Trial Outcomes & Findings for PF-07321332/Ritonavir and Ritonavir on Dabigatran Study in Healthy Participants (NCT NCT05064800)
NCT ID: NCT05064800
Last Updated: 2024-03-29
Results Overview
Cmax was defined as maximum observed plasma concentration.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
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
Results posted on
2024-03-29
Participant Flow
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
Participant milestones
| Measure |
Dabigatran 75mg=>PF-07321332 300mg+Ritonavir 100mg+Dabigatran 75mg=>Ritonavir 100mg+Dabigatran 75mg
For participants in Sequence 1:
In Period 1, participants received Dabigatran orally as a 75 mg single dose followed by a 3-day washout.(Treatment 1) In Period 2, participants received PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose, followed by a 3-day washout. (Treatment 2) In Period 3, participants received ritonavir 100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose. (Treatment 3)
|
Dabigatran 75mg=>Ritonavir 100mg+Dabigatran 75mg=>PF-07321332 300mg+Ritonavir 100mg+Dabigatran 75mg
For participants in Sequence 6:
In Period 1, participants received Dabigatran orally as a 75 mg single dose followed by a 3-day washout.
In Period 2, participants received ritonavir 100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
In Period 3, participants received PF-07321332/ritonavir 300 mg/100 mg q12h as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose. Treatment 2 was followed by a 3-day washout.
|
PF-07321332 300mg+Ritonavir 100mg+Dabigatran 75mg=>Dabigatran 75mg=>Ritonavir 100mg+Dabigatran 75mg
For participants in Sequence 5:
In Period 1, participants received PF-07321332/ritonavir 300 mg/100 mg q12h as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose. Treatment 2 was followed by a 3-day washout.
In Period 2, participants received Dabigatran orally as a 75 mg single dose followed by a 3-day washout.
In Period 3, participants received ritonavir 100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
PF-07321332 300mg+Ritonavir 100mg+Dabigatran 75mg=>Ritonavir 100mg+Dabigatran 75mg=>Dabigatran 75mg
For participants in Sequence 3:
In Period 1, Participants received PF-07321332/ritonavir 300 mg/100 mg q12h as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose. Treatment 2 was followed by a 3-day washout.
In Period 2, Participants received ritonavir 100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
In Period 3, Participants received Dabigatran orally as a 75 mg single dose followed by a 3-day washout.
|
Ritonavir 100mg+Dabigatran 75mg=>Dabigatran 75mg=>PF-07321332 300mg+Ritonavir 100mg+Dabigatran 75mg
For participants in Sequence 2:
In Period 1, Participants received ritonavir 100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
In Period 2, Participants received Dabigatran orally as a 75 mg single dose followed by a 3-day washout.
In Period 3, Participants received PF-07321332/ritonavir 300 mg/100 mg q12h as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose. Treatment 2 was followed by a 3-day washout.
|
Ritonavir 100mg+Dabigatran 75mg=>PF-07321332 300mg+Ritonavir 100mg+Dabigatran 75mg=>Dabigatran 75mg
For participants in Sequence 4:
In Period 1, Participants received ritonavir 100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
In Period 2, Participants received PF-07321332/ritonavir 300 mg/100 mg q12h as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose. Treatment 2 was followed by a 3-day washout.
In Period 3, Participants received Dabigatran orally as a 75 mg single dose followed by a 3-day washout.
|
|---|---|---|---|---|---|---|
|
Period 1
STARTED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Period 1
COMPLETED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 2
STARTED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Period 2
COMPLETED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Period 3
COMPLETED
|
4
|
4
|
4
|
4
|
3
|
4
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Dabigatran 75mg=>PF-07321332 300mg+Ritonavir 100mg+Dabigatran 75mg=>Ritonavir 100mg+Dabigatran 75mg
For participants in Sequence 1:
In Period 1, participants received Dabigatran orally as a 75 mg single dose followed by a 3-day washout.(Treatment 1) In Period 2, participants received PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose, followed by a 3-day washout. (Treatment 2) In Period 3, participants received ritonavir 100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose. (Treatment 3)
|
Dabigatran 75mg=>Ritonavir 100mg+Dabigatran 75mg=>PF-07321332 300mg+Ritonavir 100mg+Dabigatran 75mg
For participants in Sequence 6:
In Period 1, participants received Dabigatran orally as a 75 mg single dose followed by a 3-day washout.
In Period 2, participants received ritonavir 100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
In Period 3, participants received PF-07321332/ritonavir 300 mg/100 mg q12h as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose. Treatment 2 was followed by a 3-day washout.
|
PF-07321332 300mg+Ritonavir 100mg+Dabigatran 75mg=>Dabigatran 75mg=>Ritonavir 100mg+Dabigatran 75mg
For participants in Sequence 5:
In Period 1, participants received PF-07321332/ritonavir 300 mg/100 mg q12h as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose. Treatment 2 was followed by a 3-day washout.
In Period 2, participants received Dabigatran orally as a 75 mg single dose followed by a 3-day washout.
In Period 3, participants received ritonavir 100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
PF-07321332 300mg+Ritonavir 100mg+Dabigatran 75mg=>Ritonavir 100mg+Dabigatran 75mg=>Dabigatran 75mg
For participants in Sequence 3:
In Period 1, Participants received PF-07321332/ritonavir 300 mg/100 mg q12h as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose. Treatment 2 was followed by a 3-day washout.
In Period 2, Participants received ritonavir 100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
In Period 3, Participants received Dabigatran orally as a 75 mg single dose followed by a 3-day washout.
|
Ritonavir 100mg+Dabigatran 75mg=>Dabigatran 75mg=>PF-07321332 300mg+Ritonavir 100mg+Dabigatran 75mg
For participants in Sequence 2:
In Period 1, Participants received ritonavir 100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
In Period 2, Participants received Dabigatran orally as a 75 mg single dose followed by a 3-day washout.
In Period 3, Participants received PF-07321332/ritonavir 300 mg/100 mg q12h as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose. Treatment 2 was followed by a 3-day washout.
|
Ritonavir 100mg+Dabigatran 75mg=>PF-07321332 300mg+Ritonavir 100mg+Dabigatran 75mg=>Dabigatran 75mg
For participants in Sequence 4:
In Period 1, Participants received ritonavir 100 mg every 12 hours (q12h) as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
In Period 2, Participants received PF-07321332/ritonavir 300 mg/100 mg q12h as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose. Treatment 2 was followed by a 3-day washout.
In Period 3, Participants received Dabigatran orally as a 75 mg single dose followed by a 3-day washout.
|
|---|---|---|---|---|---|---|
|
Period 3
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
PF-07321332/Ritonavir and Ritonavir on Dabigatran Study in Healthy Participants
Baseline characteristics by cohort
| Measure |
Enrolled Set
n=24 Participants
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.
|
|---|---|
|
Age, Customized
<18
|
0 Participants
n=5 Participants
|
|
Age, Customized
18-44
|
9 Participants
n=5 Participants
|
|
Age, Customized
45-64
|
15 Participants
n=5 Participants
|
|
Age, Customized
>=65
|
0 Participants
n=5 Participants
|
|
Age, Customized
Unspecified
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
17 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiracial
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
Cmax was defined as maximum observed plasma concentration.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
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
|
154.1 ng/mL
Geometric Coefficient of Variation 72
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
AUCinf was defined as the area under the plasma concentration-time curve from time 0 extrapolated to infinity
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
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
|
1177 ng*hr/mL
Geometric Coefficient of Variation 66
|
—
|
PRIMARY outcome
Timeframe: 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-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
AUClast was defined as area under the plasma concentration time curve from time 0 to the time of the last measurable concentration.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
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
|
1178 ng*hr/mL
Geometric Coefficient of Variation 68
|
—
|
SECONDARY outcome
Timeframe: 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-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
Cmax was defined as maximum observed plasma concentration
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
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
|
117.9 ng/mL
Geometric Coefficient of Variation 123
|
—
|
SECONDARY outcome
Timeframe: 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-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinity
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUCinf
|
625.6 ng*hr/mL
Geometric Coefficient of Variation 61
|
1079 ng*hr/mL
Geometric Coefficient of Variation 65
|
—
|
SECONDARY outcome
Timeframe: 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-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
AUClast was defined as area under the plasma concentration time curve from time 0 to the time of the last measurable concentration.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUClast
|
595.0 ng*hr/mL
Geometric Coefficient of Variation 65
|
909.3 ng*hr/mL
Geometric Coefficient of Variation 124
|
—
|
SECONDARY outcome
Timeframe: From Pre-dose on Day 1 to Day 48Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study
All-Causality AEs
|
3 Participants
|
5 Participants
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study
Treatment-Related AEs
|
0 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study
All-Causality SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study
Treatment-Related SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
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
|
0 Participants
|
0 Participants
|
|
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
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From pre-dose on Day 1 to Day 3Population: All participants with at least one observation of the given laboratory test while on study treatment or during lag time.
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.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
Ery. Mean Corpuscular Hemoglobin (pg/cell) < 0.9x LLN
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
Eosinophils (10^3/mm^3) > 1.2x ULN
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
Activated Partial Thromboplastin Time (sec) > 1.1x ULN
|
0 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
Bilirubin (mg/dL) > 1.5x ULN
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
Fibrinogen (mg/dL) > 1.25x Baseline
|
1 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
URINE Hemoglobin ≥ 1
|
6 Participants
|
6 Participants
|
6 Participants
|
|
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
Nitrite ≥ 1
|
3 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
Leukocyte Esterase ≥ 1
|
4 Participants
|
4 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: From pre-dose on Day 1 to Day 3Population: All participants evaluated against criteria.
Single supine blood pressure and pulse rate tests were assessed against the criteria specified in the sponsor reporting standards.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Number of Participants With Vital Signs of Potential Clinical Concern
Systolic Blood Pressure Value < 90 mmHg
|
2 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Vital Signs of Potential Clinical Concern
Systolic Blood Pressure Change ≥ 30 mmHg increase
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Vital Signs of Potential Clinical Concern
Systolic Blood Pressure Change ≥ 30 mmHg decrease
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Vital Signs of Potential Clinical Concern
Diastolic Blood Pressure Value < 50 mmHg
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Vital Signs of Potential Clinical Concern
Diastolic Blood Pressure Change ≥ 20 mmHg increase
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Vital Signs of Potential Clinical Concern
Diastolic Blood Pressure Change ≥ 20 mmHg decrease
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Vital Signs of Potential Clinical Concern
Pulse Rate Value < 40 bpm
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Vital Signs of Potential Clinical Concern
Pulse Rate Value > 120 bpm
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From pre-dose on Day 1 to Day 3Population: All participants evaluated against criteria.
QT interval, QTc, PR, RR, QRS and heart rate tests were assessed against the criteria specified in the sponsor reporting standards.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
n=24 Participants
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Number of Participants With ECG Values of Potential Clinical Concern
PR Interval not Otherwise Specified Value ≥ 300 MSEC
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With ECG Values of Potential Clinical Concern
PR Interval not Otherwise Specified %Change ≥ 25/50%
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With ECG Values of Potential Clinical Concern
QRS Interval not Otherwise Specified Value ≥ 140 MSEC
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With ECG Values of Potential Clinical Concern
QRS Interval not Otherwise Specified %Change ≥ 50%
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With ECG Values of Potential Clinical Concern
QTCF not Otherwise Specified 450 MSEC ≤ Value < 480 MSEC
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With ECG Values of Potential Clinical Concern
QTCF not Otherwise Specified 480 MSEC ≤ Value < 500 MSEC
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With ECG Values of Potential Clinical Concern
QTCF not Otherwise Specified Value ≥ 500 MSEC
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With ECG Values of Potential Clinical Concern
QTCF not Otherwise Specified 30 MSEC ≤ Change < 60 MSEC
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With ECG Values of Potential Clinical Concern
QTCF not Otherwise Specified Change ≥ 60 MSEC
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
Tmax was defined as time to first occurrence of Cmax
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Time to First Occurrence of Cmax (Tmax)
|
2.000 hours
Interval 2.0 to 4.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
Tmax was defined as time to first occurrence of Cmax.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Tmax
|
2.000 hours
Interval 1.0 to 4.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
t½ was defined as terminal half-life of Dabigatran (Total) PK Parameters (PF-07321332/ritonavir co-administered with dabigatran.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
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 outcome
Timeframe: Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
t½ was defined as terminal half-life of Dabigatran (Total).
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): t½
|
10.16 hours
Standard Deviation 1.3350
|
—
|
—
|
SECONDARY outcome
Timeframe: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Plasma PF-07321332 PK Parameters: Cmax
|
4065 ng/mL
Geometric Coefficient of Variation 76
|
—
|
—
|
SECONDARY outcome
Timeframe: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
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.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Plasma PF-07321332 PK Parameters: AUCtau
|
30080 ng*hr/mL
Geometric Coefficient of Variation 78
|
—
|
—
|
SECONDARY outcome
Timeframe: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
t½ was defined as terminal half-life of PF-07321332.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Plasma PF-07321332 PK Parameters: t½
|
3.969 hours
Standard Deviation 0.53736
|
—
|
—
|
SECONDARY outcome
Timeframe: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
Tmax was defined as time to first occurrence of Cmax.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Plasma PF-07321332 PK Parameters: Tmax
|
2.000 hours
Interval 1.0 to 4.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
CL/F was defined as apparent clearance of drug from plasma.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Plasma PF-07321332 PK Parameters: CL/F
|
9.975 L/hr
Geometric Coefficient of Variation 78
|
—
|
—
|
SECONDARY outcome
Timeframe: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dosePopulation: All participants assigned to investigational product and treated who have at least 1 concentration measured.
Vz/F was defined as apparent volume of distribution.
Outcome measures
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 Participants
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
PF-07321332/ritonavir 300 mg/100 mg every 12 hours (q12h) was administered as a multiple dose over a period of 2 days. In the morning on Treatment 2 Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Plasma PF-07321332 PK Parameters: Vz/F
|
56.48 Liters
Geometric Coefficient of Variation 29
|
—
|
—
|
Adverse Events
Treatment 1: Dabigatran 75 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment 1: Dabigatran 75 mg
n=24 participants at risk
Dabigatran was administered orally as a 75 mg single dose followed by a 3-day washout.
|
Treatment 2: PF-07321332 300 mg + Ritonavir 100 mg + Dabigatran 75 mg
n=24 participants at risk
PF-07321332/ritonavir 300 mg/100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
Treatment 3: Ritonavir 100 mg + Dabigatran 75 mg
n=24 participants at risk
ritonavir 100 mg q12h was administered as a multiple dose over a period of 2 days. In the morning on Day 2, 75 mg of dabigatran was administered orally as a single dose.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/24 • From Study Day 1 up to Study Day 48
Same event may appear as adverse event (AE) and serious AE, what is presented as distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all participants who were randomized and received at least 1 confirmed dose of investigational product.
|
4.2%
1/24 • From Study Day 1 up to Study Day 48
Same event may appear as adverse event (AE) and serious AE, what is presented as distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all participants who were randomized and received at least 1 confirmed dose of investigational product.
|
8.3%
2/24 • From Study Day 1 up to Study Day 48
Same event may appear as adverse event (AE) and serious AE, what is presented as distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all participants who were randomized and received at least 1 confirmed dose of investigational product.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER