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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT05491733

Collaborator

(none)

Enrollment

Location

Arms

3.7

Actual Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Invasive Fungal Infections	Drug: APX001 Drug: APX001A	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Mar 2, 2021

Actual Primary Completion Date :

May 13, 2021

Actual Study Completion Date :

Jun 23, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.