Psoriasis
Conditions
Brief summary
This is a phase 1, multi-center, open-label, drug-drug interaction (DDI) and PK study in subjects with moderate to severe plaque psoriasis. It is designed to evaluate the effect of brodalumab on midazolam PK in addition to assessing single dose PK of brodalumab in subjects with moderate to severe plaque psoriasis.
Detailed description
Approximately 30 subjects will be enrolled into two groups. Group 1 consists of 20 subjects and will receive 2 oral doses of midazolam and a single subcutaneous (SC) dose of brodalumab. Group 2 consists of 10 subjects and will receive a single SC dose of brodalumab.
Interventions
DRUGBrodalumab
Group 1 consists of 20 subjects and will receive 2 oral doses of midazolam and a single SC dose of brodalumab. Group 2 consists of 10 subjects and will receive a single SC dose of brodalumab.
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subject has had stable moderate to severe plaque psoriasis for at least 6 months * body mass index (BMI) between ≥ 18.0 and ≤ 38.0 kg/m2 * body weight between ≥ 50 and ≤ 130 kg * no known history of active tuberculosis
Exclusion criteria
* Female subjects who are lactating/breastfeeding * History or evidence of clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Maximum Observed Concentration of Midazolam After a Single Dose of Brodalumab | Day 1 to day 9 | Midazolam pharmacokinetic parameter estimates after single oral dose of Midazolam 2 mg on Day 1 and Day 9 and a single administration of Brodalumab 210 mg on Day 2 with PK sampling collected on Day 30 |
| The Area Under Drug Concentration Time Curve From Zero to Infinity (AUCinf) | Day 1 to Day 9 | Midazolam pharmacokinetic parameter estimates after single oral dose of Midazolam 2 mg on Day 1 and Day 9 and a single administration of Brodalumab 210 mg on Day 2 with PK sampling collected on day 30 |
| The Area Under the Drug-concentration Curve of Midazolam After a Single Dose of Brodalumab From Zero Tot he Last Time of Quantifiable Concentration | Day 1 to Day 9 | Midazolam pharmacokinetic parameter estimates after single oral dose of Midazolam 2 mg on Day 1 and Day 9 and a single administration of Brodalumab 210 mg on Day 2 |
Countries
Australia, New Zealand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Midazolam (MDZ) 2mg oral (Day 1 and Day 9) Brodalumab 210mg SC (Day 2) | 21 |
| Cohort 2 Brodalumab 140mg SC (Day1) | 10 |
| Total | 31 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 10 Participants | 31 Participants |
| Age, Continuous | 41.2 years STANDARD_DEVIATION 10.9 | 46.8 years STANDARD_DEVIATION 15.6 | 43 years STANDARD_DEVIATION 12.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 8 Participants | 24 Participants |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 24 Participants |
| Sex: Female, Male Male | 6 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 20 | 5 / 10 |
| serious Total, serious adverse events | 0 / 20 | 0 / 10 |
Outcome results
Primary
The Area Under Drug Concentration Time Curve From Zero to Infinity (AUCinf)
Midazolam pharmacokinetic parameter estimates after single oral dose of Midazolam 2 mg on Day 1 and Day 9 and a single administration of Brodalumab 210 mg on Day 2 with PK sampling collected on day 30
Time frame: Day 1 to Day 9
Population: 20 subjects analyzed after the discontinuation of 1 subject by sponsor decision
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | The Area Under Drug Concentration Time Curve From Zero to Infinity (AUCinf) | 41.5 hr*ng/mL | Standard Deviation 22.1 |
Primary
The Area Under the Drug-concentration Curve of Midazolam After a Single Dose of Brodalumab From Zero Tot he Last Time of Quantifiable Concentration
Midazolam pharmacokinetic parameter estimates after single oral dose of Midazolam 2 mg on Day 1 and Day 9 and a single administration of Brodalumab 210 mg on Day 2
Time frame: Day 1 to Day 9
Population: 20 subjects are now analyzed after the discontinuation of 1 subject by sponsor decision
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | The Area Under the Drug-concentration Curve of Midazolam After a Single Dose of Brodalumab From Zero Tot he Last Time of Quantifiable Concentration | 39 hr*ng/mL | Standard Deviation 19.2 |
Primary
The Maximum Observed Concentration of Midazolam After a Single Dose of Brodalumab
Midazolam pharmacokinetic parameter estimates after single oral dose of Midazolam 2 mg on Day 1 and Day 9 and a single administration of Brodalumab 210 mg on Day 2 with PK sampling collected on Day 30
Time frame: Day 1 to day 9
Population: Analysis population is now 20 subjects after 1 subject was discontinued by sponsor decision
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | The Maximum Observed Concentration of Midazolam After a Single Dose of Brodalumab | 11.5 nanograms per milliliter | Standard Deviation 4.59 |