Clinical trial NCT01849094: Evaluating the Safety, Pharmacokinetics and Haemodynamic Effect of a Slow Release Oral Formulation of Milrinone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Healthy
Heart Failure
Lead sponsor: The Alfred
Sponsor class: OTHER
First posted: 2013-05-08
Enrollment: 9
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic profile - to demonstrate stable plasma levels
timeFrame: 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours
Secondary outcomes:
measure: (Heart Failure cohort) - to demonstrate evidence of haemodynamic benefit
timeFrame: 6 hours
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Nucleus Network
state: Victoria
Study officials:
References: