- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02230579
Phase I Study of Ascending Doses of MMV390048 in Healthy Adult Volunteers
A Single Centre, Two-part, Double-blind, Randomized, Placebo-controlled Phase I Study to Investigate the Safety, Tolerability, and Pharmacokinetic Profile of Ascending Doses of MMV390048 in Healthy Adult Volunteers
This is a first-in-human study of MMV390048. The study will evaluate the safety, tolerability and pharmacokinetic properties of escalating single and multiple doses of MMV390048 when administered to healthy male volunteers and female volunteers of non-childbearing potential.
In addition, the effect of food on the pharmacokinetics and tolerability of MMV390048 will be investigated.
Study Overview
Status
Conditions
Detailed Description
The study is a single centre, double-blind, randomised, placebo-controlled, ascending dose study in healthy male and female volunteers (of non-childbearing potential) aged 18 to 55 years.
The study will be divided into two parts. The first part will comprise up to seven fasted cohorts (8 to 10 volunteers in each) that will receive a single, ascending dose (SAD) of MMV390048 to assess its safety, tolerability and pharmacokinetic profile. The starting dose administered to the first cohort will be 5 mg. An additional cohort (cohort 8, re-using volunteers from one of the previous cohorts) will receive a single dose of MMV390048 in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability of the compound.
The data obtained from each cohort during the SAD part of the study will undergo a formal review by the Safety Review Team (SRT). Should the safety profile of the compound be deemed acceptable, and the pharmacokinetic parameters indicate that acceptable levels of the drug to elicit a pharmacodynamic response can be achieved in human plasma, the study will then proceed to the second part.
During the second part of the study volunteers will receive multiple, ascending doses (MAD) of MMV390048 to assess the pharmacokinetics, safety and tolerability following multiple oral doses. Up to three cohorts of eight volunteers each will be enrolled into this part of the study. Each volunteer will receive three consecutive daily doses of MMV390048.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Cape Town, South Africa
- Cinical Pharmacology, University of Cape Town
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- written informed consent
- Male and female (of non-childbearing potential); age 18 to 55 years, in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening
- Hematology, clinical chemistry and urinalysis results at screening that are within the local laboratory reference range or, if outside the range, not clinically significant. AST, ALT, lactate dehydrogenase, total bilirubin, haptoglobin and hemoglobin must be within the normal reference ranges
- Body weight at least 50kg and body mass index within 18 to 32kg/m2
- Good peripheral venous access
- Able to communicate well with the investigator, to understand and comply with the requirements of the study
- Agree to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to move away from the study area for the duration of the study
Exclusion Criteria:
- Any acute illness upon admission to the unit on Day -1 or prior to dosing on Day 1
- Use of any other investigational drug within 30 days or five half-lives (whichever is longer) prior to the first dose of MMV390048
- history of hypersensitivity to any drugs
- history of anaphylaxis or severe allergic reaction
- Resting vital signs at either screening or baseline outside the defined ranges
- Orthostatic changes in blood pressure and heart rate measurements greater than: 20 mmHg drop in systolic blood pressure; 10 mmHg drop in diastolic blood pressure; 20 beats per minute increase in heart rate
- history of clinically significant ECG abnormalities, or any of the defined ECG abnormalities at either screening or baseline
- History of malignancy of any organ system (other than localized 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
- Pregnant or nursing (lactating) women
- Women of child-bearing potential
- males physiologically capable of conceiving offspring UNLESS the volunteer agrees to use condoms and ensure that his partner(s) is either not of child-bearing potential or uses a highly effective method of contraception for the entire duration of the study and for twelve weeks following the last study drug administration
- Smokers (use of tobacco products in the previous three months)
- Use of any prescription drugs, herbal supplements, over--the--counter medication or dietary supplements (vitamins included) within four weeks prior to initial dosing
- Intake of grapefruit, grapefruit juice or other products containing grapefruit within 28 days of the first drug administration of the study drug
- Excessive intake of caffeine drinks or energy drinks within 48 hours before admission defined as more than three 250 ml cups of coffee a day
- Donation or loss of 400 ml or more of blood within eight weeks prior to screening or initial dosing
- Plasma donation (>100 ml) within 60 days prior to first dosing
- Hemoglobin levels below 12.5 g/dl (males) or 11.5 g/dl (females) at screening
- Haptoglobin levels outside the reference range
- Positive direct anti-globulin test
- Liver enzymes other than ALT, AST and lactate dehydrogenase elevated ≥1.5 x ULN within two weeks prior to initial dosing
- history of autonomic dysfunction within 3 years and/or recurrent history
- History of immunodeficiency diseases, including a confirmed positive HIV test result
- Positive Hepatitis B surface antigen or Hepatitis C antibody test result
- History of recurrent infection
- history of endocrine disease, in particular adrenal disorders such as Cushing's syndrome or Addison's disease, or diabetes mellitus
- history of Gilbert's Syndrome
- history of photosensitivity
- history of any food allergy
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardise the safety of the volunteer or the objectives of the study
- History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or urea values, or abnormal urinary constituents
- History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the tests and laboratory assays at screening and/or baseline
- Any clinically significant mental disorder that could limit the validity of informed consent or the volunteer's ability to comply with protocol requirements
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort SAD1 Fasted
Five fasted cohorts will receive a single, ascending dose of MMV390048.
The starting dose will be 5mg.
Cohort SAD6 will receive a single dose in a fed state
|
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Other Names:
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Other Names:
|
Experimental: Cohort SAD2 Fasted
Five fasted cohorts will receive a single, ascending dose of MMV390048.
The starting dose will be 5mg.
Cohort SAD6 will receive a single dose in a fed state
|
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Other Names:
Supplied as "powder in bottle" formulation for reconstitution pre-dose.
Other Names:
|
Experimental: Cohort SAD3 Fasted
Five fasted cohorts will receive a single, ascending dose of MMV390048.
The starting dose will be 5mg.
Cohort SAD6 will receive a single dose in a fed state
|
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Other Names:
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Other Names:
|
Experimental: Cohort SAD4 Fasted
Five fasted cohorts will receive a single, ascending dose of MMV390048.
The starting dose will be 5mg.
Cohort SAD6 will receive a single dose in a fed state
|
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Other Names:
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Other Names:
|
Experimental: Cohort SAD5 Fasted
Five fasted cohorts will receive a single, ascending dose of MMV390048.
The starting dose will be 5mg.
Cohort SAD6 will receive a single dose in a fed state
|
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Other Names:
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Other Names:
|
Experimental: Cohort SAD6 Fed
Cohort SAD6, reusing volunteers from one of the previous cohorts, will receive a single dose in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability
|
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Other Names:
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Adverse Events
Time Frame: up to D29 or longer according to half life
|
Subject will be in-house up to D3, and then have a follow up visit at the site on D5, 7, 10, 14, 19, 26, 29 or longer according to half life
|
up to D29 or longer according to half life
|
Area Under the Plasma Concentration Versus Time Curve (AUC) of MMV390048
Time Frame: 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose
|
Pk blood collection - additional PK point may be planned final visit depending on emerging PK data, unnecessary PK points could be eliminated for the latter cohorts Investigate the effect of food on the pharmacokinetic and tolerability of the investigational drug in cohort 4 and 8
|
0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose
|
Half-life of MMV390048
Time Frame: 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose
|
Pk blood collection Investigate the effect of food on the pharmacokinetic and tolerability of the investigational drug in cohort 4 and 8
|
0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determine ex Vivo Efficacy (IC50)
Time Frame: up to 144 hr post dose
|
Blood collection to determine efficacy of investigational drug against parasites using an ex vivo malaria assay - this was done only for cohort 3 The experimentally obtained bioassay IC50 values were determined and compared to IC50 obtained with reference serum sample spiked with a known amount of MMV390048 titrated into the P. falciparum assay.
|
up to 144 hr post dose
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Karen Barnes, Prof, University of Cape Town
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- MMV_MMV390048_14_01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malaria
-
University of California, San FranciscoCenters for Disease Control and Prevention; University of Massachusetts, Amherst and other collaboratorsRecruitingPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaLao People's Democratic Republic
-
Medicines for Malaria VentureAsociacion Civil Selva AmazonicaCompletedPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaPeru
-
Menzies School of Health ResearchInternational Centre for Diarrhoeal Disease Research, Bangladesh; Addis Ababa... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaEthiopia, Bangladesh, Indonesia
-
University of OxfordWellcome Trust; Ministry of public Health AfghanistanCompletedVivax Malaria | Uncomplicated Falciparum MalariaAfghanistan
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
Gadjah Mada UniversityMenzies School of Health Research; Eijkman Institute for Molecular Biology; Timika...Completed
-
London School of Hygiene and Tropical MedicineWorld Health Organization; United Nations High Commissioner for Refugees; HealthNet... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaPakistan
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
University of IbadanShin Poong Pharm Co Ltd 161 yoksam-ro, Gangnam-Gu Seoul 135-925, Korea; Institute...CompletedPlasmodium Falciparum Malaria | Uncomplicated Malaria | Malaria FeverNigeria
-
Research Institute for Tropical Medicine, PhilippinesWorld Health OrganizationCompletedTES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014 (TES)Malaria | Vivax Malaria | Falciparum Malaria | Malaria Recrudescence
Clinical Trials on MMV390048 5mg
-
Medicines for Malaria VentureRichmond Pharmacology LimitedCompleted
-
Medicines for Malaria VentureQ-Pharm Pty Limited; Clinical Network Services (CNS) Pty Ltd; QIMR Berghofer...Completed
-
Medicines for Malaria VentureJimma University; University of GondarTerminated
-
Medicines for Malaria VentureQ-Pharm Pty LimitedTerminatedMalaria, FalciparumAustralia
-
Medicines for Malaria VentureQ-Pharm Pty Limited; Clinical Network Services (CNS) Pty Ltd; QIMR Berghofer...Completed
-
Medicines for Malaria VentureSanaria Inc.; ICON Clinical Research; University of Cape Town; Datamap; PrimeVigilance... and other collaboratorsWithdrawn
-
Eisai Co., Ltd.Completed
-
University of EdinburghNHS LothianCompleted
-
Vigonvita Life SciencesCompletedErectile DysfunctionChina
-
Yuhan CorporationActive, not recruitingHypertension | HypercholesterolemiaKorea, Republic of