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

NCT ID: NCT01849094

Last Updated: 2015-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2014-12-31

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

Conditions

Healthy; Heart Failure

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

milrinone 10mg ER

Intervention Type: DRUG

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

milrinone 14mg

Intervention Type: DRUG

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

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)

Group Type: ACTIVE_COMPARATOR

Milrinone 6mg

Intervention Type: DRUG

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

milrinone 14mg

Intervention Type: DRUG

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

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)

Group Type: ACTIVE_COMPARATOR

Milrinone 6mg

Intervention Type: DRUG

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

milrinone 14mg

Intervention Type: DRUG

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

Interventions

Milrinone 6mg

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

Intervention Type: DRUG

milrinone 10mg ER

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

Intervention Type: DRUG

milrinone 14mg

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

Intervention Type: DRUG

Other Intervention Names

Milirone; Milirone

Eligibility Criteria

Inclusion Criteria

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

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

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

The Alfred

OTHER

Sponsor Role: lead

Responsible Party

Prof David Kaye

Head, Experimental Cardiology and Heart Failure Division Baker Heart Research Institute & Cardiologist, Heart Centre, Alfred Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Alfred Hospital

Melbourne, Victoria, Australia

Nucleus Network

Melbourne, Victoria, Australia

Countries

Australia

Other Identifiers

DK-MIL-1

Identifier Type: -

Identifier Source: org_study_id