A Bioequivalence Study of APX001 High-load and Low-load Tablets

A 3-Treatment, 3-Period, 6-Sequence Randomized Crossover Single-Dose Study Evaluating the Bioequivalence of High-Load and Low-Load Oral Tablet Formulations of Apx001 and the Effect of Food on the Absorption of Apx001 From the High-Load Tablet In Healthy Subjects

A study to learn about the bioequivalence (the biochemical similarity of two medicines that share the same active ingredient and desired outcome for patients) of the study medicine called APX001 in healthy participants.

Study Overview

• Status: Completed
• Conditions: Invasive Fungal Infections
• Intervention / Treatment: Drug: APX001; Drug: APX001A

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Pharmaceuticals Research Associates, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive.
• Minimum body weight of 50 kg.
• Screening hematology, clinical chemistry, coagulation, and urinalysis consistent with overall good health and having an estimated glomerular filtration rate (eGFR) >80 mL/min, based on creatinine clearance calculation by the Cockcroft-Gault formula.

Exclusion Criteria:

• Having 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 neurological disorders including abnormal movements or seizures.
• 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.
• Significant and/or acute illness or chronic infection, as judged by the investigator, including, but not limited to: upper airway infection, urinary tract infection, or skin infection within 30 days prior to the first study drug administration.
• Taking any drug or herbal CYP3A modulator (e.g., erythromycin; St. John's Wort) within 4 weeks (or 5 half-lives, whichever is longer) or any other nutrients known to modulate CYP3A activity (e.g., grapefruit juice; Seville orange) within 2 weeks prior to the first admission.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: APX001 Treatment A; Oral tablet with a 25% drug load (low-load) in fasted participants	Drug: APX001; Low-load oral tablet; Other Names: fosmanogepix; Drug: APX001A; High-load oral tablet; Other Names: fosmanogepix
Experimental: APX001A Treatment B; Oral tablet with a high drug load in fasted participants	Drug: APX001; Low-load oral tablet; Other Names: fosmanogepix; Drug: APX001A; High-load oral tablet; Other Names: fosmanogepix
Experimental: APX001A Treatment C; Oral tablet with a high drug load in participants that are not fasted.	Drug: APX001; Low-load oral tablet; Other Names: fosmanogepix; Drug: APX001A; High-load oral tablet; Other Names: fosmanogepix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax)	Predose, 0.5, 1, 2, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 168, and 312 hours post dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)	Predose, 0.5, 1, 2, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 168, and 312 hours post dose
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Predose, 0.5, 1, 2, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 168, and 312 hours post dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]	Predose, 0.5, 1, 2, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 168, and 312 hours post dose
Area Under the Curve From Time Zero to 24 hours (AUC0-24)	Predose, 0.5, 1, 2, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 168, and 312 hours post dose
Percentage of Area Under the Curve Extrapolated to Infinity (%AUCextra)	Predose, 0.5, 1, 2, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 168, and 312 hours post dose
Plasma Decay Half-Life (t1/2)	Predose, 0.5, 1, 2, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 168, and 312 hours post dose
Apparent Terminal Elimination Rate Constant (λz)	Predose, 0.5, 1, 2, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 168, and 312 hours post dose
Apparent Total clearance, Calculated as Dose/AUCinf (CL/F)	Predose, 0.5, 1, 2, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 168, and 312 hours post dose
Apparent Volume of Distribution at Terminal Phase (Vz/F)	Predose, 0.5, 1, 2, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 168, and 312 hours post dose
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)	Baseline through Day 14
Number of Participants With Change From Baseline in Laboratory Tests Results	Baseline through Day 14
Number of Participants With Clinically Significant Change in Vital Signs	Baseline through Day 14
Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Abnormalities	Baseline through Day 14
Number of Participants With Abnormalities in Physical Examinations	Baseline through Day 14

Collaborators and Investigators

• Sponsor: Basilea Pharmaceutica
• Investigators: Study Director: Marc Engelhardt, Basilea Pharmaceutica International Ltd, Allschwil

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): March 2, 2021
• Primary Completion (Actual): May 13, 2021
• Study Completion (Actual): June 23, 2021

Study Registration Dates

• First Submitted: August 4, 2022
• First Submitted That Met QC Criteria: August 4, 2022
• First Posted (Actual): August 8, 2022

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: candida; fosmanogepix; aspergillus; fusarium; mucorales; rhizopus; scedosporium
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Invasive Fungal Infections
• Other Study ID Numbers: APX001-108; C4791008 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No