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Evaluating the Safety, Pharmacokinetics and Haemodynamic Effect of a Slow Release Oral Formulation of Milrinone

Sponsor
The Alfred (Other)
Overall Status
Completed
CT.gov ID
NCT01849094
Collaborator
(none)
9
Enrollment
2
Locations
3
Arms
19
Duration (Months)
4.5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To determine the pharmacokinetic profile of a new (extended release) formulation of milrinone and to demonstrate evidence of hemodynamic effect

Primary: Pharmacokinetic profile - to demonstrate stable plasma levels Secondary (HF cohort)

  • to demonstrate evidence of haemodynamic benefit

Study Design: Open label

Condition or Disease Intervention/Treatment Phase
  • Drug: Milrinone 6mg
  • Drug: milrinone 10mg ER
  • Drug: milrinone 14mg
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
9 participants
Allocation:
Non-Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Study Start Date :
May 1, 2013
Actual Primary Completion Date :
Dec 1, 2014
Actual Study Completion Date :
Dec 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Milrinone 6mg

single oral dose of 6mg ER milrinone tablet (Part A). 1. single intravenous infusion of milrinone (per Alfred Hospital protocol. 50ug/kg loading dose over 15 mins followed by infusion at 0.375 ug/kg/min for 6 hrs) - Part B.

Drug: milrinone 10mg ER
Administration of study medications, PK sampling If Part B - add on 6 hour haemodynamic invasive measurements
Other Names:
  • Milirone

    • Drug: milrinone 14mg
    Administration of study medications, PK sampling If Part B - add on 6 hour haemodynamic invasive measurements
    Other Names:
  • Milirone

    		•
    Active Comparator: Milrinone 10mg ER

    single oral dose of 10 mg ER milrinone tablet (Part A) single oral dose of 10 mg ER milrinone tablet (Part B)

    Drug: Milrinone 6mg
    Administration of study medications, PK sampling If Part B - add on 6 hour haemodynamic invasive measurements

    Drug: milrinone 14mg
    Administration of study medications, PK sampling If Part B - add on 6 hour haemodynamic invasive measurements
    Other Names:
  • Milirone

    		•
    Active Comparator: Milrinone 14mg

    single oral dose of 14 mg ER milrinone tablet (Part A) single dose of 14 mg ER milrinone tablet 4. single oral dose of 18 mg ER milrinone tablet (if the group average plasma milrinone levels is less than 150 ug/L with 15 mg dose) - (Part B)

    Drug: Milrinone 6mg
    Administration of study medications, PK sampling If Part B - add on 6 hour haemodynamic invasive measurements

    Drug: milrinone 14mg
    Administration of study medications, PK sampling If Part B - add on 6 hour haemodynamic invasive measurements
    Other Names:
  • Milirone

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Pharmacokinetic profile - to demonstrate stable plasma levels [0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours]

      Laboratory Analysis: Plasma milrinone concentration

    Secondary Outcome Measures

    1. (Heart Failure cohort) - to demonstrate evidence of haemodynamic benefit [6 hours]

      ECG and Blood pressure and HR Monitoring Swan Ganz insertion for haemodynamic measurements (RA volume , RVSP, CO, PA, PAWP)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Part A: Healthy volunteers; Part B: Heart failure patients Inclusion Criteria - Part A Healthy Volunteers
    Participants must:

    1. Provide written informed consent prior to any study procedure and agree to adhere to all protocol requirements

    2. Be aged between 18 to 45 years old inclusive at the time of consent

    3. Be in good general health without clinically significant medical history

    4. Have a body mass index (BMI) between 19- 30 kg/m2 inclusive

    5. Documented 12-lead ECG with no clinically significant abnormalities, as determined by the Investigator

    6. No clinically significant abnormalities in screening or Day 0 laboratory tests, as determined by the Investigator;

    7. Female subjects of reproductive potential must have a negative serum pregnancy (β-HCG) test at screening and a negative urine pregnancy test at Day 0 prior to dosing. Female subjects must also be non-lactating

    8. Negative Human Immunodeficiency Virus (HIV), Hepatitis B and Hepatitis C Screening test results

    Inclusion Criteria - Part B Heart Failure Patients

    Participants must:

    1. Provide written informed consent prior to any study procedure and agree to adhere to all protocol requirements

    2. Heart Failure patients with LVEF less than45%

    3. NYHA II-III

    4. Stable medications (for greater than 48hrs)

    5. Systolic BP greater than 90

    Exclusion Criteria:
    • Exclusion Criteria - Part A Healthy Volunteers
    Participants will not be enrolled if they meet any of the following criteria:

    1. If female, pregnant or lactating

    2. Receipt of any investigational agent or drug within 30 days or 5 half-lives (whichever is longer) prior to the first dose of Investigational product

    3. Use of prescription drugs within 4 weeks prior to first dosing. Subjects who have used over the counter medication excluding paracetamol, topical over the counter medications and routine vitamins but including megadose (intake of 20 to 600 times the recommended daily dose) vitamin therapy within 7 days of first dosing, unless agreed as non-clinically relevant by the Principal Investigator

    4. No clinically relevant findings in the medical history, laboratory examination and physical examination, especially with regards to cardiovascular system and renal function

    5. A positive urine test for drugs of abuse or alcohol at Screening or on the day of admittance to the Study Unit

    6. Normal dietary habits

    7. Any major surgical procedure within one month of entry into the study

    8. Have difficulties communicating reliably with the Investigator or unlikely to co-operate with the requirements of the study.

    9. Any other condition which in the view of the Investigator is likely to interfere with study or put the subject at risk.

    Exclusion Criteria - Part B Heart Failure Patients

    1. Unstable heart failure including NYHA IV symptoms

    2. Treatment with intravenous inotropes or mechanical circulatory support.

    3. Unstable rhythm including frequent non-sustained ventricular tachycardia or poorly controlled atrial fibrillation (ventricular rate >100).

    4. Severe renal impairment Cr>200umol/L or dialysis.

    5. Life-threatening haematological, hepatic or pulmonary disease.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Alfred Hospital Melbourne Victoria Australia 3004
    2 Nucleus Network Melbourne Victoria Australia 3004

    Sponsors and Collaborators

    • The Alfred

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Prof David Kaye, Head, Experimental Cardiology and Heart Failure Division Baker Heart Research Institute & Cardiologist, Heart Centre, Alfred Hospital, The Alfred
    ClinicalTrials.gov Identifier:
    NCT01849094
    Other Study ID Numbers:
    • DK-MIL-1
    First Posted:
    May 8, 2013
    Last Update Posted:
    Jan 14, 2015
    Last Verified:
    Jan 1, 2015
    Additional relevant MeSH terms:
    Heart Failure
    Milrinone

    Study Results

    No Results Posted as of Jan 14, 2015