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

Healthy Participant Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04962022
• Other study ID #: C4671015
• Secondary ID: 2021-003308-42
• Status: Completed
• Phase: Phase 1
• Start date: July 20, 2021
• Est. completion date: September 30, 2021

Study information

• Verified date: August 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 30, 2021
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Participant

Intervention

Drug:
• PF-07321332/ritonavir
Administered orally every 12 hours for days for a total of 5 doses from Day 1 through Day 3
• Itraconazole
Administered orally once daily for 8 days from Days 1 through 8
• PF-07321332/ritonavir
Administered orally BID for 3 day for a total on 5 doses starting on Day 4 through Day 6

Locations

Country	Name	City	State
Belgium	Brussels Clinical Research Unit	Brussels	Bruxelles-capitale, Région DE

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	Area Under the Plasma Concentration-time Profile From Time Zero to Time Tau (t), 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	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.

External Links

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