Safety, Pharmacokinetics, Bioavailability, Food Effect, Drug-Drug Interaction Study of APX001 Administered Orally

A Phase 1, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of APX001, to Investigate the Effect of Food on APX001 and to Investigate the Drug-Drug Interaction Potential of APX001

This is a Phase l double-blind, placebo-controlled, randomized study to investigate the safety, tolerability, pharmacokinetics, bioavailability and food effect of single doses of APX001 administered intravenously and orally, followed by an evaluation of the safety, tolerability, pharmacokinetics and drug-drug interaction potential of multiple doses of APX001 administered orally.

Study Overview

• Status: Completed
• Conditions: Fungal Infection
• Intervention / Treatment: Drug: APX001 single IV dose; Drug: Matching placebo control; Drug: APX001 single oral dose 1; Drug: APX001 single oral dose 2; Drug: APX001 single oral dose 3; Drug: APX001 single oral dose fasted; Drug: APX001 single oral dose fed; Drug: APX001 multiple oral doses 1; Drug: APX001 multiple oral doses 2; Drug: APX001 multiple oral doses 3; Drug: Cytochrome P450 substrates

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • PRA Health Sciences
  • Groningen, Netherlands, 9728 NZ
    • PRA Health Sciences (PRA) - Early Development Services (EDS)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Women of childbearing potential must agree to avoid pregnancy during the study and to use contraception at least 2 weeks before the start of the study until 3 months after the last dose of study drug.
• Males with partner(s) of childbearing potential must agree to use appropriate barrier contraception from the screening period until 3 months after the last dose of study drug.
• Screening hematology, clinical chemistry, coagulation and urinalysis consistent with overall good health.
• No significantly abnormal findings on physical examination, ECG and vital signs.
• Willing and able to provide written informed consent.

Exclusion Criteria:

• Any uncontrolled or active major systemic disease including, but not limited to: cardiovascular, pulmonary, gastrointestinal, metabolic, urogenital, neurological, immunological, psychiatric, or neoplastic disorder with metastatic potential.
• History or presence of malignancy within the past year. Subjects who have been successfully treated with no recurrence of basal cell carcinoma of the skin or carcinoma in-situ of the cervix may be enrolled.
• Use of prescription medication within 14 days prior to the first dose of study drug and throughout the study.
• Use of non-prescription or over-the-counter medications within 7 days prior to the first dose of study drug and throughout the study.
• Positive results on any of the following Screening laboratory tests: serum pregnancy test, urine alcohol test, urine drugs of abuse, hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1a, Period A; single intravenous dose, crossover	Drug: APX001 single IV dose; Drug: Matching placebo control
Experimental: Cohort 1a, Period B; single oral dose, crossover	Drug: Matching placebo control; Drug: APX001 single oral dose 1
Experimental: Cohort 1a, Period C; single oral dose	Drug: Matching placebo control; Drug: APX001 single oral dose 2
Experimental: Cohort 1a, Period D; single oral dose, crossover	Drug: Matching placebo control; Drug: APX001 single oral dose 3
Experimental: Cohort 1b, Period E; Single oral dose under fasted conditions, crossover	Drug: Matching placebo control; Drug: APX001 single oral dose fasted
Experimental: Cohort 1b, Period F; Single oral dose under fed conditions, crossover	Drug: Matching placebo control; Drug: APX001 single oral dose fed
Experimental: Cohort 2; Multiple oral doses	Drug: Matching placebo control; Drug: APX001 multiple oral doses 1
Experimental: Cohort 3; Multiple oral doses	Drug: Matching placebo control; Drug: APX001 multiple oral doses 2
Experimental: Cohort 4; Multiple oral doses in presence of CYP probe substrates	Drug: APX001 single IV dose; Drug: APX001 multiple oral doses 3; Drug: Cytochrome P450 substrates

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of single and multiple oral doses of APX001 as measured by adverse events (AEs), physical examinations (PE), vital signs (VS), laboratory safety tests, urinalysis and 12-lead electrocardiograms (ECG).	21 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics of single and multiple doses of APX001 as measured by maximum observed concentration (Cmax).	21 days
Pharmacokinetics of single and multiple doses of APX001 as measured by volume of distribution (Vd).	21 days
Pharmacokinetics of single and multiple doses of APX001 as measured by elimination rate constant (Kel).	21 days
Pharmacokinetics of single and multiple dose of APX001 as measured by area under the curve (AUC).	21 days
Pharmacokinetics of single and multiple doses of APX001 as measured by terminal half life (t1/2).	21 days
Pharmacokinetics of single and multiple doses of APX001 as measured by accumulation ratio.	21 days

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2016
• Primary Completion (Actual): April 20, 2017
• Study Completion (Actual): April 20, 2017

Study Registration Dates

• First Submitted: November 1, 2016
• First Submitted That Met QC Criteria: November 4, 2016
• First Posted (Estimate): November 8, 2016

Study Record Updates

• Last Update Posted (Actual): September 26, 2022
• Last Update Submitted That Met QC Criteria: September 23, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses
• Other Study ID Numbers: APX001-102; C4791002 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO