A Clinical Trial of the Study Medicine (Called Fosmanogepix) in Participants With Varying Degrees of Hepatic Function.

NCT05582187 | Completed Phase 1 FDA Drug

• 1 other identifier: C4791019
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

The primary purpose of this open-label study is to characterize the plasma pharmacokinetics (PK) of manogepix (active moiety of fosmanogepix) in participants with varying degrees of hepatic function following administration of a single oral dose of fosmanogepix. All participants will receive 1 dose of fosmanogepix by mouth before breakfast on the first day at the study clinic. Serial blood samples will be collected to understand how fosmanogepix is changed and eliminated from the body. Participants will also receive physical examination and other tests. This will help to understand if fosmanogepix is safe. Participants will be involved in this study for 4 to 9 weeks (maximum). There will be 2 to 4 study visits at the study clinic.

Conditions

Hepatic Impairment

Keywords

fosmanogepix; manogepix; hepatic impairment; PF-07842805; APX001; APX001a

Outcome Measures

Primary Outcomes (6)

• Maximum Observed Plasma Concentration (Cmax) of manogepix

  pre-dose, 1, 2, 3, 4, 5, 6, 12, 24, 48, 96, 168, 240 hours postdose

• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of manogepix

  pre-dose, 1, 2, 3, 4, 5, 6, 12, 24, 48, 96, 168, 240 hours postdose

• Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of manogepix

  pre-dose, 1, 2, 3, 4, 5, 6, 12, 24, 48, 96, 168, 240 hours postdose

• Unbound Maximum Observed Plasma Concentration (Cmaxu) of manogepix

  pre-dose, 1, 2, 3, 4, 5, 6, 12, 24, 48, 96, 168, 240 hours postdose

• Unbound Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastu) of manogepix

  pre-dose, 1, 2, 3, 4, 5, 6, 12, 24, 48, 96, 168, 240 hours postdose

• Unbound Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)u] of manogepix

  pre-dose, 1, 2, 3, 4, 5, 6, 12, 24, 48, 96, 168, 240 hours postdose

Secondary Outcomes (4)

• Number of Participants Reporting Treatment-emergent adverse events (AEs)

  Screening to follow-up (Day 28-35)

• Number of participants with clinically significant change from baseline in vital signs

  From Day -1 to Day 11

• Number of participants with clinically significant change from baseline in laboratory parameters

  From Day -1 to Day 11

• Number of participants with clinically significant change from baseline in electrocardiogram (ECG) findings

  From Day -1 to Day 11

Study Arms (5)

Cohort 1: Fosmanogepix participants with mild hepatic impairment

EXPERIMENTAL

Participants with mild hepatic impairment will receive a single dose of fosmanogepix, administered orally as 1 fosmanogepix tablet under fasted conditions.

Drug: Fosmanogepix

Cohort 2: Fosmanogepix Participants with moderate hepatic impairment

EXPERIMENTAL

Participants with moderate hepatic impairment will receive a single dose of fosmanogepix, administered orally as 1 fosmanogepix tablet under fasted conditions.

Drug: Fosmanogepix

Cohort 3: Fosmanogepix Participants with severe hepatic impairment

EXPERIMENTAL

Participants with severe hepatic impairment will receive a single dose of fosmanogepix, administered orally as 1 fosmanogepix tablet under fasted conditions.

Drug: Fosmanogepix

Cohort 4: Fosmanogepix Participants with normal hepatic function (control group)

EXPERIMENTAL

Participants with normal hepatic function will receive a single dose of fosmanogepix, administered orally as 1 fosmanogepix tablet under fasted conditions.

Drug: Fosmanogepix

Cohort 5: Fosmanogepix Participants with severe hepatic impairment (new dose level)

EXPERIMENTAL

Participants with severe hepatic impairment will receive a single dose of fosmanogepix, administered orally as 2 fosmanogepix tablets under fasted conditions.

Drug: Fosmanogepix

Interventions

Fosmanogepix DRUG

a single dose of fosmanogepix administered by mouth under fasted conditions

Cohort 1: Fosmanogepix participants with mild hepatic impairment; Cohort 2: Fosmanogepix Participants with moderate hepatic impairment; Cohort 3: Fosmanogepix Participants with severe hepatic impairment; Cohort 4: Fosmanogepix Participants with normal hepatic function (control group); Cohort 5: Fosmanogepix Participants with severe hepatic impairment (new dose level)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body mass index (BMI) of 17.5 to 40.0 kg/m2 (42 kg/m2 for participants of Cohort 3), inclusive; and a total body weight greater than 50 kg (greater than 110 lb)
• For participants with hepatic impairment (Cohorts 1-3, and Cohort 5): Stable hepatic impairment that meets the criteria for Class A, B, or C of the Child Pugh classification with no clinically significant change in disease status within the 28 days prior to the screening visit
• For participants with normal hepatic function (Cohort 4): No clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests
• Stable concomitant medications for the management of individual participants' medical history

You may not qualify if:

• Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection);
• Ongoing medical history of neurological disorders including abnormal movements or seizures (Note exception: stable history of peripheral neuropathy);
• Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy;
• A diagnosis of hepatic dysfunction secondary to any acute ongoing hepatocellular process that is documented by medical history, physical examination, liver biopsy, hepatic ultrasound, computerized tomography scan, or MRI;
• Signs of clinically active Grade 2, 3 or 4 hepatic encephalopathy (ie, equal or greater than Grade 2 Portal Systemic Encephalopathy score)

Sponsors & Collaborators

• Basilea Pharmaceutica: lead
• Biomedical Advanced Research and Development Authority: collaborator

Study Sites (2)

Inland Empire Liver Foundation

Rialto, California, 92337, United States

Location

Genesis Clinical Research, LLC

Tampa, Florida, 33603, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: This is an open label, single dose, parallel cohort study

Study Record Dates

• First Submitted: October 12, 2022
• First Posted: October 17, 2022
• Study Start: October 31, 2022
• Primary Completion: October 16, 2025
• Study Completion: October 16, 2025
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)