A Study to Learn Safety and Blood Levels of PF-07817883 in Healthy People

NCT05580003 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: C50910012022-002871-12
• Study Type: interventional
• Target: 94
• Locations: 2 countries
• Sites: 2

Brief Summary

The purpose of this clinical trial is to learn if the study medicine (called PF-07817883) is safe and how it goes in and out of the body in healthy people. PF-07817883 is for the potential treatment of COVID-19. Participants will take PF-07817883 by mouth up to 2 times a day. This study may also evaluate how much PF-07817883 gets into the body when taken as pill. We may study if people's diets can affect this study medicine. We may also examine how PF-07817883 is processed and removed by the human body. Finally, we may look into if PF-07817883 has potential to interact with midazolam.

Conditions

Healthy

Keywords

Oral Antiviral; COVID-19; Protease Inhibitor; Mpro; PF-07817883

Outcome Measures

Primary Outcomes (19)

• Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.

  From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 48 days)

• Part 1: Number of Participants With Laboratory Test Abnormalities

  Laboratory parameters included: (lymphocytes less than (\<) 0.8\*lower limit of normal \[LLN\] \[10\^3 per millimeter cube {mm3}\], lymphocytes/leukocytes \<0.8\*LLN \[percentage {%}\], neutrophils \<0.8\*LLN \[10\^3/mm3\], neutrophils/leukocytes \<0.8\*LLN \[%\], monocytes/leukocytes greater than (\>) 1.2\*upper limit of normal \[ULN\] \[%\], partial thromboplastin time \>1.1\*ULN \[seconds\]), chemistry (bicarbonate \<0.9\*LLN \[milliequivalents per liter {mEq/L}\], creatine kinase \>2.0\*ULN \[units per liter {U/L}\], lipase \>1.5\*ULN \[U/L\]), and urinalysis (urine hemoglobin greater than or equal to \[\>=\] 1, leukocyte esterase \>=1). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.

  From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 48 days)

• Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria

  Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value less than (\<) 90 millimeter of mercury (mmHg), change greater than or equal to (\>=) 30 mmHg increase, change \>= 30 mmHg decrease; DBP: value \< 50 mmHg, change \>= 20 mmHg increase, change \>= 20 mmHg decrease; PR: value \< 40 beats per minute (bpm), value \> 120 bpm.

  Up to Day 2 of each period

• Part 1: Number of Participants With Electrocardiogram (ECG) Abnormalities

  Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.

  Up to Day 2 of each period

• Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.

  From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 55 days)

• Part 2: Number of Participants With Laboratory Test Abnormalities

  Laboratory parameters included: hematology (lymphocytes/leukocytes \>1.2\*ULN \[%\], neutrophils \<0.8\*LLN \[10\^3/mm3\], neutrophils/leukocytes \<0.8\*LLN \[%\], monocytes/leukocytes \>1.2\*ULN \[%\]), chemistry (urate \>1.2\*ULN \[milligrams per deciliter\] {mg/dL}), and urinalysis (ketones \>=1, urine hemoglobin \>=1). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.

  From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 55 days)

• Part 2: Number of Participants With Vital Signs Meeting Pre-Defined Criteria

  Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value \< 90 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; DBP: value \< 50 mmHg, change \>= 20 mmHg increase, change \>= 20 mmHg decrease; PR: value \< 40 bpm, value \> 120 bpm. 4. Number of participants with vital signs meeting any of the pre-defined criteria is reported in this outcome measure.

  Up to Day 12

• Part 2: Number of Participants With Electrocardiogram (ECG) Abnormalities

  Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.

  Up to Day 12

• Part 3:Ratio Based on Area Under Plasma Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) and Area Under Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) of Oral Formulation and Suspension

  Data for AUClast and AUCinf are reported in the descriptive section. AUClast was calculated by the linear/log trapezoidal method. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis. Ratio based on AUClast and AUCinf of oral formulation and suspension were reported in statistical analysis.

  Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

• Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Oral Formulation and Suspension

  Data for Cmax are reported in the descriptive section. Ratio based on Cmax of oral formulation and suspension were reported in statistical analysis.

  Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

• Part 4: Percentage of Total Dose Administered Recovered in Urine

  The percentage of total dose administered recovered in urine was reported in this outcome measure.

  Up to 144 hours post-dose

• Part 4: Percentage of Total Dose Administered Recovered in Feces

  The percentage of total dose administered recovered in feces was reported in this outcome measure.

  Up to 144 hours post-dose

• Part 4: Percentage of Total Dose Administered Recovered in Urine and Feces

  The percentage of total dose administered recovered in urine and feces was reported in this outcome measure.

  Up to 144 hours post-dose

• Part 5: Maximum Observed Concentration (Cmax) of Midazolam

  Cmax of midazolam was reported in this outcome measure.

  Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm

• Part 5: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Midazolam

  AUCinf of midazolam was reported in this outcome measure. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.

  Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm

• Part 6: Number of Participants With TEAEs

  An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.

  From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 52 days)

• Part 6: Number of Participants With Laboratory Test Abnormalities

  Laboratory parameters included: hematology (lymphocytes \<0.6\*LLN \[10\^3/mm3\], lymphocytes/leukocytes \>1.2\*ULN \[%\], neutrophils \<0.8\*LLN \[10\^3/mm3\], neutrophils/leukocytes \<0.8\*LLN \[%\], basophils/leukocytes \>1.2\*ULN \[%\], eosinophils/leukocytes \>1.2\*ULN \[%\], monocytes/leukocytes \>1.2\*ULN \[%\], partial thromboplastin time \>1.1\*ULN \[seconds\], prothrombin time \>1.1\*ULN \[seconds\]), chemistry (bicarbonate \<0.9\*LLN \[mEq/L\], creatine kinase \> 2.0\*ULN \[U/L\], lipase \> 1.5\*ULN \[U/L\], urobilinogen \>=1 \[ehrlich units/deciliter\] {EU/dL}) and urinalysis (urine hemoglobin \>=1, leukocyte esterase \>=1, ketones \>=1, bacteria \>20 \[per low power field\] {/lpf}). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.

  From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 52 days)

• Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria

  Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value \< 90 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; DBP: value \< 50 mmHg, change \>= 20 mmHg increase, change \>= 20 mmHg decrease; PR: value \< 40 bpm, value \> 120 bpm.

  Up to Day 6 of each period

• Part 6: Number of Participants According to Categorization of ECG Data

  Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured QTcF interval, aggregate 450 milliseconds (msec) \< value \<= 480 msec and QTcF interval, aggregate 30 msec \< change \<= 60 msec. Number of participants with abnormalities in ECG were reported in this outcome measure.

  Up to Day 6 of each period

Secondary Outcomes (64)

• Part 1: Maximum Observed Concentration (Cmax) of PF-07817883

  Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

• Part 1: Time for Cmax (Tmax) of PF-07817883

  Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

• Part 1: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883

  Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

• Part 1: Dose Normalized Cmax (Cmax[dn]) of PF-07817883

  Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

• Part 1: Dose Normalized AUClast (AUClast[dn]) of PF-07817883

  Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

Study Arms (25)

PF-07817883 Dose 1 in PART-1

EXPERIMENTAL

Drug: PF-07817883

PF-07817883 Dose 2 in PART-1

EXPERIMENTAL

Drug: PF-07817883

PF-07817883 Dose 3 in PART-1

EXPERIMENTAL

Drug: PF-07817883

PF-07817883 Dose 4 in PART-1

EXPERIMENTAL

Drug: PF-07817883

PF-07817883 Dose 5 in PART-1

EXPERIMENTAL

Optional dose levels

Drug: PF-07817883

PF-07817883 Dose 6 in PART-1

EXPERIMENTAL

Optional dose levels

Drug: PF-07817883

Placebo in PART-1

PLACEBO COMPARATOR

A single dose of placebo

Drug: Placebo

PF-07817883 DR1 in PART-2

EXPERIMENTAL

DR=Dosing regimen; twice a day

Drug: PF-07817883

PF-07817883 DR2 in PART-2

EXPERIMENTAL

Drug: PF-07817883

PF-07817883 DR3 in PART-2

EXPERIMENTAL

Optional dosing regimen

Drug: PF-07817883

PF-07817883 DR4 in PART-2

EXPERIMENTAL

Optional dosing regimen

Drug: PF-07817883

PF-07817883 in Japanese in PART-2

EXPERIMENTAL

Optional dosing regimen to be studied in Japanese population

Drug: PF-07817883

PF-07817883 in Chinese in PART-2

EXPERIMENTAL

Optional dosing regimen to be studied in Chinese population

Drug: PF-07817883

Placebo in PART-2

PLACEBO COMPARATOR

Drug: Placebo

PF-07817883 Suspension Fasted in PART-3

EXPERIMENTAL

PART-3 is optional

Drug: PF-07817883

PF-07817883 FORM-1 Fasted in PART-3

EXPERIMENTAL

First solid oral formulation (FORM1)

Drug: PF-07817883

PF-07817883 FORM-2 Fasted in PART-3

EXPERIMENTAL

Second solid oral formulations (FORM-2) is optional

Drug: PF-07817883

PF-07817883 FORM-1 Fed in PART-3

EXPERIMENTAL

Drug: PF-07817883

PF-07817883 FORM-2 Fed in PART-3

EXPERIMENTAL

Drug: PF-07817883

PF-07817883 in PART-4

EXPERIMENTAL

PART-4 is optional

Drug: PF-07817883

Midazolam 5 mg in PART-5

EXPERIMENTAL

Single dose of 5 mg alone

Drug: Midazolam

Midazolam 5 mg with PF-07817883 in PART-5

EXPERIMENTAL

Single dose of 5 mg on Day 10 with multiple doses (twice a day) of PF-07817883

Drug: PF-07817883; Drug: Midazolam

PF-07817883 in PART-6

EXPERIMENTAL

A single dose at supratherapeutic exposure administered as divided doses (1h apart)

Drug: PF-07817883

Placebo in PART-6

PLACEBO COMPARATOR

A single dose of placebo administered as divided doses (1h apart)

Drug: Placebo

Moxifloxacin 400 mg in PART-6 (open label)

ACTIVE COMPARATOR

Moxifloxacin 400 mg at 0h followed by placebo at 1h

Drug: Placebo; Drug: Moxifloxacin

Interventions

PF-07817883 DRUG

Oral suspension or solid oral formulation(s)

Midazolam 5 mg with PF-07817883 in PART-5; PF-07817883 DR1 in PART-2; PF-07817883 DR2 in PART-2; PF-07817883 DR3 in PART-2; PF-07817883 DR4 in PART-2; PF-07817883 Dose 1 in PART-1; PF-07817883 Dose 2 in PART-1; PF-07817883 Dose 3 in PART-1; PF-07817883 Dose 4 in PART-1; PF-07817883 Dose 5 in PART-1; PF-07817883 Dose 6 in PART-1; PF-07817883 FORM-1 Fasted in PART-3; PF-07817883 FORM-1 Fed in PART-3; PF-07817883 FORM-2 Fasted in PART-3; PF-07817883 FORM-2 Fed in PART-3; PF-07817883 Suspension Fasted in PART-3; PF-07817883 in Chinese in PART-2; PF-07817883 in Japanese in PART-2; PF-07817883 in PART-4; PF-07817883 in PART-6

Placebo DRUG

Placebo suspension

Moxifloxacin 400 mg in PART-6 (open label); Placebo in PART-1; Placebo in PART-2; Placebo in PART-6

Midazolam DRUG

midazolam oral solution

Midazolam 5 mg in PART-5; Midazolam 5 mg with PF-07817883 in PART-5

Moxifloxacin DRUG

Moxifloxacin 400 mg tablet

Moxifloxacin 400 mg in PART-6 (open label)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female subjects between ages of 18-60 years. Male only in part-4.
• Body Mass Index (BMI) of 17.5 to 30.5kg/m2; and a total body weight \>50kg (110lbs). A body weight of \>45 kg may be considered in selected cases.
• Japanese subjects who have four Japanese biologic grandparents born in Japan
• Chinese participants who were born in mainland China and both parents are of the Chinese descent.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
• Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, intestinal resection).
• Positive test result for SARS-CoV-2 infection at the time of screening or Day-1.
• Have received COVID-19 vaccine within 7 days before screening or have received only one of the 2 required doses of COVID-19 vaccine
• Use of tobacco or nicotine containing products in excess of the equivalents of 5 cigarettes per day or 2 chews of tobacco per day
• Use of prescription or nonprescription drugs and dietary and herbal supplements within 28 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Pfizer Clinical Research Unit - Brussels

Brussels, Bruxelles-capitale, Région de, B-1070, Belgium

Location

Related Links

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

MeSH Terms

Conditions

COVID-19

Interventions

Midazolam; Moxifloxacin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: PART-1, 2 and 6 are double-blind, sponsor-open while PART-3, 4 and 5 are open label
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: PART-1 and -2 are a randomized, double-blind, sponsor-open, placebo-controlled trial to evaluate safety, tolerability and PK of single and multiple escalating oral doses of PF 07817883 in healthy adult participants, respectively. PART-1 is crossover while PART-2 is parallel cohort study design. PART-2 of the study may also evaluate the safety, tolerability and PK in Japanese and Chinese participants. PART-3 is a randomized, open-label, cross-over, study to evaluate relative bioavailability and food effect of up to 2 new PF 07817883 oral formulations. PART-4 is an open label, non-randomized, single period cohort to evaluate the metabolism and excretion of PF 07817883. PART-5 is an open-label, randomized, cross-over cohort to evaluate the effect of steady state PF-07817883 on PK of midazolam in healthy participants. PART-6 is a sponsor-open, randomized, 3-treatment, 3-period, cross over study to evaluate safety, tolerability, and PK of PF 07817883 at supratherapeutic exposure.

Study Record Dates

• First Submitted: October 11, 2022
• First Posted: October 14, 2022
• Study Start: October 17, 2022
• Primary Completion: September 15, 2023
• Study Completion: September 15, 2023
• Last Updated: November 21, 2024
• Results First Posted: November 21, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); US (1)