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NCT05005312

Study to Estimate the Effects of Hepatic Impairment on the Pharmacokinetics (PK) of PF-07321332

Completed Phase 1 Results posted Last updated 6 September 2023
What this trial tests

Phase 1 trial testing PF-07321332 in Hepatic Impairment in 17 participants. Completed in 7 December 2021.

Timeline
31 August 2021
Primary endpoint
7 December 2021
7 December 2021

Quick facts

Lead sponsorPfizer
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposebasic science
Enrollment17
Start date31 August 2021
Primary completion7 December 2021
Estimated completion7 December 2021
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

Adults 18 to 75, any sex, with Hepatic Impairment. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Observed Plasma Concentration (Cmax) of Plasma PF-07321332 Primary · Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours

Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation was expressed in percentage.

GroupValue95% CI
Normal Hepatic Function1.886± 20
Moderate Hepatic Impairment1.923± 48
Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-07321332 Primary · Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours

AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation was expressed in percentage.

GroupValue95% CI
Normal Hepatic Function14.97± 36
Moderate Hepatic Impairment14.86± 43
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-07321332 Primary · Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours

AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation was expressed in percentage.

GroupValue95% CI
Normal Hepatic Function15.24± 36
Moderate Hepatic Impairment15.06± 43
Number of Participants With an Treatment Emergent Adverse Event (TEAE) Secondary · Up to 2 months

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason.

Participants with adverse events (All Causalities)
GroupValue95% CI
Normal Hepatic Function3
Moderate Hepatic Impairment4
Participants with adverse events (Treatment Related)
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment3
Number of Participants With Abnormal Electrocardiograms (ECGs) Secondary · Up to 2 months

ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (\>=) 300 millisecond (msec), b) \>=25% increase when baseline is \> 200 msec or \>=50% increase when baseline is less than or equal to (\<=) 200 msec. 2\. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) \>=140 msec, b) \>=50% increase from baseline. 3\. QTcF i

PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 300
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Change ≥ 25/50%
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 140
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Change ≥ 50%
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
QT INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value > 500
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): 450 < Value ≤ 480
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): 480 < Value ≤ 500
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value > 500
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
Number of Participants With Abnormal Vital Signs Secondary · Up to 2 months

Criteria for vital signs abnormalities: increase or decrease from baseline in systolic blood pressure (SBP) \>=30 mm Hg and increase or decrease from baseline in diastolic blood pressure (DBP) \>=20 mm Hg; the value of SBP \<90 mm Hg; the value of DBP \<50 mm Hg; the value of pulse rate \<40 bpm or \>120 bpm.

SBP: Value <90mmHg
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
SBP: Change >= 30 mmHg increase from baseline
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment1
SBP: Change >= 30 mmHg decrease from baseline
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
DBP: Value <50 mmHg
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
DBP: Change >= 20 mmHg increase from baseline
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
DBP: Change >= 20 mmHg decrease from baseline
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
Pulse Rate: Value <40 bpm
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
Pulse Rate: Value >120 bpm
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment0
Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) Secondary · Up to 2 months

Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology; clinical chemistry; urinalysis.

HEMATOLOGY: Platelets (10^3/mm^3) <0.5× lower limit of normal (LLN)
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment1
HEMATOLOGY: Eosinophils (10^3/mm^3) >1.2× upper limit of normal (ULN)
GroupValue95% CI
Normal Hepatic Function1
Moderate Hepatic Impairment2
HEMATOLOGY: Monocytes (10^3/mm^3) >1.2× ULN
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment1
CLINICAL CHEMISTRY: Direct Bilirubin (mg/dL) >1.5× ULN
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment1
CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L) >3.0× ULN
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment1
CLINICAL CHEMISTRY: Calcium (mg/dL) >1.1× ULN
GroupValue95% CI
Normal Hepatic Function1
Moderate Hepatic Impairment0
CLINICAL CHEMISTRY: Glucose (mg/dL) >1.5× ULN
GroupValue95% CI
Normal Hepatic Function0
Moderate Hepatic Impairment1
URINALYSIS: URINE Hemoglobin ≥1
GroupValue95% CI
Normal Hepatic Function1
Moderate Hepatic Impairment0

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study treatment to the last dose of study treatment date +35 days (up to 2 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Normal Hepatic Function
Serious: 0/8 (0%)
Deaths: 0/8
Moderate Hepatic Impairment
Serious: 0/8 (0%)
Deaths: 0/8
Other adverse events (10 terms — click to expand)

ReactionSystemNormal Hepatic FunctionModerate Hepatic Impairment
DysgeusiaNervous system disorders
NauseaGastrointestinal disorders
Injection site pruritusGeneral disorders
Urinary tract infectionInfections and infestations
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
SomnolenceNervous system disorders
ChromaturiaRenal and urinary disorders
Dermatitis contactSkin and subcutaneous tissue disorders
EcchymosisSkin and subcutaneous tissue disorders

Data from ClinicalTrials.gov NCT05005312 adverse events section.

Sponsor's own description

The study is to estimate the effect of hepatic impairment on the plasma PK of PF-07321332/ritonavir. Findings from this study will be used to develop dosing recommendations so that the dose and/or dosing interval may be adjusted appropriately in the presence of hepatic impairment.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Molnupiravir and Its Antiviral Activity Against COVID-19.
    Tian L, Pang Z, Li M, Lou F, et al · · 2022 · cited 99× · PMID 35444647 · DOI 10.3389/fimmu.2022.855496
  2. Races of small molecule clinical trials for the treatment of COVID-19: An up-to-date comprehensive review.
    Hu S, Jiang S, Qi X, Bai R, et al · · 2022 · cited 68× · PMID 34762760 · DOI 10.1002/ddr.21895
  3. New Perspectives on Antimicrobial Agents: Molnupiravir and Nirmatrelvir/Ritonavir for Treatment of COVID-19.
    Atmar RL, Finch N. · · 2022 · cited 30× · PMID 35862759 · DOI 10.1128/aac.02404-21
  4. Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection.
    Chen W, Liang B, Wu X, Li L, et al · · 2023 · cited 23× · PMID 36345404 · DOI 10.1016/j.jpha.2022.10.005
  5. Paxlovid: A promising drug for the challenging treatment of SARS-COV-2 in the pandemic era.
    Niraj N, Mahajan SS, Prakash A, Sarma P, et al · · 2022 · cited 20× · PMID 36722557 · DOI 10.4103/ijp.ijp_291_22
  6. Dosing recommendation of nirmatrelvir/ritonavir using an integrated population pharmacokinetic analysis.
    Chan PLS, Singh RSP, Cox DS, Shi H, et al · · 2023 · cited 6× · PMID 37803876 · DOI 10.1002/psp4.13039
  7. Effect of Hepatic Impairment on the Pharmacokinetics of Nirmatrelvir/Ritonavir, the First Oral Protease Inhibitor for the Treatment of COVID-19.
    Singh RSP, LaBadie RR, Toussi SS, Shi H, et al · · 2024 · cited 3× · PMID 37751891 · DOI 10.1002/jcph.2353

Verify or expand the search:

Other trials of PF-07321332

Trials testing the same drug.

Other recruiting trials for Hepatic Impairment

Currently open trials in the same condition.

Other Pfizer trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT05005312.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing