A Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of PLX-4545 in Healthy Volunteers
A Phase 1, Randomized, Placebo-Controlled, Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of PLX-4545 in Healthy Subjects
Plexium Australia Pty Ltd
96 participants
Nov 21, 2023
Interventional
Conditions
Summary
The purpose of this study is to assess the safety, tolerability (how well an individual can tolerate a drug), pharmacokinetics (how a drug moves into, through and out of the body) and pharmacodynamics (the effect of a drug on the body) of single and multiple ascending doses of PLX-4545 in healthy volunteers. PLX-4545 may be indicated for use in patients with cancer that present as solid tumours, but a trial of the drug in healthy volunteers is needed before trials in cancer patients can proceed. Who is it for? You may be eligible for this study if you are aged 18 to 65 years and are in good general health without a clinically significant medical history. People who have been diagnosed with cancer will not be eligible for this study. Study details This trial will be conducted across three parts. In the first study (Part 1), healthy volunteer participants will be assigned by chance to receive either a single dose of PLX-4545 or placebo, to be taken after a fasting period. All participants will have their vital signs checked (heart rate, blood pressure, temperature, etc), and will provide blood samples for testing. If the drug appears safe, additional participants will be assigned by chance to receive a larger single dose of PLX-4545 or placebo, followed by blood testing. This will continue until a maximum safe dose is determined. In the second study (Part 2), healthy volunteer participants will be assigned by chance to receive either multiple doses of PLX-4545 or placebo to be taken once per day for 14 days. All participants will have their vital signs checked (heart rate, blood pressure, temperature, etc), and will provide blood samples for testing. If the drug appears safe, additional participants will be assigned by chance to receive a larger daily dose of PLX-4545 or placebo for 14 days, followed by blood testing. This will continue until a maximum safe dose is determined. In the third study (Part 3), healthy volunteer participants will be assigned by chance to receive either a single dose of PLX-4545 after fasting conditions or immediately after a high fat meal. All participants will have their vital signs checked and will provide blood samples for testing to determine the effect of food on PLX-4545. Once participants have completed their first dose, they will be asked to take another dose either after fasting or a meal, whichever they did not do for the first dose round. It is hoped this research will determine the maximum dose of PLX-4545 that can be administered safely without causing severe reactions. The healthy volunteer study will help define the starting doses of PLX-4545 to be evaluated in a subsequent Phase 1 clinical trial in cancer patients for determining the recommended dose to support a Phase 2 clinical study.
Eligibility
Inclusion Criteria7
- A participant is eligible for inclusion in this study if all of the following criteria are met:
- Male or female subjects 18 years to 65 years old at the time of informed consent.
- Must have a body mass index of 18.5 to 32.0 kg/m2, inclusive, and weigh at least 50 kg at Screening.
- Must be otherwise healthy and free from illness or disease as determined by medical history, vital signs, physical examinations, ECGs, laboratory studies, and/or other tests performed within 28 days prior to drug administration, as judged by the Investigator.
- Must be able to swallow capsules.
- Must be willing and able to understand the study procedures and comply with all aspects of the protocol and confinement periods.
- Must be able to give signed informed consent and any locally required authorization prior to any protocol-related procedures.
Exclusion Criteria14
- Participants are not eligible for this study if any of the following criteria apply:
- Has presence or history of hypersensitivity to murine proteins or any drug or other allergies which are considered, in the opinion of the Investigator, to contraindicate study participation.
- Has recently received any vaccination within 12 weeks prior to randomization, or who intends to receive a live vaccination during the study.
- Is known to be seropositive for human immunodeficiency virus (HIV).
- Has a positive result for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen, or antibody to hepatitis C virus (HCV).
- Use of any investigational drug or product, or participation in an investigational drug study within 30 days prior to dosing or 5 half-lives of the drug (whichever is longest).
- Has previous exposure to antibody therapies within 6 months or administration of immunoglobulins within 6 months prior to study drug administration.
- Has a history of donating 1 unit of blood (450 mL) in the 3 months prior to study drug administration or who intends to donate within 3 months of their last scheduled study visit.
- Has a history of hypertension or a blood pressure >160/90 mmHg at Screening or a history of recurrent hypotensive events considered as clinically relevant or a blood pressure <95/50 mmHg at Screening.
- Is currently taking or who has taken any prescription or non-prescription medication within 7 days of study drug administration including aspirin, dietary or mega dose vitamin supplements, and herbal preparations (except paracetamol, hormone replacement therapies, and/or hormonal contraceptives).
- Active smoker and/or user of nicotine-containing products unless the participant agrees to discontinue smoking/use of nicotine-containing products from 2 weeks before first study drug administration through to study completion, including the Follow-up period.
- Has a history of febrile illness within 5 days prior to the first dose or symptoms of and active infection within 14 days prior to first dose.
- Unable to adhere to the required dietary restrictions
- Criteria, that in the opinion of the investigator, would interfere with the subject's participation in the study.
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Interventions
The study is designed to evaluate the safety, pharmacokinetics and pharmacodynamics in healthy adult participants after administration of increasing doses of PLX-4545. The study consists of 3 parts (unique participants will only be enrolled in each part): - Part 1: Single Ascending Dose (SAD): participants will receive a single oral dose of PLX-4545 (2.5 mg up to 200 mg) or placebo. Dosing will occur in the clinic. - Part 2: Multiple Ascending Dose (MAD): participants will receive a single oral dose of PLX-4545 (10 mg up to 200 mg) or placebo daily for 14 days. Part 2 will commence after at least 3 cohorts have completed Part 1. Dosing will occur in the clinic. - Part 3: Food Effect (FE): participants will receive a single dose of PLX-4545 under fed (consumption of breakfast comprising 507g fat, 139 g protein, 284g carbohydrate) and fasted (minimum 10 hours with water permitted) conditions. A 7-day washout is required between dosing in the fasting and fed conditions. Part 3 will commence after completion of Part 1. Dosing will occur in the clinic.
Locations(1)
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ACTRN12623001265662