Trial Outcomes & Findings for Study to Evaluate the Effect of Multiple-Dose Ritlecitinib on the Pharmacokinetics (PK) of Tolbutamide (NCT NCT05097716)
NCT ID: NCT05097716
Last Updated: 2023-10-06
Results Overview
Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
12 participants
Primary outcome timeframe
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, and 36 hours post-dose of tolbutamide in Period 1 (Days 1 and 2) and Period 2 (Days 10 and 11)
Results posted on
2023-10-06
Participant Flow
A total of 12 participants were enrolled in the study. All participants were treated in Period 1 (tolbutamide treatment alone). Ten participants were treated in Period 2 (multiple dose ritlecitinib plus single dose tolbutamide treatment).
Participant milestones
| Measure |
Period 1: Tolbutamide and Period 2: Ritlecitinib + Tolbutamide
Participants in Period 1 were dosed with a single administration of tolbutamide 500 mg tablet on Day 1. Period 1 was immediately followed by Period 2 with no washout. Participants in Period 2 were dosed with oral 200 mg ritlecitinib once daily (QD) for 10 days followed by administration of a single dose of 500 mg tolbutamide oral tablet within approximately 5 minutes after administration of ritlecitinib on the morning of Day 10.
|
|---|---|
|
Period 1
STARTED
|
12
|
|
Period 1
COMPLETED
|
10
|
|
Period 1
NOT COMPLETED
|
2
|
|
Period 2
STARTED
|
10
|
|
Period 2
COMPLETED
|
10
|
|
Period 2
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Period 1: Tolbutamide and Period 2: Ritlecitinib + Tolbutamide
Participants in Period 1 were dosed with a single administration of tolbutamide 500 mg tablet on Day 1. Period 1 was immediately followed by Period 2 with no washout. Participants in Period 2 were dosed with oral 200 mg ritlecitinib once daily (QD) for 10 days followed by administration of a single dose of 500 mg tolbutamide oral tablet within approximately 5 minutes after administration of ritlecitinib on the morning of Day 10.
|
|---|---|
|
Period 1
Adverse Event
|
1
|
|
Period 1
Close contact with highly-transmissible infection
|
1
|
Baseline Characteristics
Study to Evaluate the Effect of Multiple-Dose Ritlecitinib on the Pharmacokinetics (PK) of Tolbutamide
Baseline characteristics by cohort
| Measure |
Male
n=9 Participants
Male participants were healthy adults between 18-65 years of age. No contraception methods were required for male participants in this study.
|
Female
n=3 Participants
Female participants were healthy adults between 18-65 years of age. A female participant was eligible to participate if she was not pregnant or breastfeeding, and at least 1 of the following conditions applied: was not a woman of childbearing potential, OR was a woman of childbearing potential using a contraceptive method that was highly effective.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
Mean
|
37.4 Years
STANDARD_DEVIATION 12.57 • n=93 Participants
|
48.7 Years
STANDARD_DEVIATION 11.15 • n=4 Participants
|
40.3 Years
STANDARD_DEVIATION 12.78 • n=27 Participants
|
|
Age, Continuous
Median
|
36.0 Years
n=93 Participants
|
53.0 Years
n=4 Participants
|
37.0 Years
n=27 Participants
|
|
Age, Customized
<18
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Customized
18-44
|
6 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Age, Customized
45-64
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
|
Age, Customized
>=65
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White
|
5 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
4 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, and 36 hours post-dose of tolbutamide in Period 1 (Days 1 and 2) and Period 2 (Days 10 and 11)Population: Analysis population included all participants treated who had at least 1 concentration in at least 1 treatment period.
Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data.
Outcome measures
| Measure |
Period 1: Tolbutamide
n=12 Participants
Participants in Period 1 were dosed with a single administration of tolbutamide 500 mg tablet on Day 1.
|
Period 2: Ritlecitinib + Tolbutamide
n=10 Participants
Participants in Period 2 were dosed with oral 200 mg ritlecitinib QD for 10 days followed by administration of a single dose of 500 mg tolbutamide oral tablet within approximately 5 minutes after administration of ritlecitinib on the morning of Day 10.
|
Period 2: Ritlecitinib + Tolbutamide
Participants in Period 2 were dosed with oral 200 mg ritlecitinib QD for 10 days followed by administration of a single dose of 500 mg tolbutamide oral tablet within approximately 5 minutes after administration of ritlecitinib on the morning of Day 10.
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Tolbutamide Administered With and Without Ritlecitinib
|
44240 ng/mL (nanogram/milliliter)
Geometric Coefficient of Variation 15
|
45740 ng/mL (nanogram/milliliter)
Geometric Coefficient of Variation 17
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, and 36 hours post-dose in Period 1 (Days 1 and 2) and Period 2 (Days 10 and 11)Population: Analysis population included all participants treated who had at least 1 concentration in at least 1 treatment period.
AUCinf was defined as area under the plasma concentration time profile from time 0 extrapolated to infinite time.
Outcome measures
| Measure |
Period 1: Tolbutamide
n=12 Participants
Participants in Period 1 were dosed with a single administration of tolbutamide 500 mg tablet on Day 1.
|
Period 2: Ritlecitinib + Tolbutamide
n=10 Participants
Participants in Period 2 were dosed with oral 200 mg ritlecitinib QD for 10 days followed by administration of a single dose of 500 mg tolbutamide oral tablet within approximately 5 minutes after administration of ritlecitinib on the morning of Day 10.
|
Period 2: Ritlecitinib + Tolbutamide
Participants in Period 2 were dosed with oral 200 mg ritlecitinib QD for 10 days followed by administration of a single dose of 500 mg tolbutamide oral tablet within approximately 5 minutes after administration of ritlecitinib on the morning of Day 10.
|
|---|---|---|---|
|
Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Tolbutamide Administered With and Without Ritlecitinib
|
608600 ng*hr/mL
Geometric Coefficient of Variation 20
|
586500 ng*hr/mL
Geometric Coefficient of Variation 30
|
—
|
SECONDARY outcome
Timeframe: From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)Population: Analysis population included all participants assigned to the study intervention and who took at least 1 dose of the study intervention. Participants were analyzed according to the intervention they actually received.
An adverse event (AE) was any untoward medical occurrence in a clinical investigation where participants were administered a product; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug.
Outcome measures
| Measure |
Period 1: Tolbutamide
n=12 Participants
Participants in Period 1 were dosed with a single administration of tolbutamide 500 mg tablet on Day 1.
|
Period 2: Ritlecitinib + Tolbutamide
n=10 Participants
Participants in Period 2 were dosed with oral 200 mg ritlecitinib QD for 10 days followed by administration of a single dose of 500 mg tolbutamide oral tablet within approximately 5 minutes after administration of ritlecitinib on the morning of Day 10.
|
Period 2: Ritlecitinib + Tolbutamide
n=10 Participants
Participants in Period 2 were dosed with oral 200 mg ritlecitinib QD for 10 days followed by administration of a single dose of 500 mg tolbutamide oral tablet within approximately 5 minutes after administration of ritlecitinib on the morning of Day 10.
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|---|---|---|---|
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - All Causalities and Treatment Related
All-Causality
|
1 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - All Causalities and Treatment Related
Treatment-Related
|
0 Participants
|
0 Participants
|
1 Participants
|
Adverse Events
Period 1: Tolbutamide
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Period 2: Ritlecitinib
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Period 2: Ritlecitinib + Tolbutamide
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 |
Period 1: Tolbutamide
n=12 participants at risk
Participants in Period 1 were dosed with a single administration of tolbutamide 500 mg tablet on Day 1.
|
Period 2: Ritlecitinib
n=10 participants at risk
Participants in Period 2 were dosed with oral 200 mg ritlecitinib QD for 10 days.
|
Period 2: Ritlecitinib + Tolbutamide
n=10 participants at risk
Participants in Period 2 were dosed with oral 200 mg ritlecitinib QD for 10 days followed by administration of a single dose of 500 mg tolbutamide oral tablet within approximately 5 minutes after administration of ritlecitinib on the morning of Day 10.
|
|---|---|---|---|
|
General disorders
Pain
|
0.00%
0/12 • From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)
The same event may appear as both an AE and a serious adverse event (SAE). An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
10.0%
1/10 • From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)
The same event may appear as both an AE and a serious adverse event (SAE). An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
0.00%
0/10 • From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)
The same event may appear as both an AE and a serious adverse event (SAE). An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
|
Infections and infestations
COVID-19
|
8.3%
1/12 • From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)
The same event may appear as both an AE and a serious adverse event (SAE). An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
0.00%
0/10 • From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)
The same event may appear as both an AE and a serious adverse event (SAE). An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
10.0%
1/10 • From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)
The same event may appear as both an AE and a serious adverse event (SAE). An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/12 • From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)
The same event may appear as both an AE and a serious adverse event (SAE). An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
0.00%
0/10 • From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)
The same event may appear as both an AE and a serious adverse event (SAE). An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
10.0%
1/10 • From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)
The same event may appear as both an AE and a serious adverse event (SAE). An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.00%
0/12 • From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)
The same event may appear as both an AE and a serious adverse event (SAE). An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
10.0%
1/10 • From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)
The same event may appear as both an AE and a serious adverse event (SAE). An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
0.00%
0/10 • From screening up to a follow-up phone call between 28 and 35 calendar days after the last administration of the investigational product and early termination (if applicable)
The same event may appear as both an AE and a serious adverse event (SAE). An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place