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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participant
• Intervention / Treatment: Drug: PF-07321332/ritonavir; Drug: PF-07321332/ritonavir; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles-capitale, Région DE
    • Brussels, Bruxelles-capitale, Région DE, Belgium, B-1070
      • Brussels Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1; PF-07321332/ritonavir orally	Drug: PF-07321332/ritonavir; Administered orally every 12 hours for days for a total of 5 doses from Day 1 through Day 3; Drug: PF-07321332/ritonavir; Administered orally BID for 3 day for a total on 5 doses starting on Day 4 through Day 6
Experimental: Period 2; Itraconazole + PF-07321332/ritonavir orally.	Drug: PF-07321332/ritonavir; Administered orally every 12 hours for days for a total of 5 doses from Day 1 through Day 3; Drug: PF-07321332/ritonavir; Administered orally BID for 3 day for a total on 5 doses starting on Day 4 through Day 6; Drug: Itraconazole; Administered orally once daily for 8 days from Days 1 through 8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of PF-07321332	The Cmax of PF-07321332 in the study was observed directly from data.	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.
Area Under the Plasma Concentration-time Profile From Time Zero to Time Tau (τ), Where Tau=12-hour Dosing Interval(AUCtau) for PF-07321332	The AUCtau of PF-07321332 was determined by Linear/Log trapezoidal method.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	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 on-treatment period.	Screening up to Day 35
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	Safety laboratory assessments included urinalysis, hematology, chemistry and other. All the safety laboratory samples were collected following at least a 4-hour fast.	Screening up to Day 9 of Period 2 or Early termination/discontinuation.
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings	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.	Screening up to Day 9 of Period 2 or Early termination/discontinuation.
Change From Baseline in Vital Signs Data - Supine Systolic Blood Pressure	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.	Screening up to Day 9 of Period 2 or Early termination/discontinuation.
Change From Baseline in Vital Signs Data - Supine Diastolic Blood Pressure	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.	Screening up to Day 9 of Period 2 or Early termination/discontinuation.
Change From Baseline in Vital Signs Data - Supine Pulse Rate	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.	Screening up to Day 9 of Period 2 or Early termination/discontinuation.
Time for Cmax (Tmax) for PF-07321332	PF-07321332 Tmax was observed directed from data	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(t1/2) of PF-07321332	Terminal half-life was defined as the time measured for the plasma concentration of drug to decrease by one half.	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
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration(AUClast) of PF-07321332	AUClast of PF-07321332 was determined by Linear/Log trapezoidal method.	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.
Apparent Clearance(CL/F) of PF-07321332	CL/F was apparent clearance.	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.
Apparent Volume of Distribution (Vz/F) of PF-07321332	Vz/F was apparent volume of distribution.	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.

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2021
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: July 10, 2021
• First Submitted That Met QC Criteria: July 10, 2021
• First Posted (Actual): July 14, 2021

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Itraconazole; Drug-drug interaction; CYP3A4 inhibitor
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; 14-alpha Demethylase Inhibitors; Ritonavir; Itraconazole; Nirmatrelvir
• Other Study ID Numbers: C4671015; 2021-003308-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No