CompletedNCT02230579Updated Jul 17, 2019Results posted

Phase I Study of Ascending Doses of MMV390048 in Healthy Adult Volunteers

A Phase 1 interventional study of MMV390048 5mg and MMV390048 20mg in Malaria, sponsored by Medicines for Malaria Venture. Completed at 1 site in South Africa. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-07-17.

Sponsored by Medicines for Malaria Venture · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 48
Allocation: Randomized
Ages: 18 Years to 55 Years
Sex: All

Study summary

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.

Read the 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.

Conditions studied

Malaria

Browse trials for

Malaria 1,299

Keywords

safety
tolerability
malaria

In context

Malaria

1,299 studies on the registry are indexed under Malaria; 86 are open to participants now.

This study's enrollment of 48 is below the median of 220 across 1,027 interventional studies indexed under Malaria.

Browse Malaria studies →

Lead sponsor

Medicines for Malaria Venture is the lead sponsor of 66 studies on the registry; 3 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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 design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single group
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 48 participants (actual)

Study arms

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
Drug: MMV390048 5mg · Drug: Placebo to match MMV390048
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
Drug: MMV390048 20mg · Drug: Placebo to match MMV390048
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
Drug: MMV390048 40mg · Drug: Placebo to match MMV390048
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
Drug: MMV390048 80mg · Drug: Placebo to match MMV390048
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
Drug: MMV390048 120mg · Drug: Placebo to match MMV390048
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
Drug: MMV390048 40mg · Drug: Placebo to match MMV390048

Interventions

DrugMMV390048 5mg
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Also known as: MMV390048
DrugMMV390048 20mg
Supplied as "powder in bottle" formulation for reconstitution pre-dose.
Also known as: MMV390048
DrugMMV390048 40mg
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Also known as: MMV390048
DrugMMV390048 80mg
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Also known as: MMV390048
DrugMMV390048 120mg
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Also known as: MMV390048
DrugPlacebo to match MMV390048
Supplied as "powder in bottle" formulation for reconstitution pre-dose
Also known as: Placebo

What researchers measure

Primary outcomes

Number of Participants With Adverse Events
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
Time frame: up to D29 or longer according to half life
Area Under the Plasma Concentration Versus Time Curve (AUC) of MMV390048
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
Time frame: 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
Pk blood collection Investigate the effect of food on the pharmacokinetic and tolerability of the investigational drug in cohort 4 and 8
Time frame: 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose

Secondary outcomes

Determine ex Vivo Efficacy (IC50)
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.
Time frame: up to 144 hr post dose

Results

Posted Oct 29, 2018

Participant flow

For the purposes of this study, subjects that were re-used in SAD6 were treated as separate subjects, i.e. the entire trial population comprised 48 subjects, eight subjects in 6 cohorts.

Participant flow — Overall Study
Milestone	Cohort SAD1 Fasted	Cohort SAD2 Fasted	Cohort SAD3 Fasted	Cohort SAD4 Fasted	Cohort SAD5 Fasted	Cohort SAD6 Fed	Placebo
Started	6	6	6	6	6	6	12
Completed	6	6	6	6	6	6	12
Not completed	0	0	0	0	0	0	0

Outcome measures

PrimaryNumber of Participants With Adverse Events

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

Time frame:: up to D29 or longer according to half life
Reported as:: Count of participants · Participants

Number of Participants With Adverse Events
Participants	Cohort SAD1 Fasted	Cohort SAD2 Fasted	Cohort SAD3 Fasted	Cohort SAD4 Fasted	Cohort SAD5 Fasted	Cohort SAD6 Fed	Placebo
Number of Participants With Adverse Events	4	5	5	6	6	6	11

PrimaryArea Under the Plasma Concentration Versus Time Curve (AUC) of MMV390048

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

Time frame:: 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose
Reported as:: Median · h*ng/mL

Area Under the Plasma Concentration Versus Time Curve (AUC) of MMV390048
h*ng/mL	Cohort SAD1 Fasted	Cohort SAD2 Fasted	Cohort SAD3 Fasted	Cohort SAD4 Fasted	Cohort SAD5 Fasted	Cohort SAD6 Fed
Area Under the Plasma Concentration Versus Time Curve (AUC) of MMV390048	2136.9 (903.1 to 3718.7)	32727.2 (24895.2 to 38914.3)	21050.7 (6325.4 to 37934.6)	58668.2 (40246 to 125655.1)	156036.2 (13053 to 208989.4)	29004.6 (15775.1 to 72735.3)

SecondaryDetermine ex Vivo Efficacy (IC50)

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.

Time frame:: up to 144 hr post dose
Reported as:: Mean · ng/ml

Determine ex Vivo Efficacy (IC50)
ng/ml	Cohort SAD1 Fasted	Cohort SAD2 Fasted	Cohort SAD3 Fasted	Cohort SAD4 Fasted	Cohort SAD5 Fasted	Cohort SAD6 Fed
Determine ex Vivo Efficacy (IC50)	—	—	9.475 (9.1 to 9.85)	—	—	—

PrimaryHalf-life of MMV390048

Pk blood collection Investigate the effect of food on the pharmacokinetic and tolerability of the investigational drug in cohort 4 and 8

Time frame:: 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose
Reported as:: Median · hours

Half-life of MMV390048
hours	Cohort SAD1 Fasted	Cohort SAD2 Fasted	Cohort SAD3 Fasted	Cohort SAD4 Fasted	Cohort SAD5 Fasted	Cohort SAD6 Fed
Half-life of MMV390048	163.1 (86.9 to 297.0)	326.1 (221.6 to 348.0)	192.6 (84.2 to 486.2)	200.3 (154.1 to 457.1)	252.3 (132.5 to 263.5)	210.8 (111.3 to 461.1)

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cohort SAD1 Fasted	—	0/6 (0%)	4/6 (66.7%)
Cohort SAD2 Fasted	—	0/6 (0%)	5/6 (83.3%)
Cohort SAD3 Fasted	—	0/6 (0%)	5/6 (83.3%)
Cohort SAD4 Fasted	—	0/6 (0%)	6/6 (100%)
Cohort SAD5 Fasted	—	1/6 (16.7%)	6/6 (100%)
Cohort SAD6 Fed	—	0/6 (0%)	6/6 (100%)
Placebo	—	0/12 (0%)	11/12 (91.7%)

Most frequent serious events

Most frequent serious events
Event	Cohort SAD1 Fasted	Cohort SAD2 Fasted	Cohort SAD3 Fasted	Cohort SAD4 Fasted	Cohort SAD5 Fasted	Cohort SAD6 Fed	Placebo
generalised myoclonusNervous system disorders	0/6	0/6	0/6	0/6	1/6	0/6	0/12

Most frequent other events

Showing 10 of 18

Most frequent other events
Event	Cohort SAD1 Fasted	Cohort SAD2 Fasted	Cohort SAD3 Fasted	Cohort SAD4 Fasted	Cohort SAD5 Fasted	Cohort SAD6 Fed	Placebo
Medical device site reactionInfections and infestations	3/6	0/6	1/6	5/6	3/6	5/6	5/12
Blood CK increasedBlood and lymphatic system disorders	0/6	0/6	3/6	1/6	2/6	0/6	0/12
ContusionGeneral disorders	3/6	0/6	0/6	0/6	0/6	0/6	0/12
DizinessNervous system disorders	0/6	0/6	2/6	0/6	0/6	0/6	0/12
DiarrhoeaGastrointestinal disorders	0/6	1/6	1/6	1/6	0/6	2/6	1/12
Influenza like illnessGeneral disorders	0/6	2/6	2/6	2/6	0/6	1/6	2/12
HeadacheGeneral disorders	0/6	1/6	2/6	1/6	1/6	1/6	1/12
Thermal burnSkin and subcutaneous tissue disorders	0/6	0/6	0/6	0/6	0/6	2/6	0/12
Neutrophil count decreasedInvestigations	0/6	0/6	1/6	0/6	0/6	1/6	0/12
UrticariaSkin and subcutaneous tissue disorders	0/6	1/6	0/6	0/6	0/6	1/6	0/12

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Cohort SAD1 Fasted	Cohort SAD2 Fasted	Cohort SAD3 Fasted	Cohort SAD4 Fasted	Cohort SAD5 Fasted	Cohort SAD6 Fed	Placebo	Total
Mean	29.3 (19 to 44)	34 (24 to 51)	37 (29 to 49)	30 (21 to 51)	23.7 (19 to 30)	34 (20 to 50)	32.7 (19 to 50)	31.7 (19 to 51)

Sex: Female, Male
Sex: Female, Male(Participants)	Cohort SAD1 Fasted	Cohort SAD2 Fasted	Cohort SAD3 Fasted	Cohort SAD4 Fasted	Cohort SAD5 Fasted	Cohort SAD6 Fed	Placebo	Total
Female	0	2	2	1	0	2	1	8
Male	6	4	4	5	6	4	11	40

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Cohort SAD1 Fasted	Cohort SAD2 Fasted	Cohort SAD3 Fasted	Cohort SAD4 Fasted	Cohort SAD5 Fasted	Cohort SAD6 Fed	Placebo	Total
American Indian or Alaska Native	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0
Black or African American	4	4	4	4	6	4	9	35
White	0	0	0	0	0	0	1	1
More than one race	0	0	0	0	0	0	0	0
Unknown or Not Reported	2	2	2	2	0	2	2	12

Study locations

1 site

Cinical Pharmacology, University of Cape Town
Cape Town, South Africa

References and documents

Publications

Sinxadi P, Donini C, Johnstone H, Langdon G, Wiesner L, Allen E, Duparc S, Chalon S, McCarthy JS, Lorch U, Chibale K, Mohrle J, Barnes KI. Safety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy Volunteers. Antimicrob Agents Chemother. 2020 Mar 24;64(4):e01896-19. doi: 10.1128/AAC.01896-19. Print 2020 Mar 24. PubMed 31932368 ↗

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 17, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02230579
Lead sponsor: Medicines for Malaria Venture
Collaborators: University of Cape Town
Responsible party: Sponsor
First posted: Sep 3, 2014
Start date: May 2014
Primary completion: Feb 2015
Completion: Feb 2015
Results posted: Oct 29, 2018
Last update: Jul 17, 2019

Study contacts

Karen Barnes, Prof

principal investigator · University of Cape Town

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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