Clinical trial NCT02607774: Investigate Effect of Secukinumab on the PK of Midazolam in Patients With Mod to Sev Plaque Psoriasis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Moderate to Severe Plaque Psoriasis
Keywords: Plaque psoriasis
disease-drug-drug-interaction
midazolam
secukinumab
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-11-18
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Moderate to severe plaque psoriasis as defined at baseline by: PASI score of 12 or greater and IGA mod 2011 score of 3 or greater (based on a scale of 0 - 4) and Body Surface Area (BSA) affected by plaque-type psoriasis of 10% or greater.
* Chronic plaque-type psoriasis considered inadequately controlled by: topical treatment and/or; phototherapy and/or previous systemic therapy
* Men or women at least 18 years of age or older at time of screening.

Exclusion Criteria:

* Forms of psoriasis other than chronic plaque-type
* Pregnant or nursing (lactating) women,
* History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection.
* Subjects with known history of hypersensitivity to midazolam

Primary outcomes:
measure: Cmax (maximum plasma) concentration
timeFrame: Days -7, 8 and 36
measure: AUC0-12 (area under the plasma concentration-time curve from time zero to time 12 hours )
timeFrame: Days -7, 8 and 36
measure: AUClast (area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration)
timeFrame: Days -7, 8 and 36
measure: AUCinf (area under the plasma concentration-time curve from time zero to infinity)
timeFrame: Days -7, 8 and 36
Secondary outcomes:
measure: safety and tolerability (including; Blood pressure,Pulse Rate,AEs/SAEs, Blood chemistry, Hematology, ECGs and physical exam
timeFrame: Throughout the entire trial; beginning at screening through Day 253 (end of trial)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Hot Springs
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Fair Lawn
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Verona
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Webster
country: United States
facility: Novartis Investigative Site
state: Texas
city: Norfolk
country: United States
facility: Novartis Investigative Site
state: Virginia
Study officials:
References: