Healthy
Conditions
Keywords
Fosmanogepix, Manogepix, Chinese, Pharmacokinetics, Healthy adults
Brief summary
The purpose of this study was to investigate the pharmacokinetics and safety of the investigational drug fosmanogepix including its active moiety manogepix following a single dose and multiple doses (by intravenous infusion (IV) or orally) in healthy Chinese adults. The study consisted of 2 consecutive Parts (Part-1, single-dose part followed by Part-2, multiple-dose part) including a total of 54 subjects (32 subjects in Part-1 and 22 subjects in PART-2) randomized.
Detailed description
Part-1 duration including screening period was up to 64 days including 4 visits at the clinical site and Part-2 duration including screening period was up to 70 days including 5 visits at the clinical site. The study included a total of 4 study sub-groups (Cohorts 1-4) in which fosmanogepix or placebo was administered in different strengths orally or IV. Subjects were enrolled and randomly assigned to study drug. During the study, serial blood samples were collected to understand how fosmanogepix was changed and eliminated from the body. The primary objective of PART-1 (Single-dose) was to evaluate the pharmacokinetic (PK) profile of manogepix (active moiety of fosmanogepix) after single dose administration in healthy adult Chinese subjects. The primary objective of PART-2 (Multiple-dose) was to evaluate the PK profile of manogepix (active moiety of fosmanogepix) after repeated doses in healthy adult Chinese subjects. All data analyses are descriptive (no statistical analysis is provided).
Interventions
DRUGOral Fosmanogepix
Oral Tablet
DRUGIV Fosmanogepix
IV infusion
DRUGIV placebo
Matching IV placebo
DRUGoral placebo
Matching oral placebo
Sponsors
Basilea Pharmaceutica
Biomedical Advanced Research and Development Authority
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Main criteria for inclusion and exclusion: * Body mass index (BMI) of 18.0 to 30.0 kg/m2 inclusive, and a total body weight \> 45 kg for females and \> 50 kg for males at Screening. * Subjects who were overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, vital signs, creatinine, and estimated creatinine clearance (Cockcroft-Gault formula). Main
Exclusion criteria
* Active acute or chronic infection, including, but not limited to upper airway infection, urinary tract infection, or skin infection at Screening. * Any condition possibly affecting drug absorption. * Medical history of neurological disorders including abnormal movements or seizures. * Use of prescription or non-prescription drugs, including vaccines, and dietary and herbal supplements from Screening or within five half-lives (whichever is longer) prior to the first dose of study drug and throughout the study. * Screening supine blood pressure (BP) ≥ 140 mmHg (systolic) or ≥ 90 mmHg (diastolic), and pulse rate (PR) \> 100 beats per minute (bpm) or \< 50 bpm, following at least 5 minutes of supine rest. * Body temperature higher than 37.5 °C. * Screening supine 12 lead ECG demonstrating clinically relevant abnormalities that may affect subject safety or interpretation of study results. * Subjects with any of the following abnormalities in clinical laboratory tests at Screening, as assessed by the local laboratory and confirmed by a single repeat test, if deemed necessary: * AST or ALT ≥ 1.0 × ULN. * Total bilirubin ≥ 1.5 × ULN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Manogepix in Part-1 | pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240 hours postdose | Pharmacokinetic (PK) parameter Cmax for manogepix after a single oral administration of 400 mg or 800 mg fosmanogepix or after a single IV infusion of 600 mg or 1,000 mg fosmanogepix over 3 hours to healthy Chinese subjects |
| Time to Peak Manogepix Concentration (Tmax) of Manogepix in Part-1 | pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240 hours postdose | PK parameter Tmax for manogepix after a single oral administration of 400 mg or 800 mg fosmanogepix or after a single IV infusion of 600 mg or 1,000 mg fosmanogepix over 3 hours to healthy Chinese subjects |
| Area Under the Plasma Concentration vs. Time Curve for 0-24 Hours (AUC24) of Manogepix in Part-1 | pre-dose, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose | PK parameter AUC 24 for manogepix after a single oral administration of 400 mg or 800 mg fosmanogepix or after a single IV infusion of 600 mg or 1,000 mg fosmanogepix over 3 hours to healthy Chinese subjects |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Manogepix in Part-1 | pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240 hours postdose | PK parameter AUClast for manogepix after a single oral administration of 400 mg or 800 mg fosmanogepix or after a single IV infusion of 600 mg or 1,000 mg fosmanogepix over 3 hours to healthy Chinese subjects |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Manogepix in Part-1 | pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240 hours postdose | PK parameter AUC (0 - ∞) for manogepix after a single oral administration of 400 mg or 800 mg fosmanogepix or after a single IV infusion of 600 mg or 1,000 mg fosmanogepix over 3 hours to healthy Chinese subjects |
| Maximum Observed Plasma Concentration (Cmax) of Manogepix in Part-2 | pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240, 360 hours postdose on Day 7 | PK parameter Cmax after fosmanogepix administration as an IV infusion twice 12 hours apart on Day 1 followed by an IV maintenance daily dose from Day 2 to Day 7 or followed by an IV maintenance dose on Day 2 and Day 3, and then switched to oral administration (of fosmanogepix or placebo) daily from Day 4 to Day 7 |
| Time to Peak Manogepix Concentration (Tmax) of Manogepix in Part-2 | pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240, 360 hours postdose on Day 7 | PK parameter Tmax after fosmanogepix administration as an IV infusion twice 12 hours apart on Day 1 followed by an IV maintenance daily dose on Day 2 and Day 3, and then switched to oral administration (of fosmanogepix or placebo) daily from Day 4 to Day 7 |
| Area Under the Concentration-time Curve at Steady State Over the Dosing Interval Tau (AUCtau) of Manogepix in Part-2 | pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240, 360 hours postdose on Day 7 | PK parameter AUCtau after fosmanogepix administration as an IV infusion twice 12 hours apart on Day 1 followed by an IV maintenance daily dose from Day 2 to Day 7 or followed by an IV maintenance dose on Day 2 and Day 3, and then switched to oral administration (of fosmanogepix or placebo) daily from Day 4 to Day 7 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fraction of Unbound Manogepix in Plasma in Part 1 | pre-dose and 3 hours postdose | The fraction of unbound manogepix has been assessed after single dose administration (oral / IV) |
| Number of Subjects With Treatment-emergent AE (TEAE) in Part-1 | Up to 36 days | A TEAE was defined as any event not present prior to the first administration of the study drug, or any event already present that worsens in either severity or frequency following exposure to the study drug |
| Number of Subjects With TEAE in Part-2 | Up to 42 days | A TEAE was defined as any event not present prior to the first administration of the study drug, or any event already present that worsens in either severity or frequency following exposure to the study drug |
Countries
China
Participant flow
Recruitment details
The study was conducted at one site in China
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 33.2 years STANDARD_DEVIATION 5.84 |
| BMI (kg/m2) | 21.35 Kg/m2 STANDARD_DEVIATION 1.1 |
| Height (cm) | 160.7 Cm STANDARD_DEVIATION 10.67 |
| Race/Ethnicity, Customized Asian | 52 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 5 Participants |
| Weight (kg) | 65.70 Kg STANDARD_DEVIATION 8.45 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 4 |
| other Total, other adverse events | 5 / 6 | 3 / 6 | 0 / 6 | 1 / 6 | 0 / 8 | 5 / 8 | 7 / 8 | 2 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 4 |
Outcome results
None listed