Trial Outcomes & Findings for A Study to Assess the Effects of Nemolizumab on Cytochrome P450 Substrates in Participants With Moderate-to-Severe Atopic Dermatitis (NCT NCT04562116)

Last Updated: 2024-12-05

Results Overview

AUC (0-infinity) was defined as AUC from time 0 to infinity, calculated as the sum of AUC (0-last) and C(last)/lambda(z); where C(last) was the last observed measurable (non-BQL) concentration; and lambda(z) was apparent terminal elimination rate constant. Probe drugs included Caffeine, Metoprolol Tartrate, Midazolam, Omeprazole and Warfarin Sodium. Change in AUC(0-infinity) of each of the 5 probe drugs before (Baseline) and after 9-week nemolizumab treatment is reported.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

Baseline (before nemolizumab injection, at Week 0) and Week 10 (after nemolizumab injection): Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 72 and 120 hours post-dose

Results posted on

2024-12-05

Participant Flow

The study was conducted at 2 sites in the United States and Bulgaria from 08 December 2021 to 07 June 2023.

A total of 48 participants were screened, out of which 17 participants were enrolled in this study and 16 participants received at least 1 dose of nemolizumab.

Participant milestones

Participant milestones
Measure	CYP 450 Substrates Plus Nemolizumab Participants received a single oral dose of selected, commercially available, cytochrome P450 substrates (CYP450-S) (caffeine 100 milligrams \[mg\], warfarin sodium 10 mg, midazolam 2 mg, omeprazole 20 mg, and metoprolol tartrate 100 mg) on Day 1. After a 1-week washout period, participants received a 60 mg loading dose of nemolizumab via 2 consecutive subcutaneous (SC) 30-mg injections at the Week 1 visit, followed by a single 30-mg injection once every 4 weeks (Q4W) at Week 5 and Week 9. Participants received a second oral dosing of CYP450-S at Week 10.
Overall Study STARTED	17
Overall Study Safety Population	16
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	CYP 450 Substrates Plus Nemolizumab Participants received a single oral dose of selected, commercially available, cytochrome P450 substrates (CYP450-S) (caffeine 100 milligrams \[mg\], warfarin sodium 10 mg, midazolam 2 mg, omeprazole 20 mg, and metoprolol tartrate 100 mg) on Day 1. After a 1-week washout period, participants received a 60 mg loading dose of nemolizumab via 2 consecutive subcutaneous (SC) 30-mg injections at the Week 1 visit, followed by a single 30-mg injection once every 4 weeks (Q4W) at Week 5 and Week 9. Participants received a second oral dosing of CYP450-S at Week 10.
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	3

Baseline Characteristics

A Study to Assess the Effects of Nemolizumab on Cytochrome P450 Substrates in Participants With Moderate-to-Severe Atopic Dermatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CYP 450 Substrates Plus Nemolizumab n=17 Participants Participants received a single oral dose of selected, commercially available, CYP450-S (caffeine 100 mg, warfarin sodium 10 mg, midazolam 2 mg, omeprazole 20 mg, and metoprolol tartrate 100 mg) on Day 1. After a 1-week washout period, participants received a 60 mg loading dose of nemolizumab via 2 consecutive SC 30-mg injections at the Week 1 visit, followed by a single 30-mg injection Q4W at Week 5 and Week 9. Participants received a second oral dosing of CYP450-S at Week 10.
Age, Continuous	47.0 years STANDARD_DEVIATION 7.64 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (before nemolizumab injection, at Week 0) and Week 10 (after nemolizumab injection): Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 72 and 120 hours post-dose

Population: Analysis was performed on the per-protocol population, which included all participants who completed the treatment period without any major protocol deviations or any other event that could render the probe drugs plasma concentration-time profiles unreliable. Here, number analyzed signifies the number of participants evaluable for each specified category.

Outcome measures

Outcome measures
Measure	Before Nemolizumab Injections n=14 Participants Plasma pharmacokinetic parameters assessed before Nemolizumab injections i.e., at Baseline (Week 0).	After Nemolizumab Injections n=14 Participants Plasma pharmacokinetic parameters assessed after 9 weeks of Nemolizumab injections i.e., at Week 10.
Change in Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Omeprazole	932 hour*microgram per liter Standard Deviation 851	976 hour*microgram per liter Standard Deviation 715
Change in Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Warfarin Sodium	20268 hour*microgram per liter Standard Deviation 5261	20399 hour*microgram per liter Standard Deviation 4153
Change in Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Midazolam	27.7 hour*microgram per liter Standard Deviation 1.60	29.6 hour*microgram per liter Standard Deviation 15.0
Change in Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Caffeine	27064 hour*microgram per liter Standard Deviation 16807	25281 hour*microgram per liter Standard Deviation 15146
Change in Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Metoprolol Tartrate	822 hour*microgram per liter Standard Deviation 698	845 hour*microgram per liter Standard Deviation 792

PRIMARY outcome

Timeframe: Baseline (before nemolizumab injection, at Week 0) and Week 10 (after nemolizumab injection): Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 72 and 120 hours post-dose

AUC (0-last) was defined as AUC from time 0 to the time of the last measurable (non-BQL) concentration, calculated by linear-linear trapezoidal summation. Probe drugs included Caffeine, Metoprolol Tartrate, Midazolam, Omeprazole and Warfarin Sodium. Change of AUC(0-last) of each of the 5 probe drugs before (Baseline) and after 9-week nemolizumab treatment is reported.

Outcome measures

Outcome measures
Measure	Before Nemolizumab Injections n=14 Participants Plasma pharmacokinetic parameters assessed before Nemolizumab injections i.e., at Baseline (Week 0).	After Nemolizumab Injections n=14 Participants Plasma pharmacokinetic parameters assessed after 9 weeks of Nemolizumab injections i.e., at Week 10.
Change in Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last]) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Caffeine	25294 hour*microgram per liter Standard Deviation 15633	23805 hour*microgram per liter Standard Deviation 13334
Change in Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last]) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Metoprolol Tartrate	803 hour*microgram per liter Standard Deviation 666	820 hour*microgram per liter Standard Deviation 742
Change in Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last]) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Midazolam	26.5 hour*microgram per liter Standard Deviation 12.4	28.5 hour*microgram per liter Standard Deviation 13.9
Change in Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last]) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Omeprazole	892 hour*microgram per liter Standard Deviation 825	796 hour*microgram per liter Standard Deviation 718
Change in Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last]) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Warfarin Sodium	18034 hour*microgram per liter Standard Deviation 4100	18068 hour*microgram per liter Standard Deviation 3470

PRIMARY outcome

Timeframe: Baseline (before nemolizumab injection, at Week 0) and Week 10 (after nemolizumab injection): Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 72 and 120 hours post-dose

Cmax was defined as the maximum observed plasma concentration. Probe drugs included Caffeine, Metoprolol Tartrate, Midazolam, Omeprazole and Warfarin Sodium. Cmax of each of the 5 probe drugs before (Baseline) and after 9-week nemolizumab treatment is reported.

Outcome measures

Outcome measures
Measure	Before Nemolizumab Injections n=14 Participants Plasma pharmacokinetic parameters assessed before Nemolizumab injections i.e., at Baseline (Week 0).	After Nemolizumab Injections n=14 Participants Plasma pharmacokinetic parameters assessed after 9 weeks of Nemolizumab injections i.e., at Week 10.
Maximum Observed Plasma Concentration (Cmax) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Metoprolol Tartrate	200 micrograms per liter Standard Deviation 131	187 micrograms per liter Standard Deviation 114
Maximum Observed Plasma Concentration (Cmax) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Midazolam	12.8 micrograms per liter Standard Deviation 5.31	11.8 micrograms per liter Standard Deviation 4.09
Maximum Observed Plasma Concentration (Cmax) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Omeprazole	374 micrograms per liter Standard Deviation 205	349 micrograms per liter Standard Deviation 290
Maximum Observed Plasma Concentration (Cmax) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Warfarin Sodium	695 micrograms per liter Standard Deviation 159	651 micrograms per liter Standard Deviation 174
Maximum Observed Plasma Concentration (Cmax) of Each of the 5 Probe Drugs Before and After 9-week Nemolizumab Treatment Caffeine	3922 micrograms per liter Standard Deviation 1563	3688 micrograms per liter Standard Deviation 1512

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Analysis was performed on the safety population. The safety population included all participants who received at least 1 dose of nemolizumab.

An AE is defined as any untoward medical occurrence in a study participant administered a medicinal product which does not necessarily have a causal relationship with this treatment. SAE is any untoward medical occurrence that at any dose may results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. A TEAE is defined as an AE that occurs on or after the first date of study drug(s) administration until the date of last study visit. An AESI is a noteworthy treatment-emergent event for the study drug that should be monitored closely and reported promptly.

Outcome measures

Outcome measures
Measure	Before Nemolizumab Injections n=16 Participants Plasma pharmacokinetic parameters assessed before Nemolizumab injections i.e., at Baseline (Week 0).	After Nemolizumab Injections Plasma pharmacokinetic parameters assessed after 9 weeks of Nemolizumab injections i.e., at Week 10.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) TEAEs	0 Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) AESIs	0 Participants	—
Number of Participants With Treatment Emergent Adverse Events (TEAEs), AEs of Special Interest (AESIs), and Serious AEs (SAEs) SAEs	0 Participants	—

Adverse Events

CYP 450 Substrates Plus Nemolizumab

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Clinical Operations

Galderma

Phone: 08179615000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER