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NCT04962022

Drug-Drug Interaction Study Assessing Effect of Itraconazole on PF-07321332/Ritonavir in Healthy Participants

Completed Phase 1 Results posted Last updated 13 July 2023
What this trial tests

Phase 1 trial testing PF-07321332/ritonavir in Healthy Participant in 12 participants. Completed in 30 September 2021.

Timeline
20 July 2021
Primary endpoint
30 September 2021
30 September 2021

Quick facts

Lead sponsorPfizer
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designcrossover
Maskingnone
Primary purposebasic science
Enrollment12
Start date20 July 2021
Primary completion30 September 2021
Estimated completion30 September 2021
Sites1 location across Belgium

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

Adults 18 to 60, any sex, with Healthy Participant. 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 Concentration (Cmax) of PF-07321332 Primary · Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2.

The Cmax of PF-07321332 in the study was observed directly from data.

GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted4678± 17
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted5546± 15
Area Under the Plasma Concentration-time Profile From Time Zero to Time Tau (τ), Where Tau=12-hour Dosing Interval(AUCtau) for PF-07321332 Primary · Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2.

The AUCtau of PF-07321332 was determined by Linear/Log trapezoidal method.

GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted33350± 20
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted46290± 18
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Secondary · Screening up to Day 35

An Adverse event (AE) was any untoward medical occurrence in a participant. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth, was a suspected transmission via a Pfizer product of an infectious agent,pathogenic or non-pathogenic, was considered serious. The focus of AE summaries was on treatment-emergent AE (TEAE). An AE was considered TEAE if the event occurred during the

Participants with TEAEs
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted7
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted10
Participants with serious TEAEs
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted0
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted0
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) Secondary · Screening up to Day 9 of Period 2 or Early termination/discontinuation.

Safety laboratory assessments included urinalysis, hematology, chemistry and other. All the safety laboratory samples were collected following at least a 4-hour fast.

Monocytes/Leukocytes(%)> 1.2 ✖ ULN
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted1
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted2
Bicarbonate(mEq/L) > 1.1 ✖ ULN
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted6
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted0
Fibrinogen(mg/dl) > 1.25 ✖ Baseline
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted0
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted1
Leukocyte Esterase >= 1
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted0
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted1
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings Secondary · Screening up to Day 9 of Period 2 or Early termination/discontinuation.

Triplicate 12-lead ECG readings approximately 2 minutes apart were taken at each test. All ECG assessments were made after at least a 5-minute rest in a supine position and prior to any blood draws or vital sign measurements.

PR interval, Aggregate (msec) Value >= 300
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted0
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted0
PR interval, Aggregate (msec) %Change >= 25/50%
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted0
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted0
QRS Duration, Aggregate (msec) Value >= 140
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted0
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted0
QRS Duration, Aggregate (msec) %Change >= 50%
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted0
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted0
QTcF interval, Aggregate (msec) 450 < Value < = 480
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted0
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted0
QTcF interval, Aggregate (msec) 480 < Value < = 500
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted0
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted0
QTcF interval, Aggregate (msec) Value > 500
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted0
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted0
QTcF interval, Aggregate (msec) 30 < Change < = 60
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted0
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted0
Change From Baseline in Vital Signs Data - Supine Systolic Blood Pressure Secondary · Screening up to Day 9 of Period 2 or Early termination/discontinuation.

Vital signs(systolic and diastolic blood pressure, and pulse rate) were measured with participants after having a rest for at least 5 minutes in a supine position. Vital signs assessment were performed after collection of ECGs and prior to collection of blood draws if scheduled at the same time.

Period 1/Day 3 0 hour (H)
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted1.4± 9.84
Period 1/Day 3 1H 30min
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted1.5± 9.03
Period 2/Day 4 0H
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted2.6± 11.34
Period 2/Day6 0H
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted3.6± 8.43
Period 2/Day6 1H
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted5.5± 10.11
Period 2/Day6 1H 30min
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted5.3± 13.52
Period 2/Day6 72 H
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted6.4± 10.11
Change From Baseline in Vital Signs Data - Supine Diastolic Blood Pressure Secondary · Screening up to Day 9 of Period 2 or Early termination/discontinuation.

Vital signs(systolic and diastolic blood pressure, and pulse rate) were measured with participants after having a rest for at least 5 minutes in a supine position. Vital signs assessment were performed after collection of ECGs and prior to collection of blood draws if scheduled at the same time.

Period 1/Day 3 0H
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted-0.9± 4.97
Period 1/Day 3 1H 30min
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted0.5± 4.74
Period 2/Day 4 0H
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted4.1± 4.09
Period 2/Day 6 0H
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted3.5± 4.44
Period 2/Day 6 1H
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted4.9± 4.87
Period 2/Day 6 1H 30min
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted4.2± 5.44
Period 2/Day 6 72H
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted2.9± 6.28
Change From Baseline in Vital Signs Data - Supine Pulse Rate Secondary · Screening up to Day 9 of Period 2 or Early termination/discontinuation.

Vital signs(systolic and diastolic blood pressure, and pulse rate) were measured with participants after having a rest for at least 5 minutes in a supine position. Vital signs assessment were performed after collection of ECGs and prior to collection of blood draws if scheduled at the same time.

Period 1/Day 3 0 H
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted 0/1-0.5± 5.92
Period 1/Day 3 1 H 30 min
GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted 0/1-3.1± 4.64
Period 2/Day 4 0 H
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted-2.4± 5.50
Period 2/Day 6 0 H
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted-2.5± 8.26
Period 2/Day 6 1 H
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted-0.8± 10.84
Period 2/Day 6 1 H 30 min
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted-2.1± 12.79
Period 2/Day 6 72 H
GroupValue95% CI
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted0.3± 9.96
Time for Cmax (Tmax) for PF-07321332 Secondary · Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2

PF-07321332 Tmax was observed directed from data

GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted1.0200.500 – 2.08
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted1.7000.500 – 4.00
Terminal Half-life(t1/2) of PF-07321332 Secondary · Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2

Terminal half-life was defined as the time measured for the plasma concentration of drug to decrease by one half.

GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted8.255± 1.9465
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted7.793± 0.89019
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration(AUClast) of PF-07321332 Secondary · Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2.

AUClast of PF-07321332 was determined by Linear/Log trapezoidal method.

GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted41840± 21
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted74430± 21
Apparent Clearance(CL/F) of PF-07321332 Secondary · Days 1, 2, 3 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours postdose on Day 3) in Period 1; Days 1, 4, 5, 6 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, and 72 hours postdose on Day 6) of Period 2.

CL/F was apparent clearance.

GroupValue95% CI
PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted8.990± 20
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted6.478± 18

Adverse events — posted to ClinicalTrials.gov

Time frame: From screening up to Day 35.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PF-07321332 (Suspension)/Ritonavir 300/100 mg BID, Fasted
Serious: 0/12 (0%)
Deaths: 0/12
Itraconazole 200 mg QD + PF-07321332(Suspension)/Ritonavir 300/100 mg BID, Fasted
Serious: 0/11 (0%)
Deaths: 0/11
Other adverse events (39 terms — click to expand)

ReactionSystemPF-07321332 (Suspension)/R…Itraconazole 200 mg QD + P…
DiarrhoeaGastrointestinal disorders
Abdominal painGastrointestinal disorders
HeadacheNervous system disorders
Breath odourGastrointestinal disorders
DysgeusiaNervous system disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
DizzinessNervous system disorders
AstheniaGeneral disorders
FatigueGeneral disorders
Atrioventricular block first degreeCardiac disorders
Abdominal discomfortGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
Abdominal pain lowerGastrointestinal disorders
Anorectal discomfortGastrointestinal disorders
Change of bowel habitGastrointestinal disorders
Dry mouthGastrointestinal disorders
DyspepsiaGastrointestinal disorders
EructationGastrointestinal disorders
FlatulenceGastrointestinal disorders
Gastrointestinal motility disorderGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
VomitingGastrointestinal disorders
Restless legs syndromeNervous system disorders
InsomniaPsychiatric disorders
PollakiuriaRenal and urinary disorders
Testicular painReproductive system and breast disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
EcchymosisSkin and subcutaneous tissue disorders
Feeling hotGeneral disorders
Influenza like illnessGeneral disorders
Injection site painGeneral disorders
Vessel puncture site haematomaGeneral disorders
Vessel puncture site painGeneral disorders
Back painMusculoskeletal and connective tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Musculoskeletal stiffnessMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Ear discomfortEar and labyrinth disorders

Data from ClinicalTrials.gov NCT04962022 adverse events section.

Sponsor's own description

The purpose of this study is to estimate the effect of a strong inhibitor of CYP3A4 (itraconazole) on the pharmacokinetics (PK) of PF-07321332/ritonavir in healthy participants.

Publications & conference data

8 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. Endocytosis and Transcytosis of SARS-CoV-2 Across the Intestinal Epithelium and Other Tissue Barriers.
    Knyazev E, Nersisyan S, Tonevitsky A. · · 2021 · cited 30× · PMID 34557180 · DOI 10.3389/fimmu.2021.636966
  5. 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
  6. 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
  7. Oral Drugs Against COVID-19.
    Mikus G, Foerster KI, Terstegen T, Vogt C, et al · · 2022 · cited 14× · PMID 35302484 · DOI 10.3238/arztebl.m2022.0152
  8. 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

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