Clinical trial NCT05582187: A Clinical Trial of the Study Medicine (Called Fosmanogepix) in Participants With Varying Degrees of Hepatic Function.
Official title: A Phase 1, Open-label, Single-dose, Parallel Cohort Study to Assess the Pharmacokinetics and Safety of Fosmanogepix (PF 07842805) in Adult Participants With Varying Degrees of Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: fosmanogepix
manogepix
hepatic impairment
PF-07842805
APX001
APX001a
Lead sponsor: Basilea Pharmaceutica
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2022-10-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is an open label, single dose, parallel cohort study
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Key Inclusion Criteria:

* 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): 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

Key Exclusion Criteria:

* 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)

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of manogepix
timeFrame: pre-dose, 1, 2, 3, 4, 5, 6, 12, 24, 48, 96, 168, 240 hours postdose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of manogepix
timeFrame: pre-dose, 1, 2, 3, 4, 5, 6, 12, 24, 48, 96, 168, 240 hours postdose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of manogepix
timeFrame: pre-dose, 1, 2, 3, 4, 5, 6, 12, 24, 48, 96, 168, 240 hours postdose
measure: Unbound Maximum Observed Plasma Concentration (Cmaxu) of manogepix
timeFrame: pre-dose, 1, 2, 3, 4, 5, 6, 12, 24, 48, 96, 168, 240 hours postdose
measure: Unbound Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastu) of manogepix
timeFrame: pre-dose, 1, 2, 3, 4, 5, 6, 12, 24, 48, 96, 168, 240 hours postdose
measure: Unbound Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)u] of manogepix
timeFrame: pre-dose, 1, 2, 3, 4, 5, 6, 12, 24, 48, 96, 168, 240 hours postdose
Secondary outcomes:
measure: Number of Participants Reporting Treatment-emergent adverse events (AEs)
timeFrame: Screening to follow-up (Day 28-35)
measure: Number of participants with clinically significant change from baseline in vital signs
timeFrame: From Day -1 to Day 11
measure: Number of participants with clinically significant change from baseline in laboratory parameters
timeFrame: From Day -1 to Day 11
measure: Number of participants with clinically significant change from baseline in electrocardiogram (ECG) findings
timeFrame: From Day -1 to Day 11
Other outcomes:
Locations:
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: Tampa
country: United States
facility: Genesis Clinical Research, LLC
state: Florida
Study officials:
References: