Brodalumab Drug-Drug Interaction (DDI) and Intensive Pharmacodynamic (PK) Study in Psoriasis Subjects

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-label Study to Evaluate the Effect of Brodalumab on the Pharmacokinetics of Midazolam and Assess Single-Dose Brodalumab Pharmacokinetics in Subjects With Moderate to Severe Plaque Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Brodalumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brodalumab 140mg SC<br>open label, all subjects receive brodulamab | Drug: Brodalumab<br>* 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.<br>* Other names: AMG 827;|
| Experimental: Midazolam (MDZ) 2mg oral, Brodalumab 210mg SC<br>MDZ 2mg oral (Day 1 and Day 9), Brodalumab 210mg SC (Day 2) | Drug: Brodalumab<br>* 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.<br>* Other names: AMG 827;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Day 1 to day 9 | 
| 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 | Day 1 to Day 9 | 
| 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 | Day 1 to Day 9 |