Clinical trial NCT04962022: Drug-Drug Interaction Study Assessing Effect of Itraconazole on PF-07321332/Ritonavir in Healthy Participants
Official title: COVID-19: A PHASE 1, OPEN-LABEL, FIXED SEQUENCE, 2-PERIOD CROSSOVER STUDY TO ESTIMATE THE EFFECT OF ITRACONAZOLE ON THE PHARMACOKINETICS OF PF-07321332/RITONAVIR IN HEALTHY PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participant
Keywords: Drug-drug interaction
Itraconazole
CYP3A4 inhibitor
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-07-14
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a Phase I, fixed sequence, 2-period study to evaluate the effect of the strong CYP3A4 inhibitor, itraconazole, on the PK of PF-07321332 and ritonavir in healthy participants. A total of 12 healthy participants will be enrolled into this study.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Male and female participants who are overtly healthy as determined by medical evaluation including medical history, PE, laboratory tests, vital signs and standard 12 lead ECGs.
2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Female participants must have a negative pregnancy test.
4. BMI of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb). -

Exclusion Criteria:

1. Positive test result for SARS-CoV-2 infection at the time of Screening or Day -1.
2. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
3. Clinically relevant abnormalities requiring treatment (eg, acute myocardial infarction, unstable ischemic conditions, evidence of ventricular dysfunction, serious tachy or brady arrhythmias) or indicating serious underlying heart disease (eg, prolonged PR interval, cardiomyopathy, heart failure greater than NYHA 1, underlying structural heart disease, Wolff Parkinson-White syndrome).
4. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
5. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed.
6. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic (eg, contact with positive case, residence, or travel to an area with high incidence) that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

Primary outcomes:
measure: Maximum Observed Concentration (Cmax) of PF-07321332
timeFrame: 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.
measure: Area Under the Plasma Concentration-time Profile From Time Zero to Time Tau (τ), Where Tau=12-hour Dosing Interval(AUCtau) for PF-07321332
timeFrame: 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.
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Screening up to Day 35
measure: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: Screening up to Day 9 of Period 2 or Early termination/discontinuation.
measure: Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings
timeFrame: Screening up to Day 9 of Period 2 or Early termination/discontinuation.
measure: Change From Baseline in Vital Signs Data - Supine Systolic Blood Pressure
timeFrame: Screening up to Day 9 of Period 2 or Early termination/discontinuation.
measure: Change From Baseline in Vital Signs Data - Supine Diastolic Blood Pressure
timeFrame: Screening up to Day 9 of Period 2 or Early termination/discontinuation.
measure: Change From Baseline in Vital Signs Data - Supine Pulse Rate
timeFrame: Screening up to Day 9 of Period 2 or Early termination/discontinuation.
measure: Time for Cmax (Tmax) for PF-07321332
timeFrame: 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
measure: Terminal Half-life(t1/2) of PF-07321332
timeFrame: 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
measure: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration(AUClast) of PF-07321332
timeFrame: 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.
measure: Apparent Clearance(CL/F) of PF-07321332
timeFrame: 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.
measure: Apparent Volume of Distribution (Vz/F) of PF-07321332
timeFrame: 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.
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Brussels Clinical Research Unit
state: Bruxelles-capitale, Région DE
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: