Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PLX5622 in Healthy Adult Volunteers

A Phase 1 First in Human Double-Blind, Placebo-Controlled, Randomized, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PLX5622 in Healthy Adult Volunteers

The purpose of this study is to study the safety and tolerability of a single dose of PLX5622 in healthy, adult human volunteers. This will be the first time PLX5622 has been taken by humans.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PLX5622; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Cetero Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adult male and female subjects, 18-65 years of age inclusive
• BMI 18 to 32 kg/m2 inclusive
• Female subjects must be surgically sterile or postmenopausal for the past year and have a negative urine pregnancy test. Male subjects and their partners of childbearing potential must be willing to use two methods of contraception, one of which must be a barrier method (e.g. condom) for up to 90 days after the last study drug administration.
• Willing and able to remain in the clinical research unit as required by the protocol
• Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements

Exclusion Criteria:

• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
• History or presence of any disease, medical condition, or surgery, which may have an effect on drug absorption, metabolism, distribution, or excretion of the investigational product
• Laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel, and urinalysis) that the investigator believes show clinically relevant significant abnormalities for the normal reference range
• Any abnormality in the ECG (including QTc ≥450 msec) that in the opinion of the investigator increases the risk of participating in the study
• History or presence of alcoholism or drug abuse within the year prior to dosing
• Tobacco use, either current or within 3 months prior to dosing
• Use of any prescription medications or herbal remedies within 14 days prior to dosing, or use of over-the-counter medications or vitamins within 7 days prior to dosing, unless approved by the Sponsor
• Donation of whole blood within 56 days prior to the study
• Plasma donation within 7 days prior to the study
• Participation in an investigational device study or receipt of an investigational drug within 4 weeks prior to dosing
• Positive urine test for drugs of abuse
• Confirmed HIV, hepatitis B, or hepatitis C infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: single oral dose of 200 mg PLX5622; 6 subjects will be randomized to take a single oral dose of PLX5622 and 2 subjects will be randomized to take placebo.	Drug: PLX5622; PLX5622 drug substance is an achiral,small molecule Fms kinase inhibitor. The drug product is available in capsule form, to be taken orally, in dosage strengths of 25 mg and 100 mg with matching placebo
Active Comparator: single oral dose of 400 mg PLX5622; 6 subjects will be randomized to take a single oral dose of PLX5622 and 2 subjects will be randomized to take placebo.	Drug: PLX5622; PLX5622 drug substance is an achiral,small molecule Fms kinase inhibitor. The drug product is available in capsule form, to be taken orally, in dosage strengths of 25 mg and 100 mg with matching placebo
Active Comparator: single oral dose of 800 mg PLX5622; 6 subjects will be randomized to take a single oral dose of PLX5622 and 2 subjects will be randomized to take placebo.	Drug: PLX5622; PLX5622 drug substance is an achiral,small molecule Fms kinase inhibitor. The drug product is available in capsule form, to be taken orally, in dosage strengths of 25 mg and 100 mg with matching placebo
Active Comparator: single oral dose of 1600 mg PLX5622; 6 subjects will be randomized to take a single oral dose of PLX5622 and 2 subjects will be randomized to take placebo.	Drug: PLX5622; PLX5622 drug substance is an achiral,small molecule Fms kinase inhibitor. The drug product is available in capsule form, to be taken orally, in dosage strengths of 25 mg and 100 mg with matching placebo
Active Comparator: single oral dose of 1000 mg PLX5622; 6 subjects will be randomized to take a single oral dose of PLX5622 and 2 subjects will be randomized to take placebo.	Drug: PLX5622; PLX5622 drug substance is an achiral,small molecule Fms kinase inhibitor. The drug product is available in capsule form, to be taken orally, in dosage strengths of 25 mg and 100 mg with matching placebo
Active Comparator: single oral dose of 1400 mg PLX5622; 6 subjects will be randomized to take a single oral dose of PLX5622 and 2 subjects will be randomized to take placebo.	Drug: PLX5622; PLX5622 drug substance is an achiral,small molecule Fms kinase inhibitor. The drug product is available in capsule form, to be taken orally, in dosage strengths of 25 mg and 100 mg with matching placebo
Placebo Comparator: Placebo; 2 patients per cohort will be randomly assigned to take placebo. 12 patients total will be randomized to take placebo in this study.	Drug: Placebo; Matching placebo for PLX5622.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety-Number of patients with adverse events	Subjects will take one oral dose of PLX5622 on Day 1. Physical examinations, vital signs, 12-lead electrocardiograms (ECG), adverse events, hematology, serum chemistry, coagulation, and urinalysis will be used to assess safety throughout the Days 1-4 of the study and on the follow up study visit on day 7. Adverse events will be monitored and reviewed for safety issues/abnormal changes in the above mentioned tests.	7 days
Tolerability-Number of patients with adverse events	Subjects will take one oral dose of PLX5622 on Day 1. Physical examinations, vital signs, 12-lead electrocardiograms (ECG), adverse events, hematology, serum chemistry, coagulation, and urinalysis will be used to assess safety throughout the Days 1-4 of the study and on the follow up study visit on day 7. Adverse events will be monitored and reviewed for tolerability issues/abnormal changes in the above mentioned tests.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profile: Measurement of area under the plasma-concentration-time curve	Pharmacokinetic (PK) samples will be collected prior to dosing and at 0.5, 1, 2, 4, 8, 12, 24, 26, 48, 60 and 72 hours following dosing. The pharmacokinetic profile of plasma PLX5622 will be analyzed by measurement of area under the plasma concentration-time curve [AUC0-t, AUC0-inf, AUC0-24].	7 days
Pharmacokinetic evaulation: Measurement of Peak Concentration	Pharmacokinetic (PK) samples will be collected prior to dosing and at 0.5, 1, 2, 4, 8, 12, 24, 26, 48, 60 and 72 hours following dosing. The pharmacokinetic profile of plasma PLX5622 will be analyzed by measurement of peak concentration (Cmax) and time to peak concentration (Tmax).	7 days
Pharmacokinetic profile: Measurement of half life and terminal elimination rate constant	Pharmacokinetic (PK) samples will be collected prior to dosing and at 0.5, 1, 2, 4, 8, 12, 24, 26, 48, 60 and 72 hours following dosing. The pharmacokinetic profile of plasma PLX5622 will be analyzed by measurement of half-life (T1/2), and terminal elimination rate constant (Kel).	7 Days

Collaborators and Investigators

• Sponsor: Plexxikon
• Investigators: Principal Investigator: Gregory Haugen, MD, Cetero Research, San Antonio

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: January 18, 2011
• First Submitted That Met QC Criteria: January 24, 2011
• First Posted (Estimate): January 25, 2011

Study Record Updates

• Last Update Posted (Estimate): March 30, 2015
• Last Update Submitted That Met QC Criteria: March 26, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Tolerability; PLX5622
• Other Study ID Numbers: PLX115-01