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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01849094




Registration number
NCT01849094
Ethics application status
Date submitted
30/04/2013
Date registered
8/05/2013
Date last updated
14/01/2015

Titles & IDs
Public title
Evaluating the Safety, Pharmacokinetics and Haemodynamic Effect of a Slow Release Oral Formulation of Milrinone
Scientific title
Secondary ID [1] 0 0
DK-MIL-1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy 0 0
Heart Failure 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Milrinone 6mg
Treatment: Drugs - milrinone 10mg ER
Treatment: Drugs - milrinone 14mg

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.

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)

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)


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

Treatment: Drugs: milrinone 10mg ER
Administration of study medications, PK sampling If Part B - add on 6 hour haemodynamic invasive measurements

Treatment: Drugs: milrinone 14mg
Administration of study medications, PK sampling If Part B - add on 6 hour haemodynamic invasive measurements
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pharmacokinetic profile - to demonstrate stable plasma levels
Timepoint [1] 0 0
0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours
Secondary outcome [1] 0 0
(Heart Failure cohort) - to demonstrate evidence of haemodynamic benefit
Timepoint [1] 0 0
6 hours

Eligibility
Key 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
Minimum age
18 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2014
Sample size
Target
Accrual to date
Final
9
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [2] 0 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
The Alfred
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT01849094
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01849094