Safety, Tolerability and Pharmacokinetic Profile of Ascending Oral Doses of MMV390048, Part A

NCT02783820 | Completed Phase 1 Results DMC

• 1 other identifier: MMV_MMV390048_16_01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I study will evaluate the safety, tolerability and pharmacokinetic properties of escalating single doses of reformulated MMV390048 when administered to healthy men and women of non-childbearing potential (WNCBP) under fasted conditions (Part A).

Conditions

Malaria

Keywords

malaria, single ascending dose,

Outcome Measures

Primary Outcomes (1)

• Safety of MMV390048 - Number of Adverse Events

  Number of observed and self-reported Adverse Events (AE) (unexpected toxicities, adverse events encountered during or after investigational drug administration)

  28 days post administration of a single oral dose of MMV390048 to healthy volunteers

Secondary Outcomes (7)

• PK Cmax

  28 days

• PK Tmax

  28 days

• PK Total Exposure AUClast

  28 days

• PK Total Exposure AUCinf

  28 days

• PK Distribution and Clearance (CL/F)

  28 days

Study Arms (6)

MMV390048 40 mg

EXPERIMENTAL

MMV390048 40 mg, tablets, single dose

Drug: MMV390048 40 mg

Placebo to match MMV390048 40 mg

PLACEBO COMPARATOR

Placebo to match MMV390048 40 mg, tablets, single dose

Drug: Placebo to match MMV390048 40 mg

MMV390048 80 mg

EXPERIMENTAL

MMV390048 80 mg, tablets, single dose

Drug: MMV390048 80 mg

Placebo to match MMV390048 80 mg

PLACEBO COMPARATOR

Placebo to match MMV390048 80 mg, tablets, single dose

Drug: Placebo to match MMV390048 80 mg

MMV390048 120 mg

EXPERIMENTAL

MMV390048 120 mg, tablets, single dose

Drug: MMV390048 120 mg

Placebo to match MMV390048 120 mg

PLACEBO COMPARATOR

Placebo to match MMV390048 120 mg, tablets, single dose

Drug: Placebo to match MMV390048 120 mg

Interventions

MMV390048 40 mg DRUG

MMV390048 40 mg

Placebo to match MMV390048 40 mg DRUG

Placebo to match MMV390048 40 mg

MMV390048 80 mg DRUG

MMV390048 80 mg

Placebo to match MMV390048 80 mg DRUG

Placebo to match MMV390048 80 mg

MMV390048 120 mg DRUG

MMV390048 120 mg

Placebo to match MMV390048 120 mg DRUG

Placebo to match MMV390048 120 mg

Eligibility Criteria

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

You may qualify if:

• Completion of the written informed consent process.
• 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.
• 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.
• 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).
• 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.
• Total body weight greater than 50 kg and a body mass index (BMI) within the range of 18 to 32 kg/m2 (inclusive).

You may not qualify if:

• Male subjects with a female partner(s) who is (are) pregnant or lactating from the time of the administration 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.
• 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).
• 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.
• 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.
• Any surgical or medical condition possibly affecting drug absorption (e.g. cholecystectomy, gastrectomy, bowel disease, etc.), distribution, metabolism or excretion.
• Previous splenectomy.
• A history of photosensitivity.
• 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)
• 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

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Clinical Network Services (CNS) Pty Ltd: collaborator
• Q-Pharm Pty Limited: collaborator
• QIMR Berghofer Medical Research Institute: collaborator

Study Sites (1)

Q Pharm Clinics

Herston, QLD 4006, Australia

Location

Related Publications (1)

• McCarthy JS, Donini C, Chalon S, Woodford J, Marquart L, Collins KA, Rozenberg FD, Fidock DA, Cherkaoui-Rbati MH, Gobeau N, Mohrle JJ. A Phase 1, Placebo-controlled, Randomized, Single Ascending Dose Study and a Volunteer Infection Study to Characterize the Safety, Pharmacokinetics, and Antimalarial Activity of the Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048. Clin Infect Dis. 2020 Dec 17;71(10):e657-e664. doi: 10.1093/cid/ciaa368.

  PMID: 32239164 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
• Organization: Medicines for Malaria Venture

doninic@mmv.org

+41 22 555 0312

Study Officials

• James McCarthy, Prof

  Q-Pharm Pty Ltd and QIMR Berghofer Medical Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: May 19, 2016
• First Posted: May 26, 2016
• Study Start: May 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: June 11, 2020
• Results First Posted: June 11, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)