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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02783820
Registration number
NCT02783820
Ethics application status
Date submitted
19/05/2016
Date registered
26/05/2016
Date last updated
11/06/2020
Titles & IDs
Public title
Safety, Tolerability and Pharmacokinetic Profile of Ascending Oral Doses of MMV390048, Part A
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Scientific title
A Single Centre, Two-part, Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of Ascending Oral Doses of MMV390048 and Its Antimalarial Activity Against Plasmodium Falciparum in Healthy Adult Subjects
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Secondary ID [1]
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MMV_MMV390048_16_01
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Malaria
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Condition category
Condition code
Infection
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Other infectious diseases
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Infection
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Studies of infection and infectious agents
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - MMV390048 40 mg
Treatment: Drugs - Placebo to match MMV390048 40 mg
Treatment: Drugs - MMV390048 80 mg
Treatment: Drugs - Placebo to match MMV390048 80 mg
Treatment: Drugs - MMV390048 120 mg
Treatment: Drugs - Placebo to match MMV390048 120 mg
Experimental: MMV390048 40 mg - MMV390048 40 mg, tablets, single dose
Placebo Comparator: Placebo to match MMV390048 40 mg - Placebo to match MMV390048 40 mg, tablets, single dose
Experimental: MMV390048 80 mg - MMV390048 80 mg, tablets, single dose
Placebo Comparator: Placebo to match MMV390048 80 mg - Placebo to match MMV390048 80 mg, tablets, single dose
Experimental: MMV390048 120 mg - MMV390048 120 mg, tablets, single dose
Placebo Comparator: Placebo to match MMV390048 120 mg - Placebo to match MMV390048 120 mg, tablets, single dose
Treatment: Drugs: MMV390048 40 mg
Treatment: Drugs: Placebo to match MMV390048 40 mg
Treatment: Drugs: MMV390048 80 mg
Treatment: Drugs: Placebo to match MMV390048 80 mg
Treatment: Drugs: MMV390048 120 mg
Treatment: Drugs: Placebo to match MMV390048 120 mg
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Safety of MMV390048 - Number of Adverse Events
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Assessment method [1]
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Number of observed and self-reported Adverse Events (AE) (unexpected toxicities, adverse events encountered during or after investigational drug administration)
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Timepoint [1]
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28 days post administration of a single oral dose of MMV390048 to healthy volunteers
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Secondary outcome [1]
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PK Cmax
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Assessment method [1]
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Estimation of the maximum plasma concentration over 28 days post administration of a single dose of MMV390048 using non-compartmental methods
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Timepoint [1]
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28 days
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Secondary outcome [2]
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PK Tmax
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Assessment method [2]
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Estimation of the time to maximum plasma concentration over 28 days post administration of a single dose of MMV390048 using non-compartmental methods
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Timepoint [2]
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28 days
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Secondary outcome [3]
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PK Total Exposure AUClast
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Assessment method [3]
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Estimation of the last quantifiable concentration over 28 days post administration of a single dose of MMV390048 using non-compartmental methods
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Timepoint [3]
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28 days
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Secondary outcome [4]
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PK Total Exposure AUCinf
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Assessment method [4]
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Estimation of the area under the plasma concentration time curve over 28 days post administration of a single dose of MMV390048 using non-compartmental methods
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Timepoint [4]
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28 days
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Secondary outcome [5]
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PK Distribution and Clearance (CL/F)
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Assessment method [5]
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Apparent oral clearance (CL/F) over 28 days post administration of a single dose of MMV390048 using non-compartmental methods
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Timepoint [5]
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28 days
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Secondary outcome [6]
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PK Distribution and Clearance (Vz/F)
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Assessment method [6]
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Apparent volume of distribution (Vz/F) over 28 days post administration of a single dose of MMV390048 using non-compartmental methods
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Timepoint [6]
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28 days
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Secondary outcome [7]
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PK Distribution and Clearance (t½)
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Assessment method [7]
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Terminal half-life (t½) over 28 days post administration of a single dose of MMV390048 using non-compartmental methods
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Timepoint [7]
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28 days
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Eligibility
Key inclusion criteria
1. Completion of the written informed consent process.
2. Men or WNCBP age 18 to 55 years, in good health as determined by past medical history,
physical examination, vital signs, electrocardiogram, and laboratory tests at
screening.
3. Male subjects agree to use acceptable methods of contraception if the male subject's
partner could become pregnant from the time of the first administration of study
medication until 130 (90+40) days following administration of the investigational
medicinal product. One of the following acceptable methods of contraception must be
utilized:
- Condom and occlusive cap (diaphragm or cervical/vault caps)
- Surgical sterilization (vasectomy with documentation of azoospermia) and a
barrier method (condom or occlusive cap [diaphragm or cervical/vault caps].
- The subject's female partner uses oral contraceptives (combination
estrogen/progesterone pills), injectable progesterone or subdermal implants and a
barrier method (condom or occlusive cap [diaphragm or cervical/vault caps].
- The subject's female partner uses medically prescribed topically-applied
transdermal contraceptive patch and a barrier method (condom or occlusive cap
[diaphragm or cervical/vault caps].
- The subject's female partner has undergone documented tubal ligation (female
sterilization). In addition, a barrier method (condom or occlusive cap [diaphragm
or cervical/vault caps].
- The subject's female partner has undergone documented placement of an
intrauterine device or intrauterine system. In addition, a barrier method (condom
or occlusive cap [diaphragm or cervical/vault caps].
- True abstinence: when this is in line with the preferred and usual lifestyle of
the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception. Abstinent subjects have to agree to use 1 of the above-mentioned
contraceptive methods, if they start sexual relationships during the study and
for up to 100 days after the last dose of study drug.
4. Women subjects must be of non-childbearing potential (WNCBP) as per one of the
following definitions:
- Natural (spontaneous) post-menopausal defined as being amenorrhoeic for at least
12 months without an alternative medical cause with a screening follicle
stimulating hormone level consistent with local laboratory levels for
post-menopause.
- Premenopausal with irreversible surgical sterilization by hysterectomy and/or
bilateral oophorectomy or salpingectomy at least 6 months before screening (as
determined by subject medical history).
5. Haematology, clinical chemistry and urinalysis results at screening that are within
the local laboratory reference range or, if outside the range, not clinically
significant as judged by the Investigator. More specifically, serum creatinine,
hepatic transaminase enzymes (AST ALT), and total bilirubin (unless the subject has
documented Gilbert syndrome) should not exceed the upper laboratory norm and
haemoglobin must be equal to or higher than the lower limit of the normal range.
6. Total body weight greater than 50 kg and a body mass index (BMI) within the range of
18 to 32 kg/m2 (inclusive).
7. Non-smoker or ex-smoker for more than 90 days prior to screening, or smoke no more
than 5 cigarettes per day as determined by history. Must be able to abstain from
smoking during the inpatient stay.
8. Willing and able to comply with all scheduled visits, treatment plan, laboratory
tests, and other study procedures.
9. Agree to stay in contact with the study site for the duration of the study and up to 2
weeks following the end of study visit, provide updated contact information as
necessary, and have no current plans to move away from the study area for the duration
of the study.
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Minimum age
18
Years
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Maximum age
55
Years
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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Key exclusion criteria
1. Male subjects with a female partner(s) who is (are) pregnant or lactating from the
time of the administration of study medication.
2. Women of childbearing potential, defined as all women physiologically capable of
becoming pregnant, including women whose career, lifestyle, or sexual orientation
precludes intercourse with a male partner and women whose partners have been
sterilized by vasectomy or other means.
3. Evidence or history of clinically significant haematological, renal, endocrine,
pulmonary, gastrointestinal (including gallbladder), cardiovascular (including a
family history of long QT syndrome or sudden death), hepatic, psychiatric, neurologic,
or allergic disease (including drug or food allergies, anaphylaxis or other severe
allergic reactions but excluding untreated, asymptomatic, seasonal allergies at the
time of dosing).
4. History of malignancy of any organ system (other than localised basal cell carcinoma
of the skin), treated or untreated, within the past five years, regardless of whether
there is evidence of local recurrence or metastases.
5. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation of
study results and, in the judgment of the Investigator, would make the subject
inappropriate for entry into this study.
6. Any surgical or medical condition possibly affecting drug absorption (e.g.
cholecystectomy, gastrectomy, bowel disease, etc.), distribution, metabolism or
excretion.
7. Previous splenectomy.
8. A history of photosensitivity.
9. Subject positive for any of the following
- Anti-human immunodeficiency virus 1 or 2 antibodies (anti-HIV1 or anti-HIV2 Ab)
(ELISA)
- Hepatitis B surface antigen (HBsAg)
- Anti-hepatitis B core antibodies (anti-HBcAb)
- Anti-hepatitis C antibodies (anti-HCV)
10. Resting vital signs (measured after 5 minutes in the supine position) at screening,
pre-dose (Part A) or pre-inoculation (Part B) outside of the following study-specific
normal ranges:
- tympanic body temperature < 38.0 °C
- 90 < SBP < 140 mmHg
- 50 < DBP < 90 mmHg
- 40 < pulse rate < 100 bpm
11. Symptomatic postural hypotension at screening, irrespective of the decrease in blood
pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood
pressure =20 mmHg 2 minutes after changing from a supine to standing position.
12. A history of clinically significant ECG abnormalities, or any of the following ECG
abnormalities at screening, pre-dose (Part A and B) or pre-inoculation (Part B):
- PR >210 ms
- QRS complex >120 ms
- QTcF >450 ms
- Second or third degree atrioventricular block
- Incomplete, complete or intermittent bundle branch block
- Abnormal T wave morphology
- Left ventricular hypertrophy with repolarisation abnormalities
- Right ventricular hypertrophy.
13. Presence of acute infectious disease or fever (i.e. tympanic body temperature =38.5
ºC) within five days prior to the first dose of study medication (Part A) or the
inoculation administration (Part B).
14. Use of prescription or non-prescription drugs, herbal and dietary supplements within
14 days or 5 half-lives (whichever is the longer) prior to the first dose of study
medication (Part A) or the inoculation administration (Part B). [As an exception,
paracetamol may be used at doses of up to 1 g/day (Part A) or 2 g/day (Part B), or
ibuprofen up to 1.2 g/day (Part B). Limited use of other non-prescription medications
not believed to affect subject safety or the overall results of the study, may be
permitted on a case-by-case basis following approval by the sponsor.]
15. Recipient of any vaccination within 28 days prior to the first dose of study
medication (Part A) or the inoculation administration (Part B).
16. Urine drug screen at screening, pre-dose (Part A) or pre-inoculation (Part B) positive
for any drug as listed in Section 9.2.4 unless there is an explanation acceptable to
the medical Investigator (e.g. the subject has stated in advance that they consumed a
prescription or over the counter product which contained the detected drug) and/or the
subject has a negative urine drug screen on retest by the pathology laboratory.
17. Ingestion of any poppy seeds within the 24 hours prior to the screening blood test.
18. A positive alcohol breath test at screening, pre-dose (Part A) or pre-inoculation
(Part B).
19. History of regular alcohol consumption exceeding a weekly intake of more than 21 units
for males and more than 14 units for females (one unit is equivalent to 8-10 g of
ethanol, 285 ml of beer or lager, one glass [125 ml] of wine, or 25 ml of spirits)
within 6 months of screening.
20. History of drug habituation, or any prior intravenous usage of an illicit substance.
21. Participation in any investigational product study within 12 weeks or five half-lives
(whichever is longer) prior to the first dose of the study medication.
22. Intake of grapefruit, grapefruit juice or grapefruit-related citrus fruits (e.g.
Seville oranges, pomelos) within 28 days prior to the first dose of the study
medication.
23. Excessive consumption of beverages containing xanthine bases (e.g. more than 400 mg of
caffeine per day, equivalent to approximately 4 cups of coffee).
24. Pregnant or nursing (lactating) women.
25. Participation in any research study involving blood sampling (more than 450 ml/ unit
of blood), or blood donation to the Australian Red Cross Blood Service (ARCBS) or
other blood bank during the 8 weeks prior to IMP administration (Part A) or
inoculation (Part B).
26. Blood donation (excluding plasma donation) of any volume, within 1 month prior to
screening.
27. Medical requirement for intravenous immunoglobulin or blood transfusions.
28. Subject with poor peripheral venous access.
29. Subject unwilling or unable to comply with the restrictions described in this
protocol.
30. Any subject who, in the judgment of the Investigator, is likely to be noncompliant
during the study, or unable to cooperate because of a language problem or poor mental
development.
31. Any subject who is the Investigator or any sub-investigator, research assistant,
pharmacist, study coordinator, or other staff thereof, directly involved in conducting
the study.
32. Recent (within the last three years) and/or recurrent history of autonomic dysfunction
(e.g. recurrent episodes of fainting, palpitations, etc.).
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/05/2016
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/12/2016
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Sample size
Target
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Accrual to date
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Final
24
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Q Pharm Clinics - Herston
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Recruitment postcode(s) [1]
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QLD 4006 - Herston
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Funding & Sponsors
Primary sponsor type
Other
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Name
Medicines for Malaria Venture
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Address
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Country
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Other collaborator category [1]
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Commercial sector/Industry
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Name [1]
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Clinical Network Services (CNS) Pty Ltd
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Address [1]
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Country [1]
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Other collaborator category [2]
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Commercial sector/Industry
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Name [2]
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Q-Pharm Pty Limited
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Address [2]
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Country [2]
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Other collaborator category [3]
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Other
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Name [3]
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QIMR Berghofer Medical Research Institute
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Address [3]
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Country [3]
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Ethics approval
Ethics application status
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Summary
Brief summary
This Phase I study will evaluate the safety, tolerability and pharmacokinetic properties of
escalating single doses of reformulated MMV390048 when administered to healthy men and women
of non-childbearing potential (WNCBP) under fasted conditions (Part A).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02783820
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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James McCarthy, Prof
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Address
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Q-Pharm Pty Ltd and QIMR Berghofer Medical Research Institute
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02783820
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