NCT02607774

Investigate Effect of Secukinumab on the PK of Midazolam in Patients With Mod to Sev Plaque Psoriasis

An Open-label, Single Sequence Crossover, Study Investigating the Influence of Secukinumab Treatment on the Pharmacokinetics of Midazolam as a CYP3A4 Substrate in Patients With Moderate to Severe Plaque Psoriasis

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To determine whether secukinumab can alter the activity of cytochrome P450 (CYP) 3A4 using midazolam as probe substrate in patients with moderate-to-severe plaque psoriasis.

Detailed description

This will be an open-label, confirmatory study investigating potential disease-drug-drug interaction of secukinumab and midazolam in male and female patients with moderate-to-severe plaque psoriasis. A total of approximately 25 patients are required to obtain at least 20 completers in the study Patients who meet the eligibility criteria at screening, will have a baseline assessment day (within 1 week prior to the start of secukinumab) during which a full midazolam PK profile after a single oral dose of 5 mg will be assessed by collecting blood over the 12 hour postdose period. On Day 1 (Week 0), Day 8 (Week 1), Day 15 (Week 2), Day 22 (Week 3) and Day 29 (Week 4) patients will receive 300 mg s.c. secukinumab (2 injections of 150 mg s.c.). On Day 8 and on Day 36 (Week 5), patients will receive additional single doses of 5 mg oral midazolam (total of 3 single doses). The midazolam PK profile will be assessed over the 12 hour postdose period. On those days when midazolam PK profiles are assessed, samples will be collected and analyzed for circulating IL-6, inflammatory panel (collected at screening, baseline and pre-dose Day 1 only), total IL-17A (after following initiation of secukinumab treatment), hsCRP and for 4-beta-hydroxycholesterol (exploratory endogenous phenotyping marker of CYP3A activity). There will be an extended treatment period during which patients will receive secukinumab 300 mg s.c. at Weeks 8, 12, 16, 20 and 24. Then there will be a follow-up period of 12 weeks following the last dose administered at Week 24. Visits will be at Weeks 28, 32 and 36.

Conditions

• Moderate to Severe Plaque Psoriasis

Interventions

Type	Name	Description
DRUG	Midazolam	midazolam administered to all patients Days -7, 1 and 35.
DRUG	AIN457	secukinumab administered at Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24

Timeline

• Start date: 2015-12-17
• Primary completion: 2016-12-20
• Completion: 2016-12-20
• First posted: 2015-11-18
• Last updated: 2020-12-11

Locations

8 sites across 1 country: United States

Regulatory

• FDA-regulated drug study