Healthy Participants
Conditions
Keywords
Drug Drug Interaction, Dabigatran, P-gp Substrate, SARS-Co-V2, COVID-19, protease inhibitor, ritonavir
Brief summary
This is a drug-drug interaction study to assess the effects of PF-07321332/ritonavir and ritonavir on the Pharmacokinetic (PK) of dabigatran in healthy volunteers. PK will be evaluated for PF-07321332 and ritonavir. Dabigatran is being utilized as a P-gp substrate
Interventions
DRUGDabigatran
A single dose of Dabigatran on Day 1
DRUGPF-07321332/ritonavir + Dabigatran
PF-07321332/ritonavir twice daily (BID) for Days 1 and 2 Single dose of Dabigatran on Day 2
DRUGRitonavir + Dabigatran
Ritonavir BID on Days 1 and 2 Single dose of Dabigatran on Day 2
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
This is a Phase1, open-label,3-treatment, 6-sequence, 3-period crossover study to estimate the effect of PF-07321332/ritonavir and ritonavir on the Pharmacokinetics of dabigatran in healthy participants
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Body Mass Index (BMI) of 17.5 to 30.5 kg.m2; and a total body weight \>50 kg (110 lbs) * Female participants must have a negative pregnancy test
Exclusion criteria
* Positive test for SARS-Co-V2 at the time of screening or Day -1 * Active pathological bleeding or risk of bleeding * Positive urine drug test * History of sensitivity to heparin or heparin induced thrombocytopenia * Participants who have been vaccinated for COVID-19 in the past 7 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Maximum Plasma Concentration (Cmax) | Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose | Cmax was defined as maximum observed plasma concentration. |
| Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUCinf | Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose | AUCinf was defined as the area under the plasma concentration-time curve from time 0 extrapolated to infinity |
| Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUClast | Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose | AUClast was defined as area under the plasma concentration time curve from time 0 to the time of the last measurable concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | From Pre-dose on Day 1 to Day 48 | 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 serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. |
| Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | From pre-dose on Day 1 to Day 3 | To determine if there are any clinically significant laboratory abnormalities, the haematological, clinical chemistry (serum) and urinalysis safety tests were assessed against the criteria specified in the sponsor reporting standards. Tests including Ery. Mean Corpuscular Hemoglobin, Eosinophils, Activated Partial Thromboplastin Time, Bilirubin, Fibrinogen, URINE Hemoglobin, Nitrite, and Leukocyte Esterase tests. |
| Number of Participants With Vital Signs of Potential Clinical Concern | From pre-dose on Day 1 to Day 3 | Single supine blood pressure and pulse rate tests were assessed against the criteria specified in the sponsor reporting standards. |
| Number of Participants With ECG Values of Potential Clinical Concern | From pre-dose on Day 1 to Day 3 | QT interval, QTc, PR, RR, QRS and heart rate tests were assessed against the criteria specified in the sponsor reporting standards. |
| Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Time to First Occurrence of Cmax (Tmax) | Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose | Tmax was defined as time to first occurrence of Cmax |
| Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Tmax | Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose | Tmax was defined as time to first occurrence of Cmax. |
| Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Terminal Half-life (t½) | Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose | t½ was defined as terminal half-life of Dabigatran (Total) PK Parameters (PF-07321332/ritonavir co-administered with dabigatran. |
| Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Maximum Plasma Concentration (Cmax) | Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose | Cmax was defined as maximum observed plasma concentration |
| Plasma PF-07321332 PK Parameters: Cmax | Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose | — |
| Plasma PF-07321332 PK Parameters: AUCtau | Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose | AUCtau was defined as area under the plasma concentration-time profile from time zero to time tau (τ) the dosing interval, where tau=12 hours for twice daily (BID) dosing. |
| Plasma PF-07321332 PK Parameters: t½ | Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose | t½ was defined as terminal half-life of PF-07321332. |
| Plasma PF-07321332 PK Parameters: Tmax | Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose | Tmax was defined as time to first occurrence of Cmax. |
| Plasma PF-07321332 PK Parameters: CL/F | Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose | CL/F was defined as apparent clearance of drug from plasma. |
| Plasma PF-07321332 PK Parameters: Vz/F | Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose | Vz/F was defined as apparent volume of distribution. |
| Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): t½ | Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose | t½ was defined as terminal half-life of Dabigatran (Total). |
| Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUCinf | Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose | AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinity |
| Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUClast | Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose | AUClast was defined as area under the plasma concentration time curve from time 0 to the time of the last measurable concentration. |
Countries
United States
Participant flow
Pre-assignment details
A total of 24 participants were enrolled into the study, and 4 participants were assigned to each of the 6 sequences to receive following treatments: Treatment 1: dabigatran 75 mg orally (PO) single dose Treatment 2: PF-07321332/ritonavir 300 mg/100 mg PO q12h for 2 days + dabigatran 75 mg PO single dose on Day 2 Treatment 3: ritonavir 100 mg PO q12h for 2 days + dabigatran 75 mg PO single dose on Day 2
Participants by arm
| Arm | Count |
|---|---|
| Enrolled Set Enrolled set is defined as all participants legally authorized representative's, agreement to participate in this study following completion of the informed consent process and screening. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 3 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Enrolled Set |
|---|---|
| Age, Customized <18 | 0 Participants |
| Age, Customized 18-44 | 9 Participants |
| Age, Customized 45-64 | 15 Participants |
| Age, Customized >=65 | 0 Participants |
| Age, Customized Unspecified | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants |
| Race/Ethnicity, Customized Multiracial | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants |
| Race/Ethnicity, Customized White | 17 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 0 / 24 | 1 / 24 | 2 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUCinf
AUCinf was defined as the area under the plasma concentration-time curve from time 0 extrapolated to infinity
Time frame: Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUCinf | 625.6 ng*hr/mL | Geometric Coefficient of Variation 61 |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUCinf | 1177 ng*hr/mL | Geometric Coefficient of Variation 66 |
Comparison: Treatment 1 was Reference and Treatment 2 was Test. Natural log-transformed AUCinf of dabigatran was analyzed using mixed effect model with treatment, period and sequence as fixed effects and participant in sequence as random effect. Estimates of the adjusted mean differences(AMD)(Test-Reference) and 90%CIs were obtained from the model. The AMD and 90%CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means(Test/Reference) and 90%CI for the ratios.90% CI: [135.25, 211.35]Mixed Models Analysis
Primary
Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUClast
AUClast was defined as area under the plasma concentration time curve from time 0 to the time of the last measurable concentration.
Time frame: Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUClast | 595.0 ng*hr/mL | Geometric Coefficient of Variation 65 |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUClast | 1178 ng*hr/mL | Geometric Coefficient of Variation 68 |
Comparison: Treatment 1 was Reference and Treatment 2 was Test. Natural log-transformed AUClast of dabigatran was analyzed using mixed effect model with treatment, period and sequence as fixed effects and participant in sequence as random effect. Estimates of the adjusted mean differences(AMD)(Test-Reference) and 90%CIs were obtained from the model.The AMD and 90%CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means(Test/Reference) and 90%CI for the ratios.90% CI: [119.19, 214.9]Mixed Models Analysis
Primary
Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Maximum Plasma Concentration (Cmax)
Cmax was defined as maximum observed plasma concentration.
Time frame: Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Maximum Plasma Concentration (Cmax) | 71.87 ng/mL | Geometric Coefficient of Variation 78 |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Maximum Plasma Concentration (Cmax) | 154.1 ng/mL | Geometric Coefficient of Variation 72 |
Comparison: Treatment 1 was Reference and Treatment 2 was Test. Natural log-transformed Cmax of dabigatran was analyzed using mixed effect model with treatment, period, sequence as fixed effects; participant within sequence as a random effect. Estimates of the adjusted mean differences(AMD) (Test-Reference) and 90%CIs were obtained from the model. The AMD and 90%CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90%CI for the ratios.90% CI: [172.14, 315.54]Mixed Models Analysis
Secondary
Number of Participants With ECG Values of Potential Clinical Concern
QT interval, QTc, PR, RR, QRS and heart rate tests were assessed against the criteria specified in the sponsor reporting standards.
Time frame: From pre-dose on Day 1 to Day 3
Population: All participants evaluated against criteria.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QRS Interval not Otherwise Specified %Change ≥ 50% | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified Change ≥ 60 MSEC | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified 480 MSEC ≤ Value < 500 MSEC | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified 450 MSEC ≤ Value < 480 MSEC | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | PR Interval not Otherwise Specified Value ≥ 300 MSEC | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified 30 MSEC ≤ Change < 60 MSEC | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QRS Interval not Otherwise Specified Value ≥ 140 MSEC | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | PR Interval not Otherwise Specified %Change ≥ 25/50% | 1 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified Value ≥ 500 MSEC | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified 450 MSEC ≤ Value < 480 MSEC | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | PR Interval not Otherwise Specified Value ≥ 300 MSEC | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | PR Interval not Otherwise Specified %Change ≥ 25/50% | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QRS Interval not Otherwise Specified Value ≥ 140 MSEC | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QRS Interval not Otherwise Specified %Change ≥ 50% | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified 480 MSEC ≤ Value < 500 MSEC | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified Value ≥ 500 MSEC | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified 30 MSEC ≤ Change < 60 MSEC | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified Change ≥ 60 MSEC | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QRS Interval not Otherwise Specified Value ≥ 140 MSEC | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | PR Interval not Otherwise Specified Value ≥ 300 MSEC | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified Value ≥ 500 MSEC | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | PR Interval not Otherwise Specified %Change ≥ 25/50% | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified Change ≥ 60 MSEC | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified 450 MSEC ≤ Value < 480 MSEC | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QRS Interval not Otherwise Specified %Change ≥ 50% | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified 30 MSEC ≤ Change < 60 MSEC | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With ECG Values of Potential Clinical Concern | QTCF not Otherwise Specified 480 MSEC ≤ Value < 500 MSEC | 0 Participants |
Secondary
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
To determine if there are any clinically significant laboratory abnormalities, the haematological, clinical chemistry (serum) and urinalysis safety tests were assessed against the criteria specified in the sponsor reporting standards. Tests including Ery. Mean Corpuscular Hemoglobin, Eosinophils, Activated Partial Thromboplastin Time, Bilirubin, Fibrinogen, URINE Hemoglobin, Nitrite, and Leukocyte Esterase tests.
Time frame: From pre-dose on Day 1 to Day 3
Population: All participants with at least one observation of the given laboratory test while on study treatment or during lag time.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin (pg/cell) < 0.9x LLN | 1 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Eosinophils (10^3/mm^3) > 1.2x ULN | 1 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Activated Partial Thromboplastin Time (sec) > 1.1x ULN | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Bilirubin (mg/dL) > 1.5x ULN | 1 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Fibrinogen (mg/dL) > 1.25x Baseline | 1 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | URINE Hemoglobin ≥ 1 | 6 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Nitrite ≥ 1 | 3 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Leukocyte Esterase ≥ 1 | 4 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Activated Partial Thromboplastin Time (sec) > 1.1x ULN | 2 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Nitrite ≥ 1 | 3 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Bilirubin (mg/dL) > 1.5x ULN | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Fibrinogen (mg/dL) > 1.25x Baseline | 2 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | URINE Hemoglobin ≥ 1 | 6 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin (pg/cell) < 0.9x LLN | 1 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Eosinophils (10^3/mm^3) > 1.2x ULN | 1 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Leukocyte Esterase ≥ 1 | 4 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Activated Partial Thromboplastin Time (sec) > 1.1x ULN | 2 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Eosinophils (10^3/mm^3) > 1.2x ULN | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin (pg/cell) < 0.9x LLN | 1 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Bilirubin (mg/dL) > 1.5x ULN | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Nitrite ≥ 1 | 1 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | URINE Hemoglobin ≥ 1 | 6 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Fibrinogen (mg/dL) > 1.25x Baseline | 1 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Leukocyte Esterase ≥ 1 | 2 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study
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 serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug.
Time frame: From Pre-dose on Day 1 to Day 48
Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | All-Causality AEs | 3 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | Treatment-Related AEs | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | Treatment-Related AEs leading to discontinuation from study | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | All-Causality SAEs | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | Treatment-Related SAEs | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | All-Causality AEs leading to discontinuation from study | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | Treatment-Related SAEs | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | All-Causality AEs leading to discontinuation from study | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | All-Causality SAEs | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | All-Causality AEs | 5 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | Treatment-Related AEs leading to discontinuation from study | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | Treatment-Related AEs | 2 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | Treatment-Related AEs leading to discontinuation from study | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | All-Causality AEs | 2 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | All-Causality SAEs | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | Treatment-Related SAEs | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | All-Causality AEs leading to discontinuation from study | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study | Treatment-Related AEs | 1 Participants |
Secondary
Number of Participants With Vital Signs of Potential Clinical Concern
Single supine blood pressure and pulse rate tests were assessed against the criteria specified in the sponsor reporting standards.
Time frame: From pre-dose on Day 1 to Day 3
Population: All participants evaluated against criteria.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Systolic Blood Pressure Change ≥ 30 mmHg increase | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Diastolic Blood Pressure Change ≥ 20 mmHg decrease | 1 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Pulse Rate Value > 120 bpm | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Systolic Blood Pressure Value < 90 mmHg | 2 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Systolic Blood Pressure Change ≥ 30 mmHg decrease | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Diastolic Blood Pressure Value < 50 mmHg | 1 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Pulse Rate Value < 40 bpm | 0 Participants |
| Treatment 1: Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Diastolic Blood Pressure Change ≥ 20 mmHg increase | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Diastolic Blood Pressure Value < 50 mmHg | 1 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Systolic Blood Pressure Change ≥ 30 mmHg decrease | 1 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Diastolic Blood Pressure Change ≥ 20 mmHg decrease | 2 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Pulse Rate Value < 40 bpm | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Systolic Blood Pressure Change ≥ 30 mmHg increase | 2 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Systolic Blood Pressure Value < 90 mmHg | 2 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Pulse Rate Value > 120 bpm | 0 Participants |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Diastolic Blood Pressure Change ≥ 20 mmHg increase | 1 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Pulse Rate Value > 120 bpm | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Systolic Blood Pressure Value < 90 mmHg | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Systolic Blood Pressure Change ≥ 30 mmHg increase | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Systolic Blood Pressure Change ≥ 30 mmHg decrease | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Diastolic Blood Pressure Value < 50 mmHg | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Diastolic Blood Pressure Change ≥ 20 mmHg increase | 1 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Pulse Rate Value < 40 bpm | 0 Participants |
| Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg | Number of Participants With Vital Signs of Potential Clinical Concern | Diastolic Blood Pressure Change ≥ 20 mmHg decrease | 0 Participants |
Secondary
Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Terminal Half-life (t½)
t½ was defined as terminal half-life of Dabigatran (Total) PK Parameters (PF-07321332/ritonavir co-administered with dabigatran.
Time frame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Terminal Half-life (t½) | 9.636 hours | Standard Deviation 1.5692 |
Secondary
Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Time to First Occurrence of Cmax (Tmax)
Tmax was defined as time to first occurrence of Cmax
Time frame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Time to First Occurrence of Cmax (Tmax) | 2.000 hours |
Secondary
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUCinf
AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinity
Time frame: Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUCinf | 625.6 ng*hr/mL | Geometric Coefficient of Variation 61 |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUCinf | 1079 ng*hr/mL | Geometric Coefficient of Variation 65 |
Comparison: Treatment 1 was Reference and Treatment 3 was Test. Natural log-transformed AUCinf of dabigatran was analyzed using mixed effect model with treatment, period and sequence as fixed effects and participant in sequence as random effect. Estimates of the adjusted mean differences(AMD)(Test-Reference) and 90%CIs were obtained from the model. The AMD and 90%CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means(Test/Reference) and 90%CI for the ratios.90% CI: [135.25, 211.35]Mixed Models Analysis
Secondary
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUClast
AUClast was defined as area under the plasma concentration time curve from time 0 to the time of the last measurable concentration.
Time frame: Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUClast | 595.0 ng*hr/mL | Geometric Coefficient of Variation 65 |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUClast | 909.3 ng*hr/mL | Geometric Coefficient of Variation 124 |
Comparison: Treatment 1 was Reference and Treatment 3 was Test. Natural log-transformed AUClast of dabigatran was analyzed using mixed effect model with treatment, period and sequence as fixed effects and participant in sequence as random effect. Estimates of the adjusted mean differences(AMD)(Test-Reference) and 90%CIs were obtained from the model.The AMD and 90%CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means(Test/Reference) and 90%CI for the ratios.90% CI: [119.19, 214.9]Mixed Models Analysis
Secondary
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Maximum Plasma Concentration (Cmax)
Cmax was defined as maximum observed plasma concentration
Time frame: Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Maximum Plasma Concentration (Cmax) | 71.87 ng/mL | Geometric Coefficient of Variation 78 |
| Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Maximum Plasma Concentration (Cmax) | 117.9 ng/mL | Geometric Coefficient of Variation 123 |
Comparison: Treatment 1 was Reference and Treatment 3 was Test. Natural log-transformed Cmax of dabigatran was analyzed using mixed effect model with treatment, period, sequence as fixed effects; participant within sequence as a random effect. Estimates of the adjusted mean differences(AMD) (Test-Reference) and 90%CIs were obtained from the model. The AMD and 90%CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90%CI for the ratios.90% CI: [127.51, 231.77]Mixed Models Analysis
Secondary
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): t½
t½ was defined as terminal half-life of Dabigatran (Total).
Time frame: Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): t½ | 10.16 hours | Standard Deviation 1.335 |
Secondary
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Tmax
Tmax was defined as time to first occurrence of Cmax.
Time frame: Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Tmax | 2.000 hours |
Secondary
Plasma PF-07321332 PK Parameters: AUCtau
AUCtau was defined as area under the plasma concentration-time profile from time zero to time tau (τ) the dosing interval, where tau=12 hours for twice daily (BID) dosing.
Time frame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma PF-07321332 PK Parameters: AUCtau | 30080 ng*hr/mL | Geometric Coefficient of Variation 78 |
Secondary
Plasma PF-07321332 PK Parameters: CL/F
CL/F was defined as apparent clearance of drug from plasma.
Time frame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma PF-07321332 PK Parameters: CL/F | 9.975 L/hr | Geometric Coefficient of Variation 78 |
Secondary
Plasma PF-07321332 PK Parameters: Cmax
Time frame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma PF-07321332 PK Parameters: Cmax | 4065 ng/mL | Geometric Coefficient of Variation 76 |
Secondary
Plasma PF-07321332 PK Parameters: t½
t½ was defined as terminal half-life of PF-07321332.
Time frame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma PF-07321332 PK Parameters: t½ | 3.969 hours | Standard Deviation 0.53736 |
Secondary
Plasma PF-07321332 PK Parameters: Tmax
Tmax was defined as time to first occurrence of Cmax.
Time frame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma PF-07321332 PK Parameters: Tmax | 2.000 hours |
Secondary
Plasma PF-07321332 PK Parameters: Vz/F
Vz/F was defined as apparent volume of distribution.
Time frame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Population: All participants assigned to investigational product and treated who have at least 1 concentration measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1: Dabigatran 75 mg | Plasma PF-07321332 PK Parameters: Vz/F | 56.48 Liters | Geometric Coefficient of Variation 29 |