Clinical trial NCT02083406: Bioavailability Study of Oral OZ439 Prototype Formulations Administered With Piperaquine Phosphate (PQP)
Official title: Open Label Study to Investigate the Pharmacokinetics of Prototype Formulations of OZ439 Administered With Piperaquine Phosphate in the Fasted State to Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malaria
Keywords: Malaria
Bio-availability
Lead sponsor: Medicines for Malaria Venture
Sponsor class: OTHER
Collaborators: name: Quotient Clinical
First posted: 2014-03-11
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A single dose study to investigate how different formulations of OZ439 co-administered with PQP tablest are processed by the body when taken without food


Eligibility criteria: Inclusion Criteria:

1. Healthy males, or healthy females of non-childbearing potential ie surgically sterilised or post-menopausal (amenorrhoea for at least 1 year and confirmed by a follicle stimulating hormone result of ≥25 IU/mL
2. Age 18 to 55 years of age
3. Body mass index of 18.0 to 30.0 kg/m2 inclusive. Total body weight \>50 kg at screening
4. Willing and able to communicate and participate in the whole study
5. Must provide written informed consent
6. Must agree to use an adequate method of contraception
7. Must have liver function tests and haemoglobin within the laboratory reference range at screening and Day -1
8. Must have heart trace measurements within the defined healthy limits at screening, Day -1 and pre-dose

Exclusion Criteria:

1. Male subjects who have currently pregnant partners
2. Evidence or history of clinically significant oncological, pulmonary, chronic respiratory, hepatic, cardiovascular, haematological, metabolic, neurological, immunological, nephrological, endocrine or psychiatric disease, or current infection
3. Clinically relevant abnormalities in the heart trace including any degree of heart block, including asymptomatic bundle branch block
4. Family history of sudden death or of congenital prolongation of the QTc interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval
5. History of symptomatic cardiac arrhythmias or with clinically relevant bradycardia
6. Electrolyte disturbances, particularly hypokalemia, hypocalcaemia or hypomagnesaemia.
7. Any condition that could possibly affect drug absorption, such as gastrectomy or diarrhoea
8. History of post-antibiotic colitis
9. History of any drug or alcohol abuse in the past 2 years prior to screening
10. Subjects who have a breath carbon monoxide reading of greater than 10 ppm at screening will be excluded. Subjects who are tobacco users (including smokers and users of snuff, chewing tobacco and other nicotine or nicotine-containing products) must have stopped use within 90 days before screening.
11. Receipt of an investigational drug or participation in another clinical research study within 90 days prior to drug administration.
12. Subjects who are study site employees, or immediate family members of a study site or sponsor employee.
13. Subjects who have previously been enrolled in this study
14. Use of ANY prescription or non-prescription medications, vitamins, herbal supplements or dietary supplements, including protein supplements, within 14 days prior to the first dose of study drug and throughout the study, unless prior approval is granted by both the investigator and the sponsor. An exception will be made for intermittent use of paracetamol and hormone replacement therapy. Paracetamol at doses of, at most, 2 g per day or no more than 3 consecutive days or 6 non consecutive days, are allowed until 24 hours before dosing with study drug. Longer exclusion periods apply for:

    1. amiodarone and hydroxychloroquine (210 days)
    2. monoclonal antibodies/ immunoglobulins/ other therapeutic proteins and experimental drugs for which the half-life is not known to the investigator (120 days)
    3. experimental drugs for which half-life is known to the investigator (5 half lives plus 14 days)
    4. chloroquine, piperaquine phosphate and flunarizine (100 days)
    5. fluoxetine (75 days)
    6. benzodiazepines (for midazolam, lorazepam and triazolam, the exclusion period is 14 days), chlorpromazine, mephenytoin, nortryptyline, phenobarbital, primidone, phenprocoumone and cytochrome P450 3A4 inducers not already mentioned, including but not restricted to, rifampin, carbamazepine, oxcarbazepine, phenytoin and St John's Wort (35 days)
15. Positive hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus results
16. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator
17. Positive urine drug screen result at screening or admission to the clinical unit
18. History of intolerance or hypersensitivity to piperaquine or any 4-aminoquinolone, or ascertained or presumptive hypersensitivity to the active principle and/or formulation ingredients; history of anaphylaxis to drugs or allergic reactions in general, that the investigator considers may affect the outcome of the study
19. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
20. Presence or history of allergy requiring treatment; hayfever is allowed unless it is active
21. Donation or loss of \>400 mL of blood within 90 days prior to drug administration
22. Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
23. Subjects who do not have suitable veins for multiple blood samples as assessed by the investigator at screening
24. Failure to satisfy the investigator of fitness to participate for any other reason

Primary outcomes:
measure: OZ439 AUC(0-168h)
timeFrame: Up to 168 hours post-dose
measure: OZ439 Cmax
timeFrame: Up to 168 hours post-dose
Secondary outcomes:
measure: Piperaquine (PQ) AUC(0-168h)
timeFrame: Up to 168h post-dose
measure: PQ Cmax
timeFrame: Up to 168h post-dose
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Clinical
state: Nottinghamshire
Study officials:
affiliation: Quotient Clinical
name: Jo Collier, MBChB FFPM
role: PRINCIPAL_INVESTIGATOR
References: