A FIH Study to Investigate the Safety, Tolerability and PK of P218

NCT02885506 | Completed Phase 1 Results DMC

• 2 other identifiers: MMV_P218_15_012016-001933-29
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The First in Human (FIH) study is separated into two parts:

• The first part is a Single Ascending Dose (SAD), double-blinded, randomized and placebo-controlled, including 8 cohorts of 8 subjects (2 placebo and 6 on active drug).
• The second part is a food effect cohort with an open-labelled, randomized fed/fasted cross-over design. The main objectives of the study are to confirm safety, tolerability and Pharmacokinetics (PK) of P218 in healthy volunteers.

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of P218: Incidence, Severity and Relationship to the Investigational Product of Observed and Self-reported Adverse Events

  Number of participants with adverse events

  During 11 days post administration of a single oral dose of P218 to healthy volunteers

Secondary Outcomes (7)

• Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast)

  During 11 days post administration of a single oral dose of P218 to healthy volunteers

• Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)

  During 11 days post administration of a single oral dose of P218 to healthy volunteers

• Maximum Plasma Drug Concentration (Cmax)

  During 11 days post administration of a single oral dose of P218 to healthy volunteers

• Time to Reach Maximum (Peak) Plasma Concentration Following Drug Administration (Tmax)

  During 11 days post administration of a single oral dose of P218 to healthy volunteers

• Elimination Half-life (t1/2)

  During 11 days post administration of a single oral dose of P218 to healthy volunteers

Study Arms (10)

Cohort 1

EXPERIMENTAL

Oral administration of P218 capsules 10 mg

Drug: Oral administration of P218 capsules

Cohort 2

EXPERIMENTAL

Oral administration of P218 capsules 30 mg

Drug: Oral administration of P218 capsules

Cohort 3

EXPERIMENTAL

Oral administration of P218 capsules 100 mg

Drug: Oral administration of P218 capsules

Cohort 4

EXPERIMENTAL

Oral administration of P218 capsules 250 mg

Drug: Oral administration of P218 capsules

Cohort 5

EXPERIMENTAL

Oral administration of P218 capsules 500 mg

Drug: Oral administration of P218 capsules

Cohort 6

EXPERIMENTAL

Oral administration of P218 capsules 750 mg

Drug: Oral administration of P218 capsules

Cohort 7

EXPERIMENTAL

Oral administration of P218 capsules 1000 mg

Drug: Oral administration of P218 capsules

Cohort 8 - Pooled Placebo

PLACEBO COMPARATOR

Oral administration of P218 matching placebo

Drug: Oral administration of P218 matching placebo

Fed - Fasted

EXPERIMENTAL

Oral administration of P218 capsules 250 mg Under fed then fasted conditions.

Drug: Oral administration of P218 capsules

Fasted - Fed

EXPERIMENTAL

Oral administration of P218 capsules 250 mg Under fasted then fed conditions.

Drug: Oral administration of P218 capsules

Interventions

Oral administration of P218 capsules DRUG

Oral administration of P218 capsules. The number of capsules is determined by the dose level of the cohort.

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6; Cohort 7; Fasted - Fed; Fed - Fasted

Oral administration of P218 matching placebo DRUG

Oral administration of P218 matching placebo. The number of capsules is identical to the corresponding number of P218 capsules administered to the volunteers on the investigational drug.

Cohort 8 - Pooled Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is a healthy male or female (of non-childbearing potential), aged 18 to 45 years, inclusive.
• Satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, physical examination, vital signs, 12-lead electrocardiograms (ECG), and clinical laboratory evaluation (haematology, biochemistry, coagulation, and urinalysis) that is reasonably likely to interfere with the subject's participation in or ability to complete the study as assessed by the Investigator.
• Subject has a body weight of at least 50 kg and a Body Mass Index (BMI) of 18-25 Kg/m2, inclusive.
• Female subjects must be of non-childbearing potential:
• Natural (spontaneous) post-menopausal defined as being amenorrheic for at least 12 months without an alternative medical cause with a screening follicle stimulating hormone level \> 25 IU/L (or at the 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).
• Heterosexually active male subjects with a female spouse/partner of childbearing potential must agree to use barrier contraception (male condom), even with documented medical assessment of surgical success of a vasectomy, if your partner could become pregnant from the time of the first administration of P218 and for 100 days following this. Your partner must also use a method of highly effective contraception including:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• Oral
• Intravaginal
• Transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:
• Oral
• Injectable
• Implantable

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 hematological, renal, endocrine, pulmonary, gastrointestinal (including gallbladder), cardiovascular, 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).
• 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 surgical or medical condition possibly affecting drug absorption (e.g. cholecystectomy, gastrectomy, bowel disease, etc.), distribution, metabolism or excretion.
• Any history of gallbladder disease, including cholecystitis and/or cholelithiasis.
• 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 of megaloblastic anaemia or folate deficiency.
• History or clinical evidence of substance and/or alcohol abuse within the 12 months before screening. Alcohol abuse is defined as regular weekly intake of more than 21 units for males and 14 units for females (using alcohol tracker http://www.nhs.uk/Tools/Pages/NHSAlcoholtracker.aspx).
• Treatment with an investigational drug within 90 days or 5 half-lives preceding the first dose of study medication (or as determined by the local requirement, whichever is the longer).
• Donation of blood or blood products (excluding plasma) within 90 days prior to study medication administration.
• Use of moderate/strong inhibitors or inducers of Cytochromes P450 (CYP450) or transporters within 30 days or 5 half-lives (whichever is the longer) prior to the first dose of study medication.
• Consumption of grapefruit, grapefruit juice or grapefruit-related citrus fruits (e.g. Seville oranges, pomelos) within 30 days prior to the first dose of study medication.
• Ingestion of any poppy seeds within the 24 hours prior to screening.

Sponsors & Collaborators

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

Study Sites (1)

Richmond Pharmacology Ltd

Croydon, Surrey, CR7 7YE, United Kingdom

Location

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

0041 22 555 0312

Study Officials

• Emilie Rossignol, PhD

  Medicines for Malaria Venture

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• 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: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Part A of the study was conducted as a dose escalation, and that Part B utilized a cross-over design.

Study Record Dates

• First Submitted: August 19, 2016
• First Posted: August 31, 2016
• Study Start: August 24, 2016
• Primary Completion: December 4, 2017
• Study Completion: December 4, 2017
• Last Updated: August 1, 2019
• Results First Posted: August 1, 2019

Record last verified: 2019-05

Locations

GB (1)