Study of Single and Multiple Ascending Doses of PF-070590... | NCT04323124

ID	Type	Description	Link
2019-004918-34	EudraCT Number

Label	Type	Description	Intervention Names
Treatment	Experimental	PF-07059013 assignment	Drug: PF-07059013
Placebo	Placebo Comparator	Placebo assignment	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
PF-07059013	Drug	Participants will recieve PF-07059013	Treatment
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment Emergent Treatment-Related Adverse Event(s) (Treatment-Related TEAE)	Adverse events (AEs): any untoward medical occurrence in a clinical investigation participant administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Treatment-related TEAEs were any untoward medical occurrence attributed to study intervention. Relatedness to study treatment was determined by the investigator. Duration of participation of Part 1 and Part 3, from the screening visit to the follow-up phone call, was approximately 15 weeks. Duration of participation of Part 2, from the screening visit to the follow-up phone call, was approximately 10 weeks.	Baseline up to Follow-Up (15 weeks in Part 1 and Part 3, and 10 weeks in Part 2)
Number of Participants With Laboratory Test Findings of Potential Clinical Importance	Protocol-required safety laboratory assessments included chemistry, hematology, and urinalysis (and microscopy, if needed). Each parameter was evaluated against commonly used and widely accepted criteria. Laboratory test with abnormalities are reported. Evaluation activities as: Part 1: At Screening, Day -1, and Day 1 (at 8 hours post dose), 2, 5, 8. Part 2: At Screening, Day -1, 1, 2, 4, 7, 10, 14, 18, 21. Part 3: At Screening, Day -1, 2, 5.	Part 1: from Screening to Day 8; Part 2: from Screening to Day 21; Part 3: from Screening to Day 5.
Number of Participants With Vital Signs Findings of Potential Clinical Importance	Vital sign data included supine blood pressure, pulse rate, orthostatic blood pressure and oral temperature. Vital signs with abnormalities are reported. Evaluation activities as: Part 1: Supine blood pressure and pulse rate: At Screening, 0, 0.5, 1, 2, 5, 8, 12, 24, 36, 48, 72, 96, and 168 hours post dose. Orthostatic blood pressure, respiratory rate and oral temperature: 0, 2, 8, and 24 hours post dose. Part 2: Supine blood pressure and pulse rate: At Screening, Day 1, 2, 4, 7, 10, 14, 15, 18, 21. Orthostatic blood pressure, respiratory rate and oral temperature: Day 1, 7, 14, 18. Part 3: Supine blood pressure and pulse rate: At Screening, 0, 2, 5, 8, 12, 24, 48, and 96 hours post dose. Respiratory rate and oral temperature: 0, 24 and 96 hours post dose.

Secondary Outcomes

Measure	Description	Time Frame
PF-07059013 Blood and Plasma Maximum Observed Concentration (Cmax) of Part 1	PF-07059013 Blood and Plasma Cmax for Part 1 was evaluated. For Part 1, in period 1, participants were given PF-07059013 100 mg SD and PF-07059013 250 mg SD, all with polymer; in period 2, participants were given PF-07059013 500 mg SD and PF-07059013 1000 mg SD, all with polymer; in period 3, participants were given PF-07059013 2000 mg SD and PF-07059013 3000 mg SD, all with polymer; in period 4, participants were given PF-07059013 2000 mg SD and PF-07059013 3000 mg SD, all without polymer.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male and female (of non-child bearing potential) participants must be 18 to 55 years of age, inclusive, at the time of signing the ICD.
Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, including blood pressure, pulse rate, respiratory rate and temperature measurement, standard 12 lead ECG, laboratory tests, and cardiac monitoring (in Part 1 only).
Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

Weight:
BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria

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).
Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing at screening for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody (HCVAb). As an exception a positive HBsAb test due to hepatitis B vaccination is permissible.
Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.
Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer).
A positive urine drug test at screening or admission.
A positive urine cotinine test at screening or admission in Part 1 and 2.
Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTc interval >450 msec, complete left bundle branch block (LBBB), signs of an acute or indeterminate age myocardial infarction, ST T interval changes suggestive of myocardial ischemia, second or third degree atrioventricular (AV) block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is >450 msec, this interval should be rate corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility. Computer interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants.
Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:
- AST or ALT level ≥1.5 × ULN;
- Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN;
- PT/INR >1.2 × ULN;
- aPTT ≥1.5 × ULN;
- Hemoglobin <11.0 g/dL;
- Lactate >1 x ULN.
For Part 2 only, participants with absolute reticulocyte count >150,000/uL at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary.
History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).
Use of tobacco/nicotine containing products for Part 1 or 2, and use of more than 5 cigarettes/day for Part 3.
Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Clinical Research Unit - Brussels		Brussels	Bruxelles-capitale, Région de	B-1070	Belgium

PubMed Identifier	Type	Citation	Retractions
37584365	Derived	Lee KC, Wan KX, Barricklow J, Lim CN, Clarke S, Potts D, Holmes K, Gonzalez P, Kavetska O. Using Mitra sampling to support first-in-human pharmacokinetic evaluations for PF-07059013. Bioanalysis. 2023 Sep;15(17):1083-1094. doi: 10.4155/bio-2023-0066. Epub 2023 Aug 16.

Label	URL
To obtain contact information for a study center near you, click here.	View source

Arm/Group Information

ID	Title	Description
FG000	A->D->F->H	In Part 1, participants were given a single dose of each study intervention assigned. A->D->F->H: Placebo Single dose (SD) Polymer->PF-07059013 500 mg SD Polymer->PF-07059013 2000 mg SD Polymer->PF-07059013 2000 mg SD without (w/o) Polymer
FG001	A->E->G->I	In Part 1, participants were given a single dose of each study intervention assigned. A->E->G->I: Placebo SD Polymer->PF-07059013 1000 mg SD Polymer->PF-07059013 3000 mg SD Polymer->PF-07059013 3000 mg SD w/o Polymer
FG002	B->A->F->H	In Part 1, participants were given a single dose of each study intervention assigned. B->A->F->H: PF-07059013 100 mg SD Polymer->Placebo SD Polymer->PF-07059013 2000 mg SD Polymer->PF-07059013 2000 mg SD w/o Polymer
FG003	B->D->A->H	In Part 1, participants were given a single dose of each study intervention assigned. B->D->A->H: PF-07059013 100 mg SD Polymer->PF-07059013 500 mg SD Polymer->Placebo SD Polymer->PF-07059013 2000 mg SD w/o Polymer
FG004	C->A->G->I	In Part 1, participants were given a single dose of each study intervention assigned. C->A->G->I: PF-07059013 250 mg SD Polymer->Placebo SD Polymer->PF-07059013 3000 mg SD Polymer->PF-07059013 3000 mg SD w/o Polymer
FG005	C->E->A->I	In Part 1, participants were given a single dose of each study intervention assigned. C->E->A->I: PF-07059013 250 mg SD Polymer->PF-07059013 1000 mg SD Polymer->Placebo SD Polymer->PF-07059013 3000 mg SD w/o Polymer
FG006	Placebo MD	In Part 2, participants were given multiple doses of study intervention once daily (QD) for 14 days.
FG007	PF-07059013 800 mg MD	In Part 2, participants were given multiple doses of study intervention once daily (QD) for 14 days.
FG008	PF-07059013 1600 mg MD	In Part 2, participants were given multiple doses of study intervention once daily (QD) for 14 days.
FG009	PF-07059013 3000 mg MD	In Part 2, participants were given multiple doses of study intervention once daily (QD) for 14 days.
FG010	PF-07059013 4000 mg MD	In Part 2, participants were given multiple doses of study intervention once daily (QD) for 14 days.
FG011	P->Q->R->S	In Part 3, participants were given a single dose of study intervention assigned under fasted conditions. The presence/absence of polymer is utilized to select the preferred formulation composition. P->Q->R->S:Suspension Fasted Polymer (Small Particle Size)->Tablet Fasted w/o Polymer->Suspension Fed Polymer (Small Particle Size)->Suspension Fasted Polymer (Moderate Particle Size)
FG012	P->Q->S->R	In Part 3, participants were given a single dose of study intervention assigned under fasted conditions. The presence/absence of polymer is utilized to select the preferred formulation composition. P->Q->S->R: Suspension Fasted Polymer (Small Particle Size)->Tablet Fasted w/o Polymer->Suspension Fasted Polymer (Moderate Particle Size)->Suspension Fed Polymer (Small Particle Size)
FG013	Q->P->R->S	In Part 3, participants were given a single dose of study intervention assigned under fasted conditions. The presence/absence of polymer is utilized to select the preferred formulation composition. Q->P->R->S: Tablet Fasted w/o Polymer->Suspension Fasted Polymer (Small Particle Size)->Suspension Fed Polymer (Small Particle Size)->Suspension Fasted Polymer (Moderate Particle Size)
FG014	Q->P->S->R	In Part 3, participants were given a single dose of study intervention assigned under fasted conditions. The presence/absence of polymer is utilized to select the preferred formulation composition. Q->P->S->R: Tablet Fasted w/o Polymer->Suspension Fasted Polymer (Small Particle Size)->Suspension Fasted Polymer (Moderate Particle Size)->Suspension Fed Polymer (Small Particle Size)

ID	Title	Description
BG000	A->D->F->H	In Part 1, participants were given a single dose of study intervention assigned. A->D->F->H: Placebo Single dose (SD) Polymer->PF-07059013 500 mg SD Polymer->PF-07059013 2000 mg SD Polymer->PF-07059013 2000 mg SD without (w/o) Polymer
BG001	A->E->G->I

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Customized			Number

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Treatment Emergent Treatment-Related Adverse Event(s) (Treatment-Related TEAE)

Adverse events (AEs): any untoward medical occurrence in a clinical investigation participant administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Treatment-related TEAEs were any untoward medical occurrence attributed to study intervention. Relatedness to study treatment was determined by the investigator.

Duration of participation of Part 1 and Part 3, from the screening visit to the follow-up phone call, was approximately 15 weeks. Duration of participation of Part 2, from the screening visit to the follow-up phone call, was approximately 10 weeks.

All participants randomly assigned to study intervention and who took at least 1 dose of study intervention were included in safety analysis set. Participants were analyzed according to the product they actually received.

Posted

Count of Participants

Participants

Baseline up to Follow-Up (15 weeks in Part 1 and Part 3, and 10 weeks in Part 2)

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 24, 2020	Sep 22, 2022	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Aug 28, 2021	Sep 22, 2022	SAP_001.pdf

OG000	Part 1: Placebo Single Dose (SD) With Polymer	In Part 1, participants were given a single dose of study intervention assigned. The presence/absence of polymer is utilized to select the preferred formulation composition.
OG001	Part 1: PF-07059013 100 mg SD With Polymer	In Part 1, participants were given a single dose of study intervention assigned.
OG002	Part 1: PF-07059013 250 mg SD With Polymer	In Part 1, participants were given a single dose of study intervention assigned.
OG003	Part 1: PF-07059013 500 mg SD With Polymer	In Part 1, participants were given a single dose of study intervention assigned.
OG004	Part 1: PF-07059013 1000 mg SD With Polymer	In Part 1, participants were given a single dose of study intervention assigned.
OG005	Part 1: PF-07059013 2000 mg SD With Polymer	In Part 1, participants were given a single dose of study intervention assigned.
OG006	Part 1: PF-07059013 3000 mg SD With Polymer	In Part 1, participants were given a single dose of study intervention assigned.
OG007	Part 1: PF- 07059013 2000 mg SD Without Polymer	In Part 1, participants were given a single dose of study intervention assigned.
OG008	Part 1: PF-07059013 3000 mg SD Without Polymer	In Part 1, participants were given a single dose of study intervention assigned.
OG009	Part 2: Placebo Multiple Doses (MD) With Polymer	In Part 2, participants were given multiple doses of study intervention once daily (QD) for 14 days. The presence/absence of polymer is utilized to select the preferred formulation composition.
OG010	Part 2: PF-07059013 800 mg MD With Polymer	In Part 2, participants were given multiple doses of study intervention QD for 14 days.
OG011	Part 2: PF-07059013 1600 mg MD With Polymer	In Part 2, participants were given multiple doses of study intervention QD for 14 days.
OG012	Part 2: PF-07059013 3000 mg MD With Polymer	In Part 2, participants were given multiple doses of study intervention QD for 14 days.
OG013	Part 2: PF-07059013 4000 mg MD With Polymer	In Part 2, participants were given multiple doses of study intervention QD for 14 days.
OG014	Part 3: Suspension Fasted Polymer (Small Particle Size)	In Part 3, participants were given a single dose of study intervention assigned under fasted conditions. The presence/absence of polymer is utilized to select the preferred formulation composition.
OG015	Part 3: Tablet Fasted Without Polymer	In Part 3, participants were given a single dose of study intervention assigned under fasted conditions.
OG016	Part 3: Suspension Fed Polymer (Small Particle Size)	In Part 3, participants were given a single dose of study intervention assigned under fed conditions.