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

NCT02230579 | Completed Phase 1 Results DMC

• 1 other identifier: MMV_MMV390048_14_01
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malaria

Keywords

safety; tolerability; malaria

Outcome Measures

Primary Outcomes (3)

• 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

  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

  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

  0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 216, 312, 432, 600, 672 hours post-dose

Secondary Outcomes (1)

• Determine ex Vivo Efficacy (IC50)

  up to 144 hr post dose

Study Arms (6)

Cohort SAD1 Fasted

EXPERIMENTAL

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

Cohort SAD2 Fasted

EXPERIMENTAL

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

Cohort SAD3 Fasted

EXPERIMENTAL

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

Cohort SAD4 Fasted

EXPERIMENTAL

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

Cohort SAD5 Fasted

EXPERIMENTAL

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

Cohort SAD6 Fed

EXPERIMENTAL

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

MMV390048 5mg DRUG

Supplied as "powder in bottle" formulation for reconstitution pre-dose

Also known as: MMV390048

Cohort SAD1 Fasted

MMV390048 20mg DRUG

Supplied as "powder in bottle" formulation for reconstitution pre-dose.

Also known as: MMV390048

Cohort SAD2 Fasted

MMV390048 40mg DRUG

Supplied as "powder in bottle" formulation for reconstitution pre-dose

Also known as: MMV390048

Cohort SAD3 Fasted; Cohort SAD6 Fed

MMV390048 80mg DRUG

Supplied as "powder in bottle" formulation for reconstitution pre-dose

Also known as: MMV390048

Cohort SAD4 Fasted

MMV390048 120mg DRUG

Supplied as "powder in bottle" formulation for reconstitution pre-dose

Also known as: MMV390048

Cohort SAD5 Fasted

Placebo to match MMV390048 DRUG

Supplied as "powder in bottle" formulation for reconstitution pre-dose

Also known as: Placebo

Cohort SAD1 Fasted; Cohort SAD2 Fasted; Cohort SAD3 Fasted; Cohort SAD4 Fasted; Cohort SAD5 Fasted; Cohort SAD6 Fed

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• University of Cape Town: collaborator

Study Sites (1)

Cinical Pharmacology, University of Cape Town

Cape Town, South Africa

Location

Related Publications (1)

• 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.

  PMID: 31932368 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

MMV390048

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Dr Cristina Donini - Associate Director
• Organization: Medicines for Malaria Venture

doninic@mmv.org

00 41 22 555 03 12

Study Officials

• Karen Barnes, Prof

  University of Cape Town

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2014
• First Posted: September 3, 2014
• Study Start: May 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: July 17, 2019
• Results First Posted: October 29, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)