Trial Outcomes & Findings for Relative Bioavailability of Two Different Capsule Formulations of Sitravatinib in Healthy Adults (NCT NCT04472650)
NCT ID: NCT04472650
Last Updated: 2024-10-26
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
26 participants
Primary outcome timeframe
Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period
Results posted on
2024-10-26
Participant Flow
Participants were randomized in a 1:1 ratio in two dosing sequences in a 2-period crossover design at a single site in Australia. Periods 1 and 2 were separated by a minimum of 14 days between dose administrations. Total duration of study participation was up to approximately 8 weeks.
Participant milestones
| Measure |
Dosing Sequence 1: Sitravatinib Free Base Capsule Then Malate Salt Capsule
Sitravatinib free base capsule 120 mg on Day 1 of Period 1 then sitravatinib malate salt capsule 100 mg on Day 1 of Period 2, with a minimum washout period between dose administrations of 14 days
|
Dosing Sequence 2: Sitravatinib Malate Salt Capsule Then Free Base Capsule
Sitravatinib malate salt capsule 100 mg on Day 1 of Period 1 then sitravatinib free base capsule 120 mg on Day 1 of Period 2, with a minimum washout period between dose administrations of 14 days
|
|---|---|---|
|
Period 1 (Up to 15 Days)
STARTED
|
13
|
13
|
|
Period 1 (Up to 15 Days)
COMPLETED
|
13
|
13
|
|
Period 1 (Up to 15 Days)
NOT COMPLETED
|
0
|
0
|
|
Washout Period (Minimum 14 Days)
STARTED
|
13
|
13
|
|
Washout Period (Minimum 14 Days)
COMPLETED
|
12
|
13
|
|
Washout Period (Minimum 14 Days)
NOT COMPLETED
|
1
|
0
|
|
Period 2 (Up to 15 Days)
STARTED
|
12
|
13
|
|
Period 2 (Up to 15 Days)
COMPLETED
|
12
|
13
|
|
Period 2 (Up to 15 Days)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Dosing Sequence 1: Sitravatinib Free Base Capsule Then Malate Salt Capsule
Sitravatinib free base capsule 120 mg on Day 1 of Period 1 then sitravatinib malate salt capsule 100 mg on Day 1 of Period 2, with a minimum washout period between dose administrations of 14 days
|
Dosing Sequence 2: Sitravatinib Malate Salt Capsule Then Free Base Capsule
Sitravatinib malate salt capsule 100 mg on Day 1 of Period 1 then sitravatinib free base capsule 120 mg on Day 1 of Period 2, with a minimum washout period between dose administrations of 14 days
|
|---|---|---|
|
Washout Period (Minimum 14 Days)
Adverse Event
|
1
|
0
|
Baseline Characteristics
Relative Bioavailability of Two Different Capsule Formulations of Sitravatinib in Healthy Adults
Baseline characteristics by cohort
| Measure |
Dosing Sequence 1: Sitravatinib Free Base Capsule Then Malate Salt Capsule
n=13 Participants
Sitravatinib free base capsule 120 mg on Day 1 of Period 1 then sitravatinib malate salt capsule 100 mg on Day 1 of Period 2, with a minimum washout period between dose administrations of 14 days
|
Dosing Sequence 2: Sitravatinib Malate Salt Capsule Then Free Base Capsule
n=13 Participants
Sitravatinib malate salt capsule 100 mg on Day 1 of Period 1 then sitravatinib free base capsule 120 mg on Day 1 of Period 2, with a minimum washout period between dose administrations of 14 days
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
27.1 Years
STANDARD_DEVIATION 4.23 • n=5 Participants
|
28.2 Years
STANDARD_DEVIATION 10.19 • n=7 Participants
|
27.7 Years
STANDARD_DEVIATION 7.67 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study periodPopulation: Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib
Outcome measures
| Measure |
Sitravatinib Malate Salt Capsule
n=25 Participants
Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
Sitravatinib Free Base Capsule
n=26 Participants
Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
|---|---|---|
|
Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-∞) of Sitravatinib
|
2524.7 h*ng/mL
Geometric Coefficient of Variation 28.8
|
2892.6 h*ng/mL
Geometric Coefficient of Variation 34.5
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study periodPopulation: Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib
Outcome measures
| Measure |
Sitravatinib Malate Salt Capsule
n=25 Participants
Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
Sitravatinib Free Base Capsule
n=26 Participants
Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC0-t) of Sitravatinib
|
2458.4 h*ng/mL
Geometric Coefficient of Variation 28.2
|
2821.8 h*ng/mL
Geometric Coefficient of Variation 34.3
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study periodPopulation: Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib
Outcome measures
| Measure |
Sitravatinib Malate Salt Capsule
n=25 Participants
Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
Sitravatinib Free Base Capsule
n=26 Participants
Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Sitravatinib
|
54.96 ng/mL
Geometric Coefficient of Variation 32.9
|
62.40 ng/mL
Geometric Coefficient of Variation 37.7
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study periodPopulation: Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib
Outcome measures
| Measure |
Sitravatinib Malate Salt Capsule
n=25 Participants
Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
Sitravatinib Free Base Capsule
n=26 Participants
Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
|---|---|---|
|
Time of the Maximum Observed Plasma Concentration (Tmax) of Sitravatinib
|
8.000 Hours
Interval 6.0 to 12.02
|
8.000 Hours
Interval 6.0 to 12.0
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study periodPopulation: Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib
Outcome measures
| Measure |
Sitravatinib Malate Salt Capsule
n=25 Participants
Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
Sitravatinib Free Base Capsule
n=26 Participants
Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
|---|---|---|
|
Apparent Terminal Elimination Half-life (T1/2) of Sitravatinib
|
30.850 Hours
Interval 21.24 to 41.88
|
28.490 Hours
Interval 22.27 to 39.35
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study periodPopulation: Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib
Outcome measures
| Measure |
Sitravatinib Malate Salt Capsule
n=25 Participants
Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
Sitravatinib Free Base Capsule
n=26 Participants
Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
|---|---|---|
|
Apparent Total Plasma Clearance (CL/F) of Sitravatinib
|
39.61 Liters/hour
Geometric Coefficient of Variation 28.8
|
41.48 Liters/hour
Geometric Coefficient of Variation 34.5
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study periodPopulation: Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib
Outcome measures
| Measure |
Sitravatinib Malate Salt Capsule
n=25 Participants
Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
Sitravatinib Free Base Capsule
n=26 Participants
Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
|---|---|---|
|
Apparent Volume of Distribution (Vz/F) of Sitravatinib
|
1733.8 Liters
Geometric Coefficient of Variation 28.7
|
1780.6 Liters
Geometric Coefficient of Variation 35.3
|
SECONDARY outcome
Timeframe: Up to Week 8Population: Safety Analysis Set included participants who received at least 1 dose of sitravatinib
Adverse events (AEs) and serious adverse events are defined as an AE that starts during or after the first dose, or starts prior to the first dose and increases in severity after the first dose, including vital signs, physical examination, electrocardiogram, and laboratory parameters
Outcome measures
| Measure |
Sitravatinib Malate Salt Capsule
n=25 Participants
Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
Sitravatinib Free Base Capsule
n=26 Participants
Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
|---|---|---|
|
Number of Participants With Adverse Events
At least 1 treatment-emergent adverse event (TEAE)
|
10 Participants
|
8 Participants
|
|
Number of Participants With Adverse Events
Grade 3 or 4 TEAEs
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Serious adverse events
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
TEAE leading to permanent discontinuation of study treatment
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
TEAE leading to death
|
0 Participants
|
0 Participants
|
Adverse Events
Sitravatinib Malate Salt Capsule
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Sitravatinib Free Base Capsule
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sitravatinib Malate Salt Capsule
n=25 participants at risk
Sitravatinib malate salt capsule 100 mg on Day 1 in Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
Sitravatinib Free Base Capsule
n=26 participants at risk
Sitravatinib free base capsule 120 mg (reference) on Day 1 in Periods 1 and 2, with a minimum washout period between dose administrations of 14 days
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/25 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
3.8%
1/26 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Blood and lymphatic system disorders
Neutropenia
|
4.0%
1/25 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
3.8%
1/26 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/25 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
3.8%
1/26 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Gastrointestinal disorders
Diarrhoea
|
4.0%
1/25 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
0.00%
0/26 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Gastrointestinal disorders
Nausea
|
4.0%
1/25 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
0.00%
0/26 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Gastrointestinal disorders
Palatal ulcer
|
0.00%
0/25 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
3.8%
1/26 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
General disorders
Catheter site bruise
|
4.0%
1/25 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
0.00%
0/26 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
General disorders
Catheter site pain
|
4.0%
1/25 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
3.8%
1/26 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
General disorders
Catheter site related reaction
|
0.00%
0/25 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
3.8%
1/26 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
General disorders
Vessel puncture site bruise
|
12.0%
3/25 • Number of events 4 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
0.00%
0/26 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
General disorders
Vessel puncture site pain
|
8.0%
2/25 • Number of events 2 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
0.00%
0/26 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Investigations
Alanine aminotransferase increased
|
8.0%
2/25 • Number of events 2 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
0.00%
0/26 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/25 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
3.8%
1/26 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/25 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
3.8%
1/26 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Nervous system disorders
Dizziness
|
4.0%
1/25 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
0.00%
0/26 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Nervous system disorders
Headache
|
4.0%
1/25 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
3.8%
1/26 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/25 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
3.8%
1/26 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Nervous system disorders
Lethargy
|
0.00%
0/25 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
3.8%
1/26 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
4.0%
1/25 • Number of events 1 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
7.7%
2/26 • Number of events 2 • Up to Week 8
Safety Analysis Set included participants who received at least 1 dose of sitravatinib
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information and may request a further delay to protect its IP rights.
- Publication restrictions are in place
Restriction type: OTHER