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

Phase 1

Completed

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

• Registration Number: NCT02957929
• Lead Sponsor: Basilea Pharmaceutica

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-10-31
• Study First Submitted: 2016-11-01
• Study First Submitted QC: 2016-11-04
• Study First Posted: 2016-11-08
• Primary Completion: 2017-04-20
• Study Completion: 2017-04-20
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-16
• Last Update Posted: 2024-05-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 maximum observed concentration (Cmax).	21 days
Pharmacokinetics of single and multiple doses of APX001 as measured by accumulation ratio.	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 volume of distribution (Vd).	21 days

Trial Locations

Locations (2)

PRA Health Sciences (PRA) - Early Development Services (EDS); 🇳🇱 Groningen, Netherlands

PRA Health Sciences; 🇳🇱 Groningen, Netherlands