A Study to Evaluate the Pharmacokinetics of Oral Formulations of MMV390048 Administered Fasted to Healthy Volunteers

NCT02554799 | Completed Phase 1 Results

• 1 other identifier: MMV_MMV390048_15_01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be conducted in a single centre, as an open single dose two parallel cohorts design with oral doses of MMV390048 administered in healthy male and female subjects between 18 to 55 years of age. Subjects will be screened within 28 days prior to entering the study. On Day 1 of the study each subject will receive one of the two MMV390048 prototype formulations, at a dose of 40 mg with 240 mL of water. Subjects will be discharged on Day 3 after 48h post-dose and they will attend the unit for follow-up visits on Days 5, 7, 10, 14, 19, 26 and 29.

Conditions

Malaria

Outcome Measures

Primary Outcomes (7)

• Cmax: Peak Plasma Concentration

  Maximum concentration (Cmax) of two MMV390048 prototype formulations administered in the fasted state

  Up to 672 hours post-dose

• Tmax: Time to Reach Peak Plasma Concentration

  Time to reach maximum plasma concentration (Tmax) of two MMV390048 prototype formulations administered in the fasted state

  Up to 672 hours post-dose

• AUC: Area Under the Plasma Concentration-time Curve From Zero to Infinity

  Area under the plasma concentration-time curve (AUC) of two MMV390048 prototype formulations administered in the fasted state

  From Pre-dose to 672 hours post-dose

• Terminal Elimination Half-life (t1/2)

  Terminal elimination half-life (t1/2) of two MMV390048 prototype formulations administered in the fasted state

  Up to 672 hours post-dose

• Terminal Elimination Rate Constant (Lambda z)

  Terminal elimination rate constant (lambda z) of two MMV390048 prototype formulations administered in the fasted state

  Up to 672 hours post-dose

• Oral Plasma Clearance (CL/F)

  Oral plasma clearance (CL/F) of two MMV390048 prototype formulations administered in the fasted state

  Up to 672 hours post-dose

• Apparent Volume of Distribution (Vz/F)

  Apparent volume of distribution (Vz/F) of two MMV390048 prototype formulations administered in the fasted state

  Up to 672 hours post-dose

Other Outcomes (6)

• Time to Reach Maximum Plasma Concentration (Tmax)

  Up to 672 hours post-dose

• Area Under the Plasma Concentration-time Curve (AUC)

  Up to 672 hours post-dose

• Terminal Elimination Half-life

  Up to 672 hours post-dose

Study Arms (3)

40 mg MMV390048 tablet formulation A fasted

EXPERIMENTAL

40 mg MMV390048 tablet formulation A, in fasted state

Drug: MMV390048 formulation A

40 mg MMV390048 tablet formulation B fasted

EXPERIMENTAL

40 mg MMV390048 tablet formulation B fasted

Drug: MMV390048 formulation B

40 mg MMV390048 formulation A or B, with milk or fasted

EXPERIMENTAL

Optional cohort: 40 mg of MMV390048 in the formulation that has been shown to have the most favourable PK profile, taken with milk or in the fed state.

Drug: MMV390048 formulation A; Drug: MMV390048 formulation B

Interventions

MMV390048 formulation A DRUG

MMV390048 formulation A, tablet

40 mg MMV390048 formulation A or B, with milk or fasted; 40 mg MMV390048 tablet formulation A fasted

MMV390048 formulation B DRUG

MMV390048 formulation B, tablet

40 mg MMV390048 formulation A or B, with milk or fasted; 40 mg MMV390048 tablet formulation B fasted

Eligibility Criteria

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

You may qualify if:

• healthy male or female (non-childbearing potential) of any race, aged 18 to 55 years
• body weight at least 50kg and a body mass index 18 to 30Kg/m2
• Females must be of non-childbearing potential:
• Natural (spontaneous) post-menopausal defined (amenorrheic for at least 12 months without an alternative medical cause with a screening follicle stimulating hormone level \>25IU/L (for post-menopause).
• Premenopausal with irreversible surgical sterilization by hysterectomy
• and/or bilateral oophorectomy or salpingectomy at least 6 months before screening
• Males agree to use acceptable methods of contraception if the male subject's partner could become pregnant from the time of study medication until 120 days after administration of study medication. One of the following acceptable methods of contraception must be used:
• Condom and occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/suppository
• Surgical sterilization (vasectomy with documentation of azoospermia) and an acceptable barrier method (condom or occlusive cap \[diaphragm or cervical/vault cap\] used with spermicidal foam/gel/film/cream/suppository)
• subject's female partner uses oral contraceptives (combination estrogen / progesterone pills), injectable progesterone or sub-dermal implants and an acceptable barrier method
• subject's female partner uses medically prescribed topically applied transdermal contraceptive patch and an acceptable barrier method
• subject's female partner has undergone documented tubal ligation (female sterilization). In addition, an acceptable barrier method must be used.
• subject's female partner has undergone documented placement of an intrauterine device or intrauterine system. In addition, an acceptable barrier method must be used.
• True abstinence: when 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 120 days post-study drug
• non-smokers or ex-smokers for more than 90 days prior to screening or smoke no more than 5 cigarettes per day. If users of nicotine products (spray, patch, e-cigarette, etc.) they should use the equivalent of no more than 5 cigarettes /day

You may not qualify if:

• Male subjects with a female partner(s) who is (are) pregnant or lactating from the time of study medication
• 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
• Current or recurrent disease (e.g. cardiovascular, neurological, renal, gastrointestinal, oncologic or other conditions) that may affect the action, absorption or disposition of the study medication or could affect clinical assessments or clinical laboratory evaluations
• Current or relevant history of physical or psychiatric illness that may require treatment or make the subject unlikely to fully comply with the requirements or complete the study, or any condition that presents undue risk from the investigational product or study procedures
• Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of the participation in the study, may influence the result of the study, or the subject's ability to participate in the study
• History of photosensitivity
• History or clinical evidence of alcohol or substance abuse. Alcohol abuse is defined as regular weekly intake of more than 21 units for males and 14 units for females
• Any clinically relevant history of intolerance/allergy to milk or dairy products
• Use of an investigational product or participation in a clinical study within 90 days before study medication
• Donation of blood products or of more than 500ml of blood in 90 days prior to study medication
• Use of any prescription drugs within 14 days or within 5 times the elimination half-life (whichever period is longer) prior to study medication
• Use moderate or strong inhibitors and/or inducers of CYP450/Transporters within 4 weeks prior to study drug administration (or 5 half-lives of the compound if longer)
• Use of over-the-counter medications or dietary supplements, including vitamins and herbal supplements within 7 days of study drug. With the exception of paracetamol which may be used incidentally or for short-term treatment at a maximum of 2g/day
• Intake of grapefruit, grapefruit juice or other products containing grapefruit within 28 days prior to study drug
• Excessive intake of caffeine drinks or energy drinks within 48 hours before admission (more than three 250ml cups of coffee a day, equivalent to roughly 250mg caffeine)

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Richmond Pharmacology Limited: collaborator

Study Sites (1)

Richmond Pharmacology Ltd.

Croydon, London, CR7 7YE, United Kingdom

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

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr Cristina Donini
• Organization: Medicines for Malaria Venture

doninic@mmv.org

+41 22 555 0312

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2015
• First Posted: September 18, 2015
• Study Start: September 17, 2015
• Primary Completion: October 28, 2015
• Study Completion: October 28, 2015
• Last Updated: September 10, 2019
• Results First Posted: August 28, 2019

Record last verified: 2019-08

Locations

GB (1)