The purpose of this clinical trial is to learn about how much PF-07081532 will be taken up and processed by healthy male participants. The study consists of two parts, called study periods. In Period 1, participants will take one dose of PF-07081532 by mouth. In Period 2, participants will take one dose by mouth and one dose as an injection through a vein at the study clinic. In Period 1, participants will stay at the clinic site for up to 21 days. In Period 2, they will stay at the clinic site for 7 days. During their stays, participants will have their blood, urine, and feces collected by the study doctors several times. We will measure the level of PF-07081532 in participants' blood, urine, and feces samples. This will help us know how much the study medicine is getting taken in by the body. At the end of the study, participants will be contacted by phone to check in. Participants will be involved in this study for about 12 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
6
A single oral dose of \[14C\]PF-07081532, will be administered as a liquid formulation in study period 1.
In study period 2: a single, oral, unlabeled dose of PF-07081532 will be administered as a liquid formulation. Approximately 1 hours after the administration of the unlabeled oral dose, a single dose of \[14C\]PF-07081532 will be administered via intravenous infusion.
PRA Health Sciences
Groningen, Netherlands
Total Recovery of Radioactivity in Urine, Feces and Both Routes Combined, as Percentage of Orally Administered Radioactive Dose of [14C]PF-07081532
Urine and feces samples collected after a single oral dose of \[14C\]PF-07081532 30 mg (\~250 nCi) in Period 1 were analyzed using Accelerator Mass Spectrometry (AMS). "Blank" pre-dose urine samples were collected within the 24 hours prior to dosing, "blank" fecal samples were collected from at least 1 bowel movement within the 48 hours prior to dosing. Following oral dosing, each urine void was collected across intervals of 0-12 hours, 12-24 hours, and each subsequent 24 hour interval up to 360 hours post dose, and all feces excreted were collected across each 24 hour interval up to 360 hours post dose. Recovery of radioactivity in urine, feces, and both routes combined, determined as percentage of the orally administered radioactive dose, are reported.
Time frame: 360 hours
Relative Abundance of [14C]PF-07081532 and Its Metabolites in Plasma After A Single Oral Dose of [14]PF-07081532 in Period 1
Plasma samples collected after a single oral dose of \[14C\]PF-07081532 30 mg (\~250 nCi) were analyzed using Ultra Performance Liquid Chromatography coupled to High Resolution Mass Spectrometry (UPLC-HRMS). Relative abundance = (sum of radioactive content of fractions contributing to a particular peak/total circulating drug-related material \[total \[14C\] radioactivity in plasma\]) x 100%. Metabolites that were detected and identifiable (including coeluting metabolites reported together) are reported in this outcome measure (OM).
Time frame: Pre-dose (0 hours [hrs]) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, and 72 hrs post Period 1 Day 1 dosing
Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1
Urine and feces samples collected after a single oral dose of \[14C\]PF-07081532 30 mg (\~250 nCi) were analyzed using UPLC-HRMS. "Blank" pre-dose urine samples were collected within the 24 hours prior to dosing, "blank" fecal samples were collected from at least 1 bowel movement within the 48 hours prior to dosing. To obtain samples for evaluation of relative abundance in urine and feces, following oral dosing, each urine void was collected across intervals of 0-12 hours, 12-24 hours, and each subsequent 24 hour interval up to 96 hours post dose, and all feces excreted were collected across each 24 hour interval up to 144 hours post dose. Relative abundance was determined as sum of radioactive content of fractions contributing to a particular peak divided by total radioactive dose excreted in urine/feces respectively. Metabolites that were detected and identifiable (including coeluting metabolites reported together) are reported in this OM.
Time frame: 96 hours for urine samples and 144 hours for feces samples
Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1
Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of total \[14C\] after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. AUC for total \[14C\] is presented as nanogram equivalent \* hour/milliliter (ngEq\*hr/mL).
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
AUClast of PF-07081532 After A Single Oral Dose of [14]PF-07081532 in Period 1
Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Plasma Maximum Observed Concentration (Cmax) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1
Maximum plasma concentration of total \[14C\] after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Plasma Cmax of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
Maximum plasma concentration of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Plasma Time to Reach Cmax (Tmax) of Total [14C] and PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
Time to reach maximum plasma concentration of total \[14C\] and PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Area Under the Plasma Concentration-Time Curve to Infinity (AUCinf) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1
Area under the plasma concentration versus time curve from time zero to infinity of total \[14C\] after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
AUCinf of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
Area under the plasma concentration versus time curve from time zero to infinity of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Plasma Elimination Half Life (t1/2) of Total [14C] and PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
Plasma elimination half-life of total \[14C\] and PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Apparent Clearance of Drug From Plasma (CL/F) of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
Apparent clearance of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F was calculated as dose/AUCinf, where AUCinf was area under the plasma concentration versus time curve from time zero to infinity.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Plasma Apparent Volume of Distribution (Vz/F) of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
Apparent volume of distribution of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. Vz/F is calculated as Dose/(AUCinf \* kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve, AUCinf is area under the plasma concentration versus time curve from time zero extrapolated to infinite time.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Plasma AUClast of [14C]PF-07081532 Following Intravenous (IV) Administration of [14C]PF-07081532 in Period 2
Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of \[14C\]PF-07081532 after the participant received an oral (PO) dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Dose-Normalized Plasma AUClast (AUClast(dn) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Dose-normalized plasma AUClast of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (equivalent to 0.1 mg; approximately 1 hour after the oral dose). AUClast(dn) = AUClast/Dose, where AUClast = area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration, dose = IV dose of \[14C\]PF-07081532 (expressed in mg).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Plasma Cmax of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Maximum plasma concentration of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Dose-Normalized Plasma Cmax (Cmax (dn)) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Dose-normalized plasma Cmax of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (equivalent to 0.1 mg; approximately 1 hour after the oral dose). Cmax(dn) = Cmax/Dose, where Cmax = maximum concentration, dose = IV dose of \[14C\]PF-07081532 (expressed in mg).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Plasma Tmax of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Time to reach maximum plasma concentration of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Plasma AUCinf of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Area under the plasma concentration versus time curve from time zero to infinity of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Dose-Normalized Plasma AUCinf (AUCinf(dn)) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Dose-normalized plasma AUCinf of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (equivalent to 0.1 mg; approximately 1 hour after the oral dose). AUCinf(dn) = AUCinf/Dose, where AUCinf = area under the plasma concentration versus time curve from time zero to infinity, dose = IV dose of \[14C\]PF-07081532 (expressed in mg).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Plasma t1/2 of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Plasma terminal half life of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Plasma Clearance (CL) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Plasma clearance of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL was calculated as (IV dose of \[14C\]PF-07081532) divided by (AUCinf of \[14C\]PF-07081532), where AUCinf = Area under the plasma concentration versus time curve from time zero to infinity.
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Plasma Steady-State Volume of Distribution (Vss) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Plasma steady-state volume of distribution of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). Vss was calculated as CL \* MRT, where CL was the plasma clearance of \[14C\]PF-07081532, and MRT was the Mean Residence Time of \[14C\]PF-07081532. MRT = AUMCinf/AUCinf - (Infusion time/2), where AUMCinf was the area under the first moment curve from time zero to infinity, AUCinf = area under the plasma concentration versus time curve from time zero to infinity.
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Plasma Mean Residence Time (MRT) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Plasma mean residence time of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). MRT = AUMCinf/AUCinf - (Infusion time/2), where AUMCinf was the area under the first moment curve from time zero to infinity, AUCinf = area under the plasma concentration versus time curve from time zero to infinity.
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Absolute Oral Bioavailability (F) of PF-07081532 in Period 2
F is a measure of the rate and extent of a drug reaching the systemic circulation in its unchanged form. F was estimated as the ratio of adjusted geometric means of dose-normalized plasma AUCinf following oral unlabeled PF-07081532 and IV \[14C\]PF-07081532 in Period 2, which is equivalent to the following equation: F = (AUCpo/\[14C\]\_AUCiv)\*(\[14C\]\_Doseiv/Dosepo). AUCpo and \[14C\]\_AUCiv were the AUCinf values of unlabeled PF-07081532 and \[14C\]PF-07081532, respectively in Period 2; Dosepo and \[14C\]\_Doseiv were the 30 mg oral dose of unlabeled PF-07081532 and each participant's individual IV dose of \[14C\]PF-07081532, respectively.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hrs post oral dosing of unlabeled PF-07081532 on Period 2 Day 1
Fraction Absorbed (Fa) of PF-07081532
Fa was estimated as the ratio of adjusted geometric means of the % of administered radioactive dose excreted into urine following oral (Period 1) and IV (Period 2) dosing of \[14C\]PF-07081532. Urine radioactivity up to Day 7 in Period 1 was used to match the duration of Period 2 urine collection. Fa = (Total \[14C\]\_Urine\_PO\_Trunc/Total \[14C\]\_Urine\_IV) × (\[14C\] Doseiv/\[14C\] Dosepo). Total \[14C\]\_Urine\_PO\_Trunc = Total cumulative radioactivity excreted into urine from time zero up to Day 7 following Period 1 oral dosing, calculated as sum of (\[14C\] urine concentration × sample volume) for each collection interval. Total \[14C\]\_Urine\_IV = Total cumulative radioactivity excreted into urine from time zero to the time of last measurable concentration following Period 2 IV dosing, calculated as sum of (\[14C\] concentration × urine collection volume) for each collection interval (= sum of collection intervals). \[14C\] Dose = radioactivity dose (PO in Period 1, IV in Period 2) for each participant.
Time frame: Day 1 to Day 7 for both Period 1 and Period 2
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred after initiation of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect.
Time frame: Maximum of 11 weeks
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
Laboratory tests included hematology, clinical chemistry and urinalysis. Laboratory abnormalities reported in at least 1 participant are reported in this OM.
Time frame: Maximum of 11 weeks
Number of Participants With Post-Baseline Vital Signs Data Meeting Pre-Defined Criteria
Vital signs data included supine systolic and diastolic blood pressure (BP) and pulse rate. Potentially clinically significant vital signs abnormalities are defined as: systolic BP - minimum (min) absolute result \<90 mmHg, maximum (max) increase or decrease from baseline ≥30 mmHg; diastolic BP - min absolute result \<50 mmHg, max increase or decrease from baseline ≥20 mmHg; supine pulse rate - min absolute result \<40 beat per minute (bpm), max absolute result \>120 bpm. Participants with vital signs data meeting any criteria above are reported in this OM.
Time frame: Maximum of 11 weeks
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Defined Criteria
ECG data included heart rate, PR interval, QT interval, QT Interval (Fridericia's Correction) (QTcF) and QRS complex. Potentially clinically significant ECG abnormalities are categorized as follows: Uncorrected QT value \>500 millisecond (msec). QTcF - absolute value \>450 and ≤480 msec; absolute value \>480 and ≤500 msec; absolute value \>500 msec; increase from baseline \>30 and ≤60 msec; increase from baseline \>60 msec. PR interval - max absolute value ≥300 msec; baseline value \>200 msec and ≥25% increase from baseline; baseline value ≤200 msec and ≥50% increase from baseline. QRS complex - max absolute value ≥140 msec; ≥50% increase from baseline. Participants with ECG data meeting any criteria above are reported in this OM, if any.
Time frame: Maximum of 11 weeks