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

Healthy Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01849094
• Other study ID #: DK-MIL-1
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 30, 2013
• Last updated: January 12, 2015
• Start date: May 2013
• Est. completion date: December 2014

Study information

• Verified date: January 2015
• Source: The Alfred
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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 (ß-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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy
• Heart Failure

Intervention

Drug:
• Milrinone 6mg
Administration of study medications, PK sampling If Part B - add on 6 hour haemodynamic invasive measurements
• milrinone 10mg ER
Administration of study medications, PK sampling If Part B - add on 6 hour haemodynamic invasive measurements
• milrinone 14mg
Administration of study medications, PK sampling If Part B - add on 6 hour haemodynamic invasive measurements

Locations

Country	Name	City	State
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Nucleus Network	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
The Alfred

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic profile - to demonstrate stable plasma levels	Laboratory Analysis: Plasma milrinone concentration	0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours	Yes
Secondary	(Heart Failure cohort) - to demonstrate evidence of haemodynamic benefit	ECG and Blood pressure and HR Monitoring Swan Ganz insertion for haemodynamic measurements (RA volume , RVSP, CO, PA, PAWP)	6 hours	Yes