure

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Placebo
GGF2
Midazolam
Sponsored by
Acorda Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UCSD Medical Center
  • Orange County Research Center
  • Jacksonville Center for Clinical Research
  • Tulane University School of Medicine
  • Duke Clinical Research Unit
  • New Orleans Center for Clinical Research (NOCCR)
  • Vanderbilt University Medical Center
  • Sentara Cardiovascular Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

GGF2

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Safety and tolerability of GGF2 IV infusion in patients with heart failure assessed by review of Treatment Emergent Adverse Events (TEAE)
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

Secondary Outcome Measures

Change from baseline of 2D-Echocardiogram (2D-ECHO) or ECHO with contrast
Change from baseline of the Six-Minute Walk Test (6MWT)
Change from baseline of metabolic testing measuring maximum capacity of body to transport and use oxygen during incremental exercise (VCO2 and VO2 max)
Change from baseline of the M.D. Anderson Symptom Inventory (MDASI) score
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).

Full Information

First Posted
September 11, 2013
Last Updated
July 12, 2016
Sponsor
Acorda Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT01944683
Brief Title
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

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acorda Therapeutics

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GGF2
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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 Type
Other
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
GGF2
Intervention Type
Drug
Intervention Name(s)
Midazolam
Primary Outcome Measure Information:
Title
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)
Title
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 Outcome Measure Information:
Title
Change from baseline of 2D-Echocardiogram (2D-ECHO) or ECHO with contrast
Time Frame
Visit 1 (day-14 to day-1) and visits 2-5 (day 8 through day 90 ± 3 days)
Title
Change from baseline of the Six-Minute Walk Test (6MWT)
Time Frame
Visit 1 (day-14 to day-1) and visits 3-5 (day 14 through day 90 ± 3 days)
Title
Change from baseline of metabolic testing measuring maximum capacity of body to transport and use oxygen during incremental exercise (VCO2 and VO2 max)
Time Frame
Visit 1 (day-14 to day-1) and visits 3-5 (day 14 through day 90 ± 3 days)
Title
Change from baseline of the M.D. Anderson Symptom Inventory (MDASI) score
Description
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).
Time Frame
Visit 1 (day-14 to day-1) and visits 3-5 (day 14 through day 90 ± 3 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Eisen, MD
Organizational Affiliation
Acorda Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
UCSD Medical Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Orange County Research Center
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
Facility Name
Jacksonville Center for Clinical Research
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
Tulane University School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Duke Clinical Research Unit
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
New Orleans Center for Clinical Research (NOCCR)
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Sentara Cardiovascular Research Institute
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States

12. IPD Sharing Statement

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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

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