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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02783833




Registration number
NCT02783833
Ethics application status
Date submitted
19/05/2016
Date registered
26/05/2016

Titles & IDs
Public title
MMV390048 and Its Antimalarial Activity Against Plasmodium Falciparum in Healthy Adult Subjects, Part B
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
Secondary ID [1] 0 0
MMV_MMV390048_16_01, Part B
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MMV390048 dose to be determined mg

Experimental: MMV390048 40 mg - MMV390048 40 mg, tablets, single dose

Experimental: MMV390048 dose to be determined mg - MMV390048 dose to be determined mg, tablets, single dose


Treatment: Drugs: MMV390048 dose to be determined mg
Cohort 2 will receive a single dose of MMV390048. Depending on the data obtained from the 40mg cohort, the dose in Cohort 2 will be determined.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Effect on parasites
Timepoint [1] 0 0
28 days
Secondary outcome [1] 0 0
PK Cmax
Timepoint [1] 0 0
28 days
Secondary outcome [2] 0 0
PK Tmax
Timepoint [2] 0 0
28 days
Secondary outcome [3] 0 0
PK Total exposure AUClast
Timepoint [3] 0 0
28 days
Secondary outcome [4] 0 0
PK Total exposure AUCinf
Timepoint [4] 0 0
28 days
Secondary outcome [5] 0 0
PK distribution and clearance (CL/F)
Timepoint [5] 0 0
28 days
Secondary outcome [6] 0 0
PK distribution and clearance (Vz/F)
Timepoint [6] 0 0
28 days
Secondary outcome [7] 0 0
PK distribution and clearance (t½)
Timepoint [7] 0 0
28 days
Secondary outcome [8] 0 0
observed and self reported adverse events
Timepoint [8] 0 0
28 days

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.
Minimum age
18 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
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.).
33. Any history of malaria.
34. Participation in a previous malaria challenge study or Part A of the current study.
35. Participation in a malaria vaccine trial.
36. Has travelled to or lived (for more than 2 weeks) in a malaria-endemic country during the past 12 months.
37. Any plan to travel to a malaria-endemic country during the course of the study.
38. Evidence of increased cardiovascular disease risk (defined as >10%, 5 year risk for those greater than 35 years of age, as determined by the Australian Absolute Cardiovascular Disease Risk Calculator.39 Risk factors include sex, age, systolic blood pressure (mm/Hg), smoking status, total and HDL cholesterol (mmol/L), and reported diabetes status.
39. Frequent headaches and/or migraine, recurrent nausea, and/or vomiting (more than twice a month).
40. Subject unwilling to defer blood donations to the ARCBS for 6 months.
41. Subject who has ever received a blood transfusion.
42. Subject currently receiving, or having previously received, immunosuppressive therapy (including systemic steroids, adrenocorticotrophic hormone or inhaled steroids) at a dose or duration associated with hypothalamic-pituitary-adrenal axis suppression (e.g. 1 mg/kg/day of prednisone or its equivalent, or chronic use of inhaled high potency corticosteroids such as budesonide 800 µg per day or fluticasone 750 µg).
43. Any recent (<6 weeks) or current systemic therapy with drugs known to have potential antimalarial activity listed in Section 6.5.2.
44. Known allergy to one of the rescue medication proposed for the challenge study.
45. Subject is unwilling to abstain from consumption of quinine containing foods/beverages such as tonic water, lemon bitter, from inoculation (Day In0) to the end of the antimalarial treatment.
46. Subject lives alone (at any stage from Day In0 until at least the end of the antimalarial drug treatment).

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
Single group
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
1/05/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/01/2017
Sample size
Target
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Q-Pharm Clinics - Herston
Recruitment postcode(s) [1] 0 0
4006 - Herston

Funding & Sponsors
Primary sponsor type
Other
Name
Medicines for Malaria Venture
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Clinical Network Services (CNS) Pty Ltd
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Q-Pharm Pty Limited
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
QIMR Berghofer Medical Research Institute
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James McCarthy, Prof
Address 0 0
Q-Pharm Pty Ltd and QIMR Berghofer Medical Research Institute
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
clinical safety data (physical exam, ECG, vital signs, clinical score, AEs), lab safety data, PK data, PCR data, subject withdrawals, significant protocol deviations, SAEs.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02783833